研究者情報

マスター

アカウント（マスター）

• 氏名

  池田　敦子(イケダ　アツコ), イケダ　アツコ

所属（マスター）

• 保健科学研究院　保健科学部門　健康科学分野

所属（マスター）

• 保健科学研究院　保健科学部門　健康科学分野

独自項目

syllabus

• 2021, 大学院共通授業科目（教育プログラム）：社会と健康, Inter-Graduate School Classes(Educational Program):Health, Society and Environment, 修士課程, 大学院共通科目, Plastics, Plastic Additives, Microplastics, Health effects, Environmental pollution, Toxicology
• 2021, 予防看護学演習, Seminar on Preventive Nurcing, 修士課程, 保健科学院, 予防看護学、疾病の予防、文献検索法，論文輪講、実験計画法，研究発表技法，研究技法
• 2021, 予防看護学特論, Preventive Nurcing, 修士課程, 保健科学院, 予防看護、健康、ストレス因子、生誕反応、疾病の予防、健康の保持・増進
• 2021, 大学院共通授業科目（教育プログラム）：社会と健康, Inter-Graduate School Classes(Educational Program):Health, Society and Environment, 修士課程, 大学院共通科目, 環境、健康、リスク、法規、人
• 2021, 大学院共通授業科目（教育プログラム）：社会と健康, Inter-Graduate School Classes(Educational Program):Health, Society and Environment, 修士課程, 大学院共通科目, SDGs, Environmental Health
• 2021, 環境健康科学演習, Exercise on Environmental Health Sciences, 修士課程, 保健科学院, 環境，健康，生命，環境影響評価法，論文輪講、研究発表技法，文献検索法，実験計画法，研究技法
• 2021, 環境健康科学特論, Environmental Health Sciences, 修士課程, 保健科学院, 環境，健康，生命，環境影響評価，酸素，ミネラル，食物
• 2021, 大学院共通授業科目（教育プログラム）：社会と健康, Inter-Graduate School Classes(Educational Program):Health, Society and Environment, 修士課程, 大学院共通科目, Environment, Health, Chemicals, Policy, Toxicity, group works
• 2021, 基礎環境保健学, Basic Environmental Health Sciences, 修士課程, 医学院, 環境、健康、リスク、法規、人
• 2021, 食資源と健康, Food Resources and Health, 修士課程, 国際食資源学院, 健康，食，栄養学，環境，人類生態学，人間栄養学，脂質，酸化，糖鎖生物学，蛋白質，腸内環境，機能性食品、ポストハーベスト加工技術
• 2021, 公衆衛生看護疫学演習, Seminar on Public Health Nursing Epidemiology, 修士課程, 保健科学院, 疫学，疾病頻度，疫学研究，スクリーニング，精度管理，疾病予防，感染症の疫学，非感染性疾病の疫学，環境疫学, 空間疫学，政策疫学
• 2021, 大学院共通授業科目（教育プログラム）：社会と健康, Inter-Graduate School Classes(Educational Program):Health, Society and Environment, 修士課程, 大学院共通科目, 疫学研究
• 2021, 応用疫学, Advanced Epidemiology, 修士課程, 医学院, 疫学研究
• 2021, 大学院共通授業科目（教育プログラム）：JICA開発大学院連携プログラム, Inter-Graduate School Classes(Educational Program):JICA Development Study Program, 修士課程, 大学院共通科目, Health Sciences development, modernization of Japan, pollution, sanitation, infectious disease, industrial structure, transition of disease structure
• 2021, 大学院共通授業科目（教育プログラム）：社会と健康, Inter-Graduate School Classes(Educational Program):Health, Society and Environment, 修士課程, 大学院共通科目, 健康科学，環境，人類生態，遺伝・細胞，代謝，ストレス応答，生体計測，健康情報，栄養、精神的健康
• 2021, 公衆衛生学Ⅰ, Public Health Ⅰ, 学士課程, 医学部, 衛生・公衆衛生，健康，社会，保健統計，疫学，ライフスタイル
• 2021, 公衆衛生学Ⅱ, Public Health Ⅱ, 学士課程, 医学部, 衛生・公衆衛生，健康，環境保健，水質・空気，地球環境問題，産業保健，保健行政
• 2021, 公衆衛生学概論, Public Health and Hygienics, 学士課程, 医学部, 衛生・公衆衛生，健康，保健統計，疫学，環境保健，産業保健，保健行政
• 2021, 環境保健学, Environmental Health, 学士課程, 医学部, 環境，疫学，健康，大気，水、地球環境問題，労働環境、環境測定、論文講読、発表、リスク管理
• 2021, 公衆衛生学実習, Practice in Public Health, 学士課程, 医学部, 水質検査，室内空気試験，環境衛生，食品衛生，疲労検査，衛生試験法

researchmap

プロフィール情報

所属

• 北海道大学, 大学院保健科学研究院, 教授
• 北海道大学, 環境健康科学研究教育センター

学位

• 博士（医学）（2011年03月 北海道大学）

プロフィール情報

• 姓

  池田, イケダ

• 名

  敦子, アツコ

通称等の別名

荒木敦子

対象リソース

https://researchers.general.hokudai.ac.jp/profile/ja.5bee2d734c4426ba520e17560c007669.html
https://researchers.general.hokudai.ac.jp/profile/en.5bee2d734c4426ba520e17560c007669.html

所属

• 北海道大学, 大学院保健科学研究院, 教授
• 北海道大学, 環境健康科学研究教育センター

業績リスト

研究キーワード

• 環境疫学、健康科学、室内環境、環境化学物質、フタル酸エステル類、リン系難燃剤、有機フッ素化合物、アレルギー、性腺機能、出生コーホート   

研究分野

• ライフサイエンス / 衛生学、公衆衛生学分野：実験系を含まない
• ライフサイエンス / 衛生学、公衆衛生学分野：実験系を含む

経歴

• 2021年04月 - 現在 北海道大学 大学院保健科学研究院 教授
• 2011年04月 - 現在 北海道大学 環境健康科学研究教育センター
• 1992年04月 - 2000年11月 万有製薬株式会社 つくば研究所

学歴

• 2008年04月 - 2011年02月   北海道大学   大学院医学研究科   博士課程
• 2006年04月 - 2008年03月   北海道大学   大学院医学研究科   修士課程
• 1988年04月 - 1992年03月   東京理科大学   基礎工学部   生物工学科

論文

• Determination of plasma lysophosphatidylethanolamines (lyso-PE) by LC-MS/MS revealed a possible relation between obesity and lyso-PE in Japanese preadolescent children: the Hokkaido study.

  Nao Inoue, Siddabasave Gowda B Gowda, Divyavani Gowda, Toshihiro Sakurai, Atsuko Ikeda-Araki, Yu Ait Bamai, Rahel Mesfin Ketema, Reiko Kishi, Hitoshi Chiba, Shu-Ping Hui

  Annals of clinical biochemistry 45632241280352 - 45632241280352 2024年08月21日 [査読有り]
   

  BACKGROUND: Lysophosphatidylethanolamines (lyso-PEs) are the partial hydrolysis products of phosphatidylethanolamine. Although lyso-PEs are important biomarkers in various diseases, their determination is limited by the lack of simple and efficient quantification methods. This study aims to develop an improved quantitative method for the determination of lyso-PEs and its application to an epidemiological study. METHODS: Single reaction monitoring channels by collision-induced dissociation for seven lyso-PEs were established using liquid chromatography-tandem mass spectrometry. Plasma lyso-PEs were extracted with a single-phase method using an isotopically labeled internal standard for quantification. The proposed method was adopted to define lyso-PEs in plasma samples of children aged 9-12 years living in Sapporo, Japan. RESULTS: The limit of detection and limit of quantification for each lyso-PE ranged between 0.001-0.015 and 0.002-0.031 pmol/μL, respectively. Recoveries were found to be > 91% for all the species. The analysis results of children's plasma showed that the total lyso-PE concentrations in boys (n = 181) and girls (n = 161) were 11.53 and 11.00 pmol/μL (median), respectively. Participants were further classified by the percentage of overweight and subgrouped as underweight (n = 12), normal range (n = 292), or overweight (n = 38). Interestingly, the reduction of lyso-PE 16:0 and increased lyso-PE 22:6 were observed in overweight children compared with normal range (Fold change: 0.909 and 1.174, respectively). CONCLUSIONS: This study successfully established a simple quantitative method to determine lyso-PE concentrations. Furthermore, our method revealed the possible relation between plasma lyso-PEs and overweight status.
• Quantitative determination of plasma cholesteryl ester levels in Japanese preadolescents from the Hokkaido study using liquid chromatography/tandem mass spectrometry.

  Divyavani Gowda, Siddabasave Gowda B Gowda, Atsuko Ikeda, Rahel Mesfin Ketema, Yu Ait Bamai, Reiko Kishi, Hitoshi Chiba, Shu-Ping Hui

  Steroids 211 109498 - 109498 2024年08月13日 [査読有り]
   

  Cholesteryl esters (CE) are sterols comprising various fatty acyl chains attached to a cholesterol hydroxyl moiety. CEs are often considered plasma biomarkers of liver function; however, their absolute concentrations in the plasma of Japanese preadolescents have not been well explored. This study aimed to determine the plasma CE levels in Japanese preadolescents of different sexes, ages, and body weights living in Hokkaido, Japan using targeted liquid chromatography/tandem mass spectrometry. The analysis was performed on the non-fasting plasma of preadolescents aged 9-12 years (n = 339 healthy volunteers; 178 boys and 161 girls) from Sapporo, Hokkaido, Japan. The analysis results showed that the total CE levels in boys and girls were 871 ± 153 and 862 ± 96 pmol/μL, respectively. CE 18:2 (41 ± 2.9 %) was found to be the most abundant species followed by CE 18:1 (16 ± 1.5 %) and CE 16:0 (13 ± 1.1 %). The ω-3 fatty acid-containing CEs such as CE 18:3 and CE 20:5 were significantly lower in girls than in boys. Despite the different ages, CEs were tightly regulated in the plasma of children's, and the total CEs ranged between 844 and 906 pmol/μL in boys and 824 and 875 pmol/μL in girls. The participants were further classified into three groups based on their body mass index underweight (n = 237), normal weight (n = 94), and overweight (n = 8). Most of the quantified CEs were accumulated in the overweight group. Interestingly, CE 18:3 was significantly upregulated in the overweight group compared to that in the normal range, and the area under the receiver operating characteristic curve was 0.73, suggesting that it could be a possible marker for obesity. This study marks the initial investigation of absolute CE levels in the plasma of children and can help elucidate the relationship between CEs and childhood obesity.
• Link between Wi-Fi, cordless devices, mobile phone usage patterns, and behavioral problems among Japanese children: A prospective cohort study.

  Ammara Ajmal, Keiko Yamazaki, Naomi Tamura, Yu Ait Bamai, Toshio Yoshikawa, Takashi Hikage, Atsuko Ikeda, Reiko Kishi

  Environmental research 261 119715 - 119715 2024年08月02日 [査読有り]
   

  BACKGROUND: With the recent advent of technology, it is important to confirm the health and safety of the youth. This study aimed to prospectively evaluate the relationship between Wi-Fi, cordless phones, and mobile phone usage patterns and behavioral problems. METHODS: This study involved 2465 children aged 8-17 years from the Hokkaido Study on Environment and Children's Health from October 2020 to January 2021, with a follow-up from September 2021 to March 2022. The mother-child dyad provided information on the presence of residential Wi-Fi and cordless phones, cordless phone call duration, and mobile phone usage pattern (duration of calls using mobile network and internet, online audio streaming, online video streaming, and playing online games) via a baseline questionnaire. Based on the scores on Strength and Difficulties Questionnaire at baseline and follow-up, the children were categorized into four groups: normal, persistent, improved, and concurrent. RESULTS: No significant association was found between Wi-Fi, mobile phone calls via mobile networks, and behavioral problems. Cordless phone at home had higher odds for improvement in total difficulty scores, and cordless phone for calling more than 4 min per week had lower odds of persistent problematic prosocial behavior. Longer duration of mobile phone calling via the internet (>40 min/week) had higher odds of concurrent total difficulties. Mobile phone calling via mobile network for <5 min per week had higher odds for improved total difficulty scores. Audio streaming via mobile phones for 60-120 min had lower odds of persistent total difficulties. CONCLUSION: Our results showed sporadic findings between residential RF-EMF indoor sources and mobile phone usage pattern. These observed findings could be affected by residual confounding and chance findings. Ongoing follow-up studies are necessary to further explore this association through detailed exposure assessment and addressing the potential limitations of our study.
• Alterations in plasma short-chain fatty acids in preadolescence children: The Hokkaido study.

  Yonghan Li, Siddabasave Gowda B Gowda, Divyavani Gowda, Atsuko Ikeda, Yu Ait Bamai, Rahel Mesfin Ketema, Reiko Kishi, Hitoshi Chiba, Shu-Ping Hui

  Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 1242 124191 - 124191 2024年07月15日 [査読有り]
   

  The purpose of this study is to explore the plasma short-chain fatty acid (SCFA) concentrations in 9-12-year-old Japanese children collected in the Hokkaido study, focusing on how factors such as age, sex, and body mass index (BMI) correlate with these levels. The Hokkaido Study on Children's Health is an ongoing longitudinal study since 2002, encompassing 20,926 pregnant women in Hokkaido Prefecture, Japan, between 2003 and 2012. We contacted 1881 children aged 9-12 born between April 2006 and January 2010, and 342 non-fasting plasma samples (boys = 181, girls = 161) were obtained from this cohort, alongside assessments of their height and weight. Plasma SCFA concentrations were determined using N,N-dimethylethylenediamine derivatization method coupled with liquid chromatography-mass spectrometry. Ethyl acetate was used to extract SCFAs from plasma, and the recovery ranged from 83 % to 108 %. Our findings indicate that acetic acid had the highest concentration across all age groups and sexes. The concentrations of butyric acid, valeric acid, and hexanoic acid increased with age, peaking in 12-year-old children. Conversely, the level of 4-hydroxy valeric acid showed a decreasing trend with increasing age groups. This study also explored the correlation between BMI and SCFA concentrations, comparatively higher level of propionic acid was observed in the overweight group. The results obtained in this study enhance our understanding of the role of SCFAs in the growth and development of children and provide a foundation for future nutritional intervention and health promotion strategies.
• Prenatal risk factors of indoor environment and incidence of childhood eczema in the Japan Environment and Children's Study

  Yu Ait Bamai, Chihiro Miyashita, Atsuko Ikeda, Keiko Yamazaki, Sumitaka Kobayashi, Sachiko Itoh, Yasuaki Saijo, Yoshiya Ito, Eiji Yoshioka, Yukihiro Sato, Reiko Kishi, Michihiro Kamijima, Shin Yamazaki, Yukihiro Ohya, Nobuo Yaegashi, Koichi Hashimoto, Chisato Mori, Shuichi Ito, Zentaro Yamagata, Hidekuni Inadera, Takeo Nakayama, Tomotaka Sobue, Masayuki Shima, Hiroshige Nakamura, Narufumi Suganuma, Koichi Kusuhara, Takahiko Katoh

  Environmental Research 2024年07月 [査読有り]
  
• Development of Older Adults' Perceptions on Community-based Connectedness with People Scale: Reliability and validity evaluation.

  Mami Kikuchi, Atsuko Ikeda, Michiyo Hirano

  Japan journal of nursing science : JJNS e12583  2024年01月12日 [査読有り]
   

  AIM: We developed a self-assessment scale-Older Adults' Perceptions of Community-based Connectedness with People-to assess older adults' comprehensive perceptions of their connectedness with others in the community. A specific aim of this study is to evaluate the reliability and validity of this scale. METHODS: Participants consisted of 1000 men and women aged 65 years or older, living in Sapporo, Hokkaido, Japan. Factorial validity was assessed using exploratory and confirmatory factor analysis, while concurrent validity was assessed using correlation analysis. Reliability was confirmed by Cronbach's α coefficient using the internal consistency method, and the stability coefficient was confirmed using the test-retest method. RESULTS: Responses were received from 380 participants, and 358 participants who responded to all items were included in the analysis. The developed scale comprised 22 items with three factors: "Perception of Inclusion" (α = .947), "Perception of Reciprocity through Reception" (α = .937), and "Perception of Reciprocity through Provision" (α = .910). Correlation analyses indicated that concurrent scales were positively correlated with Ikigai and negatively correlated with loneliness on the total scale. The model fit was comparative fit index = 0.933, goodness-of-fit index = 0.854, adjusted goodness-of-fit index = 0.818, and root mean square of approximation = 0.081. The stability coefficient of the total scale scores was 0.875 (95% CI: [0.830, 0.908]). CONCLUSIONS: The developed scale had adequate reliability and validity. The perceptions of connectedness measured using this scale can be used by public health and nursing care professionals to prevent loneliness and isolation among older adults living in the community.
• Heavy metals and trace elements in maternal blood and prevalence of congenital limb abnormalities among newborns: the Japan Environment and Children's Study.

  Atsuko Ikeda, Megasari Marsela, Chihiro Miyashita, Takeshi Yamaguchi, Yasuaki Saijo, Yoshiya Ito, Hiroyoshi Iwata, Sachiko Itoh, Mariko Itoh, Keiko Yamazaki, Naomi Tamura, Sumitaka Kobayashi, Reiko Kishi

  Environmental health and preventive medicine 29 36 - 36 2024年 [査読有り]
   

  BACKGROUND: Heavy metals such as lead (Pb) and cadmium (Cd) have been associated with adverse pregnancy and developmental outcomes, including congenital abnormalities. This study investigated the association between exposure to heavy metals and trace elements during fetal life and congenital limb abnormalities in infants. METHODS: This study is based on a prospective ongoing nationwide birth cohort from the Japan Environment and Children's Study (JECS). The concentrations of Cd, Pb, mercury (Hg), selenium (Se), and manganese (Mn) were measured in maternal blood collected during the mid-late trimesters. Inclusion criteria were available from questionnaires filled in during pregnancy, including information about congenital limb abnormalities at birth or at one month. To examine the associations with limb anomalies and individual chemicals, logistic regression models were applied following log-transformation or division into quartiles of Cd, Pb, Hg, Se, and Mn concentrations. To assess the associations with the heavy metals and trace elements mixture, quantile g-computation was employed. All models were adjusted for age, maternal smoking history, maternal alcohol intake, history of smoking, and infant sex. RESULTS: Data from 90,163 participants were included in the analysis, of whom 369 had congenital limb abnormalities in any of the collected information, and 89,794 had none. Among the 369 cases of congenital limb abnormalities, there were 185 and 142 cases of polydactyly and syndactyly, respectively. The median concentrations of Pb, Cd, Hg, Se, and Mn were 5.85, 0.66, 3.64, 168, and 15.3 ng/g, respectively. There were no associations between maternal blood concentrations of Pb [adjusted odd ratio = 0.83; 95% confidence interval = 0.61, 1.11], Cd [0.87; 0.68, 1.10], Hg [0.88; 0.73, 1.07], Se [1.07; 0.44, 2.59], and Mn [0.91; 0.64, 1.30] with congenital limb abnormalities. No significant association was observed between the mixture of heavy metals and trace elements [0.85; 0.72, 1.02] and any congenital limb abnormalities. Moreover, there was no association with all polydactylies and all syndactylies, or any type of abnormality as a subdivision. CONCLUSION: At the maternal exposure levels of Cd, Pb, Hg, Se, and Mn assessed in the present study, no association was identified with the risk of developing congenital limb abnormalities in children.
• The association between flooring materials and childhood asthma: A prospective birth cohort in the Japan Environment and Children's Study.

  Hiroyoshi Iwata, Atsuko Ikeda, Mariko Itoh, Sachiko Itoh, Rahel Mesfin Ketema, Naomi Tamura, Chihiro Miyashita, Takeshi Yamaguchi, Keiko Yamazaki, Rieko Yamamoto, Maki Tojo, Yasuaki Saijo, Yoshiya Ito, Reiko Kishi

  PloS one 19 7 e0305957  2024年 [査読有り]
   

  BACKGROUND: Childhood asthma is known to be affected by a range of factors, including conditions in the indoor environment. While flooring material influences indoor air conditions, the potential association between flooring materials and childhood asthma remains poorly understood in Japan. OBJECTIVE: The present study aims to assess the association between childhood asthma incidence and the primary flooring material with the ongoing prospective nationwide birth cohort data of the Japan Environment and Children's Study (JECS). METHODS: The JECS gathered data on mothers and children through 15 Regional Centres across Japan. The present study assessed flooring materials used in the home and asthma incidence at age four among children born between 2011 and 2014. We implemented logistic regressions, setting asthma incidence among the children as the outcome and home floor type as the exposure. Additional analyses were conducted, stratifying the home's age as a proxy for tatami age, to assess whether the potential effect of tatami flooring on asthma risk is influenced by its age. RESULTS: The present study included total of 75,629 infants. For tatami flooring, the main multivariable regression and additional sub-group regression for homes over ten years old produced odds ratios of 1.09; 95% Confidence Interval (CI) [1.01-1.17] and 1.10; 95% CI [1.00-1.21] compared with flooring, respectively. CONCLUSION: These results imply that exposure to tatami flooring, particularly in older homes, may be associated with childhood asthma incidence. Moreover, our study highlights the importance of evaluating the relationship between regional and cultural differences between asthma and flooring materials.
• Contributions of the light environment and co-sleeping to sleep consolidation into nighttime in early infants: A pilot study.

  Michiko Yoshida, Atsuko Ikeda, Hiroyuki Adachi

  Early human development 189 105923 - 105923 2023年12月22日 [査読有り]
   

  BACKGROUND: Sleep consolidation into nighttime is considered the primary goal of sleep development in early infants. However, factors contributing to sleep consolidation into nighttime remain unclear. AIM: To clarify the influences of the light environment and nighttime co-sleeping on sleep consolidation into nighttime in early infants. STUDY DESIGN: Cross-sectional study. SUBJECTS AND METHODS: Sleep-wake time and light stimulation were measured in infants for 4 consecutive days using actigraphy. The infants' mothers were asked to complete a sleep events diary and a questionnaire about childcare, including "co-sleeping", defined as when the infant and mother slept on the same surface throughout the night. OUTCOME MEASURES: The data were analyzed with a focus on daytime and nighttime sleep parameters. RESULTS: Daytime light stimulation reduced daytime "active sleep", tended to reduce daytime sleep, and increased daytime waking. Nighttime light stimulation reduced nighttime "quiet sleep" and nighttime sleep and increased nighttime waking. Co-sleeping reduced nighttime waking, and, as a result, nighttime sleep time and sleep efficiency increased. Co-sleeping reduced daytime sleep and tended to increase daytime waking. Consequently, co-sleeping tended to increase the ratio of nighttime sleep to daytime sleep. CONCLUSIONS: The present findings suggest that an appropriate light environment promotes daytime waking and nighttime sleep in early infants, but it does not contribute to sleep consolidation into nighttime by itself. On the other hand, co-sleeping may promote sleep consolidation into nighttime. Therefore, further methods for safe co-sleeping need to be established while avoiding risk factors for sudden unexpected death in infancy/sudden infant death syndrome.
• Mitochondrial DNA copy number variation across three generations: a possible biomarker for assessing perinatal outcomes.

  Hisanori Fukunaga, Atsuko Ikeda

  Human genomics 17 1 113 - 113 2023年12月15日 [査読有り]
   

  BACKGROUND: Mitochondria have their own circular multi-copy genome (mtDNA), and abnormalities in the copy number are implicated in mitochondrial dysfunction, which contributes to a variety of aging-related pathologies. However, not much is known about the genetic correlation of mtDNA copy number across multiple generations and its physiological significance. METHODS: We measured the mtDNA copy number in cord blood or peripheral blood from 149 three-generation families, specifically the newborns, parents, and grandparents, of 149 families, totaling 1041 individuals. All of the biological specimens and information were provided by the Tohoku Medical Megabank Project in Japan. We also analyzed their maternal factors during pregnancy and neonatal outcomes. RESULTS: While the maternal peripheral blood mtDNA copy number was lower than that of other adult family members, it was negatively correlated with cord blood mtDNA copy number in male infants. Also, cord blood mtDNA copy numbers were negatively correlated with perinatal outcomes, such as gestation age, birth weight, and umbilical cord length, for both male and female neonates. Furthermore, the mtDNA copy number in the infants born to mothers who took folic acid supplements during pregnancy would be lower than in the infants born to mothers who did not take them. CONCLUSIONS: This data-driven study offers the most comprehensive view to date on the genetic and physiological significance of mtDNA copy number in cord blood or peripheral blood taken from three generations, totaling more than 1000 individuals. Our findings indicate that mtDNA copy number would be one of the transgenerational biomarkers for assessing perinatal outcomes, as well as that appropriate medical interventions could improve the outcomes via quantitative changes in mtDNA.
• Airborne microplastics: A narrative review of potential effects on the human respiratory system.

  Udomratana Vattanasit, Jira Kongpran, Atsuko Ikeda

  The Science of the total environment 904 166745 - 166745 2023年12月15日 [査読有り]
   

  There has been growing evidence showing the widespread of airborne microplastics (AMPs) in many regions of the world, raising concerns about their impact on human health. This review aimed to consolidate recent literature on AMPs regarding their physical and chemical characteristics, deposition in the human respiratory tract, translocation, occurrence from human studies, and toxic effects determined in vitro and in vivo. The physical characteristics influence interactions with cell membranes, cellular internalization, accumulation, and cytotoxicity resulting from cell membrane damage and oxidative stress. In addition, prolonged exposure to AMP-associated toxic chemicals might lead to significant health effects. Most toxicological assessments of AMPs in vitro and in vivo have demonstrated that oxidative stress and inflammation are major mechanisms of action for their toxic effects. Elevated reactive oxygen species production could lead to mitochondrial dysfunction, inflammatory responses, and subsequent apoptosis in experimental models. To date, there has been some evidence suggesting exposure in humans. However, the data are still insufficient, and adverse human health effects need to be investigated. Future research on the existence, exposure, and health effects of AMPs is required for developing preventive and mitigation measures to protect human health.
• Accelerating Environmental Research to Achieve Sustainable Development Goals.

  James R Mihelcic, Ricardo O Barra, Bryan W Brooks, Miriam L Diamond, Matthew J Eckelman, Jacqueline MacDonald Gibson, Sunny Guidotti, Atsuko Ikeda-Araki, Manish Kumar, Ynoussa Maiga, Jennifer McConville, Shelly L Miller, Valeria Pizarro, Fernando Rosario-Ortiz, Shuxiao Wang, Julie B Zimmerman

  Environmental science & technology 57 45 17167 - 17168 2023年11月14日
• Exposure to organophosphate flame retardants and plasticizers is positively associated with wheeze and FeNO and eosinophil levels among school-aged children: The Hokkaido study.

  Yi Zeng, Houman Goudarzi, Yu Ait Bamai, Rahel Mesfin Ketema, Maarten Roggeman, Fatima den Ouden, Celine Gys, Chihiro Miyashita, Sachiko Ito, Satoshi Konno, Adrian Covaci, Reiko Kishi, Atsuko Ikeda-Araki

  Environment international 181 108278 - 108278 2023年11月 [査読有り]
   

  Exposure to organophosphate flame retardants and plasticizers (PFRs) increases the risk of asthma and allergies. However, little is known about its association with type 2 inflammation (T2) biomarkers used in the management of allergies. The study investigated associations among urinary PFR metabolite concentrations, allergic symptoms, and T2 biomarkers. The data and samples were collected between 2017 and 2020, including school children (n = 427) aged 9-12 years living in Sapporo City, Japan, among the participants of "The Hokkaido Study on Environment and Children's Health." Thirteen urinary PFR metabolites were measured by LC-MS/MS. Allergic symptoms were assessed using the International Study of Asthma and Allergies in Childhood questionnaire. For T2 biomarkers, the peripheral blood eosinophil counts, fraction of exhaled nitric oxide level (FeNO), and serum total immunoglobulin E level were measured. Multiple logistic regression analysis, quantile-based g-computation (qg-computation), and Bayesian kernel machine regression (BKMR) were used to examine the associations between the health outcomes of the individual PFRs and the PFR mixtures. The highest concentration of PFR was Σtris(1-chloro-isopropyl) phosphates (ΣTCIPP) (Median:1.20 nmol/L). Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) was significantly associated with a high odds ratio (OR, 95%CI:1.36, 1.07-1.72) for wheeze. TDCIPP (OR, 95%CI:1.19, 1.02-1.38), Σtriphenyl phosphate (ΣTPHP) (OR, 95%CI:1.81, 1.40-2.37), and Σtris(2-butoxyethyl) phosphate (ΣTBOEP) (OR, 95%:1.40, 1.13-1.74) were significantly associated with increased odds of FeNO (≥35 ppb). ΣTPHP (OR, 95%CI:1.44, 1.15-1.83) was significantly associated with high eosinophil counts (≥300/μL). For the PFR mixtures, a one-quartile increase in all PFRs (OR, 95%CI:1.48, 1.18-1.86) was significantly associated with high FeNO (≥35 ppb) in the qg-computation model. The PFR mixture was positively associated with high FeNO (≥35 ppb) and eosinophil counts (≥300/μL) in the BKMR models. These results may suggest that exposure to PFRs increases the probability of asthma, allergies, and T2 inflammation.
• Cord blood triglyceride and total cholesterol in preterm and term neonates: reference values and associated factors from the Japan Environment and Children's Study.

  Hayato Go, Koichi Hashimoto, Hajime Maeda, Kei Ogasawara, Yohei Kume, Tsuyoshi Murata, Akiko Sato, Yuka Ogata, Kosei Shinoki, Hidekazu Nishigori, Atsuko Ikeda-Araki, Keiya Fujimori, Seiji Yasumura, Mitsuaki Hosoya

  European journal of pediatrics 182 10 4547 - 4556 2023年10月 

  This study aimed to investigate the associations between cord serum total cholesterol (TC) and triglyceride (TG)levels and perinatal factors and determine the reference levels of cord blood TC and TG in Japanese neonates. This was a prospective birth cohort study using data from the Japan Environment and Children's Study, which included data on births from 2011 to 2014 in Japan. TC and TG levels were determined in cord blood samples. A total of 70,535 pairs of neonates (male: 36,001, female: 34,524) and mothers were included. The mean cord blood TC and TG levels were 72.2 mg/dL and 24.4 mg/dL, respectively. Multiple regression analyses revealed that gestational age and birth weight were significantly associated with cord blood TC (coefficient -2.35, 95% confidence interval [CI] -2.40 - -2.22 and coefficient 0.002, 95% CI 0.002-0.003, respectively) and TG (coefficient 3.09, 95% CI 3.01-3.17 and coefficient - 0.009, 95% CI - 0.009-0.008, respectively) levels. Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term. Furthermore, the mean cord blood TC and TG levels decreased over the entire range of birth weight categories.    Conclusion: Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term. Furthermore, the mean cord blood TC and TG levels decreased over the entire range of birth weight categories in Japanese newborns. Maternal complications such as maternal parity, HDP, PROM, maternal obesity and income level were associated with cord TC and TG levels. What is Known: • No studies have ascertained the reference levels of cord blood lipid levels in Japan. What is New: • Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term.
• Exposure Trends to the Non-phthalate Plasticizers DEHTP, DINCH, and DEHA in Children from 2012 to 2017: The Hokkaido Study.

  Rahel Mesfin Ketema, Monika Kasper-Sonnenberg, Yu Ait Bamai, Chihiro Miyashita, Holger M Koch, Claudia Pälmke, Reiko Kishi, Atsuko Ikeda

  Environmental science & technology 57 32 11926 - 11936 2023年08月15日 [査読有り]
   

  Phthalates owing to their endocrine-disrupting effects are regulated in certain products, leading to their replacement with substitutions such as di-2-ethylhexyl terephthalate (DEHTP), 1,2-cyclohexane dicarboxylic acid di(isononyl) ester (DINCH), and di(2-ethylhexyl) adipate (DEHA). However, information on human exposure to these substitutes, especially in susceptible subpopulations such as children, is limited. Thus, we examined the levels and exposure trends of DEHTP, DINCH, and DEHA metabolites in 7 year-old Japanese school children. In total, 180 urine samples collected from 2012 to 2017 were used to quantify 10 DEHTP, DINCH, and DEHA metabolites via isotope dilution liquid chromatography with tandem mass spectrometry. DEHTP and DINCH metabolites were detected in 95.6 and 92.2% of the children, respectively, and DEHA was not detected. This study, annually conducted between 2012 and 2017, revealed a significant (p < 0.05) 5-fold increase in DEHTP metabolites and a 2-fold increase in DINCH metabolites. However, the maximum estimated internal exposures were still below the health-based guidance and toxicological reference values. Exposure levels to DEHTP and DINCH have increased considerably in Japanese school children. DEHA is less relevant. Future studies are warranted to closely monitor the increasing trend in different aged and larger populations and identify the potential health effects and sources contributing to increasing exposure and intervene if necessary.
• Effects of perfluorooctanoic acid (PFOA) on gene expression profiles via nuclear receptors in HepaRG cells: Comparative study with in vitro transactivation assays.

  Wataru Murase, Atsuhito Kubota, Atsuko Ikeda-Araki, Masaru Terasaki, Koji Nakagawa, Ryota Shizu, Kouichi Yoshinari, Hiroyuki Kojima

  Toxicology 494 153577 - 153577 2023年06月09日 [査読有り]
   

  Perfluorooctanoic acid (PFOA), a synthetic perfluorinated eight-carbon organic chemical, has been reported to induce hepatotoxicity, including increased liver weight, hepatocellular hypertrophy, necrosis, and increased peroxisome proliferation in rodents. Epidemiological studies have demonstrated associations between serum PFOA levels and various adverse effects. In this study, we investigated the gene expression profiles of human HepaRG cells exposed to 10 and 100 μM PFOA for 24h. Treatment with 10 and 100 μM PFOA significantly modulated the expression of 190 genes and 996 genes, respectively. In particular, genes upregulated or downregulated by 100µM PFOA included peroxisome proliferator-activated receptor (PPAR) signaling genes related to lipid metabolism, adipocyte differentiation, and gluconeogenesis. In addition, we identified the "Nuclear receptors-meta pathways" following the activation of other nuclear receptors: constitutive androstane receptor (CAR), pregnane X receptor (PXR) and farnesoid X receptor (FXR), and the transcription factor, nuclear factor E2-related factor 2 (Nrf2). The expression levels of some target genes (CYP4A11, CYP2B6, CYP3A4, CYP7A1, and GPX2) of these nuclear receptors and Nrf2 were confirmed using quantitative reverse transcription polymerase chain reaction. Next, we performed transactivation assays using COS-7 or HEK293 cells to investigate whether these signaling-pathways were activated by the direct effects of PFOA on human PPARα, CAR, PXR, FXR and Nrf2. PFOA activated PPARα in a concentration-dependent manner, but did not activate CAR, PXR, FXR, or Nrf2. Taken together, these results suggest that PFOA affects the hepatic transcriptomic responses of HepaRG cells through direct activation of PPARα and indirect activation of CAR, PXR FXR and Nrf2. Our finding indicates that PPARα activation found in the "Nuclear receptors-meta pathways" functions as a molecular initiating event for PFOA, and indirect activation of alternative nuclear receptors and Nrf2 also provide important molecular mechanisms in PFOA-induced human hepatotoxicity.
• PFOA曝露による肝細胞での遺伝子発現プロファイルと次世代への影響

  村瀬 渉, 窪田 篤人, 池田 敦子, 小島 弘幸

  環境化学物質3学会合同大会要旨集 2回 531 - 532 (一社)日本環境化学会・日本環境毒性学会・環境ホルモン学会 2023年05月
• Association between maternal multimorbidity and preterm birth, low birth weight and small for gestational age: a prospective birth cohort study from the Japan Environment and Children’s Study

  Kentaro Nakanishi, Yasuaki Saijo, Eiji Yoshioka, Yukihiro Sato, Yasuhito Kato, Ken Nagaya, Satoru Takahashi, Yoshiya Ito, Sumitaka Kobayashi, Chihiro Miyashita, Atsuko Ikeda-Araki, Reiko Kishi

  BMJ Open 13 3 e069281 - e069281 2023年03月15日 [査読有り]
   

  Objectives Multimorbidity is defined as the coexistence of two or more chronic physical or psychological conditions within an individual. The association between maternal multimorbidity and adverse perinatal outcomes such as preterm delivery and low birth weight has not been well studied. Therefore, this study aimed to investigate this association. Methods We conducted a prospective cohort study using data from the Japan Environment and Children’s Study of pregnant women between 2011 and 2014. Those with data on chronic maternal conditions were included in the study and categorised as having no chronic condition, one chronic condition or multimorbidities. The primary outcomes were the incidence of preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). Adjusted logistic regression was performed to estimate ORs (aORs) and 95% CIs. Results Of the 104 062 fetal records, 86 885 singleton pregnant women were analysed. The median maternal age and body mass index were 31 years and 20.5 kg/m², respectively. The prevalence of pregnant women with one or more chronic conditions was 40.2%. The prevalence of maternal multimorbidity was 6.3%, and that of PTB, LBW, and SGA were 4.6%, 8.1%, and 7.5%, respectively. Pre-pregnancy underweight women were the most common, observed in 15.6% of multimorbidity cases, followed by domestic violence from intimate partner in 13.0%. Maternal multimorbidity was significantly associated with PTB (aOR 1.50; 95% CI 1.33–1.69), LBW (aOR 1.49; 95% CI 1.35–1.63) and SGA (aOR 1.33; 95% CI 1.20–1.46). Conclusion Maternal multimorbidity was associated with adverse perinatal outcomes, including PTB, LBW and SGA. The risk of adverse perinatal outcomes tends to increase with a rise in the number of chronic maternal conditions. Multimorbidity becomes more prevalent among pregnant women, making our findings important for preconception counselling.
• Environmental Research Addressing Sustainable Development Goals.

  James R Mihelcic, Ricardo O Barra, Bryan W Brooks, Miriam L Diamond, Matthew J Eckelman, Jacqueline MacDonald Gibson, Sunny Guidotti, Atsuko Ikeda-Araki, Manish Kumar, Ynoussa Maiga, Jennifer McConville, Shelly L Miller, Valeria Pizarro, Fernando Rosario-Ortiz, Shuxiao Wang, Julie B Zimmerman

  Environmental science & technology 57 9 3457 - 3460 2023年03月07日
• 妊婦の母体血中水銀・セレン濃度と4歳までの児の神経発達との関連 エコチル調査

  小林 澄貴, 伊藤 佐智子, 宮下 ちひろ, アイツバマイ ゆふ, 山口 健史, 増田 秀幸, 伊藤 真利子, 山崎 圭子, 田村 菜穂美, ハンリー・シャロン, 池田 敦子, 西條 泰明, 伊藤 善也, 岸 玲子

  日本衛生学雑誌 78 Suppl. S173 - S173 (一社)日本衛生学会 2023年03月
• 前思春期のビスフェノール類曝露と性・ステロイドホルモン値との関連 北海道スタディ

  池田 敦子, 山口 健史, アイツバマイ ゆふ, 池中 良徳, ケテマ・ラヘルメスフィ, 曾 怡, 中村 明枝, 橘田 岳也, 今 雅史, 篠原 信雄, 真部 淳, 宮下 ちひろ, コバチ・アドリアン, 岸 玲子

  日本衛生学雑誌 78 Suppl. S181 - S181 (一社)日本衛生学会 2023年03月
• 化粧品使用による有機フッ素化合物の曝露推計

  藤谷 倫子, 原田 浩二, 増田 秀幸, 山口 健史, アイツバマイ ゆふ, 池田 敦子

  日本衛生学雑誌 78 Suppl. S200 - S200 (一社)日本衛生学会 2023年03月
• 化粧品使用による有機フッ素化合物の曝露推計

  藤谷 倫子, 原田 浩二, 増田 秀幸, 山口 健史, アイツバマイ ゆふ, 池田 敦子

  日本衛生学雑誌 78 Suppl. S200 - S200 (一社)日本衛生学会 2023年03月
• E-waste in Vietnam: a narrative review of environmental contaminants and potential health risks.

  Kritika Poudel, Rahel Mesfin Ketema, Hien Thi Thu Ngo, Atsuko Ikeda, Machiko Minatoya

  Reviews on environmental health 2023年02月09日 

  Informal electronic waste (e-waste) dismantling activities contribute to releasing hazardous compounds in the environment and potential exposure to humans and their health. These hazardous compounds include persistent organic pollutants (POPs), polycyclic aromatic hydrocarbons (PAHs) and heavy metals. This review searched papers addressing hazardous compounds emitted from e-waste recycling activities and their health effects in Vietnam. Based on the keywords searched in three electronic databases (PubMed, Psych Info, and Google scholar), we found 21 relevant studies in Vietnam. The review identifies extensive e-waste dismantling activities in Vietnam in the northern region. To measure the environmental exposure to hazardous compounds, samples such as e-waste recycling workshop dust, soil, air, and sediments were assessed, while human exposure levels were measured using participants' hair, serum, or breast milk samples. Studies that compared levels of exposure in e-waste recycling sites and reference sites indicated higher levels of PBDEs, PCBs, and heavy metals were observed in both environmental and human samples from participants in e-waste recycling sites. Among environmental samples, hazardous chemicals were the most detected in dust from e-waste recycling sites. Considering both environmental and human samples, the highest exposure difference observed with PBDE ranged from 2-48-fold higher in e-waste processing sites than in the reference sites. PCBs showed nearly 3-fold higher levels in e-waste processing sites than in reference sites. In the e-waste processing sites, age-specific higher PCB levels were observed in older recycler's serum samples. Among the heavy metals, Pb was highly detected in drinking water, indoor soil and human blood samples. While high detection of Ni in cooked rice, Mn in soil and diet, Zn in dust and As in urine were apparent. Exposure assessment from human biomonitoring showed participants, including children and mothers from the e-waste processing areas, had higher carcinogenic and non-carcinogenic risks than the reference sites. This review paper highlights the importance of further comprehensive studies on risk assessments of environmentally hazardous substances and their association with health outcomes at e-waste processing sites.
• How does formal and informal industry contribute to lead exposure? A narrative review from Vietnam, Uruguay, and Malaysia.

  Kritika Poudel, Atsuko Ikeda, Hisanori Fukunaga, Marie-Noel Brune Drisse, Lesley Jayne Onyon, Julia Gorman, Amalia Laborde, Reiko Kishi

  Reviews on environmental health 2023年02月06日 [査読有り]
   

  INTRODUCTION: Lead industries are one of the major sources of environmental pollution and can affect human through different activities, including industrial processes, metal plating, mining, battery recycling, etc. Although different studies have documented the various sources of lead exposure, studies highlighting different types of industries as sources of environmental contamination are limited. Therefore, this narrative review aims to focus mainly on lead industries as significant sources of environmental and human contamination. CONTENT: Based on the keywords searched in bibliographic databases we found 44 relevant articles that provided information on lead present in soil, water, and blood or all components among participants living near high-risk areas. We presented three case scenarios to highlight how lead industries have affected the health of citizens in Vietnam, Uruguay, and Malaysia. SUMMARY AND OUTLOOK: Factories conducting mining, e-waste processing, used lead-acid battery recycling, electronic repair, and toxic waste sites were the primary industries for lead exposure. Our study has shown lead exposure due to industrial activities in Vietnam, Uruguay, Malaysia and calls for attention to the gaps in strategic and epidemiologic efforts to understand sources of environmental exposure to lead fully. Developing strategies and guidelines to regulate industrial activities, finding alternatives to reduce lead toxicity and exposure, and empowering the public through various community awareness programs can play a crucial role in controlling exposure to lead.
• Change of radiofrequency electromagnetic exposure of children from 2020 to 2021: A report from Hokkaido Study

  Keiko Yamazaki, Naomi Tamura, Chihiro Miyashita, Toshio Yoshikawa, Atsuko Ikeda-Araki, Takashi Hikage, Manabu Omiya, Masahiro Mizuta, Miwa Ikuyo, Kazuhiro Tobita, Teruo Onishi, Masao Taki, Soichi Watanabe, Reiko Kishi

  2023 35th General Assembly and Scientific Symposium of the International Union of Radio Science, URSI GASS 2023 2023年 

  We recorded Japanese children's exposure to radiofrequency electromagnetic fields (RF-EMF) using personal exposure meters from 2020 to 2021. There was no difference in the total exposure level during 2020 and 2021, in each recording place. However, the levels of each frequency bands were found to change between the recording years. The results suggest that the composition of the frequency bands to which children were exposed changed between 2020 and 2021 in Japan.
• Human Body Blockage Effects on Personal Exposimeter Device in 4G/5G Frequency Bands for Epidemiological Research on Children's Health

  Sakura Tsuruga, Manabu Omiya, Chihiro Miyashita, Kaito Sugimura, Keiko Yamazaki, Naomi Tamura, Takashi Hikage, Atsuko Ikeda-Araki, Reiko Kishi

  2023 IEEE International Symposium on Antennas and Propagation, ISAP 2023 2023年 

  Due to the spread of smartphones and other wireless devices, and the decline in the age of starting to use these devices, children are increasingly exposed to RF-EMF. Therefore, it is required to conduct epidemiological research about the effect on children's health and RF exposure in the general environment. In this study, we precisely estimate the effects of human body blockage on personal exposure assessment tools in frequency bands, including 5G, using the FDTD method to investigate the dosimetry protocol for epidemiologic research.
• Cross-sectional associations between early mobile device usage and problematic behaviors among school-aged children in the Hokkaido Study on Environment and Children's Health.

  Chihiro Miyashita, Keiko Yamazaki, Naomi Tamura, Atsuko Ikeda-Araki, Satoshi Suyama, Takashi Hikage, Manabu Omiya, Masahiro Mizuta, Reiko Kishi

  Environmental health and preventive medicine 28 22 - 22 2023年 [査読有り]
   

  BACKGROUND: Concerns have been raised about the adverse health impacts of mobile device usage. The objective of this cross-sectional study was to examine the association between a child's age at the first use of a mobile device and the duration of use as well as associated behavioral problems among school-aged children. METHODS: This study focused on children aged 7-17 years participating in the Hokkaido Study on Environment and Children's Health. Between October 2020 and October 2021, the participants (n = 3,021) completed a mobile device use-related questionnaire and the strengths and difficulties questionnaire (SDQ). According to the SDQ score (normal or borderline/high), the outcome variable was behavioral problems. The independent variable was child's age at first use of a mobile device and the duration of use. Covariates included the child's age at the time of survey, sex, sleep problems, internet addiction, health-related quality of life, and history of developmental concerns assessed at health checkups. Logistic regression analysis was performed for all children; the analysis was stratified based on the elementary, junior high, and senior high school levels. RESULTS: According to the SDQ, children who were younger at their first use of a mobile device and used a mobile device for a longer duration represented more problematic behaviors. This association was more pronounced among elementary school children. Moreover, subscale SDQ analysis showed that hyperactivity, and peer and emotional problems among elementary school children, emotional problems among junior high school children, and conduct problems among senior high school children were related to early and long usage of mobile devices. CONCLUSIONS: Elementary school children are more sensitive to mobile device usage than older children, and early use of mobile devices may exacerbate emotional instability and oppositional behaviors in teenagers. Longitudinal follow-up studies are needed to clarify whether these problems disappear with age.
• Associated congenital anomalies and syndromes of 248 infants with orofacial clefts born between 2011 and 2014 in the Japan environment and children's study.

  Yukihiro Sato, Eiji Yoshioka, Yasuaki Saijo, Yasuhito Kato, Ken Nagaya, Satoru Takahashi, Yoshiya Ito, Sumitaka Kobayashi, Yu Ait Bamai, Keiko Yamazaki, Sachiko Itoh, Chihiro Miyashita, Atsuko Ikeda-Araki, Reiko Kishi

  Congenital anomalies 63 1 9 - 15 2023年01月 

  This study aimed to document the complication status of infants with orofacial clefts born between 2011 and 2014 in Japan. This was a descriptive study using data from the Japan Environment and Children's Study. Among 103 060 pregnancies, 248 infants with orofacial clefts were included (livebirth, 239; stillbirth, 4; miscarriage, 5). The items of interest were complication status of orofacial clefts: isolated (typical orofacial clefts only); multi-malformed (orofacial clefts with unrelated major defects); syndromic (orofacial clefts with a syndrome or a chromosomal defect). Regarding the cleft subtypes, of 248 infants with orofacial clefts, 104 had cleft lip with cleft palate (CLP) (41.9%), 68 had cleft lip without cleft palate (CL) (27.4%), 58 had cleft palate without cleft lip (CP) (23.4%), and 18 were nonclassified (7.3%). In infants with CLP, the proportions of isolated, multi-malformed, and syndromic phenotypes were 73.1%, 15.4%, and 11.5%, respectively. In infants with CL, the proportions were 79.4%, 16.2%, and 4.4%, respectively. In infants with CP, the proportions were 69.0%, 13.8%, and 17.2%, respectively. The most frequently associated congenital anomaly was congenital heart disease. In infants with syndromic CLP, 41.7% had trisomy 13. In infants with syndromic CP, 80.0% had the Pierre Robin sequence. Congenital heart disease could be the most frequently associated congenital anomaly. The most frequently associated syndrome could be trisomy 13 in those with CLP and Pierre Robin sequence in those with CP.
• 胎児期フタル酸エステル類曝露による思春期発来への影響 北海道スタディ

  山口 健史, 池田 敦子, アイツバマイ ゆふ, 宮下 ちひろ, 池中 良徳, 中村 明枝, 今 雅史, 藤谷 倫子, 原田 浩二, 岸 玲子

  DOHaD研究 10 2 46 - 46 (一社)日本DOHaD学会 2022年10月
• Measurement of personal radio frequency exposure in Japan: The Hokkaido Study on the Environment and Children's health.

  Keiko Yamazaki, Atsuko Ikeda-Araki, Chihiro Miyashita, Naomi Tamura, Toshio Yoshikawa, Takashi Hikage, Manabu Omiya, Masahiro Mizuta, Miwa Ikuyo, Kazuhiro Tobita, Teruo Onishi, Masao Taki, Soichi Watanabe, Reiko Kishi

  Environmental research 216 Pt 1 114429 - 114429 2022年09月26日 

  The opportunities for exposure to radiofrequency electromagnetic fields (RF-EMF) among children are increasing. Children's exposure to RF-EMF in Japan was recorded using a personal exposure meter (ExpoM-RF), and factors associated with the exposure examined. A total of 101 children, aged 10-15 years old, participated in the prospective birth cohort "Hokkaido study". RF-EMF data were recorded in the 700 MHz-5.8 GHz frequency range for 3 days. The recorded data were summarized into six groups of frequency bands: downlink from mobile phone base stations (DL), uplink from mobile phones to a base station (UL), Wireless Local Area Network (LAN), terrestrial digital TV broadcasting (digital TV), 2.5 GHz and 3.5 GHz Time Division Duplex (TDD), 1.9 GHz TDD, and total (the summation of power density in all measured frequency bands). A questionnaire was used to document the internet environment (at home) and mobile phone usage. Personal RF-EMF exposure in Japanese children was lower than that reported in studies in Europe. The DL signals from mobile phone base stations were the most significant contributors to total exposure, while Wireless LAN and digital TV were only higher at home. The urban residence was consistently associated with increases in the four groups of frequency bands (DL, UL, digital TV, and TDD). TDD level has several associations with mobile phone usage (calls using mobile phones, video viewing, text message service, and online game). The association between inattention/hyperactivity subscale of the Strengths and Difficulties Questionnaire (SDQ) and higher Wireless LAN exposure at nighttime was also noted. Further studies with additional data will shed light on factors involved in RF-EMF exposure among Japanese children.
• Null Association Between Isolated Orofacial Clefts and Sleep Duration: A Cohort Study From the Japan Environment and Children's Study

  Yukihiro Sato, Eiji Yoshioka, Yasuaki Saijo, Yasuhito Kato, Ken Nagaya, Satoru Takahashi, Yoshiya Ito, Sumitaka Kobayashi, Yu Ait Bamai, Keiko Yamazaki, Sachiko Itoh, Chihiro Miyashita, Atsuko Ikeda-Araki, Reiko Kishi

  The Cleft Palate-Craniofacial Journal 105566562211284 - 105566562211284 2022年09月26日 

  Although children with orofacial clefts have an increased risk for sleep-disordered breathing, no studies have examined the association of sleep duration. Thus, this study aimed to examine associations between orofacial clefts and sleep duration at 1 month, 6 months, 1 year, and 3 years of age in Japan. A cohort study from the Japan Environment and Children's Study. This study consisted of 91 497 children, including ones with isolated cleft lip and palate (n = 69), isolated cleft lip only (n = 48), and isolated cleft palate only (n = 37), for which recruitment was undertaken during 2011 to 2014. Seep durations (hours per day) at 1 month, 6 months, 1 year, and 3 years of age, as reported by their mothers. In the control group, mean sleep durations and standard deviations at 1 month, 6 months, 1 year, and 3 years of age were 15.2 (2.5), 13.6 (1.9), 12.9 (1.6), and 11.6 (1.2) h, respectively. Compared to the control group, linear regression models reported effect sizes and 95% confidence intervals shorter than 1 h for sleep duration of each type of isolated orofacial cleft at each time point. This study suggested null associations between isolated orofacial clefts and sleep duration at 1 month, 6 months, 1 year, and 3 years of age. Children with isolated orofacial clefts had sufficient mean sleep duration.
• Evaluating association of smoking status during pregnancy with adverse birth outcomes using urinary cotinine concentration: The Japan environment and Children's study (JECS).

  Yuki Kunori, Yasuaki Saijo, Eiji Yoshioka, Yukihiro Sato, Tomoko Kanaya, Kentaro Nakanishi, Yasuhito Kato, Ken Nagaya, Satoru Takahashi, Yoshiya Ito, Sachiko Itoh, Sumitaka Kobayashi, Chihiro Miyashita, Atsuko Ikeda-Araki, Reiko Kishi, Michihiro Kamijima, Shin Yamazaki, Yukihiro Ohya, Reiko Kishi, Nobuo Yaegashi, Koichi Hashimoto, Chisato Mori, Shuichi Ito, Zentaro Yamagata, Hidekuni Inadera, Takeo Nakayama, Tomotaka Sobue, Masayuki Shima, Hiroshige Nakamura, Narufumi Suganuma, Koichi Kusuhara, Takahiko Katoh

  Environmental research 215 Pt 2 114302 - 114302 2022年09月14日 

  Urinary cotinine concentration (UCC) reflects smoking status. However, in pregnant women, its association with adverse birth outcomes related to fetal growth is not widely known. Thus, we aimed to explore this relationship by focusing on dose-response relationships. We investigated 86,638 pregnant women enrolled between 2011 and 2014 in a prospective cohort study in Japan and observed three birth outcomes (preterm birth, low birth weight, and small-for-gestational age). We measured UCC in the second or third trimester, and categorized the participants using cut-off values (negative cotinine concentration, passive cotinine concentration, and active cotinine concentration corresponding to non-smokers, passive smokers, and active smokers, respectively). Logistic regression analyses were conducted to evaluate the risks, and dose-response relationships were visualized using restricted cubic spline curves. Analyses based on self-reported smoking status were also performed. We found that in low active and highly active cotinine concentrations, the adjusted odds ratios (aORs) of birth outcomes were significantly increased (preterm birth, 1.24 [95% CI 1.06-1.46], 1.39 [95% CI 1.19-1.62]; low birth weight, 1.40 [95% CI 1.24-1.58], 2.27 [95% CI 2.05-2.53]; small-for-gestational age, 1.35 [95% CI 1.19-1.52], 2.39 [95% CI 2.16-2.65]). Restricted cubic spline curves demonstrated risk elevations in the active cotinine concentration range. Our research revealed dose-response relationships between UCC during pregnancy and the risks of preterm birth, low birth weight, and small-for-gestational age. Measurement of UCC to ascertain smoking status during pregnancy may be a useful approach for predicting the risks of these birth outcomes.
• Maternal dietary folate intake with folic acid supplements and wheeze and eczema in children aged 2 years in the Japan Environment and Children’s Study

  Hideyuki Masuda, Sumitaka Kobayashi, Chihiro Miyashita, Sachiko Itoh, Yu Ait Bamai, Yasuaki Saijo, Yoshiya Ito, Reiko Kishi, Atsuko Ikeda-Araki

  PLOS ONE 17 8 e0272968 - e0272968 2022年08月22日 

  Maternal intake of folic acid supplements is reportedly associated with the risk of early-onset allergies in offspring. However, only a few studies have considered the intake of both folic acid supplements and dietary folate. Here, the relationship between maternal intake of folic acid supplements and allergic symptoms such as wheeze and eczema in offspring was analyzed while considering dietary folate intake. We examined 84,361 mothers and 85,114 children in the Japan Environment and Children’s Study. The participants were divided into three groups depending on maternal folic acid supplementation (“no use,” “occasional use,” and “daily use”). Each group was then subdivided into three groups based on total folic acid and dietary folate intake. Outcomes were determined considering the wheeze and eczema status of each child at the age of 2 years. The status was based on the International Study of Asthma and Allergies in Childhood. It was found that 22.1% of the mothers took folic acid supplements daily. In contrast, 56.3% of the mothers did not take these supplements. Maternal intake of folic acid supplements was not associated with wheeze and eczema in the offspring. In contrast, only dietary folate intake was positively associated with wheeze at the age of 2 (adjusted odds ratio, 1.103; 95% confidence interval, 1.003–1.212). However, there is no scientific evidence of a biological mechanism that clarifies this result. Potential confounders such as other nutrition, outdoor/indoor air pollution, and genetic factors may have affected the results. Therefore, further studies on the association between maternal intake of folic acid and allergic symptoms at the age of 3 or above are needed to confirm the results of this study. Trial registration UMIN Clinical Trials Registry (number: UMIN000030786)
• Potential determinants of T helper 2 markers and their distribution in school-aged children

  Houman Goudarzi, Atsuko Ikeda-Araki, Yu Ait Bamai, Sachiko Ito, Tasuku Inao, Isao Yokota, Chihiro Miyashita, Reiko Kishi, Satoshi Konno

  Allergology International 72 1 100 - 106 2022年08月 

  BACKGROUND: There is growing data on T helper 2 (Th2) biomarker determinants in adult populations. However, the determinants and typical range of these biomarkers have not been well studied in general populations of children. Therefore, we assessed the determinants and typical range of three Th2 biomarkers, including blood eosinophils, FeNO, and serum total IgE in 9-11-year-old children in a prospective birth cohort. METHODS: We examined the pre- and postnatal factors associated with Th2 biomarkers using multivariable logistic regression analysis (n = 428) and extended the results to the original cohort (n = 17,009) using inverse probability weighting. We also measured typical Th2 biomarker distribution in all examined children and healthy participants without allergic diseases (n = 180). RESULTS: At age 9-11, wheeze (odds ratio (OR) 7.63), rhinitis (OR 3.14), and eczema (OR 2.46) were significantly associated with increased blood eosinophils. All three allergic conditions were associated with FeNO and total serum IgE, but the ORs were smaller than those for blood eosinophils. Secondhand smoking was inversely associated with the blood eosinophils (OR, 0.38). Similar results were found in the original cohort. Male sex and prenatal factors (maternal smoking and parental history of allergies) were not independent predictors of high Th2 levels. CONCLUSIONS: In addition to wheezing and rhinitis, eczema and secondhand smoke exposure are independent factors for Th2 biomarker interpretation in children. Furthermore, the typical values and cutoff values of blood eosinophils in adults may not be applicable to children.
• Impact of prenatal exposure to mercury and selenium on neurodevelopmental delay in children in the Japan Environment and Children’s Study using the ASQ-3 questionnaire: a prospective birth cohort

  Sumitaka Kobayashi, Sachiko Itoh, Chihiro Miyashita, Yu Ait Bamai, Takeshi Yamaguchi, Hideyuki Masuda, Mariko Itoh, Keiko Yamazaki, Naomi Tamura, Sharon J.B. Hanley, Atsuko Ikeda-Araki, Yasuaki Saijo, Yoshiya Ito, Miyuki Iwai-Shimada, Shin Yamazaki, Michihiro Kamijima, Reiko Kishi

  Environment International 168 107448 - 107448 2022年08月 

  Neurodevelopmental delay is associated with neurodevelopmental disorders. Prenatal metal exposure can potentially cause neurodevelopmental delays in children. This study examines whether prenatal exposure to mercury (Hg) and selenium (Se) is associated with the risk of neurodevelopmental delays in children up to 4 years of age. Children enrolled in a prospective birth cohort of the Japan Environment and Children's Study were examined. Hg and Se levels in maternal (nchild = 48,731) and cord (nchild = 3,083) blood were analyzed by inductively coupled plasma-mass spectrometry. Neurodevelopmental delays were assessed in children between the ages of 0.5 to 4 years using the Ages and Stages Questionnaires, Third Edition. The association between exposure and outcomes was examined using the generalized estimation equation models. In maternal blood, compared to participants with Se levels in the first quartile (83.0 to < 156 ng/g), the odds ratio (95 % confidence intervals) for problem-solving ability in children of mothers in the third (168 to < 181 ng/g) and fourth quartiles (181 to 976 ng/g) were 1.08 (1.01 to 1.14) and 1.10 (1.04 to 1.17), respectively. Furthermore, communication, gross and fine motor skills, and problem-solving delays were also observed. However, prenatal Hg levels in maternal and cord blood and Se levels in the latter were not associated with neurodevelopmental delays in children. Thus, the findings of this study suggest an association between Se levels in maternal blood and slightly increased risks of neurodevelopmental delays in children up to the age of 4 years.
• Narrative review of lead poisoning in humans caused by industrial activities and measures compatible with sustainable industrial activities in Republic of Zambia

  Hokuto Nakata, Shouta M.M. Nakayama, John Yabe, Kaampwe Muzandu, Andrew Kataba, Atsuko Ikeda-Araki, Marie-Noel Brune Drisse, Lesley Jayne Onyon, Julia Gorman, Poudel Kritika, Hisanori Fukunaga, Yoshinori Ikenaka, Reiko Kishi, Mayumi Ishizuka

  Science of The Total Environment 850 157833 - 157833 2022年08月 

  Lead (Pb) pollution and human exposure to Pb, is an important issue for the international community to address being associated with 0.90 million deaths from long-term effects. The Republic of Zambia is a typical mineral resource-rich country, with long-standing mining and smelting activities of metals including Pb in several parts of the country. This narrative review provides a comprehensive overview of previous papers that have assessed human exposure to Pb and related health effects in Zambia. Environmental remediation methods that should be applied locally, ways to reduce Pb exposure of the population, and issues that need to be addressed by various sectors are discussed. Environmental remediation methods using locally available and affordable materials are needed to ensure both sustainable industrial activities and pollution prevention. In the Zambian mining towns, including Kabwe, various research activities have been conducted, including environmental monitoring, human biomonitoring and health impact assessments. The town of Kabwe, which was one of Zambia's largest Pb mining area in the 20th century, continues to have formal and informal Pb-related industries and is known as one of the most polluted areas in the world. For example, despite the World Health Organization asserting that "For an individual with a blood Pb concentration ≥ 5 μg/dL, appropriate action should be taken to terminate exposure", there are reports of blood Pb levels in Kabwe children exceeding 100 μg/dL. While Pb pollution is a global issue, not many places have such continuous and comprehensive research has been conducted, and there is much to be learned from the knowledge accumulated in these areas. Because the high levels of Pb accumulation in humans and the adverse health effects were clarified, we consider that it is important to combine mining activities, which are a key industry, with measures to prevent environmental pollution.
• Association between maternal caffeine intake during pregnancy and child development at 6 and 12 months: The Japan Environment and Children's Study

  Shinkichi Nishihara, Sumitaka Kobayashi, Atsuko Ikeda-Araki, Chihiro Miyashita, Sachiko Itoh, Keiko Yamazaki, Yu Ait Bamai, Naomi Tamura, Hideyuki Masuda, Mariko Itoh, Yasuaki Saijo, Yoshiya Ito, Reiko Kishi

  Early Human Development 171 105607 - 105607 2022年06月 

  BACKGROUND: Caffeine intake by pregnant women may have neurodevelopmental effects on the fetus due to adenosine antagonism. However, there are insufficient data and inconsistent results from epidemiological studies on the effect of maternal caffeine intake on child development. AIMS: This study examined the association between mothers' estimated caffeine intake during pregnancy and their children's score on the Japanese version of the Ages & Stages Questionnaires™ (J-ASQ) at 6 and 12 months of age. STUDY DESIGN: The study is a part of nationwide prospective birth-cohort study: the Japan Environment and Children's Study. SUBJECTS: In total, 87,106 participants with the Food Frequency Questionnaire (FFQ) data and J-ASQ at 6 or 12 months of age were included in the study. OUTCOME MEASURES: The data were analyzed by logistic regression analysis to determine whether the scores of the five subscales on the J-ASQ were below the cutoff point as the dependent variable. RESULTS: The results showed that children born to mothers who consumed >300 mg caffeine per day had a 1.11-fold increased odds of gross motor developmental delay at 12 months of age (adjusted odds ratio [AOR] = 1.114 [95 % CI: 1.013-1.226]). CONCLUSIONS: Issues in gross motor development can emerge prior to future developmental issues. Therefore, further studies on developmental outcomes in older children, including the future outcomes of the children who participated in this study, are needed.
• The associations of prenatal exposure to dioxins and polychlorinated biphenyls with neurodevelopment at 6 Months of age: Multi-pollutant approaches.

  Gyeyoon Yim, Machiko Minatoya, Marianthi-Anna Kioumourtzoglou, Andrea Bellavia, Marc Weisskopf, Atsuko Ikeda-Araki, Chihiro Miyashita, Reiko Kishi

  Environmental research 209 112757 - 112757 2022年06月 [査読有り]
   

  BACKGROUND: Prenatal exposure to persistent organic pollutants, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DL-PCBs), and nondioxin-like PCBs (NDL-PCBs), has been hypothesized to have a detrimental impact on neurodevelopment. However, the association of prenatal exposure to a dioxin and PCB mixture with neurodevelopment remains largely inconclusive partly because these chemical levels are correlated. OBJECTIVES: We aimed to elucidate the association of in utero exposure to a mixture of dioxins and PCBs with neurodevelopment measured at 6 months of age by applying multipollutant methods. METHODS: A total of 514 pregnant women were recruited between July 2002 and October 2005 in the Sapporo cohort, Hokkaido Study on Environment and Children's Health. The concentrations of individual dioxin and PCB isomers were assessed in maternal peripheral blood during pregnancy. The mental and psychomotor development of the study participants' infants was evaluated using the Bayley Scales of Infant Development-2nd Edition (n = 259). To determine both the joint and individual associations of prenatal exposure to a dioxin and PCB mixture with infant neurodevelopment, Bayesian kernel machine regression (BKMR) and quantile-based g-computation were employed. RESULTS: Suggestive inverse associations were observed between in utero exposure to a dioxin and PCB mixture and infant psychomotor development in both the BKMR and quantile g-computation models. In contrast, we found no association of a dioxin and PCB mixture with mental development. When group-specific posterior inclusion probabilities were estimated, BKMR suggested prenatal exposure to mono-ortho PCBs as the more important contributing factors to early psychomotor development compared with the other dioxin or PCB groups. No evidence of nonlinear exposure-outcome relationships or interactions among the chemical mixtures was detected. CONCLUSIONS: Applying the two complementary statistical methods for chemical mixture analysis, we demonstrated limited evidence of inverse associations of prenatal exposure to dioxins and PCBs with infant psychomotor development.
• Association between pre-pregnancy body mass index and gestational weight gain and perinatal outcomes in pregnant women diagnosed with gestational diabetes mellitus: The Japan Environment and Children's Study.

  Yoshihiro Saito, Sumitaka Kobayashi, Atsuko Ikeda-Araki, Sachiko Ito, Chihiro Miyashita, Takashi Kimura, Takumi Hirata, Akiko Tamakoshi, Michinori Mayama, Kiwamu Noshiro, Kinuko Nakagawa, Takeshi Umazume, Kentaro Chiba, Satoshi Kawaguchi, Mamoru Morikawa, Kazutoshi Cho, Hidemichi Watari, Yoshiya Ito, Yasuaki Saijo, Reiko Kishi

  Journal of diabetes investigation 13 5 889 - 899 2022年05月 [査読有り]
   

  AIMS/INTRODUCTION: We investigated the association between gestational diabetes mellitus (GDM) and perinatal outcomes stratified by pre-pregnancy body mass index (BMI) and/or gestational weight gain (GWG). MATERIALS AND METHODS: Data from the national birth cohort in the Japan Environment and Children's Study from 2011 to 2014 (n = 85,228) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The odds ratios (ORs) of perinatal outcomes were compared between women with and those without GDM. RESULTS: The OR (95% confidence interval) of having a small for gestational age infant in the GDM group with a pre-pregnancy BMI of ≥25.0 kg/m2 and insufficient GWG (<2.75 kg) was 1.78 (1.02-3.12). The OR of having a large for gestational age infant of the same BMI group with excessive GWG (>7.25 kg) was 2.04 (1.56-2.67). The OR of hypertensive disorders of pregnancy was higher in women with a BMI ≥18.5 kg/m2 in the GDM group than in the non-GDM group. CONCLUSIONS: Large for gestational age and hypertensive disorders of pregnancy were associated with pre-pregnancy BMI and GWG in either normal weight or overweight/obese women, and the relationship was strengthened when GDM was present. Women with GDM and a BMI of ≥25.0 kg/m2 are at risk of having small for gestational age and large for gestational age infants depending on GWG.
• Effects of benzotriazole UV stabilizers, UV-PS and UV-P, on the differentiation of splenic regulatory T cells via aryl hydrocarbon receptor.

  Atsuhito Kubota, Masaru Terasaki, Yuuta Sakuragi, Ryuta Muromoto, Atsuko Ikeda-Araki, Hideshige Takada, Hiroyuki Kojima

  Ecotoxicology and environmental safety 238 113549 - 113549 2022年04月29日 [査読有り]
   

  Benzotriazole UV stabilizers (BUVSs) are widely used as additives in various materials, including plastics, to prevent damage from UV-irradiation. However, despite the extensive usage of BUVSs, information on their toxicological properties is limited. In this study, we investigated the effect of BUVSs on the immune regulatory system via the aryl hydrocarbon receptor (AhR). A cell-based transactivation assay using DR-EcoScreen cells revealed that, among 13 BUVSs tested, UV-P, UV-PS, UV-9, and UV-090 activated AhR in a dose-dependent manner. In particular, the AhR agonistic activity of UV-PS was about 10-fold more potent than those of UV-P, UV-090, and UV-9, and UV-PS acted as a full agonist against AhR. In order to investigate the immune regulatory effects of these BUVSs, we orally treated C57BL/6 mice with UV-PS or UV-P (10, 30, and 100 mg/kg) and studied the differentiation of regulatory T cells (Tregs) in spleen cells. Flow-cytometry analysis revealed that the administration of UV-PS (30 and 100 mg/kg) or UV-P (100 mg/kg) significantly increased the population of CD4+-/CD25+-/Foxp3+ Tregs in the spleen. In addition, we found that the in vitro exposure of mouse splenocytes to UV-PS (10 and 30 μM) or UV-P (30 μM) as well as to TCDD (0.1 nM) significantly induced Tregs. Notably, the induction of Tregs was eliminated by co-treatment with an AhR antagonist, CH-223191, in each case. Taken together, these findings suggest that some BUVSs might induce Tregs through direct AhR activation and act as immunosuppressive modulators.
• Association of prenatal exposure to dioxin-like compounds, polychlorinated biphenyl, and methylmercury with event-related brain potentials in school-aged children: The Hokkaido study.

  Keiko Yamazaki, Sachiko Itoh, Atsuko Ikeda-Araki, Chihiro Miyashita, Tsuguhide Hori, Noriyuki Hachiya, Reiko Kishi

  Neurotoxicology 91 11 - 21 2022年04月28日 [査読有り]
   

  Previous studies have indicated that prenatal exposure to dioxin-like compounds (DLC) or polychlorinated biphenyl (PCB) has a negative association with neurodevelopment in school-aged children. Event-related brain potentials (ERP) can reveal subtle and specific differences in the modulation of cognitive processes that are assumed when they are associated with lower levels of prenatal exposure to DLC or PCBs. This prospective birth cohort study was conducted to examine the association between prenatal exposure to relatively low levels of DLC, PCB or methylmercury (MeHg), and ERP. A total of 55 children who were 13 years old participated in a 3-stimulus oddball task to detect P3a and P3b waves. The task required participants to respond to a target among random stimuli at two difficulty levels. The P3a amplitude reflects an automated attention capture process, and P3b reflects a voluntary attention allocation process. We analyzed DLC congeners in blood samples from four groups, including 7 polychlorinated dibenzo-p-dioxins (PCDD), 10 polychlorinated dibenzofuranes (PCDF), 4 non-ortho PCBs, and 8 mono-ortho PCBs. PCB-153 was chosen as an indicator because of its high correlation with the sum of 58 NDL (non-dioxin-like)-PCBs. MeHg exposure level was assessed by the mercury concentration in hair samples (HHg) taken during the perinatal period. The reaction time to the target stimulus during the oddball task shortened with the increasing MeHg exposure level. Furthermore, P3b latency, which reflect response decision and correlates with reaction time, was also shortened with increasing MeHg level in the difficult condition. These results are counterintuitive because shorter reaction times or rapid decision making reflected by P3 latency are generally favorable. This might be due to nutritional factors such as fatty acids, which have beneficial effects on brain development. The P3a amplitude decreased with non- and mono-ortho PCB and HHg levels, regardless of the difficulty level, and with PCDD, PCDF, and total DLC levels, especially in the difficult condition. P3b latency shortened with HHg, and P3b amplitude decreased with mono-ortho PCBs and PCB-153 in both conditions and with PCDD, PCDF, non-ortho PCBs, and total DLC in the difficult condition. In conclusion, we found an association between prenatal exposure to DLC and a decrease in both P3a and P3b amplitude, even when DLC levels were lower than in most previous studies. Additionally, our results suggest that the automated attention capture process reflected by P3a is associated with maternal MeHg exposure and that the voluntary attention allocation process reflected by P3b is associated with PCB-153. However, these results should be interpreted with caution because of the limitations on sample size, population bias, and statistical analyses.
• Association of exposure to prenatal perfluoroalkyl substances and estrogen receptor 1 polymorphisms with the second to fourth digit ratio in school-aged children: The Hokkaido study.

  Yoko Nishimura, Kimihiko Moriya, Sumitaka Kobayashi, Atsuko Ikeda-Araki, Fumihiro Sata, Takahiko Mitsui, Sachiko Itoh, Chihiro Miyashita, Kazutoshi Cho, Masafumi Kon, Michiko Nakamura, Takeya Kitta, Sachiyo Murai, Reiko Kishi, Nobuo Shinohara

  Reproductive toxicology (Elmsford, N.Y.) 109 10 - 18 2022年04月 [査読有り]
   

  Per- and Polyfluoroalkyl substances (PFAS) have endocrine-disrupting effects. The ratio of the lengths of the second and fourth digits (2D:4D) is a noninvasive retrospective index of prenatal exposure to sex hormones, and estrogen receptor 1 (ESR1) polymorphisms may contribute to 2D:4D determination. We investigated whether ESR1 polymorphisms modify the effects of prenatal PFAS exposure on 2D:4D. Participants (n = 1024) with complete data in a prospective birth cohort study (the Hokkaido Study) were included, and maternal plasma in the third trimester was used to examine PFAS concentrations. 2D:4D was determined from photocopies of palms of children using Vernier calipers. ESR1 polymorphisms (rs2234693, rs9340799, and rs2077647) were genotyped by TaqMan polymerase chain reaction. PFAS and 2D:4D association with ESR1 polymorphisms was assessed by multiple linear regression adjusted for potential confounding factors. A 10-fold increase in maternal perfluorooctanoic acid (PFOA) concentration was associated with a 1.54% [95% confidence interval (CI): 0.40, 2.68] increase in mean 2D:4D in children with an AA genotype at rs9340799 and a 2.24% (95% CI: 0.57, 3.92) increase in children with an AA genotype at rs2077647. A 10-fold increase in perfluorododecanoic acid (PFDoDA) was associated with a significant increase in 2D:4D in children with the AA genotype [rs9340799, 1.18% (95% CI: 0.02, 2.34); and rs2077647, 1.67% (95% CI: 0.05, 3.28)]. These associations were apparent among males. A significant gene-environment interaction between PFOA or PFDoDA and ESR1 polymorphism was detected. These findings suggest that ESR1 polymorphisms modify the effects of prenatal exposure to PFAS on sex differentiation.
• 学童のプラスチック添加剤への曝露実態 北海道スタディ

  池田 敦子, アイツバマイ ゆふ, Ketema Rahel Mesfin, Gys Celine, Bastiaensen Michiel, Covaci Adrian, 岸 玲子

  日本衛生学雑誌 77 Suppl. S206 - S206 (一社)日本衛生学会 2022年03月
• 小児の携帯情報端末の使用開始年齢と問題行動の程度との関連 北海道スタディ

  宮下 ちひろ, 山崎 圭子, 田村 菜穂美, 池田 敦子, 福永 久典, 日景 隆, 水田 正弘, 大宮 学, 岸 玲子

  日本衛生学雑誌 77 Suppl. S189 - S189 (一社)日本衛生学会 2022年03月
• 子どものスクリーンタイムおよび問題行動との関連 北海道スタディ

  田村 菜穂美, 山崎 圭子, 宮下 ちひろ, 池田 敦子, 福永 久典, 日景 隆, 水田 正弘, 大宮 学, 岸 玲子

  日本衛生学雑誌 77 Suppl. S189 - S189 (一社)日本衛生学会 2022年03月
• 学童期における携帯電話等の電磁波曝露の実態調査 北海道スタディ

  山崎 圭子, 田村 菜穂美, 宮下 ちひろ, 池田 敦子, 福永 久典, 日景 隆, 水田 正弘, 大宮 学, 岸 玲子

  日本衛生学雑誌 77 Suppl. S199 - S199 (一社)日本衛生学会 2022年03月
• Nonylphenol exposure in 7-year-old Japanese children between 2012 and 2017- Estimation of daily intakes based on novel urinary metabolites.

  Benedikt Ringbeck, Daniel Bury, Atsuko Ikeda-Araki, Yu Ait Bamai, Rahel Mesfin Ketema, Chihiro Miyashita, Thomas Brüning, Reiko Kishi, Holger M Koch

  Environment international 161 107145 - 107145 2022年03月 [査読有り]
   

  Nonylphenol (NP) has been under scrutiny for decades due to its endocrine-disrupting properties and its ubiquity in the environment. Despite its widespread occurrence, robust and reliable exposure data are rare. In this study, we used human biomonitoring (HBM) measuring the novel urinary alkyl-chain-oxidized biomarkers OH-NP and oxo-NP to determine NP exposure in 7-year-old Japanese children. The new biomarkers are advantageous over measuring unchanged NP because they are not prone to external contamination. We analyzed 180 first morning void urine samples collected between 2012 and 2017. OH-NP and oxo-NP were detected in 100% and 66% of samples at median concentrations of 2.69 and 0.36 µg/L, respectively. 10-fold concentration differences between OH-NP and oxo-NP are in line with recent findings on human NP metabolism. Based on OH-NP we back-calculated median and maximum NP daily intakes (DI) of 0.14 and 0.95 µg/(kg bw*d). These DIs are rather close to but still below the current provisional tolerable daily intake of 5 µg/(kg bw*d) by the Danish Environmental Protection Agency. Between 2012 and 2017 the DIs decreased by an average of 4.7% per year. We observed no seasonal changes or gender differences and questionnaire data on food consumption, housing characteristics or pesticide use showed no clear associations with NP exposure. Urinary OH-NP was weakly associated with the oxidative stress (lipid peroxidation) biomarkers N-ε-hexanoyl-lysine (HEL) and trans-4-hydroxy-2-nonenal (HNE) (Spearman ρ = 0.30 and 0.22, respectively), but not with 8-hydroxy-2'-deoxyguanosine (8-OHdG). Further research is needed to identify and understand the major sources of NP exposure and to investigate a potential role in oxidative stress. This study is the first to investigate NP exposure in Japanese children based on robust and sensitive HBM data. It is a first step to fill the long-standing gap in quantitative human NP exposure monitoring and risk assessment.
• Severity of low pre-pregnancy body mass index and perinatal outcomes: the Japan Environment and Children's Study.

  Kentaro Nakanishi, Yasuaki Saijo, Eiji Yoshioka, Yukihiro Sato, Yasuhito Kato, Ken Nagaya, Satoru Takahashi, Yoshiya Ito, Sumitaka Kobayashi, Chihiro Miyashita, Atsuko Ikeda-Araki, Reiko Kishi

  BMC pregnancy and childbirth 22 1 121 - 121 2022年02月11日 [査読有り]
   

  BACKGROUND: The extremes of maternal pre-pregnancy body mass index (BMI) are known to be risk factors associated with obstetric and adverse perinatal outcomes. Among Japanese women aged 20 years or older, the prevalence of underweight (BMI < 18.5 kg/m2) was 11.5% in 2019. Maternal thinness is a health problem caused by the desire to become slim. This study aimed to investigate the association between the severity of maternal low pre-pregnancy BMI and adverse perinatal outcomes, including preterm birth (PTB), low birth weight (LBW), and small-for-gestational age (SGA). METHODS: We conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant individuals between 2011 and 2014. Pre-pregnancy BMI was categorized as severe-moderate underweight (BMI < 16.9 kg/m2), mild underweight (BMI, 17.0-18.4 kg/m2), low-normal weight (BMI, 18.5-19.9 kg/m2), high-normal weight (BMI, 20.0-22.9 kg/m2), overweight (BMI, 23.0-24.9 kg/m2), and obese (BMI ≥ 25.0 kg/m2). The high-normal weight group was used as the reference for statistical analyses. Adjusted logistic regression was performed to evaluate the association between pre-pregnancy BMI and PTB, LBW, and SGA. RESULTS: Of 92,260 singleton pregnant individuals, the prevalence was 2.7% for severe-moderate underweight, 12.9% for mild underweight, and 24.5% for low-normal weight. The prevalence of adverse outcomes was 4.6% for PTB, 8.1% for LBW, and 7.6% for SGA. The adjusted odds ratios (aORs) for PTB were 1.72 (95% confidence interval [CI], 1.46-2.03) for severe-moderate underweight and 1.26 (95% CI, 1.14-1.39) for mild underweight. The aORs of LBW were 2.55 (95% CI, 2.27-2.86) for severe-moderate underweight, 1.64 (95% CI, 1.53-1.76) for mild underweight, and 1.23 (95% CI, 1.16-1.31) for low-normal weight. The aORs of SGA were 2.53 (95% CI, 2.25-2.84) for severe-moderate underweight, 1.66 (95% CI, 1.55-1.79) for mild underweight, and 1.29 (95% CI, 1.21-1.38) for low-normal weight. CONCLUSIONS: A dose-response relationship was found between the severity of low pre-pregnancy BMI and PTB, LBW, and SGA. Even low-normal BMI (18.5-19.9 kg/m2) increased the risk of LBW and SGA. This study provides useful information for pre-conception counseling in lean individuals.
• Phthalates mixture on allergies and oxidative stress biomarkers among children: The Hokkaido study.

  Rahel Mesfin Ketema, Yu Ait Bamai, Chihiro Miyashita, Takeshi Saito, Reiko Kishi, Atsuko Ikeda-Araki

  Environment international 160 107083 - 107083 2022年02月 [査読有り]
   

  BACKGROUND: Exposure to individual phthalates and the mediation effect of oxidative stress in association with asthma and allergic symptoms have been studied previously. Little is known about the mixture effect of phthalates on health outcomes. Thus, we investigated the effect of a mixture of ten phthalate metabolites in association with wheeze, rhino-conjunctivitis, and eczema. The mediating effect of three oxidative stress biomarkers was also assessed. METHODS: Levels of 10 phthalate metabolites and 3 oxidative stress biomarkers were measured in 386 urine samples from 7-year-old children. Parents reported demographic and allergic symptoms using ISAAC questionnaires. Logistic regression for individual metabolites and mixture analysis weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) were fitted to examine the association between phthalate metabolite exposure and health outcomes. Baron and Kenny's regression approach was used for mediation analysis. RESULTS: In logistic regression model showed mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) (OR = 1.41, 95% CI 1.02-1.97) and mono carboxy-isononyl phthalate (cx-MINP) (OR = 1.40, 95% CI 1.07-1.86) were associated with wheeze. The WQS index had a significant association (OR = 1.46, 95% CI 1.09-1.96) with wheeze and (OR = 1.40, 95% CI 1.07-1.82) with eczema. Mono-isononyl phthalate (MINP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) were the most highly weighted metabolites. In the BKMR model, diisononyl phthalate (DINP) metabolites showed the highest group posterior inclusion probability (PIP). Among DINP metabolites, MINP in wheeze, cx-MINP in rhino-conjunctivitis and OH-MINP in eczema showed the highest conditional PIPs. The overall metabolites mixture effect was associated with eczema. We did not find any mediation of oxidative stress in the association between phthalates and symptoms. No significant association between phthalate metabolites and oxidative stress was observed in this study. CONCLUSION: Mixture of phthalate metabolites were associated with wheeze and eczema. The main contributors to the association were DEHP and DINP metabolites. No mediation of oxidative stress was observed.
• The association between prenatal perfluoroalkyl substance exposure and symptoms of attention-deficit/hyperactivity disorder in 8-year-old children and the mediating role of thyroid hormones in the Hokkaido study.

  Sachiko Itoh, Keiko Yamazaki, Satoshi Suyama, Atsuko Ikeda-Araki, Chihiro Miyashita, Yu Ait Bamai, Sumitaka Kobayashi, Hideyuki Masuda, Takeshi Yamaguchi, Houman Goudarzi, Emiko Okada, Ikuko Kashino, Takuya Saito, Reiko Kishi

  Environment international 159 107026 - 107026 2022年01月15日 [査読有り]
   

  BACKGROUND: Disruption of thyroid hormone (TH) levels during pregnancy contributes to attention deficit hyperactivity disorder (ADHD). Exposure to perfluoroalkyl substances (PFAS) during gestation may affect levels of maternal and neonatal TH; however, little is known about the effect of PFAS on ADHD mediated by TH. OBJECTIVES: We investigated the impact of maternal PFAS exposure on children's ADHD symptoms with the mediating effect of TH. METHODS: In a prospective birth cohort (the Hokkaido study), we included 770 mother-child pairs recruited between 2002 and 2005 for whom both prenatal maternal and cord blood samples were available. Eleven PFAS were measured in maternal serum obtained at 28-32 weeks of gestation using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. TH and thyroid antibody, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured in maternal blood during early pregnancy (median 11 gestational weeks) and in cord blood at birth. ADHD symptoms in the children at 8 years of age were rated by their parents using the ADHD-Rating Scale (ADHD-RS). The cut-off value was set at the 80th percentile for each sex. RESULTS: Significant inverse associations were found between some PFAS in maternal serum and ADHD symptoms among first-born children. Assuming causality, we found only one significant association: maternal FT4 mediated 17.6% of the estimated effect of perfluoroundecanoic acid exposure on hyperactivity-impulsivity among first-born children. DISCUSSION: Higher PFAS levels in maternal serum during pregnancy were associated with lower risks of ADHD symptoms at 8 years of age. The association was stronger among first-born children in relation to hyperactivity-impulsivity than with regard to inattention. There was little mediating role of TH during pregnancy in the association between maternal exposure to PFAS and reduced ADHD symptoms at 8 years of age.
• Effects of Persistent Organic Pollutants (POPs) in the Ecosystem and Human Health: Focusing on Chlorinated Chemicals

  Ikeda-Atsuko Araki, Chihiro Miyashita, Sumitaka Kobayashi, Keiko Yamazaki, Reiko Kishi

  The Handbook of Environmental Chemistry 121 - 143 2022年01月01日 [査読有り][招待有り]
  
• Environmental Impacts on Infectious Disease: A Literature View of Epidemiological Evidence.

  Peter D Sly, Brittany Trottier, Atsuko Ikeda-Araki, Dwan Vilcins

  Annals of global health 88 1 91 - 91 2022年 

  BACKGROUND: This article summarises a session from the recent Pacific Basin Consortium for Environment and Health Focus meeting on Environmental Impacts on Infectious Disease. OBJECTIVE: To provide an overview of the literature underpinning the presentations from this session. METHODS: References used in developing the presentations were obtained from the presenters. Additional references were obtained from PubMed using key words from the presentations. FINDINGS AND CONCLUSIONS: The Hokkaido longitudinal children's study has found that exposure to chemicals in early life, such as persistent organic pollutants and per/polyfluorinated compounds, is associated with a range of immunological outcomes such as decreased cord blood IgE, otitis media, wheeze, increased risk of infections and higher risk of food allergy.Epidemiological evidence links exposure to poor air quality to increased severity and mortality of Covid-19 in many parts of the world. Most studies suggest that long-term exposure has a more marked effect than acute exposure.Components of air pollution, such as a newly described combustion product known as environmentally persistent free radicals, induce oxidative stress in exposed individuals. Individuals with genetic variations predisposing them to oxidative stress are at increased risk of adverse health effects from poor air quality.
• Relations of mold, stove, and fragrance products on childhood wheezing and asthma: A prospective cohort study from the Japan Environment and Children's Study.

  Yasuaki Saijo, Eiji Yoshioka, Yukihiro Sato, Hiroshi Azuma, Yusuke Tanahashi, Yoshiya Ito, Sumitaka Kobayashi, Machiko Minatoya, Yu Ait Bamai, Keiko Yamazaki, Sachiko Itoh, Chihiro Miyashita, Atsuko Ikeda-Araki, Reiko Kishi, Michihiro Kamijima, Shin Yamazaki, Yukihiro Ohya, Nobuo Yaegashi, Koichi Hashimoto, Chisato Mori, Shuichi Ito, Zentaro Yamagata, Hidekuni Inadera, Takeo Nakayama, Hiroyasu Iso, Masayuki Shima, Youichi Kurozawa, Narufumi Suganuma, Koichi Kusuhara, Takahiko Katoh

  Indoor air 32 1 e12931  2022年01月 [査読有り]
   

  This prospective cohort study aimed to examine the associations between mold growth, type of stoves, and fragrance materials and early childhood wheezing and asthma, using data from the Japan Environment and Children's Study. Mold growth at home, usage of kerosene/gas stove, wood stove/fireplace, and air freshener/deodorizer were surveyed using a questionnaire at 1.5-year-old, and childhood wheezing and doctor-diagnosed asthma during the previous year were obtained using a 3-year-old questionnaire. Multilevel logistic regression analysis was performed to evaluate the association between exposure to childhood wheezing and asthma. A total of 60 529 children were included in the analysis. In multivariate analyses, mold growth and wood stove/fireplace had significantly higher odds ratios (ORs) for wheezing (mold growth: 1.13; 95% CI, 1.06-1.22; wood stove/fireplace: 1.23; 95% CI, 1.03-1.46). All four exposures had no significant ORs for childhood doctor-diagnosed asthma; however, in the supplemental analysis of northern regions, wood stove/fireplace had a significantly higher OR for asthma. Mold growth and wood stove/fireplace had significant associations with childhood wheezing in the northern regions. Mold elimination in the dwellings and use of clean heating (no air pollution emissions) should be taken into consideration to prevent and improve childhood wheezing and asthma.
• Associations between maternal mono-(2-ethylhexyl) phthalate levels, nuclear receptor gene polymorphisms, and fatty acid levels in pregnant Japanese women in the Hokkaido study.

  Sumitaka Kobayashi, Fumihiro Sata, Chihiro Miyashita, Atsuko Ikeda-Araki, Houman Goudarzi, Tamie Nakajima, Reiko Kishi

  Reproductive toxicology (Elmsford, N.Y.) 107 22 - 32 2022年01月 [査読有り]
   

  We assessed how the interaction between mono-(2-ethylhexyl) phthalate (MEHP) in maternal sera and the maternal genotypes associated with nuclear receptors affect fatty acid levels in a prospective birth cohort study of pregnant Japanese individuals (n = 437) recruited in Sapporo between 2002 and 2005. We analyzed MEHP and fatty acids using gas chromatography-mass spectrometry. Thirteen single nucleotide polymorphisms of peroxisome proliferator-activated receptor (PPAR) alpha, PPAR gamma (PPARG), PPARG coactivator 1A (PPARGC1A), PPAR delta, constitutive androstane receptor, liver X receptor (LXR) alpha, and LXR beta (LXRB) were analyzed using real-time PCR. Multiple linear regression models were used to confirm the influence of log10-transformed MEHP levels and maternal genotypes on log10-transformed fatty acid levels. When the effects of the interaction between MEHP levels and the maternal PPARGC1A (rs8192678) genotype on oleic acid levels were evaluated, the estimated changes (95 % confidence intervals) in oleic acid levels against MEHP levels, maternal PPARGC1A (rs8192678)-GA/AA genotype, and the interaction between them showed a mean reduction of 0.200 (0.079, 0.322), mean reduction of 0.141 (0.000, 0.283), and mean increase of 0.145 (0.010, 0.281), respectively, after adjusting for the perfluorooctanesulfonate level. The effects of the interaction between MEHP levels and maternal LXRB (rs2303044) genotype on linoleic acid levels was also significant (pint = 0.010). In conclusion, the interaction between MEHP and the maternal genotypes PPARGC1A (rs8192678) and LXRB (rs2303044) decreased fatty acid levels. Further, the interaction between MEHP and PPARGC1A (rs8192678) may have a greater effect on fatty acid levels than the interaction between PFOS and PPARGC1A.
• Relationships between maternal perfluoroalkyl substance levels, polymorphisms of receptor genes, and adverse birth outcomes in the Hokkaido birth cohort study, Japan.

  Sumitaka Kobayashi, Fumihiro Sata, Atsuko Ikeda-Araki, Chihiro Miyashita, Houman Goudarzi, Yusuke Iwasaki, Tamie Nakajima, Reiko Kishi

  Reproductive toxicology (Elmsford, N.Y.) 107 112 - 122 2022年01月 [査読有り]
   

  We assessed the associations between perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) levels in third trimester maternal serum, the maternal genotypes of genes encoding nuclear receptors, and birth outcomes. We studied a prospective birth cohort of healthy pregnant Japanese women (n = 372) recruited in Sapporo between July 2002 and October 2005. We analyzed PFOS and PFOA levels using liquid chromatography-tandem mass spectrometry and analyzed 13 single nucleotide polymorphisms (SNPs) of proliferator-activated receptor alpha, gamma, gamma coactivator 1A, delta, constitutive androstane receptor, liver X receptor alpha, and beta (LXRB) using real-time polymerase reaction (PCR). We employed multiple linear regression models to establish the influences of log10-transformed PFOS and PFOA levels and maternal genotypes on birth size. In female infants, we identified interactions between PFOS levels, the maternal genotype of LXRB (rs1405655), and birth weight. The estimated mean changes in birth weight in response to PFOS levels, the maternal genotype LXRB (rs1405655)-TC/CC (compared to TT), and their interactions were -502.9 g (95 % confidence interval [CI] = -247.3, -758.5 g), -526.3 g (95 % CI = -200.7, -852.0 g), and 662.1 g (95 % CI = 221.0, 1,103.2 g; pint = 0.003), respectively. Interactions between PFOS levels and the maternal genotype of LXRB (rs1405655) also significantly affected birth chest circumference and the Ponderal index (pint = 0.037 and 0.005, respectively). Thus, interactions between PFOS levels and the maternal genotype of LXRB (rs1405655) affects birth sizes in female infants. We found that certain SNPs modify the effects of PFOS levels on birth size.
• 一般家庭における短期/長期堆積ダストを活用したSVOCの曝露評価研究1 リン系難燃剤・可塑剤の室内濃度分布と汚染要因の解析

  戸次 加奈江, 池田 敦子, アイツバマイ ゆふ, 稲葉 洋平, 東 賢一, 金 勲, 岸 玲子

  室内環境学会学術大会講演要旨集 2021年 100 - 101 (一社)室内環境学会 2021年12月
• 一般家庭における短期/長期堆積ダストを活用したSVOCの曝露評価研究2 子どものハウスダスト中リン系難燃剤・可塑剤の一日摂取量

  池田 敦子, 戸次 加奈江, アイツバマイ ゆふ, 稲葉 洋平, 金 勲, 岸 玲子

  室内環境学会学術大会講演要旨集 2021年 102 - 103 (一社)室内環境学会 2021年12月
• Associations among perfluorooctanesulfonic/perfluorooctanoic acid levels, nuclear receptor gene polymorphisms, and lipid levels in pregnant women in the Hokkaido study

  Sumitaka Kobayashi, Fumihiro Sata, Houman Goudarzi, Atsuko Araki, Chihiro Miyashita, Seiko Sasaki, Emiko Okada, Yusuke Iwasaki, Tamie Nakajima, Reiko Kishi

  Scientific Reports 11 1 2021年12月 [査読有り]
   

  The effect of interactions between perfluorooctanesulfonic (PFOS)/perfluorooctanoic acid (PFOA) levels and nuclear receptor genotypes on fatty acid (FA) levels, including those of triglycerides, is not clear understood. Therefore, in the present study, we aimed to analyse the association of PFOS/PFOA levels and single-nucleotide polymorphisms (SNPs) in nuclear receptors with FA levels in pregnant women. We analysed 504 mothers in a birth cohort between 2002 and 2005 in Japan. Serum PFOS/PFOA and FA levels were measured using liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Maternal genotypes in PPARA (rs1800234; rs135561), PPARG (rs3856806), PPARGC1A (rs2970847; rs8192678), PPARD (rs1053049; rs2267668), CAR (rs2307424; rs2501873), LXRA (rs2279238) and LXRB (rs1405655; rs2303044; rs4802703) were analysed. When gene-environment interaction was considered, PFOS exposure (log₁₀ scale) decreased palmitic, palmitoleic, and oleic acid levels (log₁₀ scale), with the observed β in the range of − 0.452 to − 0.244; PPARGC1A (rs8192678) and PPARD (rs1053049; rs2267668) genotypes decreased triglyceride, palmitic, palmitoleic, and oleic acid levels, with the observed β in the range of − 0.266 to − 0.176. Interactions between PFOS exposure and SNPs were significant for palmitic acid (P_int = 0.004 to 0.017). In conclusion, the interactions between maternal PFOS levels and PPARGC1A or PPARD may modify maternal FA levels.
• Hypertensive Disorders during Pregnancy and Anthropometric Measurement of Children up to 7 Years of Age: The Hokkaido Birth Cohort Study in Japan.

  Kritika Poudel, Sumitaka Kobayashi, Chihiro Miyashita, Takeshi Yamaguchi, Naomi Tamura, Atsuko Ikeda-Araki, Yu Ait Bamai, Sachiko Itoh, Keiko Yamazaki, Hideyuki Masuda, Mariko Itoh, Reiko Kishi

  International journal of environmental research and public health 18 20 2021年10月18日 [査読有り]
   

  Hypertensive disorders during pregnancy (HDP) increase the risk of offspring with a low birth weight, preterm birth and small-for-gestational age; however, evidence of the anthropometric measurements during early childhood remains limited. We aimed to understand the associations between maternal HDP and anthropometric measurements of children aged up to seven years in a Japanese cohort. In total, 20,926 mother-infant pairs participated in the Hokkaido Study on Environment and Children's Health, Japan, from 2002 to 2013. Medical reports were used to confirm HDP exposure, while weight, height, height z score, and weight z score were the outcomes. The prevalence of HDP in the study population was 1.7%. The birth height of male children born to HDP mothers was smaller as compared to those born to non-HDP mothers. When adjusted with covariates, the linear regressions showed significant changes in birth weight (β: -79.3; 95% confidence interval [CI]: -154.8, -3.8), birth height (-0.67; 95% CI: -1.07, -0.26), weight at seven years (1.21; 95% CI: 0.13, 2.29), and weight gain between four and seven years (1.12; 95% CI: 0.28, 1.96) of male children exposed to HDP. Differences were more significant in male children than female. Our study showed that despite low birth weight, male children exposed to HDP caught up with their growth and gained more weight by seven years of age compared with male children not exposed to HDP, whereas no such differences were observed in female children; however, this finding requires replication.
• Associations among maternal perfluoroalkyl substance levels, fetal sex-hormone enzymatic gene polymorphisms, and fetal sex hormone levels in the Hokkaido study

  Sumitaka Kobayashi, Fumihiro Sata, Atsuko Ikeda-Araki, Chihiro Miyashita, Sachiko Itoh, Houman Goudarzi, Yusuke Iwasaki, Takahiko Mitsui, Kimihiko Moriya, Nobuo Shinohara, Kazutoshi Cho, Reiko Kishi

  Reproductive Toxicology 105 221 - 231 2021年10月 [査読有り]
   

  Prenatal sex hormones affect fetal growth; for example, prenatal exposure to low levels of androgen accelerates female puberty onset. We assessed the association of perfluoroalkyl substances (PFASs) in maternal sera and infant genotypes of genes encoding enzymes involved in sex steroid hormone biosynthesis on cord sera sex hormone levels in a prospective birth cohort study of healthy pregnant Japanese women (n = 224) recruited in Sapporo between July 2002 and October 2005. We analyzed PFAS and five sex hormone levels using liquid chromatography-tandem mass spectrometry. Cytochrome P450 (CYP) 17A1 (CYP17A1 rs743572), 19A1 (CYP19A1 rs10046, rs700519, and rs727479), 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1 rs6203), type 2 (HSD3B2 rs1819698, rs2854964, and rs4659175), 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1 rs605059, rs676387, and rs2676531), and type 3 (HSD17B3 rs4743709) were analyzed using real-time PCR. Multiple linear regression models were used to establish the influence of log10-transformed PFAS levels and infant genotypes on log10-transformed sex steroid hormone levels. When the interaction between perfluorooctanesulfonate (PFOS) levels and female infant genotype CYP17A1 (rs743572) on the androstenedione (A-dione) levels was considered, the estimated changes (95 % confidence intervals) in A-dione levels against PFOS levels, female infant genotype CYP17A1 (rs743572)-AG/GG, and interaction between them showed a mean increase of 0.445 (0.102, 0.787), mean increase of 0.392 (0.084, 0.707), and mean reduction of 0.579 (0.161, 0.997) (Pint = 0.007), respectively. Moreover, a female-specific interaction with testosterone levels was observed. A-dione and T levels showed positive main effects and negative interaction with PFOS levels and the female infant CYP17A1 genotype.
• Association between the Concentrations of Metallic Elements in Maternal Blood during Pregnancy and Prevalence of Abdominal Congenital Malformations: The Japan Environment and Children’s Study

  Chihiro Miyashita, Yasuaki Saijo, Yoshiya Ito, Atsuko Ikeda-Araki, Sachiko Itoh, Keiko Yamazaki, Sumitaka Kobayashi, Yu Ait Bamai, Hideyuki Masuda, Naomi Tamura, Mariko Itoh, Takeshi Yamaguchi, Shin Yamazaki, Reiko Kishi

  International Journal of Environmental Research and Public Health 18 19 10103 - 10103 2021年09月26日 [査読有り]
   

  Abdominal congenital malformations are responsible for early mortality, inadequate nutrient intake, and infant biological dysfunction. Exposure to metallic elements in utero is reported to be toxic and negatively impacts ontogeny. However, no prior study has sufficiently evaluated the effects of exposure to metallic elements in utero on abdominal congenital malformations. The aim of the present study was to evaluate associations between metallic elements detected in maternal blood during pregnancy and congenital abdominal malformations. Data from participants in the Japan Environment and Children’s Study was used in the present study, and contained information on singleton and live birth infants without congenital abnormalities (control: n = 89,134) and abdominal malformations (case: n = 139). Heavy metals such as mercury (Hg), lead (Pb), cadmium (Cd), and trace elements of manganese (Mn) and selenium (Se) were detected in maternal serum samples during mid- and late-gestation. Infant congenital abnormalities were identified from delivery records at birth or one month after birth by medical doctors. In a multivariate analysis adjusted to account for potential confounders, quartiles of heavy metals and trace elements present in maternal blood were not statistically correlated to the prevalence of abdominal congenital malformations at birth. This study is the first to reveal the absence of significant associations between exposure levels to maternal heavy metals and trace elements in utero and the prevalence of abdominal congenital malformations in a large cohort of the Japanese population. Further studies are necessary to investigate the impact of exposure to heavy metals and trace elements via maternal blood in offspring after birth.
• DNA methylation changes associated with prenatal mercury exposure: A meta-analysis of prospective cohort studies from PACE consortium.

  Manuel Lozano, Paul Yousefi, Karin Broberg, Raquel Soler-Blasco, Chihiro Miyashita, Giancarlo Pesce, Woo Jin Kim, Mohammad Rahman, Kelly M Bakulski, Line S Haug, Atsuko Ikeda-Araki, Guy Huel, Jaehyun Park, Caroline Relton, Martine Vrijheid, Sheryl Rifas-Shiman, Emily Oken, John F Dou, Reiko Kishi, Kristine B Gutzkow, Isabella Annesi-Maesano, Sungho Won, Marie-France Hivert, M Daniele Fallin, Marina Vafeiadi, Ferran Ballester, Mariona Bustamante, Sabrina Llop

  Environmental research 204 Pt B 112093 - 112093 2021年09月22日 [査読有り]
   

  Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10-4, p-value = 5.87 × 10-5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10-5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10-7) in GRK1 and cg02212000 (β = -0.001, p-value = 8.13 × 10-7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.
• The protocol for the study about association between radio frequency wave and children's health: The Hokkaido study on environment and children's health

  Keiko Yamazaki, Atsuko Araki, Chihiro Miyashita, Naomi Tamura, Takashi Hikage, Manabu Omiya, Masahiro Mizuta, Reiko Kishi

  2021 34th General Assembly and Scientific Symposium of the International Union of Radio Science, URSI GASS 2021 2021年08月28日 

  It is needed to clarify the association between radio frequency (RF) wave exposure and child health, especially focused on neurodevelopment. We conduct questionnaire survey on mobile phone usage and children's behavior and health status for all children in the existing Hokkaido study cohort (n = 12,000, 7-17 year-old). Additionally, we implement three types of face to face survey for neurodevelopment (cognitive assessment, electroencephalogram recording, and intelligence test), along with personal radio frequency wave exposure measurements by portable devices, on children participating the existing Hokkaido birth cohort study (n = 400, respectively). All together, we examine the association between radio frequency wave exposure and children's health, controlling for potential confounding factors. In the presentation, we introduce the protocol of our project.
• Effect of prenatal exposure to phthalates on epigenome-wide DNA methylations in cord blood and implications for fetal growth: The Hokkaido Study on Environment and Children's Health.

  Ryu Miura, Atsuko Ikeda-Araki, Toru Ishihara, Kunio Miyake, Chihiro Miyashita, Tamie Nakajima, Sumitaka Kobayashi, Mayumi Ishizuka, Takeo Kubota, Reiko Kishi

  The Science of the total environment 783 147035 - 147035 2021年08月20日 [査読有り]
   

  Prenatal exposure to phthalates negatively affects the offspring's health. In particular, epigenetic alterations, such as DNA methylation, may connect phthalate exposure with health outcomes. Here, we evaluated the association of di-2-ethylhexyl phthalate (DEHP) exposure in utero with cord blood epigenome-wide DNA methylation in 203 mother-child pairs enrolled in the Hokkaido Study on Environment and Children's Health, using the Illumina HumanMethylation450 BeadChip. Epigenome-wide association analysis demonstrated the predominant positive associations between the levels of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), in maternal blood and DNA methylation levels in cord blood. The genes annotated to the CpGs positively associated with MEHP levels were enriched for pathways related to metabolism, the endocrine system, and signal transduction. Among them, methylation levels of CpGs involved in metabolism were inversely associated with the offspring's ponderal index (PI). Further, clustering and mediation analyses suggested that multiple increased methylation changes may jointly mediate the association of DEHP exposure in utero with the offspring's PI at birth. Although further studies are required to assess the impact of these changes, this study suggests that differential DNA methylation may link phthalate exposure in utero to fetal growth and further imply that DNA methylation has predictive value for the offspring's obesity.
• Maternal psychological distress, education, household income, and congenital heart defects: a prospective cohort study from the Japan environment and children's study.

  Yasuaki Saijo, Eiji Yoshioka, Yukihiro Sato, Hiroshi Azuma, Yusuke Tanahashi, Yoshiya Ito, Sumitaka Kobayashi, Machiko Minatoya, Yu Ait Bamai, Keiko Yamazaki, Sachiko Itoh, Chihiro Miyashita, Atsuko Ikeda-Araki, Reiko Kishi

  BMC pregnancy and childbirth 21 1 544 - 544 2021年08月07日 [査読有り]
   

  BACKGROUND: The influence of maternal psychological distress on infant congenital heart defects (CHDs) has not been thoroughly investigated. Furthermore, there have been no reports on the combined effect of maternal psychological distress and socioeconomic status on infant CHDs. This study aimed to examine whether maternal psychological distress, socioeconomic status, and their combinations were associated with CHD. METHODS: We conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant women between 2011 and 2014. Maternal psychological distress was evaluated using the Kessler Psychological Distress Scale in the first trimester, while maternal education and household income were evaluated in the second and third trimesters. The outcome of infant CHD was determined using the medical records at 1 month of age and/or at birth. Crude- and confounder-adjusted logistic regression analyses were performed to evaluate the association between maternal psychological distress and education and household income on infant CHD. RESULTS: A total of 93,643 pairs of mothers and infants were analyzed, with 1.1% of infants having CHDs. Maternal psychological distress had a significantly higher odds ratio in the crude analysis but not in the adjusted analysis, while maternal education and household income were statistically insignificant. In the analysis of the combination variable of lowest education and psychological distress, the P for trend was statistically significant in the crude and multivariate model excluding anti-depressant medication, but the significance disappeared in the full model (P = 0.050). CONCLUSIONS: The combination of maternal psychological distress and lower education may be a possible indicator of infant CHD.
• An analytical survey of benzotriazole UV stabilizers in plastic products and their endocrine-disrupting potential via human estrogen and androgen receptors.

  Yuuta Sakuragi, Hideshige Takada, Hiroya Sato, Atsuhito Kubota, Masaru Terasaki, Shinji Takeuchi, Atsuko Ikeda-Araki, Yoko Watanabe, Shigeyuki Kitamura, Hiroyuki Kojima

  The Science of the total environment 800 149374 - 149374 2021年07月31日 [査読有り]
   

  Benzotriazole UV stabilizers (BUVSs) are added to various materials to prevent damage from UV-irradiation. Recently, there has been great concern regarding the endocrine-disrupting effects of exposure to microplastic-derivative BUVSs in particular. In this study, we measured the concentrations of nine representative BUVSs in the plastic bottle caps of 10 beverages, 4 food packages, and 4 plastic shopping bags purchased from Japanese grocery stores by GC-MS analysis, and found that eight BUVSs, except for 2-(3,5-di-tert-butyl-2-hydroxyphenyl)-2H-benzotriazole (UV-320), were detected from these plastic products. In particular, 2-(2-hydroxy-5-methylphenyl) benzotriazole (UV-P) and 2-(2-hydroxy-3-tert-butyl-5-methylphenyl)-5-chlorobenzotriazole (UV-326) were detected from all the bottle caps at concentrations in the order of ng/g. In addition, we characterized the agonistic and/or antagonistic activities against human estrogen receptors (ERα/β) and androgen receptor (AR) of 13 BUVSs. Results revealed that, among the 13 BUVSs, UV-P, 2-(5-tert-butyl-2-hydroxyphenyl) benzotriazole (UV-PS), 2-[2-hydroxy-5-[2-(methacryloyloxy)ethyl]phenyl]-2H-benzotriazole (UV-090) and 2-(2-hydroxy-5-tert-octylphenyl)-benzotriazole (UV-329) showed ERα and/or ERβ agonistic activity, with UV-P being the most potent based on these assays. On the other hand, UV-320 and 2-(3-s-butyl-5-tert-butyl-2-hydroxyphenyl) benzotriazole (UV-350) showed both ERα and ERβ antagonistic activities, and 2-(3,5-di-tert-amyl-2-hydroxylphenyl) benzotriazole (UV-328) and UV-329 acted as ERβ antagonists. In the AR assay, UV-P and 2-(3-allyl-2-hydroxy-5-methylphenyl)-2H-benzotriazole (UV-9) showed AR antagonistic activity although none of the test compounds showed AR agonistic activity. Taken together, our findings suggest that a series of BUVSs are present in our environments via plastic materials and several of these compounds possess endocrine-disrupting potential, such as ERα/β agonistic and/or antagonistic activity and AR antagonistic activity. UV-P and its structurally similar compounds, in particular, appear to be a cause for concern.
• Association between Early Life Child Development and Family Dog Ownership: A Prospective Birth Cohort Study of the Japan Environment and Children's Study.

  Machiko Minatoya, Atsuko Ikeda-Araki, Chihiro Miyashita, Sachiko Itoh, Sumitaka Kobayashi, Keiko Yamazaki, Yu Ait Bamai, Yasuaki Saijo, Yukihiro Sato, Yoshiya Ito, Reiko Kishi, The Japan Environment And Children's Study Group

  International journal of environmental research and public health 18 13 2021年07月02日 [査読有り]
   

  Pets may play a role in the social-emotional development of children. In particular, some studies have suggested that family dog ownership is associated with better health outcomes. To date, no study has assessed child development in association with dog ownership of different time points. The purpose of the current study was primary to investigate whether "ever" family dog ownership was associated with early child development, and secondary to further examine whether associations between family dog ownership and early child development differ among family dog ownership of status, including "past only", "current only", and "always" groups, using the data of family dog ownership obtained at multiple time points. Associations between family dog ownership and infant development at 3 years of age were examined using data from a nationwide prospective birth cohort study, the Japan Environment and Children's Study (n = 78,941). "Ever" family dog ownership was categorized to "past only", "current only", and "always". We observed that children with "ever" family dog ownership showed a significantly decreased risk of developmental delay in the communication (odds ratio [OR] = 0.87; 95% confidence interval [CI]: 0.78, 0.96), gross motor (OR = 0.83; 95% CI: 0.76, 0.92), problem-solving (OR = 0.89; 95% CI: 0.83, 0.96) and personal-social (OR = 0.86; 95% CI: 0.72, 0.92) domains compared to children with "never" family dog ownership. Furthermore, a significantly decreased risk of developmental delay in gross motor function was observed in association with living with dogs in the "past only" (OR = 0.83; 95% CI: 0.73, 0.95) and "always" (OR = 0.86; 95% CI: 0.75, 0.98). In addition, a decreased risk of developmental delay in the problem-solving domain was associated with "past" family dog ownership (OR = 0.87; 95% CI: 0.79, 0.97) and in the personal-social domain was associated with "always" family dog ownership (OR = 0.81; 95% CI = 0.68, 0.95). Given the possible positive association between early life child development and family dog ownership, living with dogs may be an important factor to be considered when assessing child development.
• Prenatal alcohol exposure and adverse fetal growth restriction: findings from the Japan Environment and Children's Study.

  Kazutoshi Cho, Sumitaka Kobayashi, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Yasuaki Saijo, Yoshiya Ito, Kazuo Sengoku, Tsuyoshi Baba, Hisanori Minakami, Yuichi Nakamura, Reiko Kishi

  Pediatric research 92 1 291 - 298 2021年06月04日 

  BACKGROUNDS: Japanese studies on the association between maternal alcohol consumption and fetal growth are few. This study assessed the effect of maternal alcohol consumption on fetal growth. METHODS: This prospective birth cohort included 95,761 participants enrolled between January 2011 and March 2014 in the Japan Environment and Children's Study. Adjusted multiple linear and logistic regression models were used to assess the association between prenatal alcohol consumption and infant birth size. RESULTS: Consumption of a weekly dose of alcohol in the second/third trimester showed a significant negative correlation with standard deviation (SD; Z) scores for body weight, body length, and head circumference at birth, respectively. Consumption of a weekly dose of alcohol during the second/third trimester had a significant positive correlation with incidences of Z-score ≤ -1.5 for birth head circumference. Associations between alcohol consumption in the second/third trimester and Z-score ≤ -1.5 for birth weight or birth length were not significant. Maternal alcohol consumption in the second/third trimester above 5, 20, and 100 g/week affected body weight, body length, and head circumference at birth, respectively. CONCLUSION: Low-to-moderate alcohol consumption during pregnancy might affect fetal growth. Public health policies for pregnant women are needed to stop alcohol consumption during pregnancy. IMPACT: This study examined the association between maternal alcohol consumption and fetal growth restriction in 95,761 pregnant Japanese women using the prospective birth cohort. Maternal alcohol consumption in the second/third trimester more than 5, 20, and 100 g/week might affect fetal growth in body weight, body length, and head circumference, respectively. The findings are relevant and important for educating pregnant women on the adverse health effects that prenatal alcohol consumptions have on infants.
• Hokkaido birth cohort study on environment and children's health: cohort profile 2021.

  Reiko Kishi, Atsuko Ikeda-Araki, Chihiro Miyashita, Sachiko Itoh, Sumitaka Kobayashi, Yu Ait Bamai, Keiko Yamazaki, Naomi Tamura, Machiko Minatoya, Rahel Mesfin Ketema, Kritika Poudel, Ryu Miura, Hideyuki Masuda, Mariko Itoh, Takeshi Yamaguchi, Hisanori Fukunaga, Kumiko Ito, Houman Goudarzi

  Environmental health and preventive medicine 26 1 59 - 59 2021年05月22日 [査読有り]
   

  BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS: Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.
• Parental educational level and childhood wheezing and asthma: A prospective cohort study from the Japan Environment and Children’s Study

  Yasuaki Saijo, Eiji Yoshioka, Yukihiro Sato, Toshinobu Miyamoto, Hiroshi Azuma, Yusuke Tanahashi, Yoshiya Ito, Sumitaka Kobayashi, Machiko Minatoya, Yu Ait Bamai, Keiko Yamazaki, Sachiko Itoh, Chihiro Miyashita, Atsuko Araki, Reiko Kishi

  PLOS ONE 16 4 e0250255 - e0250255 2021年04月16日 

  The influence of mothers’ and fathers’ educational levels in separate evaluations of asthma has not been fully investigated. This study aims to examine the associations of the mother’s and fathers’ educational levels with childhood wheeze and asthma adjusting for crude and pre-and post-natal modifiable risk factors. We conducted a prospective cohort study using data from the Japan Environment and Children’s Study, which recruited pregnant women from 2011 to 2014. The mother’s and father’s educational levels were surveyed by a questionnaire during the pregnancy, and childhood wheezing and doctor-diagnosed asthma were estimated using a 3-year questionnaire. Multilevel logistic regression analysis was performed to evaluate the association between the mother’s and father’s educational levels and childhood wheezing and asthma, adjusted for pre-and post-natal factors. A total of 69,607 pairs of parents and their single infants were analyzed. We found 17.3% of children had wheezing and 7.7% had asthma. In crude analyses, lower educational level of parents was associated with an increased risk of childhood wheezing and asthma. After full adjustment, a lower educational level of mothers was associated with an increased risk of childhood asthma (junior high school (reference: high school); odds ratio (OR): 1.17, 95% CI, 1.01–1.36), and higher educational level, especially the mother’s, was associated with an increased risk of childhood wheezing (technical junior college, technical/vocational college, or associate degree (ECD3); OR: 1.12, 95% CI, 1.06–1.18, bachelor’s degree, or postgraduate degree; OR: 1.10, 95% CI, 1.03–1.18), and asthma (ECD3; OR: 1.13, 95% CI, 1.04–1.21). Parents’ lower educational level was a crude risk factor for childhood wheezing and asthma. However, an increased risk of wheezing due to mothers’ higher educational level was found after adjusting for pre-and post-natal factors.
• DNA methylation of GFI1 as a mediator of the association between prenatal smoking exposure and ADHD symptoms at 6 years: the Hokkaido Study on Environment and Children's Health.

  Kunio Miyake, Chihiro Miyashita, Atsuko Ikeda-Araki, Ryu Miura, Sachiko Itoh, Keiko Yamazaki, Sumitaka Kobayashi, Hideyuki Masuda, Tadao Ooka, Zentaro Yamagata, Reiko Kishi

  Clinical epigenetics 13 1 74 - 74 2021年04月07日 [査読有り]
   

  BACKGROUND: Prenatal smoking exposure has been associated with childhood attention-deficit/hyperactivity disorder (ADHD). However, the mechanism underlying this relationship remains unclear. We assessed whether DNA methylation differences may mediate the association between prenatal smoking exposure and ADHD symptoms at the age of 6 years. RESULTS: We selected 1150 mother-infant pairs from the Hokkaido Study on the Environment and Children's Health. Mothers were categorized into three groups according to plasma cotinine levels at the third trimester: non-smokers (≤ 0.21 ng/mL), passive smokers (0.21-11.48 ng/mL), and active smokers (≥ 11.49 ng/mL). The children's ADHD symptoms were determined by the ADHD-Rating Scale at the age of 6 years. Maternal active smoking during pregnancy was significantly associated with an increased risk of ADHD symptoms (odds ratio, 1.89; 95% confidence interval, 1.14-3.15) compared to non-smoking after adjusting for covariates. DNA methylation of the growth factor-independent 1 transcriptional repressor (GFI1) region, as determined by bisulfite next-generation sequencing of cord blood samples, mediated 48.4% of the total effect of the association between maternal active smoking during pregnancy and ADHD symptoms. DNA methylation patterns of other genes (aryl-hydrocarbon receptor repressor [AHRR], cytochrome P450 family 1 subfamily A member 1 [CYP1A1], estrogen receptor 1 [ESR1], and myosin IG [MYO1G]) regions did not exert a statistically significant mediation effect. CONCLUSIONS: Our findings demonstrated that DNA methylation of GFI1 mediated the association between maternal active smoking during pregnancy and ADHD symptoms at the age of 6 years.
• Prevalence of childhood wheeze and modified DNA methylation at 7 years of age according to maternal folate levels during pregnancy in the Hokkaido Study

  Chihiro Miyashita, Atsuko Araki, Ryu Miura, Yu Ait Bamai, Sumitaka Kobayashi, Sachiko Itoh, Kumiko Ito, Meng-Shan Tsai, Reiko Kishi

  PEDIATRIC ALLERGY AND IMMUNOLOGY 32 3 514 - 523 2021年04月 [査読有り]
   

  Background A high dose of folic acid during pregnancy may increase the risk of asthma, wheezing, and respiratory disease in childhood. Folate acid can modify inflammation and immune susceptibility of offspring with some epigenetic differentiation, including DNA methylation. This study evaluated associations between maternal folate levels during pregnancy and childhood wheezing; furthermore, the study assessed whether maternal folate-modified DNA methylation is related to asthma.MethodsParticipants in the current study were 6651 mother-child pairs who had complete data on characteristics and who had completed at least one of the International Study of Asthma and Allergies in Childhood questionnaires when the child was 1, 2, 4, and 7 years of age. Moreover, a case-control study to assess DNA methylation at 7 years of age was conducted among 136 children who experienced wheezing and a control group of 139 children with no history of allergies.ResultsThe median of maternal serum was 16.76 nmol/L, assayed by chemiluminescent immunoassay. We found significantly increased adjusted odds ratios of childhood wheezing at 2 years age according to maternal folate levels, compared with the lowest folate quartile (odds ratio [95% confidence interval] = highest; 1.27 [1.03, 1.56], and second, 1.27 [1.05, 1.55]); however, no changes were observed at 1, 4, and 7 years of age. In a case-control study, no association of maternal folate levels with DNA methylation was observed.ConclusionOur results suggest that maternal folate did not affect persistent wheezing in school-aged children, or DNA methylation of gasdermin B, orosomucoid-like 3, and Ikaros family zinc finger 3 at 7 years of age.
• Population attributable fractions of modifiable risk factors for nonsyndromic orofacial clefts: a prospective cohort study from the Japan Environment and Children’s Study

  Yukihiro Sato, Eiji Yoshioka, Yasuaki Saijo, Toshinobu Miyamoto, Kazuo Sengoku, Hiroshi Azuma, Yusuke Tanahashi, Yoshiya Ito, Sumitaka Kobayashi, Machiko Minatoya, Yu Ait Bamai, Keiko Yamazaki, Sachiko Itoh, Chihiro Miyashita, Atsuko Araki, Reiko Kishi, Japan Environment and Children’s Study (JECS) Group

  Journal of Epidemiology 31 4 272 - 279 2021年04月 [査読有り][通常論文]
   

  Background: Population impact of modifiable risk factors on orofacial clefts is still unknown. This study aimed to estimate population attributable fractions (PAFs) of modifiable risk factors for nonsyndromic cleft lip with or without cleft palate (CL +/- P) and cleft palate only (CP) in Japan.Methods: We conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant women from 2011 to 2014. We estimated the PAFs of maternal alcohol consumption, psychological distress, maternal active and passive smoking, abnormal body mass index (BMI) (<18.5 and >= 25 kg/m(2)), and non-use of a folic acid supplement during pregnancy for nonsyndromic CL +/- P and CP in babies.Results: A total of 94,174 pairs of pregnant women and their single babies were included. Among them, there were 146 nonsyndromic CL +/- P cases and 41 nonsyndromic CP cases. The combined adjusted PAF for CL +/- P of the modifiable risk factors excluding maternal alcohol consumption was 34.3%. Only maternal alcohol consumption was not associated with CL +/- P risk. The adjusted PAFs for CL +/- P of psychological distress, maternal active and passive smoking, abnormal BMI, and non-use of a folic acid supplement were 1.4% (95% confidence interval [CI], -10.7 to 15.1%), 9.9% (95% CI, -7.0 to 26.9%), 10.8% (95% CI, -9.9 to 30.3%), 2.4% (95% CI, -7.5 to 14.0%), and 15.1% (95% CI, -17.8 to 41.0%), respectively. We could not obtain PAFs for CP due to the small sample size.Conclusions: We reported the population impact of the modifiable risk factors on CL +/- P, but not CP. This study might be useful in planning the primary prevention of CL +/- P.
• Hypertensive Disorders during Pregnancy (HDP), Maternal Characteristics, and Birth Outcomes among Japanese Women: A Hokkaido Study.

  Kritika Poudel, Sumitaka Kobayashi, Chihiro Miyashita, Atsuko Ikeda-Araki, Naomi Tamura, Yu Ait Bamai, Sachiko Itoh, Keiko Yamazaki, Hideyuki Masuda, Mariko Itoh, Kumiko Ito, Reiko Kishi

  International journal of environmental research and public health 18 7 2021年03月24日 [査読有り]
   

  Hypertension during pregnancy causes a greater risk of adverse birth outcomes worldwide; however, formal evidence of hypertensive disorders during pregnancy (HDP) in Japan is limited. We aimed to understand the association between maternal characteristics, HDP, and birth outcomes. In total, 18,833 mother-infant pairs were enrolled in the Hokkaido study on environment and children's health, Japan, from 2002 to 2013. Medical records were used to identify hypertensive disorders and birth outcomes, namely, small for gestational age (SGA), SGA at full term (term-SGA), preterm birth (PTB), and low birth weight (LBW). The prevalence of HDP was 1.9%. Similarly, the prevalence of SGA, term-SGA, PTB, and LBW were 7.1%, 6.3%, 7.4%, and 10.3%, respectively. The mothers with HDP had increased odds of giving birth to babies with SGA (2.13; 95% Confidence Interval (CI): 1.57, 2.88), PTB (3.48; 95%CI: 2.68, 4.50), LBW (3.57; 95%CI: 2.83, 4.51) than normotensive pregnancy. Elderly pregnancy, low and high body mass index, active and passive smoking exposure, and alcohol consumption were risk factors for different birth outcomes. Therefore, it is crucial for women of reproductive age and their families to be made aware of these risk factors through physician visits, health education, and various community-based health interventions.
• Secular trends of urinary phthalate metabolites in 7-year old children and association with building characteristics: Hokkaido study on environment and children's health.

  Rahel Mesfin Ketema, Yu Ait Bamai, Atsuko Ikeda-Araki, Takeshi Saito, Reiko Kishi

  International journal of hygiene and environmental health 234 113724 - 113724 2021年03月21日 [査読有り]
   

  The widespread commercial production and use of phthalates as plasticizers in consumer products have led to significant human exposure. Some phthalates are known to disrupt the endocrine system and result in adverse health outcomes. As such, they have been regulated in materials used for children's items and food packages. In this study, we examined the secular trend of urinary phthalate metabolites in children and the association between metabolites and building characteristics. In total, 400 first-morning spot urine samples of 7 years old children collected from 2012 to 2017 from an ongoing birth cohort study were examined. Parents provided information on demographics and building questionnaires. We analyzed 10 urinary phthalate metabolites from five phthalate diesters using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS): MiBP, MnBP, MBzP, MEHP, MEOHP, MEHHP, MECPP, MiNP, OH-MiNP, and cx-MiNP. A multivariable regression model with creatinine-corrected metabolite levels was applied to assess secular trends during 2012-2017. The association between metabolite levels and building characteristics was investigated using a mutual-adjusted linear regression. The metabolites MnBP, MEHP, MEOHP, MEHHP, MECPP, and OH-MiNP were detected in all samples. The highest median concentration was for MECPP 37.4 ng/mL, followed by MnBP and MEHHP at concentrations of 36.8 and 25.8 ng/mL, respectively. Overall, DBP, BBzP, and DINP metabolite concentrations in this study were comparable to or lower than those in previous studies from Japan and other countries in a similar study period. Higher concentrations of DEHP metabolites were observed in this study than in children from the USA and Germany, as per previous reports. Despite updated phthalate regulations and reports of production volume change in Japan, all the measured metabolites showed a stable trend between 2012 and 2017. Higher phthalate metabolite levels were observed among children from households with low annual income, those who lived in old buildings, and those with window opening habits of ≥1 h than ≤1 h. In contrast, children in houses that vacuumed 4 or more days/week showed a lower level of MnBP than those in houses that vacuumed ≤3 days/week. This study demonstrates that the internal exposure level of phthalates in Japanese children was stable from 2012 to 2017. Our findings suggest that phthalate exposure in children is consistent. Thus, improvements in the indoor environment, such as frequent vacuuming, may reduce exposure. Biomonitoring of phthalates is critical for elucidating their possible health effects and developing mitigation strategies.
• Trajectories of the Psychological Status of Mothers of Infants With Nonsyndromic Orofacial Clefts: A Prospective Cohort Study From the Japan Environment and Children's Study

  Yukihiro Sato, Eiji Yoshioka, Yasuaki Saijo, Toshinobu Miyamoto, Kazuo Sengoku, Hiroshi Azuma, Yusuke Tanahashi, Yoshiya Ito, Sumitaka Kobayashi, Machiko Minatoya, Yu Ait Bamai, Keiko Yamazaki, Sachiko Ito, Chihiro Miyashita, Atsuko Araki, Reiko Kishi

  CLEFT PALATE-CRANIOFACIAL JOURNAL 58 3 369 - 377 2021年03月 [査読有り][通常論文]
   

  Objective:This study examined psychological status trajectories of mothers of infants with nonsyndromic orofacial clefts in Japan.Design:Prospective cohort study.Setting:Data from the Japan Environment and Children's Study.Participants:Infants with a nonsyndromic cleft (N = 148) including cleft lip and palate (CLP; n = 72), cleft lip (CL; n = 46), and cleft palate (CP; n = 30). The control group included unaffected infants (N = 84 454).Main Outcome Measures:At 15 weeks and 27 weeks of pregnancy and 12 months after birth, the Kessler Psychological Distress Scale (clinical cutoff >= 5) was used. At 1 month and 6 months after birth, the Edinburgh Postnatal Depression Scale (clinical cutoff >= 9) was used.Results:Prenatal diagnosis rates were unavailable. Mothers of infants with CLP had higher psychological distress than controls at 27 weeks of pregnancy (prevalence ratio [PR] = 1.36, 95% CI: 1.06-1.74) and postnatal depression at 1 month after birth (PR = 2.21, 95% CI: 1.53-3.19). Mothers of infants with CP showed heightened psychological distress at 27 weeks of pregnancy (PR = 1.62, 95% CI: 1.21-2.17) and postnatal depression 6 months after birth (PR = 1.86, 95% CI: 1.01-3.43). There was no significant association between CL and maternal psychological status. At 12 months after birth, no differences in distress were found between mothers of infants with a cleft and controls.Conclusions:Mothers of infants with orofacial clefts may need psychosocial support, particularly during pregnancy and the first year after birth.
• Lower respiratory tract infections and orofacial clefts: a prospective cohort study from the Japan Environment and Children's Study.

  Yukihiro Sato, Eiji Yoshioka, Yasuaki Saijo, Toshinobu Miyamoto, Hiroshi Azuma, Yusuke Tanahashi, Yoshiya Ito, Sumitaka Kobayashi, Machiko Minatoya, Yu Ait Bamai, Keiko Yamazaki, Sachiko Ito, Chihiro Miyashita, Atsuko Araki, Reiko Kishi

  Journal of epidemiology 2021年01月13日 

  BACKGROUND: Lower respiratory tract infections (LRTIs) are a cause of inpatient and outpatient care among children. Although orofacial clefts seem to be associated with LRTIs, epidemiological studies are scarce on this topic. This study aimed to examine whether infants with orofacial clefts were associated with LRTIs. METHODS: This prospective cohort study used data from the Japan Environment and Children's Study, whose baseline recruitment was conducted during 2011-2014. This study included 81,535 participants. The number of infants with cleft lip and palate (CLP), cleft lip (CL), and cleft palate only (CP) was 67, 49, and 36, respectively. We defined history of LRTIs until 12 months' age reported by their mothers as the dependent variable. Accumulated breastfeeding duration was used as potential mediators. RESULTS: The incidence proportion of LRTIs among the control group was 6.0%. The incidence proportion among infants with CLP, CL, and CP were 11.9%, 14.3%, and 5.6%, respectively. After adjusting for covariates, compared with the control group, infants with CLP and CL were associated with risk of LRTIs (incidence risk ratio [IRR] of CLP = 2.38 [95% confidence interval = 1.30, 4.36] and of CL = 2.73 [1.40, 5.33]) , but not ones with CP (1.08 [0.28, 4.15]). Accumulated breastfeeding duration decreased the IRR of CLP only (IRR of CLP = 2.16 [1.19, 3.93]). CONCLUSIONS: Infants with orofacial clefts aged 1 year have a potentially high incidence proportion of LRTIs. Accumulated breastfeeding duration might mediate the associations of CLP.
• Occupational exposure limits for acetaldehyde, 2‐bromopropane, glyphosate, manganese and inorganic manganese compounds, and zinc oxide nanoparticle, and the biological exposure indices for cadmium and cadmium compounds and ethylbenzene, and carcinogenicity, occupational sensitizer, and reproductive toxicant classifications

  Atsuko Araki, Kenichi Azuma, Ginji Endo, Yoko Endo, Tetsuhito Fukushima, Kunio Hara, Kouji Harada, Hajime Hori, Seichi Horie, Hyogo Horiguchi, Masayoshi Ichiba, Gaku Ichihara, Tatsuya Ishitake, Akiyoshi Ito, Yuki Ito, Satoko Iwasawa, Takeyasu Kakamu, Michihiro Kamijima, Kanae Karita, Toshio Kawai, Toshihiro Kawamoto, Reiko Kishi, Shinji Kumagai, Akiko Matsumoto, Muneyuki Miyagawa, Hiroyuki Miyauchi, Yasuo Morimoto, Kasuke Nagano, Hisao Naito, Tamie Nakajima, Makiko Nakano, Tetsuo Nomiyama, Hirokazu Okuda, Masayuki Okuda, Kazuyuki Omae, Kazuhiro Sato, Tomotaka Sobue, Yasushi Suwazono, Toru Takebayashi, Tatsuya Takeshita, Akito Takeuchi, Ayano Takeuchi, Shigeru Tanaka, Mayumi Tsuji, Teruomi Tsukahara, Susumu Ueno, Jun Ueyama, Yumi Umeda, Kenya Yamamoto, Yuko Yamano, Takenori Yamauchi, Eiji Yano

  Journal of Occupational Health 63 1 2021年01月
• Short-term temporal variability of urinary biomarkers of organophosphate flame retardants and plasticizers

  Michiel Bastiaensen, Celine Gys, Govindan Malarvannan, Mihai Fotache, Jasper Bombeke, Yu Ait Bamai, Atsuko Araki, Adrian Covaci

  ENVIRONMENT INTERNATIONAL 146 2021年01月 [査読有り]
   

  Background: Exposure to organophosphate flame retardants and plasticizers (PFRs) is commonly estimated by measuring biomarker concentrations in spot urine samples. However, their concentrations in urine can vary greatly over time due to short biological half-lives and variable exposure, potentially leading to exposure misclassification. In this study, we examined the within- and between-individual and within- and between-day variability of PFR metabolites in spot and 24-hour pooled urine samples during five consecutive days.Methods: We collected all spot urine samples from 10 healthy adults for 5 days. On one additional day, we collected 24-hour pooled urine samples. Samples were analyzed by solid-phase extraction coupled to high-performance liquid chromatography tandem mass spectrometry. We calculated intraclass correlation coefficients (ICCs) to assess the reproducibility of metabolite concentrations in morning void and spot samples.Results: Fair-to-good reproducibility was observed for serial measurements of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP), 2-hydroxyethyl bis(2-butoxyethyl) phosphate (BBOEHEP) and 2-ethyl-5-hydroxyhexyl diphenyl phosphate (5-HO-EHDPHP) (ICC: 0.396 - 0.599), whereas concentrations of diphenyl phosphate (DPHP) and 2-ethylhexyl phenyl phosphate (EHPHP) were more variable in time (ICC: 0.303 and 0.234). Reproducibility improved significantly when only morning void samples were considered and when concentrations were adjusted for urinary dilution. Collecting 24-hour pooled urine could be a reliable alternative for PFR biomarkers with poor short-term temporal variability.Conclusions: The between-day variability was minor compared to variability observed within the same day, which suggests that collecting multiple samples could reduce exposure missclassification. Differences in the observed between- and within-individual variance were compound specific and related to both the nature of the exposure (e.g., diet vs other exposure routes, multiple sources) and the individual toxicokinetic properties of the investigated PFRs.
• Short-term variability of bisphenols in spot, morning void and 24-hour urine samples

  Celine Gys, Michiel Bastiaensen, Govindan Malarvannan, Yu Ait Bamai, Atsuko Araki, Adrian Covaci

  ENVIRONMENTAL POLLUTION 268 2021年01月 [査読有り]
   

  Due to worldwide regulations on the application of the high production volume industrial chemical bisphenol A (BPA) in various consumer products, alternative bisphenols such as bisphenol F (BPF) and bisphenol S (BPS) are increasingly used. To assess human exposure to these chemicals, biomonitoring of urinary concentrations is frequently used. However, the short-term variability of alternative bisphenols has not been evaluated thoroughly yet, which is essential to achieve a correct estimation of exposure. In this study, we collected all spot urine samples from ten healthy adults for five consecutive days, and an additional 24 h pooled sample. We measured the concentrations of seven bisphenols (BPAF, BPF, BPA, BPB, BPZ, BPS and BPAP) in these samples using gas chromatography coupled to tandem mass spectrometry. BPA, BPF and BPS were frequently found in spot samples (>80%), while bisphenol AP (BPAP) was detected in 43% of spot samples. Calculations of intra-class correlation coefficients (ICCs) showed that reproducibility of these four bisphenols was relatively poor (<0.01-0.200) but improved when concentrations were corrected for urine dilution using creatinine levels (0.128-0.401). Of these four bisphenols, BPF showed the best reproducibility (ICC 0.200-0.439) and BPS the most variability (ICC <0.01-0.128). In general, the within-participant variability of bisphenol levels was the largest contributor to the total variance (47-100%). We compared repeated first morning voids to 24 h pooled urine and found no significantly different concentrations for BPA, BPF, BPS, or BPAP. Levels of BPA and BPF differed significantly depending on the sampling time throughout the day. The findings in this study suggest that collecting multiple samples per participant over a few days, in predefined time windows throughout the day, could result in a more reliable estimation of internal exposure to bisphenols. (C) 2020 Elsevier Ltd. All rights reserved.
• Mediating Factors Between Parental Socioeconomic Status and Small for Gestational Age in Infants: Results from the Hokkaido Study on Environment and Children's Health

  Naomi Tamura, Tomoyuki Hanaoka, Kumiko Ito, Atsuko Araki, Chihiro Miyashita, Sachiko Ito, Sumitaka Kobayashi, Yoichi Ito, Hisanori Minakami, Kazutoshi Cho, Toshiaki Endo, Tsuyoshi Baba, Kazuo Sengoku, Toshinobu Miyamoto, Katsuhiko Ogasawara, Reiko Kishi

  MATERNAL AND CHILD HEALTH JOURNAL 25 4 645 - 655 2021年01月 [査読有り]
   

  Objectives Previous studies indicated a significant association between small for gestational age (SGA) in infants and their parents' socioeconomic status (SES). Thus, this study aimed to examine if parental factors, such as maternal smoking, and the pre-pregnancy body mass index (BMI) could mediate the associations between parental SES and SGA. Methods The participants of this study were pregnant women who enrolled in an ongoing birth cohort study, the Hokkaido study, during the first trimester of their pregnancies. A total of 14,593 live singleton births were included in the statistical analysis, of which 1011 (6.9%) were SGA. Two structural equation models were employed to evaluate the associations between parental SES, parental characteristics, and SGA. Results The effect of low SES on SGA was directly mediated by maternal pre-pregnancy BMI, smoking during the third trimester, and alcohol consumption during the first trimester in the first model, which was based the assumption of independent associations between mediating factors. In the second model, which additionally considered the mediating factors from the first model, smoking during pregnancy mediated decline in parental SES, consequently increased SGA. Moreover, an increase in pregnancy smoking status increased the prevalence of lower maternal pre-pregnancy BMI and its effect on SGA. Conclusions for Practice In this study, we observed the independent mediating effect of maternal pre-pregnancy BMI, smoking, and alcohol consumption during pregnancy on low SES and, consequently, SGA, with the additional mediating pathway of SES to smoking to low BMI on SGA.
• Between- and within-individual variability of urinary phthalate and alternative plasticizer metabolites in spot, morning void and 24-h pooled urine samples

  Michiel Bastiaensen, Govindan Malarvannan, Celine Gys, Yu Ait Bamai, Atsuko Araki, Adrian Covaci

  ENVIRONMENTAL RESEARCH 191 110248 - 110248 2020年12月 [査読有り]
   

  Due to international regulations, commonly used phthalates such as di(2-ethylhexyl) phthalate (DEHP) are being replaced by other phthalates, such as di-isononyl phthalate (DINP), and di-isodecyl phthalate (DIDP) and by alternative plasticizers (APs) with similar chemical characteristics, like di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP), or di-(2-ethylhexyl) adipate (DEHA). Urinary concentrations of metabolites are frequently used in the exposure assessment of non-persistent chemicals and for biomonitoring purposes, the intra- and inter-day variability of the metabolites should be known. However, the short-term variability of AP and several phthalate biomarkers has not been investigated yet. In this study, we collected all spot samples from 10 healthy adults for 5 consecutive days and 24h pooled urine on one additional day to investigate the short-term variability of 22 biomarkers of phthalates and APs. Metabolites of DEP, DEHP, DiBP, DnBP, DBzP, DINP and DIDP were found in high detection frequencies, while metabolites of most APs were found in approximately 50% of the samples. The short-term reproducibility of metabolites with diet as primary source (DEHP, DINP, DIDP) was poor (intraclass correlation coefficient - ICC < 0.4), whereas biomarkers of DEP, DnBP, DiBP and BBzP showed good consistency, most likely due to more continuous sources resulting in less between-day variance. ICC values of AP metabolites were similar to those of DEHP, but more studies are required to confirm these findings. Overall, reproducibility improved considerably when values were corrected for urinary dilution and when only morning voids samples were considered. Levels in morning voids samples were consistent for 5 days and comparable to 24-h pooled urine for all metabolites except for OH-MEHTP, sum DINP and sum DIDP, which supports the use of morning voids in human biomonitoring studies.
• Biomonitoring and temporal trends of bisphenols exposure in Japanese school children

  Celine Gys, Yu Ait Bamai, Atsuko Araki, Michiel Bastiaensen, Noelia Caballero-Casero, Reiko Kishi, Adrian Covaci

  ENVIRONMENTAL RESEARCH 191 110172 - 110172 2020年12月 [査読有り]
   

  The widely used chemical bisphenol A (BPA), applied in various consumer products, has been under scrutiny in the past 20 years due to its widespread detection in humans and potential detrimental effects on human health. Following the implementation of restrictions and phase-out initiatives, BPA has been replaced by other structurally similar bisphenols, which have not yet received the same level of research attention. In this study, we aimed to 1) investigated the internal exposure to seven bisphenols in morning void urine samples (n = 396) from 7-year-old children from Hokkaido, Japan and 2) assess possible time trends in the concentrations of bisphenols between 2012 and 2017. Information on demographic, indoor environment and dietary characteristics of participants were acquired through a self-administered questionnaire. All bisphenols were detected in the study population, with BPA, BPF and BPS showing detection frequencies >50%. Concentrations of bisphenols measured in the Japanese children in our study were generally lower compared to studies worldwide. We found that BPA concentrations decreased significantly over the study time period (average 6.5% per year), whereas BPS rose with 2.8% per year. Levels of BPA and BPF were higher in autumn compared to winter. Higher urinary BPF levels were significantly associated with higher concentrations of the oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine (8-OHdG). BPA and BPF levels were higher in children from families with lower household income. Bisphenol concentrations were significantly influenced by some other personal (e.g. household income), food intake (e.g. vegetables and cow milk) and indoor housing characteristics (e.g. flooring). This is the first study to report longitudinal time trends of bisphenols in Japan. The presented findings imply that further research on bisphenols is warranted in the future to monitor whether these time trends continue.
• Exposure to Radiofrequency Electromagnetic Field in the High-Frequency Band and Cognitive Function in Children and Adolescents: A Literature Review

  Toru Ishihara, Keiko Yamazaki, Atsuko Araki, Yuri Teraoka, Naomi Tamura, Takashi Hikage, Manabu Omiya, Masahiro Mizuta, Reiko Kishi

  INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 17 24 9179 - 9179 2020年12月 [査読有り]
   

  With increasing use of mobile phones, exposure to radiofrequency electromagnetic field (RF-EMF) in the high-frequency band associated with mobile phones has become a public concern, with potentially adverse effects on cognitive function in children and adolescents. However, findings regarding the relation of RF-EMF and cognitive function in children and adolescents have been inconsistent due to a number of study design-related factors, such as types of exposure and outcome measures, age of participants, and the era of study conduction. The present literature review focused on these possible factors that could explain this inconsistency. This review identified 12 eligible studies (participants ages 4 to 17 years) and extracted a total 477 relations. In total, 86% of the extracted relations were not statistically significant; in the remaining 14%, a negative relation between RF-EMF and cognitive performance was detected under limited conditions: when (1) RF-EMF was assessed using objective measurement not subjective measurement (i.e., questionnaire), (2) participants were relatively older (12 years and above) and had greater opportunity of exposure to RF-EMF, and (3) the collection of cognitive function data was conducted after 2012. Given that 86% of the extracted relations in this analysis were not statistically significant, the interpretation should be approached with caution due to the possibility of the 14% of significant relationships, extracted in this review, representing chance findings.
• Effect of the occupational environment of parents on cryptorchidism

  Takahiko Mitsui, Atsuko Araki, Chihiro Miyashita, Sachiko Ito, Takeya Kitta, Kimihiko Moriya, Nobuo Shinohara, Masayuki Takeda, Reiko Kishi

  PEDIATRICS INTERNATIONAL 62 11 1256 - 1263 2020年11月 [査読有り]
   

  Background The early detection and treatment of cryptorchidism are necessary to preserve male fertility. This study aimed to assess the effect of parents' occupational environment on the incidence of cryptorchidism in their sons.Methods The study enrolled 51 316 newborn males, whose mothers were recruited in the Japan Environment and Children's Study. We analyzed cryptorchidism incidence in male newborns according to 14 categories of occupation of their parents. We also analyzed the effect of the mother's occupational environment during gestation, including working and night-shift work, on cryptorchidism incidence. Information on occupations was obtained from self-administered questionnaires. Cryptorchidism was identified through a survey at birth or 1 month after birth using medical records.Results Cryptorchidism was identified in 305 male infants (0.59%) at birth or 1 month after birth. Weight, height, head circumference, and chest circumference at birth were significantly lower in male infants with cryptorchidism than in those without the condition. Gestational age was also shorter in mothers whose infants developed cryptorchidism. Moreover, maternal age at delivery and smoking during gestation also had an effect on cryptorchidism incidence. However, multivariate analysis of the 14 categories of occupation of parents during gestation showed no significant effect on cryptorchidism incidence in their male infants.Conclusions This study revealed that the work environment of parents did not significantly affect the incidence of cryptorchidism in their sons. However, this study might have underestimated mild and transient cases of cryptorchidism. Further studies are necessary to investigate the risk factors of cryptorchidism in relation to parents' occupation.
• Effect of prenatal exposure to per- and polyfluoroalkyl substances on childhood allergies and common infectious diseases in children up to age 7 years: The Hokkaido study on environment and children's health

  Yu Ait Bamai, Houman Goudarzi, Atsuko Araki, Emiko Okada, Ikuko Kashino, Chihiro Miyashita, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 143 2020年10月 [査読有り]
   

  Per- and polyfluoroalkyl substances (PFAS) are widely used bio-accumulative chemicals in many industrial and household products. Experimental studies reported that exposure to PFAS results in immunotoxicity. We have previously reported that prenatal exposure to PFAS decreased the risk of allergies, while it increased the risk of infectious diseases at ages 2 and 4 years. However, it remains unclear whether the adverse effects of PFAS on allergies and infectious diseases continue until a reliable age of diagnosing allergies. This study aimed at investigating the effects of prenatal exposure to PFAS on the prevalence of allergies and infectious diseases in children up to age 7, from the Hokkaido Study.Among mother-child pairs enrolled in the Hokkaido study and followed up until the age of 7 years, 2689 participants with maternal PFAS, 1st trimester of pregnancy and 7-year-old questionnaire survey data were included in this study. Eleven PFAS in the 3rd-trimester plasma were measured using ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry. Wheeze, rhino-conjunctivitis, and eczema were defined using the International Study of Asthma and Allergies on Childhood (ISAAC) questionnaire. History childhood infectious diseases diagnosed by a doctor was assessed by a mother-reported questionnaire at child's age 7. The relative risk of childhood allergies was calculated by generalized estimating equation models. The odds ratio of an episode of infectious diseases was calculated by logistic regression analysis, adjusted for potential confounders.The prevalence of various allergies and infectious diseases was: wheeze, 11.9%; rhino-conjunctivitis, 11.3%; eczema, 21.0%; chickenpox, 61.5%; otitis media, 55.7%; pneumonia, 30.6%; and respiratory syncytial virus infection, 16.8%. Prenatal exposure to perfluorooctanoic acid, perfluorodecanoic acid (PFDA), and per-fluoroundecanoic acid (PFUnDA) was inversely associated with rhino-conjunctivitis, while that for perfluorooctanoate (PFOA), perfluorooctane sulfonate, PFUnDA, perfluorododecanoic acid (PFDoDA), and per-fluorotridecanoic acid was inversely associated with eczema. For infectious diseases, PFDA and PFDoDA were associated with increased risk of pneumonia and PFOA was associated with increased risk of RSV infection among children not having any siblings (only-one-child).Our results corroborate the hypothesis on immunosuppressive and immunomodulating effects of PFAS on allergies and infectious diseases in children. These effects observed previously at 2 and 4 years continued until the age of 7 years. However, additional studies assessing inflammatory biomarkers along with ISAAC questionnaires, doctor-diagnosed allergies, and longer follow-ups are necessary to better assess the effects of exposure to chemicals on human immune outcomes.
• Risk factors for motor coordination problems in preschool-age children

  Satoshi Suyama, Kazuyori Yagyu, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Machiko Minatoya, Keiko Yamazaki, Naomi Tamura, Akio Nakai, Takuya Saito, Reiko Kishi

  PEDIATRICS INTERNATIONAL 62 10 1177 - 1183 2020年10月 [査読有り]
   

  Background Motor coordination problems (MCP) in children can sometimes be diagnosed as developmental coordination disorder. Early intervention for developmental coordination disorder is necessary because it often continues into adolescence, causing mental and physical complications. Few studies have investigated the prevalence of childhood MCP in the Japanese population, examining the risk factors for MCP. We therefore investigated the prenatal factors associated with MCP in preschool-age children.Methods This study was based on a prospective cohort study, the Hokkaido Study on Environment and Children's Health. Mothers of 4,851 children who reached the age of 5 years within the study-period received questionnaires, including the Japanese version of the Developmental Coordination Disorder Questionnaire (DCDQ-J). We examined the risk factors associated with MCP using logistic regression analysis.Results Of 3,402 returned DCDQ-J questionnaires, 3,369 were answered completely. From the 3,369 children, we categorized having MCP by using two cut-off scores: that of the DCDQ'07 and the cut-off at the 5th percentile of a total DCDQ-J score. Comparing children with and without MCP, we found significant differences in the education level of the mothers, annual household income during pregnancy, maternal alcohol consumption and smoking during pregnancy, and sex and age of the children at the time of completing the DCDQ-J by both categorizations. Adjusted logistic regression analysis revealed that maternal smoking during the first trimester of pregnancy and male sex were significantly associated with MCP.Conclusions Our results suggest that maternal smoking during pregnancy is the main factor associated with MCP in preschool-age children.
• Associations between prenatal exposure to organochlorine pesticides and thyroid hormone levels in mothers and infants: The Hokkaido study on environment and children's health

  Keiko Yamazaki, Sachiko Itoh, Atsuko Araki, Chihiro Miyashita, Machiko Minatoya, Tamiko Ikeno, Shizue Kato, Kaori Fujikura, Futoshi Mizutani, Yoichi Chisaki, Reiko Kishi

  ENVIRONMENTAL RESEARCH 189 2020年10月 [査読有り]
   

  Organochlorine pesticides (OCPs) are environmental contaminants with potentially adverse effects on neurodevelopment. Previous findings on the association between prenatal exposure to OCPs and the maternal or infant thyroid hormone system are inconsistent. Moreover, the influence of exposure to multiple OCPs and other chemical compounds is not clearly understood. Our study therefore aimed to examine the association between OCP exposure and both maternal and infant thyroid hormone systems. We also explored multiple exposure effects of OCPs and the influence of each compound using weighted quantile sum (WQS) methods. The study population included 514 participants in the Hokkaido study, recruited from 2002 to 2005 at one hospital in Sapporo, Japan. To quantify 29 OCPs, maternal blood samples were analyzed using gas chromatography/mass spectrometry. Blood samples for measuring thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were obtained from mothers during the early gestational stage (mean 11.4 weeks), and from infants between 7 and 43 days of age. The data of 333 mother child pairs with OCP and thyroid hormone measurements were included in the final analyses. Multivariate regression models showed a negative association between maternal FT4 and levels of o,p -dichlorodiphenyldichloroethylene (DDE), o,p'-dichlorodiphenyltrichlomethane (DDT), and dieldrin. The WQS analysis showed that o,p '-DDT (48.6%), cis-heptachlorepoxide (22.8%), dieldrin (15.4%) were the primary contributors to the significant multiple exposure effect of OCPs on maternal FT4. For infants, we found a positive association between FT4 and cis-nonachlor and mirex. The most contributory compounds in the multiple exposure effect were trans-nonachlor (27.1%) and cis-nonachlor (13.8%), while several compounds contributed to the WQS via small weights (0.4-9.1%). These results indicate that OCPs, even at very low levels, may influence maternal and child thyroid hormone levels, which could modulate child development.
• Lifestyle behaviors and home and school environment in association with sick building syndrome among elementary school children: a cross-sectional study

  Rahel Mesfin Ketema, Atsuko Araki, Yu Ait Bamai, Takeshi Saito, Reiko Kishi

  ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE 25 1 2020年07月 [査読有り]
   

  Background Sick building syndrome (SBS) refers to the combination of symptoms experienced by occupants of specific building characteristics. This study investigated the associations of children's lifestyle behaviors, allergies, home, and school environment with SBS symptoms. Methods A total of 4408 elementary school children living in Sapporo City, Japan participated in this study. SBS was determined on parental answers to MM080 standardized school questionnaires on symptoms that were weekly experienced by these children, and if the symptom is attributed to their home or school environment. The Japanese version of the International Study of Asthma and Allergies in Childhood questionnaire was used to assess wheeze, rhino-conjunctivitis, and eczema. A logistic regression analysis was conducted to evaluate the associations between SBS symptoms and variables by controlling the potential confounders (gender, grade, school, and parental history of allergies). A stepwise backward elimination was conducted to assess independent variables related to SBS. Results Participants revealed mucosal (6.9%), skin (2.0%), and general (0.8%) symptoms. The presence of one or more allergy was associated with increased mucosal and skin symptoms. Children who skipped breakfast, displayed faddiness (like/dislike of food), had constipation, have insufficient sleep, did not feel refreshed after sleep, and lacked deep sleep showed significantly high odds ratios with SBS symptoms. The stepwise analysis showed faddiness for mucosal symptoms and not feeling refreshed after sleep for mucosal and skin symptoms, whereas constipation and lacking deep sleep for general symptoms were independent variables in increasing the symptoms. We found no significant relationship between SBS in children and schools. Considering children's home, old building, no ventilation, wall-to-wall carpet, and heavy nearby traffic were associated with elevated mucosal symptom, while living in a multifamily home increased general symptoms. Home dampness was an independent variable in increasing all SBS symptoms. Conclusions Allergies and lifestyle behaviors were associated with increased SBS in children, including skipping breakfast, displaying faddiness, constipation, insufficient sleep, not feeling refreshed after sleep, and the lack of deep sleep. Further, dampness at home was associated with increase in all SBS symptoms. Lifestyle (e.g., eating and sleeping habits) and home (i.e., dampness) improvements might alleviate SBS symptoms in children.
• Temporal trends and determinants of PFR exposure in the Hokkaido Study

  Michiel Bastiaensen, Yu Ait Bamai, Atsuko Araki, Houman Goudarzi, Satoshi Konno, Sachiko Ito, Chihiro Miyashita, Yiming Yao, Reiko Kishi, Adrian Covaci

  INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH 228 113523 - 113523 2020年07月 [査読有り][通常論文]
   

  The phase-out of polybrominated diphenyl ethers (PBDE) flame retardants has led to the rapid increase of alternatives such as phosphate flame retardants and plasticizers (PFRs) in many consumer products. Exposure to these additive chemicals is widespread and potentially harmful to humans and the environment. In the present study, we assessed the exposure to PFRs through the analysis of metabolites in urine collected from 7-year old children from Hokkaido, Japan between 2012 and 2017. This allowed us to investigate temporal and seasonal trends for PFR metabolite concentrations and to study determinants of exposure. Thirteen metabolites of seven PFRs were measured in morning spot urine samples (n = 400). Multiple regression models were used to quantify the yearly increase in metabolite concentrations per sampling year. Information on the demographics, indoor environment and dietary habits of the participants were derived from self-administered questionnaires. PFR metabolite concentrations were comparable to our previous study of school children (7-12 years old). Eight PFR metabolites were detected in 50% of the samples. During the study time period, concentrations of three metabolites increased significantly: bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 13.3% per year), 1-hydroxy2-propyl bis(1- chloro-2-propyl) phosphate (BCIPHIPP; 12.9% per year), and 2-ethylhexyl phenyl phosphate (EHPHP; 6.7% per year). We also found seasonality as a determinant for several PFR metabolites, with 2-fold higher levels in summer for BCIPHIPP and BDCIPP. Concentrations were also significantly impacted by ventilation habits. More frequent window opening or use of mechanical ventilation was consistently associated with higher levels of PFR metabolites in children's urine. This is the first study to show that human exposure to PFRs has increased in recent years in Japan, which indicates that further research into this class of chemicals is warranted.
• Association of exposure to prenatal phthalate esters and bisphenol A and polymorphisms in the ESR1 gene with the second to fourth digit ratio in school-aged children: Data from the Hokkaido study

  Yoko Nishimura, Kimihiko Moriya, Sumitaka Kobayashi, Atsuko Araki, Fumihiro Sata, Takahiko Mitsui, Sachiko Itoh, Chihiro Miyashita, Kazutoshi Cho, Masafumi Kon, Michiko Nakamura, Takeya Kitta, Sachiyo Murai, Reiko Kishi, Nobuo Shinohara

  STEROIDS 159 108637 - 108637 2020年07月 [査読有り][通常論文]
   

  Phthalates and bisphenol A (BPA) are estrogenic endocrine disruptors. Polymorphisms in the gene encoding estrogen receptor 1 (ESR1) may contribute to the ratio of the lengths of the second and fourth digits (2D:4D), which is considered an index of prenatal exposure to sex hormones. Thus, we investigated whether ESR1 polymorphisms modify the effects of prenatal exposure to phthalates and BPA on 2D:4D in a birth cohort. Maternal serum in the first trimester was used to determine prenatal exposure to these compounds. Six hundred twenty-three children (7 years of age) provided mean 2D:4D from photocopies and were genotyped for single nucleotide polymorphisms in ESR1, particularly PvuII (T > C, dbSNP: rs2234693), XbaI (A > G, dbSNP: rs9340799), and rs2077647 (A > G). The associations among compound exposure, mean 2D:4D, and ESR1 polymorphisms were assessed by multiple linear regression adjusted for potential cofounding factors. Boys with the AG/GG genotype at rs2077647 in the group exposed to high levels of mono(2-ethylhexyl) phthalate (MEHP) or Sigma Di(2-ethylhexyl) phthalate (DEHP) showed feminized 2D:4D compared with boys with the AA genotype at rs2077647 who had low exposure to MEHP or Sigma DEHP (MEHP: increase in mean 2D:4D of 1.51%, 95% confidence interval [CI]: 0.40-2.63; Sigma DEHP: increase in mean 2D:4D of 1.37%, 95% CI: 0.25-2.49). No significant differences were found among girls. There were no associations between mean 2D:4D and metabolites other than MEHP or BPA. These data suggest that ESR1 polymorphisms modify the effects of prenatal exposure to DEHP on mean 2D:4D among boys.
• Factors correlating with serum birch pollen IgE status in pregnant women in Hokkaido, Japan: The Japan Environment and Children's Study (JECS)

  Yasuaki Saijo, Eiji Yoshioka, Yukihiro Sato, Toshinobu Miyamoto, Kazuo Sengoku, Yoshiya Ito, Sachiko Itoh, Chihiro Miyashita, Atsuko Araki, Reiko Kishi

  WORLD ALLERGY ORGANIZATION JOURNAL 13 6 100128 - 100128 2020年06月 [査読有り][通常論文]
   

  Background: Birch pollen allergy affects pregnant women, and such allergy may affect the development of allergic diseases in their children. Using nationwide birth cohort data, this study aimed to investigate the prevalence of birch pollen IgE positivity and to identify correlating factors in pregnant women in Hokkaido, Japan, a high-latitude island.Methods: Participants included 6856 pregnant women. Participants responded to questionnaires regarding lifestyle factors and history of allergies. Data regarding parity, height, and pre-pregnancy weight were collected from medical records. Blood samples were obtained from participants during the first trimester of pregnancy, and serum allergen-specific IgE titers were determined.Results: The serum of 30.2% participants was positive for birch pollen IgE (>= 0.35 UA/mL). Such positivity significantly correlated with a history of other allergic diseases, particularly food allergy and allergic rhinitis/hay fever. In multivariate logistic regression analysis, pre-pregnancy high body mass index (BMI >= 25) significantly correlated with birch pollen IgE positivity [odds ratio (OR), 1.24; 95% CI, 1.05-1.47; reference BMI, 18.5-24.9] and higher income (>= 10 million yen per year; OR,0.55; 95% CI, 0.37-0.81; reference, household income < 2 million yen per year), and second quintile level physical activity (OR,0.75; 95% CI, 0.63-0.88; reference, the first quintile of physical activity) had significant protective effects.Conclusions: Birch pollen IgE positivity in pregnant women was positively associated with food allergy, allergic rhinitis, pre-pregnant high BMI, and was negatively associated with light exercise and high household income in Hokkaido.
• Combined exposure to phthalate esters and phosphate flame retardants and plasticizers and their associations with wheeze and allergy symptoms among school children

  Atsuko Araki, Yu Ait Bamai, Michiel Bastiaensen, Nele Van den Eede, Toshio Kawai, Tazuru Tsuboi, Chihiro Miyashita, Sachiko Itoh, Houman Goudarzi, Satoshi Konno, Adrian Covaci, Reiko Kishi

  ENVIRONMENTAL RESEARCH 183 109212 - 109212 2020年04月 [査読有り][通常論文]
   

  Background: Phthalate esters and phosphate flame retardants and plasticizers (PFRs) are both used as plasticizers and are commonly detected in indoor environments. Although both phthalates and PFRs are known to be associated with children's wheeze and allergic symptoms, there have been no previous studies examining the effects of mixtures of these exposures.Objectives: To investigate the association between exposure to mixtures of phthalate esters and PFRs, and wheeze and allergic symptoms among school-aged children.Methods: A total of 128 elementary school-aged children were enrolled. Metabolites of 3 phthalate esters and 7 PFRs were measured in urine samples. Parent-reported symptoms of wheeze, rhinoconjunctivitis, and eczema were evaluated using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. In the primary model, we created a phthalate ester and PFR mixture exposure index, and estimated odds ratios (ORs) using weighted quantile sum (WQS) regression and quantile g (qg)-computation. The two highest chemicals according to qg-computation weight %s were combined to create a combination high x high exposure estimate, with ORs calculated using the "low x low" exposure group as the reference category. Concentrations of each metabolite were corrected by multiplying this value by the sex- and body size-Standardised creatinine concentration and dividing by the observed creatinine value. All models were adjusted for sex, grade, dampness index and annual house income.Results: The odds ratio of rhinoconjunctivitis for the association between exposure to chemical mixtures according to the WQS index positive models was; OR = 2.60 (95% confidence interval [CI]: 1.38-5.14). However, wheeze and eczema of the WQS index positive model, none of the WQS index negative models or qg-computation result yielded statistically significant results. Combined exposure to the two highest WQS weight %s of "high-high" Sigma TCIPP and Sigma TPHP was associated with an increased prevalence of rhino-conjunctivitis, OR = 5.78 (1.81-18.43) to the "low x low" group.Conclusions: Significant associations of mixed exposures to phthalates and PFRs and increased prevalence of rhinoconjunctivitis was found among elementary school-aged children in the WQS positive model. Mixed exposures were not associated with any of allergic symptoms in the WQS negative model or qg-computation approach. However, the combined effects of exposure to two PFRs suggested an additive and/or multiplicative interaction, potentially increasing the prevalence of rhinoconjunctivitis. A further study with a larger sample size is needed to confirm these results.
• Prenatal exposure to 11 perfluoroalkyl substances and fetal growth: A large-scale, prospective birth cohort study

  Ikuko Kashino, Seiko Sasaki, Emiko Okada, Hideyuki Matsuura, Houman Goudarzi, Chihiro Miyashita, Eisaku Okada, Yoichi M. Ito, Atsuko Araki, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 136 105355 - 105355 2020年03月 [査読有り][通常論文]
   

  Background: Prenatal maternal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) has been reportedly associated with decreased birth weight. Although a majority of epidemiological studies concerning perfluoroalkyl substances (PFAS) have focused on PFOS and PFOA, epidemiological studies of PFAS with longer carbon chains are scarce. In this study, we investigated whether prenatal maternal exposure to 11 PFAS, in particular those with longer carbon chains, is associated with fetal growth.Methods: The study included 1985 mother-infant pairs (inclusive of preterm and post-term infants), who enrolled in a large-scale, prospective birth cohort study in any of the 37 hospitals in Hokkaido, Japan between 2003 and 2009. The concentration of 11 PFAS was measured in maternal plasma collected during the third trimester of pregnancy, using ultra-performance liquid chromatography in combination with triple quadrupole mass spectrometry. Associations between the measured PFAS values and weight, length, and head circumference of all newborns at birth were examined using multiple regression analyses with adjustment for potential confounders based on data collected from medical records, questionnaires, and those for maternal plasma samples.Results: Of the 11 PFAS analyzed, prenatal perfluorononanoic acid (PFNA) [per log10-unit: regression coefficient (beta) = -96.2 g, 95% confidence intervals (95% CI), -165.3 to -27.1] and perfluorodecanoic acid (PFDA) (beta = -72.2 g, 95% CI, -138.1 to -6.3) concentrations were inversely associated with birth weight. Furthermore, PFNA concentrations were inversely associated with birth length (per Log(10) unit: beta = - 0.48 cm, 95% CI; - 0.86 to - 0.11). Maternal perfluorotridecanoic acid (PFTrDA) exposure showed a significant inverse association with birth weight only for female infants (per Log(10) unit beta = - 99.8 g, 95% CI, - 193.7 to - 6.0) (P for interaction = 0.04).Conclusions: Our findings suggest that prenatal, maternal exposure to PFAS with longer carbon chains tends to be inversely associated with birth size of newborn infants, which may indicate that these commercially used compounds have an adverse effect on fetal growth.
• Early-Life Environmental Influences on Allergic Diseases

  Ait Bamai, Y., Miyashita, C., Araki, A., Kishi, R.

  Early-life Environmental Exposure and Disease: Facts and Perspectives 2020年
• Occupational exposure limits for ethyl benzene, dimethyl terephthalate and hydrogen fluoride, and carcinogenicity and reproductive toxicant classifications The Committee for Recommendation of Occupational Exposure Limits, Japan Society for Occupational Health

  Atsuko Araki, Kenichi Azuma, Ginji Endo, Yoko Endo, Tetsuhito Fukushima, Kunio Hara, Hajime Hori, Masayoshi Ichiba, Tatsuya Ishitake, Gaku Ichihara, Akiyoshi Ito, Yuki Ito, Satoko Iwasawa, Takeyasu Kakamu, Michihiro Kamijima, Kanae Karita, Takahiko Katoh, Toshio Kawai, Toshihiro Kawamoto, Reiko Kishi, Shinji Kumagai, Yukinori Kusaka, Muneyuki Miyagawa, Hiroyuki Miyauchi, Yasuo Morimoto, Kasuke Nagano, Hisao Naito, Tamie Nakajima, Makiko Nakano, Tetsuo Nomiyama, Hirokazu Okuda, Masayuki Okuda, Kazuyuki Omae, Kazuhiro Sato, Tomotaka Sobue, Yasushi Suwazono, Toru Takebayashi, Tatsuya Takeshita, Teruomi Tsukahara, Masashi Tsunoda, Jun Ueyama, Yumi Umeda, Kenya Yamamoto, Yuko Yamano, Takenori Yamauchi, Eiji Yano

  JOURNAL OF OCCUPATIONAL HEALTH 62 1 2020年01月
• Cat and Dog Ownership in Early Life and Infant Development: A Prospective Birth Cohort Study of Japan Environment and Children's Study.

  Machiko Minatoya, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Sumitaka Kobayashi, Keiko Yamazaki, Yu Ait Bamai, Yasuaki Saijyo, Yoshiya Ito, Reiko Kishi, The Japan Environment And Children's Study Group

  International journal of environmental research and public health 17 1 2019年12月27日 [査読有り][通常論文]
   

  Contact with companion animals has been suggested to have important roles in enhancing child development. However, studies focused on child development and pet ownership at a very early age are limited. The purpose of the current study was to investigate child development in relation to pet ownership at an early age in a nationwide prospective birth cohort study: the Japan Environment and Children's Study. Associations between cat and dog ownership at six months and infant development at 12 months of age were examined in this study. Infant development was assessed using the Ages & Stages QuestionnairesTM (ASQ-3) at 12 months. Among participants of (Japan Environment and Children's Study) JECS, those with available data of cat and dog ownership at six months and data for the ASQ-3 at 12 months were included (n = 78,868). Having dogs showed higher percentages of pass in all five domains measured by ASQ-3 (communication, gross motor, fine motor, problem-solving, and personal-social) compared to those who did not have dogs. Significantly decreased odds ratios (ORs) of developmental delays were observed in association with having dogs in all fix domains (communication: OR = 0.73, gross motor: OR = 0.86, fine motor: OR = 0.84, problem-solving: OR = 0.90, personal-social: OR = 0.83). This study suggested that early life dog ownership may reduce the risks of child developmental delays.
• Prenatal tobacco exposure and ADHD symptoms at pre-school age: the Hokkaido Study on Environment and Children's Health

  Machiko Minatoya, Atsuko Araki, Sachiko Itoh, Keiko Yamazaki, Sumitaka Kobayashi, Chihiro Miyashita, Seiko Sasaki, Reiko Kishi

  ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE 24 1 74 - 74 2019年12月 [査読有り][通常論文]
   

  Background There have been inconsistent findings reported on maternal passive smoking during pregnancy and child risk of ADHD. In this study, ADHD symptoms at pre-school age children in association with prenatal passive and active tobacco smoke exposure determined by maternal plasma cotinine levels in the third trimester were investigated. Methods This was a follow-up study of the birth cohort: the Hokkaido Study on Environment and Children's Health. Children whose parents answered Strengths and Difficulties Questionnaire (SDQ) to identify child ADHD symptoms (hyperactivity/inattention and conduct problems) and total difficulties at age 5 years with available maternal plasma cotinine level at the third trimester were included (n = 3216). Cotinine levels were categorized into 4 groups; <= 0.21 ng/ml (non-smoker), 0.22-0.51 ng/ml (low-passive smoker), 0.52-11.48 ng/ml (high-passive smoker), and >= 11.49 ng/ml (active smoker). Results Maternal cotinine levels of active smokers were significantly associated with an increased risk of total difficulties (OR = 1.67) and maternal low- and high-passive smoking also increased the risk (OR = 1.11, 1.25, respectively) without statistical significance. Similarly, maternal cotinine levels of active smokers were associated with an increased risk of hyperactivity/inattention (OR = 1.49). Maternal low- and high-passive smoking and active smoking increased the risk of hyperactivity/inattention (OR = 1.45, 1.43, and OR = 1.59, respectively) only in boys. Conclusion Our findings suggested that maternal active smoking during pregnancy may contribute to the increased risk of child total difficulties and hyperactivity/inattention at pre-school age. Pregnant women should be encouraged to quit smoking and avoid exposure to tobacco smoke.
• Multiple exposures to organophosphate flame retardants alter urinary oxidative stress biomarkers among children: The Hokkaido Study

  Yu Ait Bamai, Michiel Bastiaensen, Atsuko Araki, Houman Goudarzi, Satoshi Konno, Sachiko Ito, Chihiro Miyashita, Yiming Yao, Adrian Covaci, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 131 105003 - 105003 2019年10月 [査読有り][通常論文]
   

  Organophosphate flame retardants (PFRs) are used as additives in plastics and other applications such as curtains and carpets as a replacement for brominated flame retardants. As such, exposure to PFR mixtures is widespread, with children being more vulnerable than adults to associated health risks such as allergies and inflammation. Oxidative stress is thought to be able to modulate the development of childhood airway inflammation and atopic dermatitis. To evaluate these associations, the present study investigated the relationship between urinary PFR metabolites, their mixtures and urinary oxidative stress biomarkers in children as part of the Hokkaido Study on Environment and Children's Health. The levels of the oxidative stress biomarkers, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), hexanoyl-lysine (HEL), and 4-hydroxynonenal (HNE), and of 14 PFR metabolites were measured in morning spot urine samples of 7-year-old children (n = 400). Associations between PFR metabolites or PFR metabolite mixtures and oxidative stress biomarkers were examined by multiple regression analysis and weighted quantile sum regression analysis, respectively. We found that the non-chlorinated PFR metabolites, 2-ethylhexyl phenyl phosphate (EHPHP), bis(2-butoxyethyl) phosphate (BBOEP), and diphenyl phosphate (DPHP) were associated with increased levels of oxidative stress biomarkers. Furthermore, the PFR metabolite mixture was associated with increased levels of HEL and HNE, but not 8-OHdG. The combination of elevated top 2 PFR metabolites was not associated with higher urinary oxidative stress marker levels. This is the first study to report associations between urinary PFR metabolites and oxidative stress biomarkers among children.
• Childhood allergies and obesity relationship: Identification of novel non-invasive biomarkers

  Houman Goudarzi, Satoshi Konno, Atsuko Araki, Sachiko Ito, Yu Ait Bamai, Chihiro Miyashita, Reiko Kishi

  EUROPEAN RESPIRATORY JOURNAL 54 2019年09月
• Association between perfluoroalkyl substance exposure and thyroid hormone/thyroid antibody levels in maternal and cord blood: The Hokkaido Study.

  Itoh S, Araki A, Miyashita C, Yamazaki K, Goudarzi H, Minatoya M, Ait Bamai Y, Kobayashi S, Okada E, Kashino I, Yuasa M, Baba T, Kishi R

  Environment international 133 Pt A 105139 - 105139 2019年09月 [査読有り][通常論文]
   

  BACKGROUND: Thyroid antibodies (TAs) are the most common cause of hypothyroidism during gestation. Although previous studies found that prenatal exposure to perfluoroalkyl substances (PFASs) disrupts thyroid hormones (THs) in humans, their effects on TAs during the perinatal period have not been investigated. OBJECTIVE: To explore the associations between prenatal exposure to eleven different PFASs from two different groups (carboxylates and sulfonates) and the expression of THs and TAs in maternal and cord blood while considering maternal TA status. METHODS: In a prospective birth cohort (the Hokkaido Study), we included 701 mother‑neonate pairs recruited in 2002-2005 for whom both prenatal maternal and cord blood samples were available. Eleven PFASs were measured in maternal plasma obtained at 28-32 weeks of gestation using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. THs and TAs including thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured in maternal blood during early pregnancy (median 11 gestational weeks), and in cord blood at birth. RESULTS: The median levels of TgAb and TPOAb in maternal serum were 15.0 and 6.0 IU/mL, respectively. The median TgAb level in neonates was 38.0 IU/mL, and TPOAb were detected in only 12.3% of samples. Maternal FT3 level was positively associated with PFAS levels in both TA-positive and TA-negative mothers. Maternal perfluorooctanoate was inversely associated with maternal TPOAb. Among boys, some maternal PFASs were associated with higher TSH and lower FT3 levels in maternal TA-negative group, while perfluorodecanoic acid was associated with lower TSH in maternal TA-positive group. Among girls, some PFAS of mothers showed associations with lower TSH and higher FT3 in maternal TA-negative group, while perfluorododecanoic acid was associated with lower FT4 in maternal TA-positive. Maternal PFASs showed associations with boy's TgAb inversely in maternal TA-negative group and with girl's TgAb positively in maternal TA-positive group. CONCLUSIONS: Our results suggest thyroid disrupting effects of PFAS exposure and susceptibility vary depending on maternal TA levels.
• An epigenome-wide analysis of cord blood DNA methylation reveals sex-specific effect of exposure to bisphenol A

  Ryu Miura, Atsuko Araki, Machiko Minatoya, Kunio Miyake, Mei-Lien Chen, Sumitaka Kobayashi, Chihiro Miyashita, Jun Yamamoto, Toru Matsumura, Mayumi Ishizuka, Takeo Kubota, Reiko Kishi

  SCIENTIFIC REPORTS 9 1 12369  2019年08月 [査読有り][通常論文]
   

  Exposure to bisphenol A (BPA) in utero is associated with adverse health outcome of the offspring. Differential DNA methylation at specific CpG sites may link BPA exposure to health impacts. We examined the association of prenatal BPA exposure with genome-wide DNA methylation changes in cord blood in 277 mother-child pairs in the Hokkaido Study on Environment and Children's Health, using the Illumina HumanMethylation 450 BeadChip. We observed that a large portion of BPA-associated differentially methylated CpGs with p-value < 0.0001 was hypomethylated among all newborns (91%) and female infants (98%), as opposed to being hypermethylated (88%) among males. We found 27 and 16 CpGs with a false discovery rate (FDR) < 0.05 in the analyses for males and females, respectively. Genes annotated to FDR-corrected CpGs clustered into an interconnected genetic network among males, while they rarely exhibited any interactions in females. In contrast, none of the enrichment for gene ontology (GO) terms with FDR < 0.05 was observed for genes annotated to the male-specific CpGs with p < 0.0001, whereas the female-specific genes were significantly enriched for GO terms related to cell adhesion. Our epigenome-wide analysis of cord blood DNA methylation implies potential sex-specific epigenome responses to BPA exposure.
• Occupational exposure limits for cumene, 2,4-dichlorophenoxy acetic acid, silicon carbide whisker, benzyl alcohol, and methylamine, and carcinogenicity, occupational sensitizer, and reproductive toxicant classifications

  Atsuko Araki, Kenichi Azuma, Ginji Endo, Yoko Endo, Tetsuhito Fukushima, Kunio Hara, Koji Harada, Hajime Hori, Seichi Horie, Masayoshi Ichiba, Gaku Ichihara, Masayuki Ikeda, Akiyoshi Ito, Yuki Ito, Satoko Iwasawa, Takeyasu Kakumu, Michihiro Kamijima, Kanae Karita, Takahiko Katoh, Toshio Kawai, Toshihiro Kawamoto, Shinji Kumagai, Yukinori Kusaka, Akiko Matsumoto, Muneyuki Miyagawa, Hiroyuki Miyauchi, Yasuo Morimoto, Kasuke Nagano, Hisao Naito, Tamie Nakajima, Makiko Nakano, Tetsuo Nomiyama, Hirokazu Okuda, Masayuki Okuda, Kazuyuki Omae, Haruhiko Sakurai, Kazuhiro Sato, Tomotaka Sobue, Yasushi Suwazono, Toru Takebayashi, Tatsuya Takeshita, Akito Takeuchi, Ayano Takeuchi, Masatoshi Tanaka, Shigeru Tanaka, Teruomi Tsukahara, Masashi Tsunoda, Susumu Ueno, Jun Ueyama, Yumi Umeda, Kenya Yamamoto, Yuko Yamano, Takenori Yamauchi, Eiji Yano

  JOURNAL OF OCCUPATIONAL HEALTH 61 4 328 - 330 2019年07月 [査読有り][通常論文]
  
• The relationship between prenatal psychological stress and placental abruption in Japan, The Japan Environment and Children's Study (JECS)

  Yasuyuki Kawanishi, Eiji Yoshioka, Yasuaki Sago, Toshihiro Itoh, Toshinobu Miyamoto, Kazuo Sengoku, Yoshiya Ito, Sachiko Ito, Chihiro Miyashita, Atsuko Araki, Toshiaki Endo, Kazutoshi Cho, Hisanori Minakami, Reiko Kishi, Toshihiro Kawamoto, Hirohisa Saito, Reiko Kishi, Nobuo Yaegashi, Koichi Hashimoto, Chisato Mori, Shuichi Ito, Zentaro Yamagata, Hidekuni Inadera, Michihiro Kamijima, Takeo Nakayama, Hiroyasu Iso, Masayuki Shima, Yasuaki Hirooka, Narufumi Suganuma, Koichi Kusuhara, Takahiko Katoh

  PLOS ONE 14 7 e0219379  2019年07月 [査読有り][通常論文]
   

  BackgroundPrenatal psychological stress may increase the risk of placental abruption (PA). This study aimed to clarify the effects of psychological distress during pregnancy and exposure to stressful life events in the year before or during pregnancy on the occurrence of PA in Japanese women.MethodsUsing a nationwide prospective birth cohort study, we obtained data from 103,099 women between January 2011 and March 2014. Information on exposure to 14 stressful life events and psychological distress (Kessler 6 scale) was collected using a self-administered questionnaire during pregnancy. Clinical diagnoses of PA were obtained from medical records. A total of 80,799 women with singleton births were analyzed using logistic regression models that adjusted for possible confounders.ResultsPA was diagnosed in 335 (0.4%) women. There was no significant difference in the Kessler 6 score during pregnancy between the PA group and non-PA group. Exposure to the death of a child in the year before or during pregnancy was significantly associated with PA in multigravid women (adjusted odds ratio [aOR] 3.57; 95% confidence interval [CI] 1.50-8.34). A spouse's loss of employment was significantly associated with PA in parous women (aOR 3.25; 95% CI 1.40-7.56).ConclusionsThis study identified the possible effects of exposure to the death of a child on PA occurrence that adjusted for important confounding factors.
• Association between maternal passive smoking and increased risk of delivering small-for-gestational-age infants at full-term using plasma cotinine levels from The Hokkaido Study: a prospective birth cohort

  Sumitaka Kobayashi, Fumihiro Sata, Tomoyuki Hanaoka, Titilola Serifat Braimoh, Kumiko Ito, Naomi Tamura, Atsuko Araki, Sachiko Itoh, Chihiro Miyashita, Reiko Kishi

  BMJ OPEN 9 2 e023200  2019年06月 [査読有り][通常論文]
   

  Objectives To investigate the association between plasma cotinine level measured at the 8th gestational month and the delivery of small-for-gestational-age (SGA) infants, using a highly sensitive ELISA method.Design Prospective birth cohort study from The Hokkaido Study on Environment and Children's Health.Setting Hokkaido, Japan.Participants Our sample included 15 198 mother-infant pairs enrolled in 2003-2012.Main outcome measures SGA, defined as a gestational age-specific weight Z-score below -2.Results The number of SGA infants was 192 (1.3%). The cotinine cut-off level that differentiated SGA infants from other infants was 3.03 ng/mL for both the total population and the full-term births subgroup (sensitivity 0.307; positive predictive value 2.3%). Compared with infants of mothers with a plasma cotinine level of <3.03 ng/mL, infants of mothers with a plasma cotinine level of >= 3.03 ng/mL showed an increased OR for SGA in the total population and the full-term infant group (2.02(95% CI 1.45 to 2.83) and 2.44(95% CI 1.73 to 3.44), respectively).Conclusion A plasma cotinine level of >= 3.03 ng/mL, which included both passive and active smokers, was associated with an increased risk of SGA. This finding is of important relevance when educating pregnant women about avoiding prenatal passive and active smoking due to the adverse effects on their infants, even those born at full-term.
• Biomonitoring of organophosphate flame retardants and plasticizers in children: Associations with house dust and housing characteristics in Japan

  Michiel Bastiaensen, Yu Ait Bamai, Atsuko Araki, Nele Van den Eede, Toshio Kawai, Tazuru Tsuboi, Reiko Kishi, Adrian Covaci

  ENVIRONMENTAL RESEARCH 172 543 - 551 2019年05月 [査読有り][通常論文]
   

  Indoor environments contain a wide range of new chemicals such as phosphate flame retardants and plasticizers (PFRs). Despite recent epidemiological evidence suggesting that children might be affected by widespread exposure to PFRs, questions remain about the various exposure pathways to these chemicals. Therefore, the aim of this study was to investigate exposure to PFRs by measuring the concentrations a set of urinary metabolites for schoolchildren from Japan (n = 128) and associating them with house dust concentrations and housing characteristics. Detectable concentrations of both diaryl and dialkyl phosphates (DAPS) and hydroxylated metabolites (HO-PFRs) were found in urine samples of almost all children. 2-Hydroxyethyl bis(2-butoxyethyl) phosphate (BBOEHEP) was the most frequently detected metabolite (98%) followed by 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP, 95%) and tris(chloroethyl) phosphate (TCEP). Next to BBOEHEP, two other metabolites of tris(2-butoxyethyl) phosphate (TBOEP) were also frequently detected. Significant correlations of moderate strength were found between parent compounds detected in high concentrations in house dust (TBOEP, tris(2-chloroisopropyl) phosphate (TCIPP)) and their corresponding metabolites, suggesting that dust is a primary exposure source for these PFRs. Several personal and housing characteristics, such as gender, income, and the use of PVC and ventilation were associated with metabolite concentrations in multivariate linear regression. Overall, this study showed that Japanese schoolchildren are exposed to a wide range of PFRs.
• Dose-dependent associations between prenatal caffeine consumption and small for gestational age, preterm birth, and reduced birthweight in the Japan Environment and Children's Study

  Sumitaka Kobayashi, Fumihiro Sata, Katsuyuki Murata, Yasuaki Saijo, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Machiko Minatoya, Keiko Yamazaki, Yu Ait Bamai, Reiko Kishi, Toshihiro Kawamoto, Hirohisa Saito, Reiko Kishi, Nobuo Yaegashi, Koichi Hashimoto, Chisato Mori, Shuichi Itoh, Zentaro Yamagata, Hidekuni Inadera, Michihiro Kamijima, Takeo Nakayama, Hiroyasu Iso, Masayuki Shima, Yasuaki Hirooka, Narufumi Suganuma, Koichi Kusuhara, Takahiko Katoh

  PAEDIATRIC AND PERINATAL EPIDEMIOLOGY 33 3 185 - 194 2019年05月 [査読有り][通常論文]
   

  Background Few previous studies have investigated the association between prenatal caffeine intake and birth size (small for gestational age [SGA], preterm birth, and birthweight Z-score) in Japan. Objectives We examined the dose-dependency of this association (prenatal caffeine consumption and birth size) as part of the Japan Environment and Children's Study. Methods A prospective birth cohort included 94 876 fetuses in Japan. Participants were enrolled between January 2011 and March 2014. Adjusted multiple linear regression and Cox regression models were used to examine the association between prenatal caffeine levels and infant birth size. Results The median estimated caffeine consumption during pregnancy was 125.5 mg/day, as determined by self-administered questionnaires. There were 7252 SGA infants (7.6%) and 4281 preterm birth infants (4.5%). Compared with infants of mothers whose caffeine consumption during pregnancy was in the lowest quartile (4.2 to <86.4 mg/day), infants of mothers whose caffeine consumption was in the highest quartile 4 (205.5-5080.0 mg/day) were at an increased risk of SGA (relative risk [RR] 1.18, 95% confidence interval [CI] 1.10, 1.27), and at an increased risk of preterm birth at the second trimester of gestation (RR 1.94, 95% CI 1.12, 3.37), with a 0.32-day reduction in gestational age (95% CI -0.52, -0.12) and with a 0.07 reduction in birthweight Z-score observed (95% CI -0.09, -0.05). Conclusions Prenatal caffeine consumption was associated with birth size. However, as the association between prenatal caffeine consumption and birth size was likely confounded by unpredicted potential factors, our confidence in the true causality of the association is moderate.
• Association Between Maternal Serum Folate Concentrations in the First Trimester and the Risk of Birth Defects: The Hokkaido Study of Environment and Children's Health

  Kumiko Ito, Tomoyuki Hanaoka, Naomi Tamura, Seiko Sasaki, Chihiro Miyashita, Atsuko Araki, Sachiko Ito, Hisanori Minakami, Kazutoshi Cho, Toshiaki Endo, Tsuyoshi Baba, Toshinobu Miyamoto, Kazuo Sengoku, Akiko Tamakoshi, Reiko Kishi

  JOURNAL OF EPIDEMIOLOGY 29 4 164 - 171 2019年04月 [査読有り][通常論文]
   

  Background: Low red blood cell folate concentrations during early pregnancy might cause neural tube defects. However, the association between folate concentrations and birth defects of other neural crest cell-derived organs remains unknown. We investigated the associations between birth defects and first-trimester serum folate concentrations in a birth-cohort study in Japan.Methods: In total, 14,896 women who were prior to 13 weeks of gestation were enrolled from 2003 through 2012. Birth defect information was obtained from medical records and questionnaires. The association between folate levels in the first trimester and birth defects categorized as ICD-10 cord defects and neural crest cell-derived organ defects was examined. The crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per log-transformed folate concentration were calculated using logistic regression.Results: Blood samples were obtained at a mean of 10.8 weeks of gestation. Median serum folate level was 16.5 (interquartile range, 13.4-21.5) nmol/L, and the deficiency level (less than 6.8 nmol/L) was 0.7%. There were 358 infants with birth defects. The adjusted odds ratio for any birth defect, ventricular septal defects, and cleft lip was 0.99 (95% CI, 0.74-1.32), 0.63 (95% CI, 0.30-1.33), and 4.10 (95% CI, 0.96-17.58), respectively. There were no significant associations between first-trimester maternal serum folate and the risk of birth defects.Conclusions: We were unable to demonstrate a relationship between maternal serum folate in the first trimester and birth defects. Potential confounding factors may have influenced our results.
• Association of blood mercury levels during pregnancy with infant birth size by blood selenium levels in the Japan Environment and Children's Study: A prospective birth cohort

  Sumitaka Kobayashi, Reiko Kishi, Yasuaki Saijo, Yoshiya Ito, Koji Oba, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Machiko Minatoya, Keiko Yamazaki, Yu Ait Bamai, Tosiya Sato, Shin Yamazaki, Shoji F. Nakayama, Tomohiko Isobe, Hiroshi Nitta, Toshihiro Kawamoto, Hirohisa Saito, Nobuo Yaegashi, Koichi Hashimoto, Chisato Mori, Shuichi Itoh, Zentaro Yamagata, Hidekuni Inadera, Michihiro Kamijima, Takeo Nakayama, Hiroyasu Iso, Masayuki Shima, Yasuaki Hirooka, Narufumi Suganuma, Koichi Kusuhara, Takahiko Katoh

  ENVIRONMENT INTERNATIONAL 125 418 - 429 2019年04月 [査読有り][通常論文]
   

  Background: It is necessary to determine whether there are adverse health effects of prenatal exposure to long-term, low levels of mercury and selenium. However, there are limited that reports on the association between mercury levels by selenium levels and birth size. Therefore, we examined whether maternal mercury levels during pregnancy had any effect on infant birth size, and size, and whether selenium levels influenced this relationship.Objectives: To examine the association between mercury and selenium levels during pregnancy with infant birth size.Methods: The Japan Environment and Children's Study is a prospective birth cohort conducted between 2011 and 2014. Total mercury levels and total selenium levels in maternal blood during the second and third tri-mesters were measured using Inductively Coupled Plasma-Mass Spectrometry. Birth weight and small-for-gestational-age were confirmed by medical records. Small-for-gestational-age was defined as birth weight below the 10th percentile according to standard percentile for gender, parity, and gestational age. Multiple linear and logistic regression analyses were used to examine the association between maternal mercury exposure and birth weight or small-for-gestational-age adjusted for confounders (including maternal age and body mass index pregnancy).Results: Overall, 15,444 pregnant women were included in this study. Median (inter-quartile range) of blood mercury and selenium levels were 3.66 (2.59-5.18) ng/g and 170.0 (158.0-183.0) ng/g, respectively. Compared to infants of mothers with the highest blood selenium level, those of mothers with the lowest blood selenium level had neither a significant birth weight increase (9 g, 95% confidence interval: -6, 25) nor a significant odds ratio for small-for-gestational-age (0.903, 95% confidence interval: 0.748, 1.089). Compared to infants of mothers with the lowest blood mercury level, those of mothers with the highest blood mercury level had neither a significant birth weight reduction (-12 g, 95% confidence interval: -27, 4) nor a significant odds ratio for small-for-gestational-age (0.951, 95% confidence interval: 0.786, 1.150). Compared to infants of mothers with the lowest quartile of maternal blood mercury level, all infants of mothers with the highest quartile of maternal blood mercury level had a reduced birth head circumference of 0.073 cm (95% confidence interval: -0.134, -0.011).Conclusions: There was no association between maternal blood mercury levels and small-for-gestational-age and birth weight among 15,444 pregnant women. In a Japanese population, which has a relatively higher blood mercury level than reported in Western population, reduced birth size was not found to be associated with blood mercury levels, with the exception of birth head circumference.
• For making a declaration of countermeasures against the falling birth rate from the Japanese Society for Hygiene: summary of discussion in the working group on academic research strategy against an aging society with low birth rate

  Kyoko Nomura, Kanae Karita, Atsuko Araki, Emiko Nishioka, Go Muto, Miyuki Iwai-Shimada, Mariko Nishikitani, Mariko Inoue, Shinobu Tsurugano, Naomi Kitano, Mayumi Tsuji, Sachiko Iijima, Kayo Ueda, Michihiro Kamijima, Zentaro Yamagata, Kiyomi Sakata, Masayuki Iki, Hiroyuki Yanagisawa, Masashi Kato, Hidekuni Inadera, Yoshihiro Kokubo, Kazuhito Yokoyama, Akio Koizumi, Takemi Otsuki

  ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE 24 1 14 - 14 2019年03月 [査読有り][通常論文]
   

  In 1952, the Japanese Society for Hygiene had once passed a resolution at its 22nd symposium on population control, recommending the suppression of population growth based on the idea of cultivating a healthier population in the area of eugenics. Over half a century has now passed since this recommendation; Japan is witnessing an aging of the population (it is estimated that over 65-year-olds made up 27.7% of the population in 2017) and a decline in the birth rate (total fertility rate 1.43 births per woman in 2017) at a rate that is unparalleled in the world; Japan is faced with a super-aging society with low birth rate. In 2017, the Society passed a resolution to encourage all scientists to engage in academic researches to address the issue of the declining birth rate that Japan is currently facing. In this commentary, the Society hereby declares that the entire text of the 1952 proposal is revoked and the ideas relating to eugenics is rejected. Since the Society has set up a working group on the issue in 2016, there have been three symposiums, and working group committee members began publishing a series of articles in the Society's Japanese language journal. This commentary primarily provides an overview of the findings from the published articles, which will form the scientific basis for the Society's declaration. The areas we covered here included the following: (1) improving the social and work environment to balance between the personal and professional life; (2) proactive education on reproductive health; (3) children's health begins with nutritional management in women of reproductive age; (4) workplace environment and occupational health; (5) workplace measures to counter the declining birth rate; (6) research into the effect of environmental chemicals on sexual maturity, reproductive function, and the children of next generation; and (7) comprehensive research into the relationship among contemporary society, parental stress, and healthy child-rearing. Based on the seven topics, we will set out a declaration to address Japan's aging society with low birth rate.
• Effects of prenatal sex hormones on behavioral sexual dimorphism

  Takahiko Mitsui, Atsuko Araki, Chihiro Miyashita, Sachiko Ito, Tamiko Ikeno, Seiko Sasaki, Takeya Kitta, Kimihiko Moriya, Kazutoshi Cho, Keita Morioka, Reiko Kishi, Nobuo Shinohara, Masayuki Takeda, Katsuya Nonomura

  PEDIATRICS INTERNATIONAL 61 2 140 - 146 2019年02月 [査読有り][通常論文]
   

  Background We investigated the association between the hormone environment during the prenatal period using cord blood, and gender-role play behavior in school-aged children. Methods A total of 879 school-aged children (433 boys and 446 girls) in a prospective birth cohort study in Hokkaido were enrolled to analyze the relationship between cord blood level of the sex hormones estradiol (E), testosterone (T), progesterone (P), and dehydroepiandrosterone (DHEA), and the Pre-School Activities Inventory (PSAI) score. The PSAI evaluated sex-typical characteristics, the type of preferred toys and play activities. The PSAI consists of 12 masculine and 12 feminine items, and the composite scores were calculated by subtracting the feminine score from the masculine score. Higher scores indicated male-typical behavior. Results Composite and masculine PSAI scores were significantly higher in boys. Meanwhile, the feminine score was significantly lower in boys. Although T and P were significantly higher in boys, E/T was significantly higher in girls. In a multivariate regression model, including covariates of social factors, there was no correlation between any of the hormones and PSAI score in boys. In girls, only P and E/T were positively correlated with the feminine score. Conclusions Prenatal sex hormone exposure may influence the dimorphic brain development and behavior in school-aged girls. Furthermore, the cord blood hormone levels may not fully reflect the hormone environment during the prenatal period.
• A risk score for childhood obesity constructed using predictors identified in pregnant women and 1-year-old infants: the Hokkaido

  Saijo Y, Ito Y, Yoshioka E, Sato Y, Minatoya M, Araki A, Miyashita C, Kishi R

  Clinical Pediatric Endocrinology - - - - - 2019年 [査読有り][通常論文]
  
• Chapter 9: The Hokkaido Study on Environment and Children’s Health, Part 3: Public Health Aspect in Each Cohort or Consortium. in Fumihiro Sata, Hideoki Fukuoka, Mark Hanson (Eds.)

  Kishi R, Araki A, Miyashita C, Kobayashi S, Miura R, Minatoya M

  Pre-emptive Medicine: Public Health Aspects of Developmental Origins of Health and Disease. Springer - - 145 - 163 2019年 [査読有り][通常論文]
  
• Identifying a risk score for childhood obesity based on predictors identified in pregnant women and 1-year-old infants: An analysis of the data of the Hokkaido Study on Environment and Children's Health

  Yasuaki Saijo, Yoshiya Ito, Eiji Yoshioka, Yukihiro Sato, Machiko Minatoya, Atsuko Araki, Chihiro Miyashita, Reiko Kishi

  CLINICAL PEDIATRIC ENDOCRINOLOGY 28 3 81 - 89 2019年 [査読有り][通常論文]
   

  This study aimed to construct a childhood obesity risk index based on predictors identified in pregnant women and 1-yr-old infants. The primary outcome was an identified obesity index of > 20% at 6-8 yr of age. Of a total sample size of 6,846 mother-child pairs, 80% and 20% were randomly allocated to the derivation and validation cohorts, respectively. For the derivation cohort, univariate and multivariate logistic regression analyses of data were conducted to identify the final predictors to determine the childhood obesity risk score algorithm. These included pre-pregnancy body mass index (BMI), child's gender, smoking during pregnancy, education, and obesity index at one yr of age. The beta coefficients for categories of predictor variables were each divided by the smallest value among them. The quotient was rounded off to the integer and assigned to the risk score, and a value of zero was assigned to reference categories. A total risk score was calculated for each individual. A cutoff point >= 16 had 22.2% and 21.8% positive predictive values in the derivation and validation cohorts, respectively. In conclusion, the childhood obesity risk score algorithm was constructed based on generic predictors that can be easily obtained from maternal and child health handbooks.
• Association between ESR1 polymorphisms and second to fourth digit ratio in school-aged children in the Hokkaido Study

  Yoko Nishimura, Kimihiko Moriya, Sumitaka Kobayashi, Atsuko Araki, Fumihiro Sata, Takahiko Mitsui, Sachiko Itoh, Chihiro Miyashita, Kazutoshi Cho, Masafumi Kon, Michiko Nakamura, Takeya Kitta, Sachiyo Murai, Reiko Kishi, Nobuo Shinohara

  STEROIDS 141 55 - 62 2019年01月 [査読有り][通常論文]
   

  The ratio of the lengths of the 2nd and 4th digits (2D:4D) is considered an index of prenatal exposure to androgen. Indeed, androgen receptors have been linked to digit length, but estrogen receptors are rarely investigated in this context. Thus, we investigated the association between estrogen receptor 1 (ESR1) genetic polymorphisms and 2D:4D in school-aged children. The 2D:4D ratios were determined using Vernier calipers from photocopies of palms provided by 1800 children aged 7 years who were enrolled in an ongoing prospective cohort study in Hokkaido, Japan. The children were genotyped using cord blood collected at birth for single nucleotide polymorphisms in ESR1, specifically PvuII (T > C, dbSNP: rs2234693), Xbal (A > G, dbSNP: rs9340799), and rs2077647 (A > G). The association between ESR1 polymorphisms and 2D:4D was assessed by multiple linear regression adjusted for potential cofounding factors. Boys with the GG genotype at rs9340799 had a significantly lower 2D:4D in the right hand than boys with the AA/AG genotype (- 0.96% lower, 95% confidence interval: -1.68 to - 0.24). However, this association was detected only in boys born to non-smoking mothers. No significant differences were found between rs9340799 polymorphisms and 2D:4D among girls. There was also no link between 2D:4D and polymorphisms at rs2234693 and rs2077647. These data suggest that rs9340799 polymorphisms in ESR1 may contribute to digit length and 2D:4D.
• [Toward a Declaration to Address Japan's Aging Society with Low Birth Rate: Summary of the Japanese Society for Hygiene's Working Group on Academic Research Strategy against an Aging Society with Low Birth Rate].

  Kyoko Nomura, Kanae Karita, Atsuko Araki, Emiko Nishioka, Go Muto, Miyuki Iwai-Shimada, Mariko Nishikitani, Mariko Inoue, Shinobu Tsurugano, Naomi Kitano, Mayumi Tsuji, Sachiko Iijima, Kayo Ueda, Michihiro Kamijima, Zentaro Yamagata, Kiyomi Sakata, Masayuki Iki, Hiroyuki Yanagisawa, Masashi Kato, Kazuhito Yokoyama, Akio Koizumi, Takemi Otsuki

  Nihon eiseigaku zasshi. Japanese journal of hygiene 74 0 2019年 [査読有り][通常論文]
  
• Association of filaggrin gene mutations and childhood eczema and wheeze with phthalates and phosphorus flame retardants in house dust: The Hokkaido study on Environment and Children's Health

  Yu Ait Bamai, Atsuko Araki, Toshifumi Nomura, Toshio Kawai, Tazuru Tsuboi, Sumitaka Kobayashi, Chihiro Miyashita, Masae Takeda, Hiroshi Shimizu, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 121 Pt 1 102 - 110 2018年12月 [査読有り][通常論文]
   

  Background and aim: Exposure to phthalates and phosphorus flame retardants (PFRs) is considered to be a risk factor for asthma and allergies. However, little is known about the contribution of loss-of-function mutations in the gene encoding filaggrin (FLG) gene, which are considered to be predisposing factors for eczema and asthma, to these associations. We investigated the associations between exposure to phthalates and PFRs in dust and eczema/wheeze among Japanese children, taking into consideration loss-of-function mutations in FLG.Methods: This study was part of the Hokkaido study on Environment and Children's Health. Seven phthalates and 11 PFRs in household dust were measured by gas chromatography mass spectrometry. Eczema and wheeze were assessed in children aged 7 years using the International Study of Asthma and Allergies in Childhood questionnaire. Eight FLG mutations previously identified in the Japanese population were extracted from cord blood samples. Children with one or more FLG mutations were considered to be positive for FLG mutations. The study included 296 children who had complete data (birth records, FLG mutations, first trimester and 7 years questionnaires, and phthalate/PFR levels). Odds ratios (ORs) and 95% confidential intervals (CIs) of eczema and wheeze were calculated for log-transformed phthalate/PFR levels by logistic regression. We also performed stratified analyses based on FLG mutations.Results: The prevalence rates of eczema and wheeze were 20.6% and 13.9%, respectively. Among children without any FLG mutations, Iris (1, 3-dichloro-2-propyl) phosphate (TDCIPP) increased the OR of wheeze, (OR: 1.22, CI: 1.00-1.48). Significant p values for trends were found between Iris (2-butoxyethyl) phosphate (TBOEP) and eczema and di-iso-nonyl phthalate (DiNP) and eczema among children without any FLG mutations, respectively.Conclusions: Despite our limited sample size and cross-sectional study design, the effects of indoor environmental factors on childhood eczema and wheeze were clearer in children without loss-of-function mutations in FLG than in children with mutations. Children with FLG mutations might already be cared for differently in terms of medication or parental lifestyle. Further studies in larger populations are warranted so that severity of symptoms and combinations of FLG mutations can be investigated.
• Association between prenatal exposure to organochlorine pesticides and the mental and psychomotor development of infants at ages 6 and 18 months: The Hokkaido Study on Environment and Children's Health

  Keiko Yamazaki, Atsuko Araki, Sonomi Nakajima, Chihiro Miyashita, Tamiko Ikeno, Sachiko Itoh, Machiko Minatoya, Sumitaka Kobayashi, Futoshi Mizutani, Yoichi Chisaki, Reiko Kishi

  NEUROTOXICOLOGY 69 201 - 208 2018年12月 [査読有り][通常論文]
   

  Organochlorine pesticides (OCPs) are environmental contaminants that persist in the environment and bioaccumulate through the food chain in humans and animals. Although previous studies have shown an association between prenatal OCP exposure and subsequent neurodevelopment, the levels of OCPs included in these studies were inconsistent. A hospital-based prospective birth cohort study was conducted to examine the associations between prenatal exposure to relatively low levels of OCPs and neurodevelopment in infants at 6 (n =164) and 18 (n = 115) months of age. Blood samples were analyzed using gas chromatography/mass spectrometry techniques to quantify 29 OCPs. The Bayley Scales of Infant Development 2nd edition (BSID-II) was used to assess the Mental and Psychomotor Developmental Index. After controlling for confounders, we found an inverse association between prenatal exposure to cis-heptachlor epoxide and the Mental Developmental Index at 18 months of age. Furthermore, infants born to mothers with prenatal concentrations of cis-heptachlor epoxide in the highest quartile had Mental Developmental Index scores -9.8 (95% confidence interval: -16.4, -3.1) lower than that recorded for infants born to mothers with concentrations of cis-heptachlor epoxide in the first quartile (p for trend <0.01). These results support the hypothesis that prenatal exposure to OCPs, especially cis-heptachlor epoxide, may have an adverse effect on the neurodevelopment of infants at specific ages, even at low levels. (C) 2017 Elsevier B.V. All rights reserved.
• Association of maternal serum concentration of hydroxylated polychlorinated biphenyls with maternal and neonatal thyroid hormones: The Hokkaido birth cohort study

  Sachiko Itoh, Toshiaki Baba, Motoyuki Yuasa, Chihiro Miyashita, Sumitaka Kobayashi, Atsuko Araki, Seiko Sasaki, Jumboku Kajiwara, Tsuguhide Hori, Takashi Todaka, Kaori Fujikura, Sonomi Nakajima, Shizue Kato, Reiko Kishi

  ENVIRONMENTAL RESEARCH 167 583 - 590 2018年11月 [査読有り][通常論文]
   

  Background: Evidence on the toxicity of hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) for thyroid hormones (TH) is limited, and the underlying mechanism remains unknown.Objectives: We aimed to investigate the effects of environmental prenatal exposure to OH-PCBs and maternal and neonatal TH levels, taking the maternal-fetal TH transfer into account.Methods: In this prospective birth cohort (the "Hokkaido study") we included 222 mother-neonate pairs. We measured five OH-PCB isomers in maternal serum samples either during pregnancy or within 5 days of delivery. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were obtained from maternal blood samples at an early gestational stage (median; 11.1 weeks) and from heel prick samples of neonates between 4 and 7 days after birth. Multiple linear regression analysis and structural equation modeling (SEM) were performed to investigate the associations between maternal OH-PCB and maternal and neonatal TH levels.Results: Median concentration of Sigma OH-PCBs was 25.37 pg/g wet weight. The predominant isomer was 4-OH-CB187, followed by 4-OH-CB146 + 3-OH-CB153. In the fully adjusted linear regression analysis, maternal EOH-PCBs was positively associated with maternal FT4, and 4-OH-CB187 was positively associated with both maternal and neonatal FT4 levels. Maternal OH-PCBs showed no significant association with TSH among mothers and neonates. Path analysis indicated the indirect pathway from 4-OH-CB187 exposure to increased neonatal FT4, via maternal THs and neonatal TSH.Conclusions: These findings suggest that maternal exposure to OH-PCBs during pregnancy may increase both maternal and neonatal FT4 levels. Neonatal FT4 is presumed to be increased by prenatal 4-OH-CB187 indirectly, and this process may be mediated by maternal THs and neonatal TSH.
• Contrasting associations of maternal smoking and pre-pregnancy BMI with wheeze and eczema in children

  Houman Goudarzi, Satoshi Konno, Hirokazu Kimura, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Yu Ait Bamai, Hiroki Kimura, Kaoruko Shimizu, Masaru Suzuki, Yoichi M. Ito, Masaharu Nishimura, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 639 1601 - 1609 2018年10月 [査読有り][通常論文]
   

  Background: Childhood allergies are dynamic and associated with environmental factors. The influence of prenatal maternal smoking and obesity on childhood allergies and their comorbidities remains unclear, especially in prospective cohorts with serial longitudinal observations.Objective: We examined time trends in the prevalence and comorbidity of childhood allergies, including wheeze, eczema, and rhinoconjunctivitis, using a large-scale, population-based birth cohort in Japan, and assessed the effects of prenatal maternal smoking and BMI on the risk of childhood allergies.Methods: Parents completed the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires about symptoms of allergies and their risk factors at age 1, 2, 4, and 7 years. Complete data from all pre-and postnatal questionnaires at age 1, 2, 4, and 7 were available for 3296 mother-child pairs.Results: We observed significant overlap of childhood allergies at 1, 2, 4, and 7 years. Maternal serum cotinine during pregnancy was associated with increased risk of wheezing in the children at age 1, 2, and 4 but disappeared at age 7. In contrast, maternal cotinine levels were inversely associated with the prevalence of eczema in children at age 7. We additionally observed that maternal pre-pregnancy BMI, not children's BMI, had a positive association with wheeze and an inverse association with eczema in 7-year-old children, respectively. We did not find any association of examined maternal factors and rhinoconjunctivitis.Conclusions: We demonstrated contrasting association of prenatal maternal smoking and high BMI with postnatal wheeze and eczema. For precise assessment of allergy-associated risk factors, we need to contrast risk factors for different allergic diseases since focusing solely on one allergic diseasemay result in misleading information on the role of different risk factors. (C) 2018 Elsevier B.V. All rights reserved.
• Associations between allergic symptoms and phosphate flame retardants in dust and their urinary metabolites among school children

  Atsuko Araki, Michiel Bastiaensen, Yu Ait Bamai, Nele Van den Eede, Toshio Kawai, Tazuru Tsuboi, Rahel Mesfin Ketema, Adrian Covaci, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 119 438 - 446 2018年10月 [査読有り][通常論文]
   

  Background: Phosphate flame retardants (PFRs) are ubiquitously detected in indoor environments. Despite increasing health concerns pertaining to PFR exposure, few epidemiological studies have examined PFR exposure and its effect on children's allergies.Objectives: To investigate the association between PFRs in house dust, their metabolites in urine, and symptoms of wheeze and allergies among school-aged children.Methods: A total of 128 elementary school-aged children were enrolled. House dust samples were collected from upper-surface objects. Urine samples were collected from the first morning void. Levels of 11 PFRs in dust and 14 PFR metabolites in urine were measured. Parent-reported symptoms of wheeze, rhinoconjunctivitis, and eczema were evaluated using the International Study of Asthma and Allergies in Childhood questionnaire. The odds ratios (ORs) of the Ln transformed PFR concentrations and categorical values were calculated using a logistic regression model adjusted for sex, grade, dampness index, annual house income, and creatinine level (for PFR metabolites only).Results: The prevalence rates of wheeze, rhinoconjunctivitis, and eczema were 22.7%, 36.7%, and 28.1%, respectively. A significant association between tris(1,3-dichloroisopropyl) phosphate (TDCIPP) in dust and eczema was observed: OR (95% confidence interval), 1.44 (1.13-1.82) (> limit of detection (LOD) vs < LOD). The ORs for rhinoconjunctivitis (OR = 5.01 [1.53-16.5]) and for at least one symptom of allergy (OR = 3.87 [1.22-12.3]) in the 4th quartile of Etris(2-chloro-isopropyl) phosphate (TCIPP) metabolites was significantly higher than those in the 1st quartile, with significant p-values for trend (P-trend) (0.013 and 0.024, respectively). A high OR of 2.86 (1.04-7.85) (> LOD vs < LOD) was found for hydroxy tris(2-butoxyethyl) phosphate (TBOEP)OH and eczema. OR of the 3rd tertile of bis (1,3-dichloro-2-propyl) phosphate (BDCIPP) was higher than the 1st tertile as a reference for at least one symptom (OR = 3.91 [1.25-12.3]), with a significant P-trend = 0.020.Conclusions: We found that TDCIPP in house dust, and metabolites of TDCIPP, TBOEP and TCIPP were associated with children's allergic symptoms. Despite some limitations of this study, these results indicate that children's exposure to PFR may impact their allergic symptoms.
• Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children's Health

  Machiko Minatoya, Sachiko Itoh, Keiko Yamazaki, Atsuko Araki, Chihiro Miyashita, Naomi Tamura, Jun Yamamoto, Yu Onoda, Kazuki Ogasawara, Toru Matsumura, Reiko Kishi

  ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE 23 1 43 - 43 2018年09月 [査読有り][通常論文]
   

  Background: Studies reported adverse behavioral development including internalizing and externalizing problems in association with prenatal exposure to bisphenol A (BPA) and phthalates; however, findings were not sufficient due to using different assessment tools and child ages among studies. This study aimed to examine associations between maternal serum levels of BPA and phthalate metabolites and behavioral problems at preschool age.Methods: The Strengths and Difficulties Questionnaire (SDQ) was used to assess behavioral problems at 5 years of age. BPA and phthalate metabolite levels in the first trimester maternal serum was determined by LC-MS/MS for 458 children. Variables used for adjustment were parental ages, maternal cotinine levels, family income during pregnancy, child sex, birth order, and age at SDQ completed.Results: The median concentrations of BPA, MnBP, MiBP, MEHP, and MECPP, primary and secondary metabolites of phthalates, were 0.062, 26.0, 7.0, 1.40, and 0.20 ng/ml, respectively. MECPP level was associated with increase conduct problem risk (OR = 2.78, 95% CI 1.36-5.68) overall and the association remained after child sex stratification, and odds ratios were increased with wider confidence interval (OR = 2.85, 95% CI 1.07-7.57 for boys, OR = 4.04, 95% CI 1.31-12.5 for girls, respectively). BPA, Sigma DBPm (MnBP + MiBP), and Sigma DEHPm (MEHP+MECPP) levels were not associated with any of the child behavioral problems.Conclusions: Our analyses found no significant association between BPA or summation of phthalate metabolite levels and any of the behavioral problems at 5 years of age but suggested possible association between MECPP levels and increased risk of conduct problems.
• Sex-related differences in the associations between maternal dioxin-like compounds and reproductive and steroid hormones in cord blood: The Hokkaido study

  Chihiro Miyashita, Atsuko Araki, Takahiko Mitsui, Sachiko Itoh, Houman Goudarzi, Seiko Sasaki, Jumboku Kajiwara, Tsuguhide Hori, Kazutoshi Cho, Kimihiko Moriya, Nobuo Shinohara, Katsuya Nonomura, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 117 175 - 185 2018年08月 [査読有り][通常論文]
   

  Background: Prenatal exposure to dioxin-like compounds (DLCs) irreversibly affects fetal reproductive and steroid hormone synthesis.Objective: This study aimed to assess the relationships between maternal DLCs and cord blood reproductive and steroid hormones.Methods: Participants in this study were pregnant women who enrolled in the Sapporo Cohort of the Hokkaido Study between 2002 and 2005. We quantified 29 DLCs during the 2nd and 3rd trimesters in maternal blood. Additionally, we measured the concentrations of progesterone, estradiol (E2), testosterone (T), androstenedione, dehydroepiandrosterone (DHEA), cortisol, cortisone, sex hormone-binding globulin ( SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, inhibin B, and insulin-like factor-3 (INSL3) in cord blood samples.Results: Data from 183 mother-child pairs were analyzed. We observed sex-dependent associations of DLCs on T/E2 ratios, DHEA, cortisol, cortisone, adrenal androgen/glucocorticoid (AA/GC: sum of DHEA and androstenedione)/(sum of cortisol and cortisone) ratios and SHBG. An increase in maternal DLCs related to decreased T/E2 ratios and SHBG and inhibin B levels, and increased AA/GC ratios and FSH and DHEA levels in male cord blood samples. However, an increase in maternal mono-ortho polychlorinated biphenyls related to increased cortisol, cortisone, and SHBG levels, and decreased DHEA levels and AA/GC ratios in female cord blood samples.Conclusions: Prenatal exposure to DLCs alters steroidogenesis and suppresses the secretion of inhibin B in male cord blood. Relationships between maternal DLCs and cord blood hormones differ between boys and girls. Further studies are required to clarify whether the effects of in utero exposure to DLCs on adrenal hormones extend into infancy and puberty.
• Relationship between adrenal steroid hormones in cord blood and birth weight: The Sapporo Cohort, Hokkaido Study on Environment and Children's Health

  Takahiko Mitsui, Atsuko Araki, Houman Goudarzi, Chihiro Miyashita, Sachiko Ito, Seiko Sasaki, Takeya Kitta, Kimihiko Moriya, Kazutoshi Cho, Keita Morioka, Reiko Kishi, Nobuo Shinohara, Masayuki Takeda, Katsuya Nonomura

  AMERICAN JOURNAL OF HUMAN BIOLOGY 30 4 e23127  2018年07月 [査読有り][通常論文]
   

  ObjectivesWe investigated the relationship between steroid hormone levels in cord blood and birth weight.MethodsAmong 514 participants in a prospective birth cohort study in Sapporo, the following hormone levels were measured in 294 stored cord blood samples from 135 males and 159 females: androstenedione, dehydroepiandrosterone (DHEA), cortisol, and cortisone. Birth weight information was obtained from medical records.ResultsAndrostenedione/DHEA was significantly higher in males than in females, while DHEA was significantly higher in females. Birth weight was significantly higher in males than in females. Regarding cortisone, androstenedione/DHEA, and cortisone/cortisol, a correlation was observed with birth weight in males but not in females.ConclusionsPrenatal adrenal steroids as well as converting enzymes such as 11 ss-hydrosteroid dehydrogenase type 2 and 3 ss-hydrosteroid dehydrogenase may have an impact on prenatal physical development.
• Occupational Exposure Limits for ethylidene norbornene, ethyleneimine, benomyl, and 2,3-epoxypropyl methacrylate, and classifications on carcinogenicity

  Atsuko Araki, Kenichi Azuma, Ginji Endo, Yoko Endo, Tetsuhito Fukushima, Kunio Hara, Hajime Hori, Seichi Horie, Hyogo Horiguchi, Masayoshi Ichiba, Gaku Ichihara, Masayuki Ikeda, Tatsuya Ishitake, Akiyoshi Ito, Yuki Ito, Satoko Iwasawa, Takeyasu Kakumu, Michihiro Kamijima, Kanae Karita, Takahiko Katoh, Toshio Kawai, Toshihiro Kawamoto, Shinji Kumagai, Yukinori Kusaka, Akiko Matsumoto, Muneyuki Miyagawa, Hiroyuki Miyauchi, Yasuo Morimoto, Kasuke Nagano, Hisao Naito, Tamie Nakajima, Makiko Nakano, Tetsuo Nomiyama, Hirokazu Okuda, Masayuki Okuda, Kazuyuki Omae, Haruhiko Sakurai, Kazuhiro Sato, Tomotaka Sobue, Yasushi Suwazono, Toru Takebayashi, Tatsuya Takeshita, Akito Takeuchi, Ayano Takeuchi, Masatoshi Tanaka, Shigeru Tanaka, Teruomi Tsukahara, Masashi Tsunoda, Susumu Ueno, Jun Ueyama, Yumi Umeda, Kenya Yamamoto, Yuko Yamano, Takenori Yamauchi, Eiji Yano

  JOURNAL OF OCCUPATIONAL HEALTH 60 4 333 - 335 2018年07月 [査読有り][通常論文]
  
• An epigenome-wide study of cord blood DNA methylations in relation to prenatal perfluoroalkyl substance exposure: The Hokkaido study

  Ryu Miura, Atsuko Araki, Chihiro Miyashita, Sumitaka Kobayashi, Sachiko Kobayashi, Shu-Li Wang, Chung-Hsing Chen, Kunio Miyake, Mayumi Ishizuka, Yusuke Iwasaki, Yoichi M. Ito, Takeo Kubota, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 115 21 - 28 2018年06月 [査読有り][通常論文]
   

  Background: Prenatal exposure to perfluoroalkyl substances (PFASs) influences fetal development and later in life.Objective: To investigate cord blood DNA methylation changes associated with prenatal exposure to PFASs.Methods: We assessed DNA methylation in cord blood samples from 190 mother-child pairs from the Sapporo cohort of the Hokkaido Study (discovery cohort) and from 37 mother-child pairs from the Taiwan Maternal and Infant Cohort Study (replication cohort) using the Illumina HumanMethylation 450 BeadChip. We examined the associations between methylation and PFAS levels in maternal serum using robust linear regression models and identified differentially methylated positions (DMPs) and regions (DMRs).Results: We found four DMPs with a false discovery rate below 0.05 in the discovery cohort. Among the top 20 DMPs ranked by the lowest P-values for perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) exposure, four DMPs showed the same direction of effect and P-value < 0.05 in the replication assay: cg16242615 mapped to ZBTB7A, cg21876869 located in the intergenic region (IGR) of USP2-AS1, cg00173435 mapped to TCP11L2, and cg18901140 located in IGR of NTN1. For DMRs, we found a region associated with PFOA exposure with family-wise error rate < 0.1 located in ZFP57, showing the same direction of effect in the replication cohort. Among the top five DMRs ranked by the lowest P-values that were associated with exposure to PFOS and PFOA, in addition to ZFP57, DMRs in the CYP2E1, SMAD3, SLC17A9, GFPT2, DUSP22, and TCERG1L genes showed the same direction of effect in the replication cohort.Conclusion: We suggest that prenatal exposure to PFASs may affect DNA methylation status at birth. Longitudinal studies are needed to examine whether methylation changes observed are associated with differential health outcomes.
• 母親の喫煙およびBMIと小児の喘鳴および湿疹との対照的な関連性(Contrasting associations of maternal smoking and BMI with wheeze and eczema in children)

  Goudarzi Houman, Konno Satoshi, Kimura Hirokazu, Araki Atsuko, Miyashita Chihiro, Itou Sachiko, Bamai Yu Ait, Kimura Hiroki, Shimizu Kaoruko, Suzuki Masaru, Ito Yoichi, Nishimura Masaharu, Kishi Reiko

  アレルギー 67 4-5 509 - 509 2018年05月
• 【住環境における健康リスク要因とそのマネジメント】 科学的エビデンスに基づく『新シックハウス症候群に関する相談と対策マニュアル(改訂新版)』を作成して

  岸 玲子, 吉野 博, 荒木 敦子, 西條 泰明, 東 賢一, 河合 俊夫, 大和 浩, 大澤 元毅, 柴田 英治, 田中 正敏, 増地 あゆみ, 湊屋 街子, アイツバマイ ゆふ

  日本衛生学雑誌 73 2 116 - 129 (一社)日本衛生学会 2018年05月 [査読有り][通常論文]
   

  科学的エビデンスに基づく「新シックハウス症候群に関する相談と対策マニュアル(改訂新版)」を作成したので紹介した。このマニュアルでは、近年震災や豪雨等の災害に伴って入居者が増えている仮設住宅の問題や、地球温暖化による熱中症と室内環境などの最近の問題、電磁過敏症に関する系統的レビューについて記載した。また、快適で健康な建物を実現する上で必要な基礎的な理論、設計の考え方と方法、建物の使い方、設備の調整の方法や扱い方についても解説した。
• Indoor environmental pollutants and their association with sick house syndrome among adults and children in elementary school

  Reiko Kishi, Rahel Mesfin Ketema, Yu Ait Bamai, Atsuko Araki, Toshio Kawai, Tazuru Tsuboi, Ikue Saito, Eiji Yoshioka, Takeshi Saito

  BUILDING AND ENVIRONMENT 136 293 - 301 2018年05月 [査読有り][通常論文]
   

  Sick house syndrome (SHS) derived from sick building syndrome (SBS) is used to describe symptoms that inhabitants experience due to indoor environment and personal factors, and children might be more susceptible to the effects of SHS than adults. However, there have been no comprehensive studies on effects of indoor pollutants exposure in relation to SHS. Thus, the aim of this study is to examine the association between indoor pollutants and SHS in children and adults who live in the same dwelling. This is a cross-sectional study on 184 elementary school children and 273 adults/adolescents in Sapporo, Japan. Indoor pollutants were measured in air and dust collected from 128 dwellings. Results showed children (20.6%) have higher prevalence of any symptoms than adults/adolescents (15.1%). Among SHS, mucosal symptoms were the most common in both children and adults/adolescents. Doctor diagnosed allergies, building age, dampness, and ventilation system showed significant association with prevalence of SHS. Formaldehyde, di(isobutyl) phthalate (DiBP), di(2-ethylhexyl) phthalate (DEHP), di(isononyl) phthalate (DiNP), endotoxin, and 13-glucan were detected in all dwellings. Any symptoms and mucosal symptoms were significantly associated with the exposure to 2-ethyl-1-hexanol (2E1H). Floor dust DiNP, multi-surface dust Tris(2-butoxyethyl) phosphate with mucosal symptoms and endotoxin with dermal symptoms were inversely associated in adults/adolescent. Multi-surface dust DiBP also showed inverse association with mucosal symptoms in children. 2E1H emission increased with dampness in the dwellings thus, eliminating dampness in the dwellings may reduce the emissions of 2E1H and the risk of SHS in residents.
• Determinants and Temporal Trends of Perfluoroalkyl Substances in Pregnant Women: The Hokkaido Study on Environment and Children's Health

  Meng-Shan Tsai, Chihiro Miyashita, Atsuko Araki, Sachiko Itoh, Yu Ait Bamai, Houman Goudarzi, Emiko Okada, Ikuko Kashino, Hideyuki Matsuura, Reiko Kishi

  INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 15 5 2018年05月 [査読有り][通常論文]
   

  Perfluoroalkyl substances (PFAS) are persistent bio-accumulative chemicals that impact the health of pregnant women and their children. PFAS derive from environmental and consumer products, which depend on human lifestyle, socioeconomic characteristics, and time variation. Here, we aimed to explore the temporal trends of PFAS in pregnant women and the characteristics related to maternal PFAS concentration. Our study is part of the Hokkaido Study on Environment and Children's Health, the Hokkaido large-scale cohort that recruited pregnant women between 2003 and 2011. Blood samples were acquired from pregnant women during the third trimester to measure PFAS and cotinine concentrations. Maternal basic information was collected with a baseline structured questionnaire. Eleven PFAS were measured from 2123 samples with ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. Eight PFAS were above 80% detection rate and were included in the final analysis. We used multivariable linear regression to analyze the association of pregnant women characteristics with the levels of eight PFAS. The temporal trend of PFAS was observed in two periods (August 2003 to January 2006 and February 2006 to July 2012). The concentration of perfluorooctane sulfonate (PFOS) significantly decreased from August 2003 to January 2006 and from February 2006 to July 2012. The concentrations of perfluorododecanoic acid (PFDoDA), perfluoroundecanoic acid (PFUnDA), and perfluorotridecanoic acid (PFTrDA) increased significantly between August 2003 and January 2006, whereas they decreased significantly between February 2006 and July 2012. Women with pre-pregnancy body mass index (BMI) >25 kg/m(2) had lower PFUnDA, PFDoDA, and PFTrDA levels than did those with normal BMI (18.5-24.9 kg/m(2)). Pregnant women, who were active smokers (cotinine > 11.49 ng/mL), had higher PFOS than the non-smokers (cotinine < 0.22 ng/mL). Lower levels of PFHxS, PFOS, PFOA, PFNA, and PFDA were observed in women, who had given birth to more than one child. There were also significant positive associations between PFAS levels and annual income or maternal education. PFAS levels varied in women with higher pre-pregnancy BMI, active smoking status, higher education level and annual income. The causes of the individual PFAS differences should be explored in an independent study.
• Association between DNA methylation in cord blood and maternal smoking: The Hokkaido Study on Environment and Children's Health

  Kunio Miyake, Akio Kawaguchi, Ryu Miura, Sachiko Kobayashi, Nguyen Quoc Vuong Tran, Sumitaka Kobayashi, Chihiro Miyashita, Atsuko Araki, Takeo Kubota, Zentaro Yamagata, Reiko Kishi

  SCIENTIFIC REPORTS 8 1 5654  2018年04月 [査読有り][通常論文]
   

  Maternal smoking is reported to cause adverse effects on the health of the unborn child, the underlying mechanism for which is thought to involve alterations in DNA methylation. We examined the effects of maternal smoking on DNA methylation in cord blood, in 247 mother-infant pairs in the Sapporo cohort of the Hokkaido Study, using the Infinium HumanMethylation 450K BeadChip. We first identified differentially methylated CpG sites with a false discovery rate (FDR) of <0.05 and the magnitude of DNA methylation changes (vertical bar beta vertical bar >0.02) from the pairwise comparisons of never-smokers (Ne-S), sustained-smokers (Su-S), and stopped-smokers (St-S). Subsequently, secondary comparisons between St-S and Su-S revealed nine common sites that mapped to ACSM3, AHRR, CYP1A1, GFI1, SHANK2, TRIM36, and the intergenic region between ANKRD9 and RCOR1 in Ne-S vs. Su-S, and one common CpG site mapping to EVC2 in Ne-S vs. St-S. Further, we verified these CpG sites and examined neighbouring sites using bisulfite next-generation sequencing, except for AHRR cg21161138. These changes in DNA methylation implicate the effect of smoking cessation. Our findings add to the current knowledge of the association between DNA methylation and maternal smoking and suggest future studies for clarifying this relationship in disease development.
• Effects of prenatal di(2-ethylhexyl) phthalate exposure on childhood allergies and infectious diseases: The Hokkaido Study on Environment and Children's Health

  Yu Ait Bamai, Chihiro Miyashita, Atsuko Araki, Tamie Nakajima, Seiko Sasaki, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 618 1408 - 1415 2018年03月 [査読有り][通常論文]
   

  Phthalates are widely used in consumer products, and experimental studies suggest that exposure to phthalates increase the risk of allergies. However, epidemiologic evidence on the associations between prenatal phthalate exposure and allergies/infectious diseases and cord blood immunoglobulin E (IgE) levels is limited. This study aimed to evaluate the associations between maternal mono(2-ethylhexyl) phthalate (MEHP) levels and cord blood IgE levels at birth (n = 127), as well as the risk of allergies/infectious diseases in participants up to 7 years of age; the participants were 1.5 (n = 248), 3.5 (n = 222), 7 (n = 184) years of age. Maternal blood MEHP level in the second trimester was measured using gas chromatography-mass spectrometry. Participant characteristics were obtained from the medical birth records and self-administered questionnaires during pregnancy and after delivery. Wheeze and eczema were defined according to the Japanese version of the International Study of Asthma and Allergies in Childhood and the American Thoracic Society-Division of Lung Diseases questionnaire, respectively. Infectious diseases were defined using questionnaires for each specified age. To evaluate the associations between maternal MEHP and allergies or infectious diseases, we used logistic regression analysis and generalized estimating equations analysis. Maternal MEHP levels were negatively associated with cord blood IgE levels and increased risks of allergies and infectious diseases up to 7 years of age. This is the first study to investigate the effects of prenatal MEHP exposure on IgE levels at birth and allergies/infectious diseases up to 7 years of age. Further epidemiological studies should focus on other phthalate metabolites and their health effects on larger populations. (C) 2017 Elsevier B.V. All rights reserved.
• Different Risk Factors for Very Low Birth Weight, Term-Small-for-Gestational-Age, or Preterm Birth in Japan

  Naomi Tamura, Tomoyuki Hanaoka, Kumiko Ito, Atsuko Araki, Chihiro Miyashita, Sachiko Ito, Hisanori Minakami, Kazutoshi Cho, Toshiaki Endo, Kazuo Sengoku, Katsuhiko Ogasawara, Reiko Kishi

  INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 15 2 2018年02月 [査読有り][通常論文]
   

  From 1985 to 2013, the mean birth weight of infants in Japan decreased from 3120 g to 3000 g, and the low-birth-weight rate among live births increased from 6.3% to 9.6%. No prospective study has elucidated the risk factors for poor fetal growth and preterm birth in recent Japanese parents, such as increased parental age, maternal body figure, assisted reproductive technology (ART), and socioeconomic status. Participants were mother-infant pairs (n = 18,059) enrolled in a prospective birth cohort in Hokkaido, Japan from 2002 to 2013. Parental characteristics were obtained via self-reported questionnaires during pregnancy. Medical records helped identify very-low-birth-weight (VLBW; < 1500 g), term-small-for-gestational-age (term-SGA), and preterm-birth (PTB; < 37 weeks) infants. We calculated relative risks (RRs) for PTB, VLBW, and term-SGA birth based on parental characteristics. The prevalence of PTB, VLBW, and term-SGA was 4.5%, 0.4%, and 6.5%, respectively. Aged parents and ART were risk factors for PTB and VLBW. Maternal alcohol drinking during pregnancy increased the risk; a parental educational level of >= 16 years reduced risk of term-SGA. Maternal pre-pregnancy BMI of < 18.5 kg/m(2) increased the risk of PTB and term-SGA. The RR for low BMI was highest among mothers who have low educational level. Among various factors, appropriate nutritional education to maintain normal BMI is important to prevent PTB and term-SGA in Japan.
• Association between prenatal bisphenol A and phthalate exposures and fetal metabolic related biomarkers: The Hokkaido study on Environment and Children's Health

  Machiko Minatoya, Atsuko Araki, Chihiro Miyashita, Yu Ait Bamai, Sachiko Itoh, Jun Yamamoto, Yu Onoda, Kazuki Ogasawara, Toru Matsumura, Reiko Kishi

  ENVIRONMENTAL RESEARCH 161 505 - 511 2018年02月 [査読有り][通常論文]
   

  Bisphenol A and phthalates are widely detected in human urine, blood, breast milk, and amniotic fluid. Both bisphenol A and phthalates have been suggested as playing a role in obesity epidemics. Exposure to these chemicals during fetal development, and its consequences should be concerning because they can cross the placenta. Thus, this study aimed to assess the association between prenatal exposure to bisphenol A and phthalates, and cord blood metabolic-related biomarkers. Maternal serum was used during the first trimester, to determine prenatal exposure to bisphenol A and phthalates. Levels of metabolic-related biomarkers in the cord blood were also determined. Linear regression models were applied to the 365 participants with both, exposure and biomarker assessments, adjusted for maternal age, pre-pregnancy body mass index, parity, education, and sex of the child. The level of bisphenol A was negatively associated with the leptin level (beta = -0.06, 95% confidence interval [CI]: -0.11, -0.01), but was positively associated with the high-molecular-weight adiponectin level, with marginal significance (beta = 0.03, 95%CI: 0.00, 0.06). The mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-(2-ethylhexyl) phthalate (MEHP), and summation of MEHP and MECPP to represent DEHP exposure (Sigma DEHPm) levels were inversely associated with the leptin levels (beta = -0.14, 95%CI: -0.27, -0.01; beta = -0.12, 95%CI: -0.24, 0.00 with marginal significance; beta = 0.08, 95%CI: -0.14, 0.03; and beta = -0.09, 95%CI: -0.16, -0.03, respectively). The present study provided some evidence that prenatal exposure to bisphenol A and certain phthalates may modify fetal adiponectin and leptin levels.
• Birth cohorts in Asia: The importance, advantages, and disadvantages of different-sized cohorts

  Reiko Kishi, Atsuko Araki, Machiko Minatoya, Sachiko Itoh, Houman Goudarzi, Chihiro Miyashita

  SCIENCE OF THE TOTAL ENVIRONMENT 615 1143 - 1154 2018年02月 [査読有り][通常論文]
   

  Asia contains half of the world's children, and the countries of Asia are the most rapidly industrializing nations on the globe. Environmental threats to the health of children in Asia are myriad. Several birth cohorts were started in Asia in early 2000, and currently more than 30 cohorts in 13 countries have been established for study. Cohorts can contain from approximately 100-200 to 20,000-30,000 participants. Furthermore, national cohorts targeting over 100,000 participants have been launched in Japan and Korea. The aim of this manuscript is to discuss the importance of Asian cohorts, and the advantages and disadvantages of different-sized cohorts. As for case, one small-sized (n = 514) cohort indicate that even relatively low level exposure to dioxin in utero could alter birth size, neurodevelopment, and immune and hormonal functions. Several Asian cohorts focus prenatal exposure to perfluoroalkyo substances and reported associations with birth size, thyroid hormone levels, allergies and neurodevelopment. Inconsistent findings may possibly be explained by the differences in exposure levels and target chemicals, and by possible statistical errors. In a smaller cohort, novel hypotheses or preliminary examinations are more easily verifiable. In larger cohorts, the etiology of rare diseases, such as birth defects, can be analyzed; however, they require a large cost and significant human resources. Therefore, conducting studies in only one large cohort may not always be the best strategy. International collaborations, such as the Birth Cohort Consortium of Asia, would cover the inherent limitation of sample size in addition to heterogeneity of exposure, ethnicity, and socioeconomic conditions. (C) 2017 Elsevier B.V. All rights reserved.
• Association of prenatal exposure to PCDD/Fs and PCBs with maternal and infant thyroid hormones: The Hokkaido Study on Environment and Children's Health

  Toshiaki Baba, Sachiko Ito, Motoyuki Yuasa, Eiji Yoshioka, Chihiro Miyashita, Atsuko Araki, Seiko Sasaki, Sumitaka Kobayashi, Jumboku Kajiwara, Tsuguhide Hori, Shizue Kato, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 615 1239 - 1246 2018年02月 [査読有り][通常論文]
   

  Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) are persistent organic pollutants that are universally detected. Some congeners of PCDDs, PCDFs or PCBs have dioxin-like toxicity, whereas non-dioxin-like PCBs are considered to have different toxicity. Reports of the relationships between prenatal exposure to PCDDs, PCDFs or PCBs and thyroid homeostasis in pregnant women and infants have been inconsistent. The aim of this study was to investigate the effect of maternal serum PCDD/F or PCB levels on maternal and neonatal thyroid hormone (TH) levels in a prospective cohort.Of the 514 subjects in the prospective cohort, 386 mothers and 410 infants were included for analysis. Fifteen dioxins and seventy PCBs in maternal blood collected between 23 and 41 weeks of gestation were measured using high-resolution gas chromatography and high-resolution mass spectrometry. Blood samples to measure thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were obtained from mothers at an early gestational stage (median ten weeks), and from infants between four and seven days of age, respectively. Multiple linear regression analysis was conducted.Median concentration of total PCBs, PCB 153 were 104,700, and 20,500 pg/g lipid, respectively. Median total dioxin-TEQ was 13.8 pg/g lipid. Total dioxin-TEQ, coplanar PCBs were positively associated with neonatal FT4 (beta = 0.224, 0.206, respectively). The association was stronger in boys (beta = 0.299, 0.282, respectively). Several PCDD/F and PCB isomers were also positively associated with neonatal FT4. Total PCBs or non-dioxinlike PCBs were not associated with any maternal or neonatal THs. No DLC grouping or congeners were associated with neonatal TSH. Non-ortho PCBs were positively associated with maternal FT4. Three PCB congeners had significant positive association(s) with maternal THs.In conclusion, the results of our study suggest that perinatal exposure to background-level DLCs increases neonatal FT4, especially in boys. (C) 2017 Elsevier B.V. All rights reserved.
• Association between Fetal Adipokines and Child Behavioral Problems at Preschool Age: The Hokkaido Study on Environment and Children's Health

  Machiko Minatoya, Sachiko Itoh, Atsuko Araki, Naomi Tamura, Keiko Yamazaki, Chihiro Miyashita, Reiko Kishi

  INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 15 1 2018年01月 [査読有り][通常論文]
   

  Studies have suggested associations between maternal obesity and mental health problems of their children. However, the underlying mechanism is largely unknown. A possible mechanism can be via inflammatory states and the other possible mechanism is metabolic hormone-induced programming. Cross-talk between adipokines, including inflammatory cytokines and metabolic hormones secreted from adipose tissue and the central nervous system needs to be further investigated to elucidate the mechanism. Thus, the aim of this study was to investigate the association between fetal adipokine levels and child behavioral problems at preschool age. Cord blood adiponectin, leptin, tumor necrosis factor- (TNF-) and interleukin 6 (IL-6) levels were measured and child behavioral problems were assessed using the Strengths and Difficulties Questionnaire at preschool age. Logistic regression models adjusted by related maternal factors were performed to examine the association between cord blood adipokines and child behavioral problems. Three hundred and sixty-one children were included in the final analysis. A significant association between decreased hyperactivity/inattention and increased leptin was found (OR = 0.22, 95% CI: 0.06-0.89). Cord blood adiponectin, TNF- and IL-6 levels were not associated with child behavioral problems. Our findings suggested that cord blood adipokines, particularly, leptin level, may be a predictor of hyperactivity/inattention problems at preschool age.
• [New Scientific Evidence-based Public Health Guidelines and Practical Manual for Prevention of Sick House Syndrome].

  Reiko Kishi, Hiroshi Yoshino, Atsuko Araki, Yasuaki Saijo, Kenichi Azuma, Toshio Kawai, Hiroshi Yamato, Haruki Osawa, Eiji Shibata, Masatoshi Tanaka, Ayumi Masuchi, Machiko Minatoya, Yu Ait Bamai

  Nihon eiseigaku zasshi. Japanese journal of hygiene 73 2 116 - 129 2018年 [査読有り][通常論文]
   

  Recently, we have published a book containing evidence-based public health guidelines and a practical manual for the prevention of sick house syndrome. The manual is available through the homepage of the Ministry of Health, Labour and Welfare (http://www.mhlw.go.jp/file/06-Seisakujouhou-11130500-Shokuhinanzenbu/0000155147.pdf). It is an almost completely revised version of the 2009 version. The coauthors are 13 specialists in environmental epidemiology, exposure sciences, architecture, and risk communication. Since the 1970s, health problems caused by indoor chemicals, biological pollution, poor temperature control, humidity, and others in office buildings have been recognized as sick building syndrome (SBS) in Western countries, but in Japan it was not until the 1990s that people living in new or renovated homes started to describe a variety of nonspecific subjective symptoms such as eye, nose, and throat irritation, headache, and general fatigue. These symptoms resembled SBS and were designated "sick house syndrome (SHS)." To determine the strategy for prevention of SHS, we conducted a nationwide epidemiological study in six cities from 2003-2013 by randomly sampling 5,709 newly built houses. As a result 1,479 residents in 425 households agreed to environmental monitoring for indoor aldehydes and volatile organic compounds (VOCs). After adjustment for possible risk factors, some VOCs and formaldehyde were dose-dependently shown to be significant risk factors. We also studied the dampness of the houses, fungi, allergies, and others. This book is fully based on the scientific evidence collected through these studies and other newly obtained information, especially from the aspect of architectural engineering. In addition to SHS, we included chapters on recent information about "multi-chemical sensitivity."
• House Dust and Its Adverse Health Effects

  Araki, A., Ait Bamai, Y., Ketema, R.M., Kishi, R.

  Nihon eiseigaku zasshi. Japanese journal of hygiene 73 2 130 - 137 2018年 [査読有り][通常論文]
  
• [Importance of Two Birth Cohorts (n=20,926 and n=514): 15 Years' Experience of the Hokkaido Study on Environment and Children's Health: Malformation, Development and Allergy].

  Reiko Kishi, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Machiko Minatoya, Sumitaka Kobayashi, Keiko Yamazaki, Yu Ait Bamai, Ryu Miura, Naomi Tamura

  Nihon eiseigaku zasshi. Japanese journal of hygiene 73 2 164 - 177 2018年 [査読有り][通常論文]
   

  Since "Our Stolen Future" by Theo Colborn was published in 1996, global interest on the impact of chemical substances, such as the endocrine-disrupting action of chemicals, has increased. In Japan, "The Hokkaido Study on Environment and Children's Health: Malformation, Development and Allergy" was launched in 2001. It was a model of Japan Environment and Children's Study of the Ministry of the Environment. In a large-scale, Hokkaido cohort, we obtained the consent of 20,926 mothers at the organogenesis stage with the cooperation of 37 obstetrics clinics in Hokkaido. We tracked the effects of endocrine disruptors on developmental disorders. In a small-scale Sapporo cohort, we observed in detail the neuropsychiatric development of children with the consent of 514 mothers in their late pregnancy. We examined how prenatal exposure to low concentrations of environmental chemicals affect the development of organs and the postnatal development of children. Maternal exposure to POPs, such as PCB/dioxins and perfluorinated alkyl substances, has affected not only children's birth size, thyroid functions, and sex hormone levels, but also postnatal neurodevelopment, infection, and allergy among others. The associations of short-half-life substances, such as DEHP and BPA, with obesity, ASD, and ADHD have been investigated. Gene-environment interactions have been found for smoking, caffeine, folic acid, and PCB/dioxin. In 2015, our center was officially designated as the WHO Collaborating Centre for Environmental Health and Prevention of Chemical Hazards, and we continue to the contribute to the global perspectives of child health.
• Prenatal exposure to dioxin-like compounds is associated with decreased cord blood IgE and increased risk of wheezing in children aged up to 7 years: The Hokkaido study

  Chihiro Miyashita, Yu Ait Bamai, Atsuko Araki, Sachiko Itoh, Machiko Minatoya, Asumitaka Kobayashi, Jumboku Kajiwara, Tsuguhide Hori, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 610 191 - 199 2018年01月 [査読有り][通常論文]
   

  Introduction: In utero exposure to dioxin-like compounds (DLCs) may cause imbalance of immune development in early infancy. However, there are few epidemiological studies into the effects of in utero exposure to DLCs on allergies and infections during childhood. This study evaluates associations between concentrations of maternal DLCs and cord blood immunoglobulin (Ig) E, as well as allergies and infections during childhood.Method: We recruited 514 pregnant women in a maternity hospital in Sapporo, Japan, and measured concentrations of DLCs in 426 maternal blood samples using high-resolution gas chromatography/high-resolution mass spectrometry. We examined the relationship between concentrations of maternal DLCs and cord blood IgE at birth (n = 239), as well as for allergies and infections in children at 3.5 (n = 327) and 7 (n = 264) years, using regression analysis adjusted for confounding variables.Results: We found a positive association between maternal DLC concentrations and frequency of wheezing in children aged up to 7 years [odds ratio (OR); 7.81 (95% confidence interval (CI), 1.42 to 42.9)]. At 3.5 years, boys showed inverse associations between maternal DLC concentrations and cord blood IgE [partial regression coefficient; -0.87 (95% CI), -1.68 to -0.06], and frequency of wheezing [OR; 0.03 (95% CI), 0.00 to 0.94] but girls did not.Discussion: As one reason for the significant association observed at 7 but absent at 3.5 years, we suggest that allergic symptoms are more obvious in older children due to matured immune function.Conclusion: The findings suggest that prenatal exposure to DLCs may modify offspring immune responses and result in increased risk of allergy among children of school age. (C) 2017 Elsevier B.V. All rights reserved.
• Prenatal organochlorine pesticide exposure and the disruption of steroids and reproductive hormones in cord blood: The Hokkaido study

  Atsuko Araki, Chihiro Miyashita, Takahiko Mitsui, Houman Goudarzi, Futoshi Mizutani, Youichi Chisaki, Sachiko Itoh, Seiko Sasaki, Kazutoshi Cho, Kimihiko Moriya, Nobuo Shinohara, Katsuya Nonomura, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 110 1 - 13 2018年01月 [査読有り][通常論文]
   

  Certain organochlorine pesticides (OCPs) are designated as persistent organic pollutants and are regulated in many countries. The effects of OCPs on pediatric endocrinology are a concern; however, only limited data exist from human studies on maternal OCP exposure and its effects on infants' hormone levels. This study was conducted as part of the Hokkaido Study Sapporo Cohort, a prospective birth cohort study in Japan. Participants included 514 women who enrolled at 23-35 weeks of gestation between 2002 and 2005; maternal blood samples were collected in late pregnancy, and 29 OCPs were measured. Reproductive and steroid hormone levels in cord blood were also determined. Characteristics of mothers and their infants were obtained from self-administered questionnaires and medical records. Ultimately, 232 samples with both OCP and hormone data were analyzed. Fifteen of 29 investigated OCPs were detected in over 80% of the samples, with p, p'-dichlorodiphenyldi-chloroethylene showing the highest concentration (median value: 619 pg/g-wet). The association between OCPs and sex hormone levels varied by sex. Linear regression models after sex stratification showed that chlordanes, cis-hexachlorobenzene, heptachlor epoxide, Mirex, and toxaphenes in maternal blood were inversely associated with testosterone, cortisol, cortisone, sex hormone-binding globin, prolactin, and androstenedione-dehydroepiandrosterone (DHEA) and testosterone-androstenediones ratios among boys. Furthermore, these OCPs were positively correlated with DHEA, follicle stimulating hormone (FSH), and adrenal androgen-glucocorticoid and FSH-inhibin B ratios among boys. In categorical quartile models, testosterone and DHEA were inversely and positively associated with OCPs, respectively. Estradiol-testosterone and adrenal androgen-glucocorticoid ratios tended to increase with increasing OCP concentrations in the higher quartile, while the testosterone-androstenedione ratio tended to decrease. Sex hormone-binding globulin and prolactin showed an inverse association with OCPs. Among girls, the linear regression model showed that only p, p'-dichlorodiphenyltrichloroethane was inversely associated with the level of DHEA and the adrenal androgen-glucocorticoid ratio, but was positively associated with cortisone levels. However, no associations were observed using the quartile categorical model. These results suggest that prenatal exposure to OCPs disrupt reproductive hormones of fetuses in utero among boys, even at relatively low levels.
• Prevalence and Risk of Birth Defects Observed in a Prospective Cohort Study: The Hokkaido Study on Environment and Children's Health

  Tomoyuki Hanaoka, Naomi Tamura, Kumiko Ito, Seiko Sasaki, Atsuko Araki, Tamiko Ikeno, Chihiro Miyashita, Sachiko Ito, Hisanori Minakami, Kazutoshi Cho, Toshiaki Endo, Tsuyoshi Baba, Toshinobu Miyamoto, Kazuo Sengoku, Reiko Kishi

  JOURNAL OF EPIDEMIOLOGY 28 3 125 - 132 2018年 [査読有り][通常論文]
   

  Background: Prevalence rates of all anomalies classified as birth defects, including those identified before the 22nd gestational week, are limited in published reports, including those from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). In our birth cohort study, we collected the data for all birth defects after 12 weeks of gestation.Methods: Subjects in this study comprised 19,244 pregnant women who visited one of 37 associated hospitals in the Hokkaido Prefecture from 2003 through 2012, and completed follow-up. All birth defects after 12 weeks of gestation, including 55 marker anomalies associated with environmental chemical exposures, were recorded. We examined parental risk factors for birth defects and the association between birth defects and risk of growth retardation.Results: Prevalence of all birth defects was 18.9/1,000 births. The proportion of patients with birth defects delivered between 12 and 21 weeks of gestation was approximately one-tenth of all patients with birth defects. Among those with congenital malformation of the nerve system, 39% were delivered before 22 weeks of gestation. All patients with anencephaly and encephalocele were delivered before 22 weeks of gestation. We observed different patterns of parental risk factors between birth defect cases included in ISBDSR and cases not included. Cases included in ISBDSR were associated with an increased risk of preterm birth. Cases not included in ISBDSR were associated with an increased risk of being small for gestational age at term.Conclusions: Data from our study complemented the data from ICBDSR. We recommend that birth defects not included in ICBDSR also be analyzed to elucidate the etiology of birth defects.
• [Environmental Chemical Exposure and Its Effects on Infants' Reproductive Hormones].

  Atsuko Araki, Sachiko Itoh, Chihiro Miyashita, Machiko Minatoya, Reiko Kishi

  Nihon eiseigaku zasshi. Japanese journal of hygiene 73 3 313 - 321 2018年 [査読有り][通常論文]
   

  In recent years, the birthrate has been continuously declining in Japan. The main causes of the decline are social factors. On the other hand, there is increasing evidence that many environmental chemicals show endocrine disrupting properties. Thus, we hypothesized that exposure to these chemicals would also be a causal for the fertility crisis. In this review, we examined current evidence that focused on environmental chemical exposure in utero and its association with reproductive hormones in children. We have included the findings from a prospective birth cohorts, the Hokkaido Study on Environment and Children's Health Sapporo cohort. According to the literature, environmental chemical levels in utero, such as polychlorinated biphenyl, dioxins, perfluorinated chemical substances, phthalates, and bisphenol A were somewhat associated with the levels of reproductive hormones, such as testosterone, estradiol, progesterone, inhibin B, and insulin-like factor-3 in cord blood, in early childhood and adolescence. The literature also suggests the association between exposure to these chemicals and brain-sexual differentiation or the anogenital distance, which suggests the disruption of androgen shower during the developmental stage in the fetal period. There are still knowledge gaps on whether these hormones at an early stage affect the pubertal development and reproductive functions in later life. In addition, alternative chemicals are produced after banning one type. The health effects of alternative chemicals should be evaluated. Effects of exposure to a mixture of the chemicals should also be examined in future studies. In conclusion, the prevention of environmental chemical hazards in relation to human reproductive function is important. It would be one of the countermeasures to the falling birthrate caused by fertility issues.
• Association of prenatal passive smoking and metabolic gene polymorphisms with child growth from birth to 3 years of age in the Hokkaido Birth Cohort Study on Environment and Children's Health

  Titilola Serifat Braimoh, Sumitaka Kobayashi, Fumihiro Sata, Seiko Sasaki, Houman Goudarzi, Thamar Ayo Yila, Atsuko Araki, Chihiro Miyashita, Hisanori Minakami, Tsuyoshi Baba, Kazuo Sengoku, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 605 995 - 1002 2017年12月 [査読有り][通常論文]
   

  Although the effects of prenatal passive smoking on birth weight have been reported, the effects of metabolic gene polymorphisms on passive smoking have not been studied. Therefore, we investigated the effects of maternal passive smoking and metabolic gene polymorphisms on child growth up to 3 years of age using cotinine as a biomarker. We included 1356 Japanese participants in a prospective cohort between 2003 and 2007 (cotinine levels at the third trimester <= 0.21 ng/mL and 0.22 to 11.48 ng/mL for non-passive and passive smokers, respectively), and measured child outcomes such as weight, length, head circumference, and Kaup index. Additionally, we analyzed cytochrome P450 1A1 (CYP1A1), epoxide hydrolase 1 (EPHX1), and two N-acetyltransferase 2 (NAT2) genotypes using real-time polymerase chain reaction methods. Associations were investigated using multiple regression models. Kaup index gain from birth up to 3 years of age was significantly smaller in children born to passive smokers than in those born to non-passive smokers (-0.34 kg/m(2); 95% confidence interval: -0.67, -0.01). Maternal CYP1A1 genotype was not associated with prenatal passive smoking and Kaup index gain, but was significantly associated with prenatal passive smoking and head circumference gain from birth up to 3 years of age (-0.75 cm; 95% confidence interval:-1.39, -0.12). Thus, this study suggests that prenatal passive smoking may have potent effects on postnatal growth frombirth up to 3 years of age. Moreover, children with maternal CYP1A1 genotype may be more susceptible to the effects of prenatal passive smoking. (C) 2017 Elsevier B.V. All rights reserved.
• Cord blood BPA level and child neurodevelopment and behavioral problems: The Hokkaido Study on Environment and Children's Health

  Machiko Minatoya, Atsuko Araki, Sonomi Nakajima, Seiko Sasaki, Chihiro Miyashita, Keiko Yamazaki, Jun Yamamoto, Toru Matumura, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 607 351 - 356 2017年12月 [査読有り][通常論文]
  
• Modification of adverse health effects of maternal active and passive smoking by genetic susceptibility: Dose-dependent association of plasma cotinine with infant birth size among Japanese women-The Hokkaido Study

  Sumitaka Kobayashi, Fumihiro Sata, Seiko Sasaki, Titilola Serifat Braimoh, Atsuko Araki, Chihiro Miyashita, Houman Goudarzi, Sachiko Kobayashi, Reiko Kishi

  REPRODUCTIVE TOXICOLOGY 74 94 - 103 2017年12月 [査読有り][通常論文]
   

  Objectives: We aimed to assess the individual dose-response effects of eight maternal polymorphisms encoding polycyclic aromatic hydrocarbon-metabolizing and DNA-repair genes on prenatal cotinine levels according to infant birth size.Methods: In total, 3263 Japanese pregnant women were assigned to five groups based on plasma cotinine levels during the 8th month of pregnancy, as measured using ELISA (cut-offs: 0.21, 0.55, 11.48, and 101.67 ng/mL). Analyses were performed using multiple linear regression.Results: Birth weight reduction showed a dose-dependent relationship with prenatal cotinine levels (P for trend < 0.001). When considering the specific aromatic hydrocarbon receptor (AHR) (G >A, Arg554Lys; db SNP ID: rs2066853) and X-ray cross-complementing gene 1 (XRCC1) (C> T, Arg194Trp, rs1799782) genotypes, a larger birth weight reduction was noted among infants born to mothers with the highest cotinine level.Conclusion: Infants born to women with specific AHR and XRCC1 genotypes may have higher genetic risks for birth weight reduction. (C) 2017 Elsevier Inc. All rights reserved.
• Cord Blood Bisphenol A Levels and Reproductive and Thyroid Hormone Levels of Neonates The Hokkaido Study on Environment and Children's Health

  Machiko Minatoya, Seiko Sasaki, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Jun Yamamoto, Toru Matsumura, Takahiko Mitsui, Kimihiko Moriya, Kazutoshi Cho, Keita Morioka, Hisanori Minakami, Nobuo Shinohara, Reiko Kishi

  EPIDEMIOLOGY 28 S3 - S9 2017年10月 [査読有り][通常論文]
   

  Background: Bisphenol A (BPA) is widely used and BPA exposure is nearly ubiquitous in developed countries. While animal studies have indicated adverse health effects of prenatal BPA exposure including reproductive dysfunction and thyroid function disruption possibly in a sex-specific manner, findings from epidemiologic studies have not been enough to prove these adverse effects. Given very limited research on human, the aim of this study was to investigate associations between cord blood BPA levels and reproductive and thyroid hormone levels of neonates and whether associations differed by neonate sex.Methods: The study population included 514 participants of the Hokkaido study recruited from 2002 to 2005 at one hospital in Sapporo, Japan. The BPA level in cord blood was determined by ID-LC/MS/MS, and the limit of quantification was 0.040 ng/ml. We measured nine types of reproductive hormone levels in cord blood, and thyroid hormone levels were obtained from neonate mass screening test data. There were 283 subjects, who had both BPA and hormone levels measurements, included for the final analyses.Results: The geometric mean of cord blood BPA was 0.051 ng/ml. After adjustment, BPA level was negatively associated with prolactin (PRL) (beta = -0.38). There was an interaction between infant sex and BPA levels on PRL; a weak negative association was found in boys (beta = -0.12), whereas a weak positive association was found in girls (beta = 0.14). BPA level showed weak positive association with testosterone, estradiol, and progesterone levels in boys. No association was found between BPA and thyroid hormone levels.Conclusions: Our findings suggested that fetal BPA levels might be associated with changes in certain reproductive hormone levels of neonates in a sex-specific manner, though further investigations are necessary.
• Gender-specific association of exposure to non-dioxin-like polychlorinated biphenyls during pregnancy with methylation levels of H19 and long interspersed nuclear element-1 in cord blood in the Hokkaido study

  Sumitaka Kobayashi, Fumihiro Sata, Chihiro Miyashita, Ryu Miura, Kaoru Azumi, Sachiko Kobayashi, Houman Goudarzi, Atsuko Araki, Mayumi Ishizuka, Takashi Todaka, Jumboku Kajiwara, Tsuguhide Hori, Reiko Kishi

  TOXICOLOGY 390 135 - 145 2017年09月 [査読有り][通常論文]
   

  Background: Associations between prenatal exposure to polychlorinated biphenyls (PCBs) and reduced birth size, and between DNA methylation of insulin-like growth factor-2 (IGF-2), HI 9 locus, and long interspersed nuclear element-1 (LINE-1) and reduced birth-size are well established. To date, however, studies on the associations between prenatal exposure to PCBs and alterations in methylation of IGF-2, H19, and LINE-1 are lacking. Thus, in this study, we examined these associations with infant-gender stratification.Methods: We performed a prospective birth cohort study using the Sapporo cohort from the previously described Hokkaido Birth Cohort Study on Environment and Children's Health conducted between 2002 and 2005 in Japan. In the final 169 study participants included in this study, we measured the concentrations of various non dioxin-like PCBs in maternal blood during pregnancy using high-resolution gas chromatography/high-resolution mass spectrometry. IGF-2, H19 and LINE-1 methylation levels in cord blood were measured using the bisulfite pyrosequencing methods Finally, we assessed the associations between prenatal exposure to various PCBs and the gene methylation levels using multiple regression models stratified by infant gender.Results: We observed a 0.017 (95% confidence interval [CI]: 0.003-0.031) increase in the log(10)-transformed H19 methylation levels (%) in cord blood for each ten-fold increase in the levels of decachlorinated biphenyls (decaCBs) in maternal blood among all infants. Similarly, a 0.005 (95% CI: 0.000-0.010) increase in the log(10)-transformed LINE-1 methylation levels (%) in cord blood was associated with each ten-fold increase in heptachlorinated biphenyls (heptaCBs) in maternal blood among all infants. In particular, we observed a dose-dependent association of the decaCB levels in maternal blood with the H19 methylation levels among female infants (P value for trend = 0.040); likewise a dose-dependent association of heptaCB levels was observed with LINE-I methylation levels among female infants (P value for trend = 0.015). Moreover, these associations were only observed among infants of primiparous women.Conclusion: Our results suggest that the dose-dependent association between prenatal exposure to specific non-dioxin-like PCBs and increases in the H19 and LINE-1 methylation levels in cord blood might be more predominant in females than in males.
• Association of prenatal exposure to perfluoroalkyl substances with cord blood adipokines and birth size: The Hokkaido Study on environment and children's health

  Machiko Minatoya, Sachiko Itoh, Chihiro Miyashita, Atsuko Araki, Seiko Sasaki, Ryu Miura, Houman Goudarzi, Yusuke Iwasaki, Reiko Kishi

  ENVIRONMENTAL RESEARCH 156 175 - 182 2017年07月 [査読有り][通常論文]
   

  Perfluoroalkyl substances (PFASs) are synthetic chemicals that persist in the environment and in humans. There is a possible association between prenatal PFASs exposure and both neonate adipokines and birth size, yet epidemiological studies are very limited. The objective of this study was to examine associations of prenatal exposure to PFASs with cord blood adipokines and birth size. We conducted birth cohort study, the Hokkaido Study. In this study, 168 mother-child pairs were included. Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in maternal blood were determined by liquid chromatography tandem mass spectrometry. Cord blood adiponectin and leptin levels were measured by ELISA and RIA, respectively. Birth weight and ponderal index (PI) were obtained from birth record. The median maternal PFOS and PFOA were 5.1 and 1.4 ng/ mL, respectively. The median total adiponectin and leptin levels were 19.4 mu g/mL and 6.2 ng/mL, respectively. Adjusted linear regression analyses found that PFOS level was positively associated with total adiponectin levels (beta=0.12, 95% CI:0.01, 0.22), contrary was negatively associated with PI (beta=-2.25, 95% CI:-4.01,- 0.50). PFOA level was negatively associated with birth weight (beta=-197, 95% CI:- 391,- 3). Leptin levels were not associated with PFASs levels. PFOS and adiponectin levels showed marginal dose-response relationship and both PFOS and PFOA and birth size showed significant dose-response relationships. Results from this study suggested that prenatal PFASs exposure may alter cord blood adiponectin levels and may decrease birth size.
• Prenatal exposure to perfluoroalkyl acids and prevalence of infectious diseases up to 4 years of age

  Houman Goudarzi, Chihiro Miyashita, Emiko Okada, Ikuko Kashino, Chi-Jen Chen, Sachiko Ito, Atsuko Araki, Sumitaka Kobayashi, Hideyuki Matsuura, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 104 132 - 138 2017年07月 [査読有り][通常論文]
   

  Perfluoroalkyl acids (PFAAs) are synthetic chemicals with ability to repel oils and water, and have been widely used in many industrial and household applications such as adhesives and water-and stain-repellent surfaces to nonstick coatings. Animal studies have shown that PFAAs have immunotoxic effects. However, few epidemiological studies have investigated the effects of PFAAs on infectious diseases occurrence. We examined the relationship between prenatal exposure to PFAAs and prevalence of infectious diseases up to 4 years of life. A total of 1558 mother-child pairs, who were enrolled in the Hokkaido Study on Environment and Children's Health, were included in this data analysis. Eleven PFAAs were measured in maternal plasma taken at 28-32 weeks of gestation using ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry. Participant characteristics were obtained from medical birth records and self-administered questionnaires during pregnancy and after delivery. Physicians' diagnosis of common infectious diseases including otitis media, pneumonia, respiratory syncytial virus infection, and varicella up to 4 years were extracted from the mother-reported questionnaires. The number of children who developed infectious diseases up to 4 years of age was as follows: otitis media, 649 (41.4%); pneumonia, 287 (18.4%); respiratory syncytial virus infection, 197 (12.6%); varicella 589 (37.8%). A total of 1046 (67.1%) children had at least one of the diseases defined as total infectious diseases. After adjusting for appropriate confounders, PFOS levels in the highest quartile were associated with increased odds ratios (ORs) of total infectious diseases (Q4 vs. Q1 OR: 1.61; 95% CI: 1.18, 2.21; p for trend = 0.008) in all children. In addition, perfluorohexane sulfonate (PFHxS) was associated with a higher risk of total infectious diseases only among girls (Q4 vs. Q1 OR: 1.55, 95% CI: 0.976, 2.45; p for trend = 0.045). We found no association between infectious diseases and other examined PFAAs. Our findings suggest that prenatal exposure to PFOS and PFHxS may associated with infectious diseases occurrence in early life. Therefore, prenatal exposure to PFAAs may be immunotoxic for the immune system in offspring. (C) 2017 Elsevier Ltd. All rights reserved.
• Associated factors of behavioural problems in children at preschool age: the Hokkaido study on environment and children's health

  Minatoya, M., Itoh, S., Araki, A., Tamura, N., Yamazaki, K., Nishihara, S., Miyashita, C., Kishi, R.

  Child: Care, Health and Development 43 3 385 - 392 2017年05月 [査読有り][通常論文]
  
• Effects of prenatal perfluoroalkyl acid exposure on cord blood IGF2/H19 methylation and ponderal index: The Hokkaido Study

  Sachiko Kobayashi, Kaoru Azumi, Houman Goudarzi, Atsuko Araki, Chihiro Miyashita, Sumitaka Kobayashi, Sachiko Itoh, Seiko Sasaki, Mayumi Ishizuka, Hiroyuki Nakazawa, Tamiko Ikeno, Reiko Kishi

  JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY 27 3 251 - 259 2017年05月 [査読有り][通常論文]
   

  Prenatal exposure to perfluoroalkyl acids (PFAAs) influences fetal growth and long-term health. However, whether PFAAs affect offspring DNA methylation patterns to influence health outcomes is yet to be evaluated. Here, we assessed effect of prenatal PFAA exposure on cord blood insulin-like growth factor 2 (IGF2), H19, and long interspersed element 1 (LINE1) methylation and its associations with birth size. Mother-child pairs (N = 177) from the Hokkaido Study on Environment and Children's Health were included in the study. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) levels in maternal serum were measured by liquid chromatography-tandem mass spectrometry. IGF2, H19, and LINE1 methylation in cord blood DNA was determined by pyrosequencing. After full adjustment in multiple linear regression models, IGF2 methylation showed a significant negative association with log-unit increase in PFOA (partial regression coefficient = -0.73; 95% confidence interval: -1.44 to -0.02). Mediation analysis suggested that reduced IGF2 methylation explained similar to 21% of the observed association between PFOA exposure and reduced ponderal index of the infant at birth. These results indicated that the effects of prenatal PFOA exposure could be mediated through DNA methylation. Further study will be required to determine the potential for long-term adverse health effects of reduced IGF2 methylation induced by PFOA exposure.
• LEVEL OF PRENATAL ADRENAL STEROIDS HORMONES AFFECTS BODY WEIGHT AT BIRTH

  Takahiko Mitsui, Atsuko Araki, Sachiko Ito, Chihiro Miyashita, Kimihiko Moriya, Takeya Kitta, Kazutoshi Cho, Keita Morioka, Nobuo Shinohara, Masayuki Takeda, Reiko Kishi, Katsuya Nonomura

  JOURNAL OF UROLOGY 197 4 E475 - E475 2017年04月 [査読有り][通常論文]
  
• 殺虫用途の農薬への曝露とADHDを中心とした神経発達障害との関連についての疫学研究動向

  西原 進吉, 荒木 敦子, 宮下 ちひろ, 山崎 圭子, 岸 玲子

  北海道公衆衛生学雑誌 30 2 27 - 40 北海道公衆衛生学会 2017年03月 [査読無し][通常論文]
   

  我が国では神経発達障害の子どもが増加傾向にある。近年、殺虫用途等で使用される農薬への曝露がその一因であるとも考えられている。そこで、本稿では、胎児期、乳幼児期、学童期における農薬曝露と、注意欠如/多動性障害を中心とした神経発達への影響に関する近年の研究動向について検討を行うことを目的とした。医学文献データベースPubMedを用いて、有機塩素系、有機リン系、ピレスロイド系、カーバメイト系、ネオニコチノイド系農薬と、注意欠如・多動性障害、不注意、多動、神経発達、行動発達を検索用語として、文献検索を行った。得られた176編の論文から、農薬と神経発達に直接関係する疫学論文40編に焦点をあてて検討した。その結果、有機リン系農薬については、胎児期曝露の影響がみられること、生後曝露の影響は一貫しないこと、有機塩素系農薬についても、胎児期曝露の影響を示す報告が多いことが示された。一方、ピレスロイド系農薬では、胎児期よりも出生後の影響が強い可能性が示唆された。カーバメイト系農薬については、胎児期曝露の影響が示唆されたが、論文数は2編のみであった。ネオニコチノイド系農薬については報告が1編のみであった。精神発達においては、検索内容に関する評価項目が多岐にわたり、また、影響が表出する年齢も異なる可能性があることから、農薬曝露と精神発達の関連についての研究報告数は、現状では不十分であり、さらなる研究の蓄積が望まれる。(著者抄録)
• Prenatal di(2-ethylhexyl) phthalate exposure and disruption of adrenal androgens and glucocorticoids levels in cord blood: The Hokkaido Study

  Atsuko Araki, Takahiko Mitsui, Houman Goudarzi, Tamie Nakajima, Chihiro Miyashita, Sachiko Itoh, Seiko Sasaki, Kazutoshi Cho, Kimihiko Moriya, Nobuo Shinohara, Katsuya Nonomura, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 581 297 - 304 2017年03月 [査読有り][通常論文]
   

  Di(2-ethylhexyl) phthalate (DEHP) is known for its endocrine disrupting properties. We previously demonstrated that prenatal DEHP exposure is associated with decreased progesterone levels and testosterone/estradiol ratio in the cord blood. However, evidence of the effects of prenatal DEHP exposure on adrenal androgen and glucocorticoids in infants is scarce. Thus, the objectives of this study were to investigate the association between prenatal DEHP exposure and adrenal androgen and glucocorticoids, and to discuss its effects on steroid hormone profiles in infants. This is part of a birth cohort study: The Hokkaido Study on Environment and Children's Health, Sapporo Cohort. Among the 514 participants, 202 mother-infant pairs with available data on maternal mono (2ethylhexyl) phthalate (MEHP), adrenal androgen (dehydroepiandrostenedione [DHEA] and androstenedione) and glucocorticoid (cortisol and cortisone) cord blood levels were included in this study. After adjusting for potential confounders, a linear regression analysis showed that maternal MEHP levels were associated with reduced cortisol and cortisone levels and glucocorticoid/adrenal androgen ratio, whereas increased DHEA levels and DHEA/androstenedione ratio. In a quartile model, when comparing the adjusted least square means in the 4th quartile of MEHP with those in the 1st quartile, cortisol and cortisone levels and glucocorticoid/adrenal androgen ratio decreased, whereas DHEA/androstenedione and cortisol/cortisone ratios increased. Significant p-value trends for cortisol and cortisone levels, cortisol/cortisone ratio, and glucocorticoid/adrenal androgen ratio were observed. In combination with the previous results of reduced progesterone levels and testosterone/estradiol ratio, prenatal exposure to DEHP altered the steroid hormone profiles of infants. Further studies investigating the long-term effects of DEHP exposure on growth, neurodevelopment, and gonad and reproductive function are required. (C) 2016 Elsevier B.V. All rights reserved.
• 子どもを取り巻く環境と健康(第24回)(最終回) 誰もが健康な人生のスタートを 世界で進む出生コーホート研究

  岸 玲子, 湊屋 街子, 荒木 敦子, 宮下 ちひろ

  公衆衛生 81 2 175 - 183 (株)医学書院 2017年02月 [査読無し][通常論文]
   

  環境化学物質のリスクコミュニケーションでは,日本国内で人々が実際どのような濃度に曝露されているかが重要である.それによって健康障害のリスクの大きさが異なるからである.アウトカムについては多様な影響をしっかり観察する必要がある.因果関係の議論は複雑な要因について一つ一つ糸を解きほぐすように慎重に進める.本連載では日本で初めての本格的な出生コーホート研究(北海道スタディと東北コホート)の科学的な成果を中心に示してきたが,本稿では世界的な研究の現状を伝えるとともに今後の課題を紹介する.誰もが健康な人生のスタートを切ることができるように,環境と子どもの健康問題の重要性を理解していただけるよう願っている.(著者抄録)
• Prenatal di-2-ethylhexyl phthalate exposure and cord blood adipokine levels and birth size: The Hokkaido study on environment and children's health

  Machiko Minatoya, Atsuko Araki, Chihiro Miyashita, Seiko Sasaki, Yuko Goto, Tamie Nakajima, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 579 606 - 611 2017年02月 [査読有り][通常論文]
   

  Di-2-ethylhexyl phthalate (DEHP) is one of the most widely used phthalates. Metabolites of DEHP are detectable in majority of the population. Findings on adverse health outcomes, particularly birth weight in association with prenatal exposure to DEHP remain equivocal. Besides, there is insufficient evidence to address influence on metabolic function from epidemiological studies.Thus, our objective was to investigate cord blood adipokine levels and birth size in association with prenatal DEHP exposure in prospective birth cohort study. Mono-2-methylhexyl phthalate (MEHP), primary metabolite of DEHP was determined as exposure by using maternal blood sample of 3rd trimester. Leptin and adiponectin levels in cord blood were measured as markers of metabolic function. Birth weight and length were obtained from birth record. Association between maternal MEHP levels and cord blood adiponectin and leptin levels, birth weight and ponderal index (PI) were examined for 167 mother-child pairs who had both MEHP and cord blood adipokine measurements.The median MEHP level was 8.81 ng/ml and the detection rate was 100%. There was no sex difference in MEHP levels. Both leptin and adiponectin levels were higher in girls than in boys. MEHP level was positively associated with adiponectin level among boys and was negatively associated with leptin level among girls. MEHP level were negatively associated with PI only in girls and this could be due to decreased leptin level.This study suggested that prenatal DEHP exposure may be associated with cord blood adipokine and birth size. The influence potentially be sex-specific and could be more significant in girls. (C) 2016 Published by Elsevier B.V.
• The Hokkaido Birth Cohort Study on Environment and Children's Health: cohort profile-updated 2017

  Reiko Kishi, Atsuko Araki, Machiko Minatoya, Tomoyuki Hanaoka, Chihiro Miyashita, Sachiko Itoh, Sumitaka Kobayashi, Yu Ait Bamai, Keiko Yamazaki, Ryu Miura, Naomi Tamura, Kumiko Ito, Houman Goudarzi

  ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE 22 1 46  2017年 [査読有り][通常論文]
   

  The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary study goals are (1) to examine the effects of low-level environmental chemical exposures on birth outcomes, including birth defects and growth retardation; (2) to follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders and perform a longitudinal observation of child development; (3) to identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) to identify the additive effects of various chemicals, including tobacco smoking. The purpose of this report is to update the progress of the Hokkaido Study, to summarize the recent results, and to suggest future directions. In particular, this report provides the basic characteristics of the cohort populations, discusses the population remaining in the cohorts and those who were lost to follow-up at birth, and introduces the newly added follow-up studies and case-cohort study design. In the Sapporo cohort of 514 enrolled pregnant women, various specimens, including maternal and cord blood, maternal hair, and breast milk, were collected for the assessment of exposures to dioxins, polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances, phthalates, bisphenol A, and methylmercury. As follow-ups, face-to-face neurobehavioral developmental tests were conducted at several different ages. In the Hokkaido cohort of 20,926 enrolled pregnant women, the prevalence of complicated pregnancies and birth outcomes, such as miscarriage, stillbirth, low birth weight, preterm birth, and small for gestational age were examined. The levels of exposure to environmental chemicals were relatively low in these study populations compared to those reported previously. We also studied environmental chemical exposure in association with health outcomes, including birth size, neonatal hormone levels, neurobehavioral development, asthma, allergies, and infectious diseases. In addition, genetic and epigenetic analyses were conducted. The results of this study demonstrate the effects of environmental chemical exposures on genetically susceptible populations and on DNA methylation. Further study and continuous follow-up are necessary to elucidate the combined effects of chemical exposure on health outcomes.
• The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study

  Houman Goudarzi, Atsuko Araki, Sachiko Itoh, Seiko Sasaki, Chihiro Miyashita, Takahiko Mitsui, Hiroyuki Nakazawa, Katsuya Nonomura, Reiko Kishi

  ENVIRONMENTAL HEALTH PERSPECTIVES 125 1 111 - 118 2017年01月 [査読有り][通常論文]
   

  BACKGROUND: Perfluorinated chemicals (PFCs) disrupt cholesterol homeostasis. All steroid hormones are derived from cholesterol, and steroid hormones such as glucocorticoids and androgenic hormones mediate several vital physiologic functions. However, the in utero effects of PFCs exposure on the homeostasis of these steroid hormones are not well understood in humans.OBJECTIVES: We examined the relationship between prenatal exposure to perfluorooctane sulfonate (PFOS)/perfluorooctanoate (PFOA) and cord blood levels of glucocorticoid and androgenic hormones.METHODS: We conducted a hospital-based birth cohort study between July 2002 and October 2005 in Sapporo, Japan (n = 514). In total, 185 mother-infant pairs were included in the present study. Prenatal PFOS and PFOA levels in maternal serum samples were measured using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Cord blood levels of glucocorticoid (cortisol and cortisone) and androgenic hormones [dehydroepiandrosterone (DHEA) and androstenedione] were also measured in the same way.RESULTS: We found a dose-response relationship of prenatal PFOS, but not PFOA, exposure with glucocorticoid levels after adjusting for potential confounders. Cortisol and cortisone concentrations were -23.98-ng/mL (95% CI: -0.47.12, -11.99; p for trend = 0.006) and -63.21-ng/mL (95% CI: -132.56, -26.72; p for trend < 0.001) lower, respectively, in infants with prenatal PFOS exposure in the fourth quartile compared with those in the first quartile. The highest quartile of prenatal PFOS exposure was positively associated with a 1.33-ng/mL higher DHEA level compared with the lowest quartile (95% CI: 0.17, 1.82; p for trend = 0.017), whereas PFOA showed a negative association with DHEA levels (quartile 4 vs. quartile 1: -1.23 ng/mL, 95% CI: -1.72, -0.25; p for trend = 0.004). We observed no significant association between PFCs and androstenedione levels.CONCLUSIONS: Our results indicate that prenatal exposure to PFCs is significantly associated with glucocorticoid and DHEA levels in cord blood.
• Dioxin-metabolizing genes in relation to effects of prenatal dioxin levels and reduced birth size: The Hokkaido study

  Sumitaka Kobayashi, Fumihiro Sata, Chihiro Miyashita, Seiko Sasaki, Susumu Ban, Atsuko Araki, Houman Goudarzi, Jumboku Kajiwara, Takashi Todaka, Reiko Kishi

  REPRODUCTIVE TOXICOLOGY 67 111 - 116 2017年01月 [査読有り][通常論文]
   

  Objectives: We investigated the effects of maternal polymorphisms in 3 genes encoding dioxin metabolizing enzymes in relation to prenatal dioxin levels on infant birth size in Japan.Methods: We examined the relationship between dioxin exposure and birth size in relation to the polymorphisms in the genes encoding aromatic hydrocarbon receptor (AHR [G > A, Arg554Lys]), cytochrome P450 (CYP) 1A1 (T6235C), and glutathione S-transferase mu I (GSTM1; Non-null/null) in 421 participants using multiple linear regression models.Results: In mothers carrying the GSTM1 null genotype, a ten-fold increase in total dioxin toxic equivalency was correlated with a decrease in birth weight of -345g (95% confidence interval: -584, -105).Conclusions: We observed adverse effects of maternal GSTM1 null genotype on birth weight in the presence of dioxins exposure during pregnancy. (C) 2016 Elsevier Inc. All rights reserved.
• Quantifying bisphenol A in maternal and cord whole blood using isotope dilution liquid chromatography/tandem mass spectrometry and maternal characteristics associated with bisphenol A

  Jun Yamamoto, Machiko Minatoya, Seiko Sasaki, Atsuko Araki, Chihiro Miyashita, Toru Matsumura, Reiko Kishi

  CHEMOSPHERE 164 25 - 31 2016年12月 [査読有り][通常論文]
   

  Bisphenol A (BPA) is endocrine disrupting chemical that have been detected among general population. Exposure levels among pregnant women and their fetus are yet largely unknown among Japanese. We have developed a new method of measuring total BPA in whole blood samples by using isotopic dilution liquid chromatography-tandem mass spectrometry (ID-LC/MS/MS). For eliminating possible contaminations, we have used glass cartridge instead of polypropylene cartridge and successfully reduced background levels. Additionally gap retention technique was applied to improve sensitivity. We also confirmed no external contamination by measuring free BPA in the samples. The limit of quantification (LOQ) was 0.040 ng/ml. With this developed method, we determined total BPA concentrations of 59 maternal blood at delivery and 285 cord blood samples in prospective birth cohort study and investigated factors possibly related to total BPA levels. Total BPA levels ranged from below LOQ to 0.419 ng/ml and for maternal blood and from below LOQ to 0.217 ng/ml for cord blood, respectively. The geometric mean was 0.051 ng/ml for maternal blood and 0.046 ng/ml for cord blood, respectively. Although no correlation was observed between maternal and fetal blood levels of total BPA, our result suggested fetal exposure to EPA. We have found that younger mothers, frequent beef and pork consumption during pregnancy were positively associated with maternal total BPA levels. We confirmed in utero exposure to BPA, which highlights the importance of further studies of investing the effects of fetus BPA exposure on health outcomes. (C) 2016 Elsevier Ltd. All rights reserved.
• Exposure to phthalates in house dust and associated allergies in children aged 6-12 years

  Yu Ait Bamai, Atsuko Araki, Toshio Kawai, Tazuru Tsuboi, Ikue Saito, Eiji Yoshioka, Shi Cong, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 96 16 - 23 2016年11月 [査読有り][通常論文]
   

  Phthalates are widely used as plasticizers in household products. Several studies have reported an association between phthalate exposure and an increased risk of allergies. The present study estimated phthalate exposure in children aged 6-12 years and assessed potential correlations with allergies. House dust samples were collected from floors and multi-surface objects >35 cm above the floor. Urine samples were collected from the first morning void of the day. Daily phthalate intake (DIdust and DI) was estimated using both house dust and urinary metabolite concentrations. Exposure to di-2-ethylhexyl phthalate (DEHP) in floor dust was associated with parental-reported rhino-conjunctivitis. After stratification by gender, this trend was found to only occur in boys. Furthermore, urinary mono-isobutyl phthalate was inversely associated with parental-reported wheeze in boys. DIdust of benzyl butyl phthalate (BBzP) and DEHP were significantly correlated with DI_BBzP and DI_DEHP, respectively. These correlations were stronger with floor than with multi-surface dust. Our results suggest that, among Japanese children, house dust from low surfaces, such as living room floors, might play a meaningful role in the indoor environmental exposure pathway for BBzP and DEHP. (C) 2016 Elsevier Ltd. All rights reserved.
• Combined effects of AHR, CYP1A1, and XRCC1 genotypes and prenatal maternal smoking on infant birth size: Biomarker assessment in the Hokkaido Study

  Sumitaka Kobayashi, Fumihiro Sata, Seiko Sasaki, Titilola Serifat Braimoh, Atsuko Araki, Chihiro Miyashita, Houman Goudarzi, Sachiko Kobayashi, Reiko Kishi

  REPRODUCTIVE TOXICOLOGY 65 295 - 306 2016年10月 [査読有り][通常論文]
   

  Objectives: We investigated the individual and combined effects of maternal polymorphisms encoding the aromatic hydrocarbon receptor (AHR; rs2066853), cytochrome P450 (CYP) 1A1 (rs1048963), and the X-ray-complementing gene 1 (XRCC1; rs1799782) and prenatal smoking in relation to infant birth size.Methods: Totally, 3263 participants (1998 non-smokers and 1265 smokers) were included in the study between 2003 and 2007. Two groups of mothers were distinguished by plasma cotinine levels by ELISA measured during the third trimester (cut-off= 11.48 ng/mL). We conducted data analysis using multiple linear regression models.Results: Infants whose mothers smoked and had AHR-GG, CYP1A1-AG/GG, and XRCC1-CT/TT genotypes weighed, -145 g less than those born of mothers who did not smoke and had the AHR-GA/AA, CYP1A1-AA, and XRCC1-CC genotypes (95% CI: 241, 50).Conclusions: We demonstrated that infants whose mothers smoked during pregnancy with the combination of AHR, CYP1A1, and XRCC1 polymorphisms had lower birth size. (C) 2016 Elsevier Inc. All rights reserved.
• Association of perfluoroalkyl substances exposure in utero with reproductive hormone levels in cord blood in the Hokkaido Study on Environment and Children's Health

  Sachiko Itoh, Atsuko Araki, Takahiko Mitsui, Chihiro Miyashita, Houman Goudarzi, Seiko Sasaki, Kazutoshi Cho, Hiroyuki Nakazawa, Yusuke Iwasaki, Nobuo Shinohara, Katsuya Nonomura, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 94 51 - 59 2016年09月 [査読有り][通常論文]
   

  Background: Exposure to perfluoroalkyl substances (PFASs) may disrupt reproductive function in animals and humans. Although PFASs can cross the human placental barrier, few studies evaluated the effects of prenatal PFAS exposure on the fetus' reproductive hormones.Objective: To explore the associations of prenatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) with cord blood reproductive hormones.Methods: In the prospective birth cohort (Sapporo cohort of the Hokkaido study), we included 189 mother-infant pairs recruited in 2002-2005 with both prenatal maternal and cord blood samples. PFOS and PFOA levels in maternal blood after the second trimester were measured via liquid chromatography-tandem mass spectrometry. We also measured cord blood levels of the fetuses' reproductive hormones, including estradiol (E2), total testosterone (T), progesterone (P4), inhibin B, insulin-like factor 3, steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone, and prolactin (PRL).Results: The median PFOS and PFOA levels in maternal serum were 5.2 ng/mL and 1.4 ng/mL, respectively. In the fully adjusted linear regression analyses of the male infants, maternal PFOS levels were significantly associated with E2 and positively, and T/E2, P4, and inhibin B inversely; PFOA levels were positively associated with inhibin B levels. Among the female infants, there were significant inverse associations between PFOS levels and P4 and PRL levels, although there were no significant associations between PFOA levels and the female infants' reproductive hormone levels.Conclusions: These results suggest that the fetal synthesis and secretion of reproductive hormones may be affected by in utero exposure to measurable levels of PFOS and PFOA. (C) 2016 Elsevier Ltd. All rights reserved.
• Effects of prenatal exposure to perfluoroalkyl acids on prevalence ofallergic diseases among 4-year-old children

  Houman Goudarzi, Chihiro Miyashita, Emiko Okada, Ikuko Kashino, Sumitaka Kobayashi, Chi-Jen Chen, Sachiko Ito, Atsuko Araki, Hideyuki Matsuura, Yoichi M. Ito, Reiko Kishi

  ENVIRONMENT INTERNATIONAL 94 124 - 132 2016年09月 [査読有り][通常論文]
   

  Perfluoroalkyl acids (PFAAs) are ubiquitous chemicals extremely resistant and widespread throughout the environment, frequently being detected in human blood samples. Animal studies have revealed that exposure to PFAAs results in immunotoxicity. However, the association between PFAAs, especially long-chain PFAAs, and allergies in humans is not well established. We examined whether prenatal exposure to PFAAs is associated with allergic diseases among 4-year-old children in a large-scale prospective birth cohort in Hokkaido, Japan. In total, 1558 mother-child pairs were included in this study and prenatal levels of eleven PFAAs were measured in maternal plasma samples obtained between 28 and 32 weeks of pregnancy by using ultra-performance liquid chromatography-tandem mass spectrometry. Participant demographic and characteristic information were obtained from self-administered pre- and postnatal questionnaires and medical birth records. Infant allergies were assessed using the Japanese version of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three questionnaire, which was administered 4 years post-delivery. Symptoms included eczema, wheezing and rhinoconjunctivitis with a prevalence of 19.0%, 18.7%, and 5.4%, respectively. Associations of PFAA quartiles with allergic outcomes were examined using logistic models. Adjusted odds ratios (ORs) in the 4th quartile vs. 1st quartile (Q4 vs. Q1) for total allergic diseases (including at least one allergic outcome) significantly decreased for perfluorododecanoic acid (PFDoDa) (Q4 vs. Q1 OR: 0.621; 95% confidence interval (CI): 0.454, 0.847) andperfluorotridecanoic acid (PFTrDA) (Q4 vs. Q1 OR: 0.712; 95% CI: 0.524, 0.966) in all children. We obtained similar results when examining the association between PFAAs and eczema. The adjusted OR (Q4 vs. Q1) for wheezing in relation to higher maternal PFHxS levels was 0.728 (95% CI: 0.497, 1.06) in all children. In conclusion, prenatal exposure to long-chain PFAAs, such as PFDoDa and PFTrDA may have an immunosuppressive effect on allergic diseases in 4-year-old children. (C) 2016 Published by Elsevier Ltd.
• Effects of prenatal phthalate exposure on thyroid hormone levels, mental and psychomotor development of infants: The Hokkaido Study on Environment and Children's Health

  Machiko Minatoya, Sonomi Naka Jima, Seiko Sasaki, Atsuko Araki, Chihiro Miyashita, Tamiko Ikeno, Tamie Nakajima, Yuko Goto, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 565 1037 - 1043 2016年09月 [査読有り][通常論文]
   

  Di (2-ethylhexyl) phthalate (DEHP) is commonly used phthalates and concerns of adverse effects of prenatal DEHP exposure on neonatal thyroid hormone (TH) and neurodevelopment are increasing. However, there is no report regarding association between prenatal DEHP exposure and infant neurodevelopment including TH levels in Japanese population. Thus the aim of present study was to evaluate the associations between prenatal DEHP exposure and mental and psychomotor development of infants 6 and 18 months along with investigating influence on neonatal free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels in the prospective birth cohort study.Maternal blood samples collected between 23 and 41 weeks of gestation was analyzed for mono (2-ethylhexyl) phthalate (MEHP), metabolite of DEHP levels. Neonatal FT4 and TSH were obtained from mass screening data. Infant neurodevelopment was assessed by Bayley Scale of Infant Development second edition at 6 and 18 month of age. For the final analysis, 328 participants were included.The median levels of maternal MEHP was 10.6 ng/ml, neonatal TSH and FT4 was 2.20 mu U/ml and 2.03 ng/ml, respectively. We did not find any associations between prenatal DEHP exposure and neonatal TH levels or infant mental and psychomotor development at 6 and 18 month.In this study, prenatal DEHP exposure did not showadverse effects on infant TH levels or mental and psychomotor development in early life stage. However, our previous study revealed negative effects of prenatal DEHP exposure on sex hormone levels, continuous investigation on neurodevelopment in later life in association with prenatal DEHP exposure is necessary. (C) 2016 Published by Elsevier B.V.
• Effects of adrenal androgens during the prenatal period on the second to fourth digit ratio in school-aged children

  Takahiko Mitsui, Atsuko Araki, Houman Goudarzi, Chihiro Miyashita, Sachiko Ito, Seiko Sasaki, Takeya Kitta, Kimihiko Moriya, Kazutoshi Cho, Keita Morioka, Reiko Kishi, Nobuo Shinohara, Masayuki Takeda, Katsuya Nonomura

  STEROIDS 113 46 - 51 2016年09月 [査読有り][通常論文]
   

  Objectives: We investigated the relationship between the levels of adrenal steroid hormones in cord blood and the second to fourth digit ratio (2D/4D), which is regarded as an indirect method to investigate the putative effects of prenatal exposure to androgens, in school-aged children.Materials and methods: Of the 514 mother-child pairs who participated in the prospective cohort study of birth in Sapporo between 2002 and 2005, the following adrenal steroid hormone levels in 294 stored cord blood samples (135 males and 159 females) were measured; cortisol, cortisone, androstenedione and dehydroepiandrosterone (DHEA). A total of 190 out of 350 children who were currently school-aged and contactable for this survey sent back photocopies of their palms for 2D/4D measurements.Results: 2D/4D in all right hands, left hands, and mean values was significantly lower in males than in females (p < 0.01). DHEA levels were significantly higher in females. A multivariate regression model showed that 2D/4D negatively correlated with DHEA in males only (p < 0.01). No correlations were observed in the other adrenal steroid hormones tested in males or in any adrenal steroid hormones in females.Conclusion: DHEA is mainly secreted in large amounts by the adrenal gland and is transformed into active sex-steroid hormones in peripheral tissues. The present study demonstrated that sex differences in digits were influenced by adrenal androgens during the prenatal period, possibly through intracrinological processes for androgen receptors located in fetal cartilaginous tissues. (C) 2016 Elsevier Inc. All rights reserved.
• 環境省「エコチル調査」開始4年を経ての集計結果の報告 全国と北海道の参加者の喫煙・食物アレルギー等について

  土川 陽子, 西條 泰明, 伊藤 善也, 吉岡 英治, 川西 康之, 堤 裕幸, 遠藤 俊明, 馬場 剛, 小林 正樹, 水上 尚典, 有賀 正, 長 和俊, 白石 秀明, 千石 一雄, 宮本 敏伸, 東 寛, 荒木 敦子, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 湊屋 街子, 小林 澄貴, アイツバマイ ゆふ, 山崎 圭子, 西原 進吉, 田村 菜穂美, 岸 玲子

  北海道母性衛生学会誌 45 33 - 38 北海道母性衛生学会 2016年08月 [査読無し][通常論文]
  
• 子どもを取り巻く環境と健康(第18回) 葉酸摂取の胎児発育や先天異常,生後アレルギーへの影響

  宮下 ちひろ, 伊藤 久美子, 荒木 敦子, 岸 玲子

  公衆衛生 80 8 615 - 621 (株)医学書院 2016年08月 [査読無し][通常論文]
   

  妊娠中の葉酸は胎児の成長に不可欠で,妊娠中の葉酸欠乏は妊娠高血圧症や子宮内胎児発育遅延などの原因として報告されている.2000年に厚生労働省は胎児の神経管閉鎖障害の発生リスクを低減するため,妊娠を計画する女性に葉酸サプリメントを1日400μg内服することを推奨した.本稿では,日本の妊婦の葉酸サプリメント摂取と葉酸値に影響する要因,神経管閉鎖障害および児のアレルギー発症リスクとの関連について記述する.(著者抄録)
• Predictors of folate status among pregnant Japanese women: the Hokkaido Study on Environment and Children's Health, 2002-2012

  Thamar A. Yila, Atsuko Araki, Seiko Sasaki, Chihiro Miyashita, Kumiko Itoh, Tamiko Ikeno, Eiji Yoshioka, Sumitaka Kobayashi, Houman Goudarzi, Toshiaki Baba, Titilola Braimoh, Hisanori Minakami, Toshiaki Endo, Kazuo Sengoku, Reiko Kishi

  BRITISH JOURNAL OF NUTRITION 115 12 2227 - 2235 2016年06月 [査読有り][通常論文]
   

  The International Clearinghouse for Birth Defects, Surveillance and Research reports a rise in the prevalence rate of spina bifida in Japan. We determined first-trimester folate status of Hokkaido women and identified potential predictors. Participants were 15 266 pregnant women of the Hokkaido Study on Environment and Children's Health Cohort. Data were extracted from self-reported questionnaires and biochemical assay results. Demographic determinants of low folate status were younger maternal age (adjusted OR (AOR) 1.48; 95% CI 1.32, 1.66), lower educational level (AOR 1.27; 95% CI 1.17, 1.39) and lower annual income (AOR 1.11; 95% CI 1.01, 1.22). Plasma cotinine concentrations of 1.19-65.21 nmol/l increased the risk of low folate status (AOR 1.20; 95% CI 1.10, 1.31) and concentrations > 65.21 nmol/l further increased the risk (AOR 1.91; 95% CI 1.70, 2.14). The most favourable predictor was use of folic acid (FA) supplements (AOR 0.19; 95% CI 0.17, 0.22). Certain socio-demographic factors influence folate status among pregnant Japanese women. Modifiable negative and positive predictors were active and passive tobacco smoking and use of FA supplements. Avoiding both active and passive tobacco smoking and using FA supplements could improve the folate status of Japanese women.
• The Association between Prenatal Yoga and the Administration of Ritodrine Hydrochloride during Pregnancy: An Adjunct Study of the Japan Environment and Children's Study

  Yasuyuki Kawanishi, Yasuaki Saijo, Eiji Yoshioka, Yoshihiko Nakagi, Takahiko Yoshida, Toshinobu Miyamoto, Kazuo Sengoku, Yoshiya Ito, Chihiro Miyashita, Atsuko Araki, Reiko Kishi

  PLOS ONE 11 6 e0158155  2016年06月 [査読有り][通常論文]
   

  IntroductionWhile the beneficial effects of prenatal yoga have been reported in recent years, little is known about its effectiveness in pregnant Japanese women. Despite several adverse effects, ritodrine hydrochloride is frequently prescribed to suppress preterm labor in Japan, and its usage may therefore indicate cases of preterm labor. This study aimed to clarify the association between prenatal yoga and ritodrine hydrochloride use during pregnancy.MethodsAn observational study was conducted as an adjunct study by the Hokkaido unit of the Japan Environment and Children's Study. Information on prenatal yoga practice was collected using a self-questionnaire between March 21, 2012, and July 7, 2015, targeting women who had recently delivered. Ritodrine hydrochloride use was identified from medical records. A total of 2,692 women were analyzed using logistic regression models that adjusted for possible confounders.ResultsThere were 567 (21.1%) women who practiced prenatal yoga, which was associated with a lower risk of ritodrine hydrochloride use (adjusted odds ratio [OR] 0.77; 95% CI 0.61-0.98). This was especially evident in women with a total practice duration that exceeded 900 minutes throughout their pregnancy (adjusted OR 0.54; 95% CI 0.38-0.76). A sensitivity analysis that excluded patients with threatened abortion during the study period produced similar results.ConclusionsPrenatal yoga was associated with a lower risk of ritodrine hydrochloride use, particularly in women with more than 900 minutes of practice time over the course of their pregnancy. Prenatal yoga may be a beneficial option for pregnant women in the selection of alternative therapies.
• 環境化学物質の次世代影響に関する出生コホート研究 環境と子どもの健康に関する北海道スタデイの成果と課題

  岸 玲子, 宮下 ちひろ, 荒木 敦子

  アンチ・エイジング医学 12 2 211 - 220 (株)メディカルレビュー社 2016年04月 [査読無し][通常論文]
   

  2001年に「環境と子どもの健康に関する北海道スタディ」を立ち上げるに至った背景と目的、本スタディの特徴について述べた。本スタディは大小2つの前向きコホートから成り、一つは地域ベースの37医療機関における大規模コホートで、母児20929名のペアである。もう一つは札幌の一産科医療機関を受診した妊婦を対象にした小規模コホートで、母児14名のペアである。小規模コホートでは、PCB・ダイオキシン類、有機フッ素化合物(PFAA)等の測定を終了した小児を対象に、PFAA曝露の影響を調査している。大規模ホコートでは、高精度のGC/MS分析を用いてPCDD、PCDF等の同族異性体分析やダイオキシン様PCB濃度を測定し、ダイオキシン類の毒性等価量の算出を行っている。
• 環境化学物質の胎児期曝露による児の神経発達への影響に関する疫学文献レビュー 注意欠如・多動性障害(AD/HD)・自閉症スペクトラム(ASD)を含めて

  小林 澄貴, 池野 多美子, 荒木 敦子, 山崎 圭子, 西原 進吉, 岸 玲子

  北海道公衆衛生学雑誌 29 2 31 - 40 北海道公衆衛生学会 2016年03月 [査読無し][通常論文]
   

  有機フッ素化合物を加えた合計68種類について、これらの物質曝露における児の注意欠如・多動性障害(AD/HD)や自閉症スペクトラム(ASD)関連症状を含めた神経発達への影響の疫学的知見をまとめ、今後の研究課題について検討した。胎児期の母親の環境化学物質曝露による神経発達に及ぼす影響に関する先行研究のレビューから、有機塩素系農薬、有機リン系農薬、PCB・ダイオキシン類・臭素系難燃剤、有機フッ素化合物、BPAおよびフタル酸エステル類では濃度によっては生後の神経発達に負の影響を及ぼすことが明らかになった。また、農薬ではその代謝関連のPON1とGSTP1遺伝子多型により生後の児の神経発達の遅れに差が出ること、物質によっては母親の遺伝的感受性によってその遅れに差が認められる可能性が示唆された。遺伝的にリスクが高い集団がいることを配慮した上で、妊婦が可能な限り胎児期の環境化学物質曝露を回避できる環境整備が重要と思われた。
• 子どもを取り巻く環境と健康(第13回) 環境化学物質曝露による内分泌系への影響 性ホルモン

  荒木 敦子, 伊藤 佐智子, 岸 玲子

  公衆衛生 80 3 221 - 227 (株)医学書院 2016年03月 [査読無し][通常論文]
  
• Prenatal exposure to perfluorinated chemicals and neurodevelopment in early infancy: The Hokkaido Study

  Houman Goudarzi, Sonomi Nakajima, Tamiko Ikeno, Seiko Sasaki, Sachiko Kobayashi, Chihiro Miyashita, Sachiko Ito, Atsuko Araki, Hiroyuki Nakazawa, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 541 1002 - 1010 2016年01月 [査読有り][通常論文]
   

  Perfluorinated chemicals (PFCs) are ubiquitous and persistent pollutants widely detected in blood samples of animals and humans across the globe. Although animal studies have shown the potential neurotoxicity of PFCs, there are few epidemiological studies regarding neurological effects of PFCs in humans, and those studies have had inconclusive results. In this study, we conducted a hospital-based prospective birth cohort study between 2002 and 2005 (n = 514) to examine the associations between prenatal perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) exposures and the neurodevelopment of infants at 6 (n = 173) and 18 (n = 133) months of age. Using the second edition of the Bayley Scales of Infant Development (BSID II), the Mental and Psychomotor Developmental Indices (MDI and PDI, respectively) were assessed. PFOS and PFOA were measured in maternal serum samples by liquid chromatography-tandem mass spectrometry. After controlling for confounders, prenatal PFOA concentrations were associated with the MDI of female (but not male) infants at 6 months of age (beta = -0.296; 95% confidence interval (CI): -11.96, -0.682). Furthermore, females born to mothers with prenatal concentrations of PFOA in the fourth quartile had MDI scores -5.05 (95% CI: -10.66 to 0.55) lower than females born to mothers with concentrations of PFOA in the first quartile (p for trend = 0.045). However, PFOA concentrations were not significantly associated with neurodevelopmental indices at 18 months of age. In addition, we did not observe any significant association between PFOS concentrations and neurodevelopmental outcomes in early infancy. In conclusion, our results suggest that prenatal PFOA exposure may affect female mental scales of neurodevelopment at 6 months of age. Further studies with larger sample sizes and longer observation periods are required to clarify sex difference of the neurodevelopmental effects. (C) 2015 Elsevier B.V. All rights reserved.
• The Relationship between the Second-to-Fourth Digit Ratio and Behavioral Sexual Dimorphism in School-Aged Children

  Takahiko Mitsui, Atsuko Araki, Chihiro Miyashita, Sachiko Ito, Tamiko Ikeno, Seiko Sasaki, Takeya Kitta, Kimihiko Moriya, Kazutoshi Cho, Keita Morioka, Reiko Kishi, Nobuo Shinohara, Masayuki Takeda, Katsuya Nonomura

  PLOS ONE 11 1 e0146849  2016年01月 [査読有り][通常論文]
   

  Sexually dimorphic brain development and behavior are known to be influenced by sex hormones exposure in prenatal periods. On the other hand, second-to forth digit ratio (2D/4D) has been used as an indirect method to investigate the putative effects of prenatal exposure to androgen. In the present study, we herein investigated the relationship between genderrole play behavior and the second-to-fourth digit ratio (2D/4D), which has been used as an indirect method to investigate the putative effects of prenatal exposure to androgens, in school-aged children. Among 4981 children who became 8 years old by November 2014 and were contactable for this survey by The Hokkaido Study of Environment and Children's Health, 1631 (32.7%), who had data for 2D/4D and Pre-school Activities Inventory (PSAI) as well as data for the survey at baseline, were available for analysis. Parents sent reports of PSAI on the sex-typical characteristics, preferred toys, and play activities of children, and black and white photocopies of the left and right hand palms via mail. PSAI consisted of 12 masculine items and 12 feminine items, and a composite score was created by subtracting the feminine score from the masculine score, with higher scores representing masculine-typical behavior. While composite scores in PSAI were significantly higher in boys than in girls, 2D/4D was significantly lower in boys than in girls. Although the presence or absence of brothers or sisters affected the composite, masculine, and feminine scored of PSAI, a multivariate regression model revealed that 2D/4D negatively correlated with the composite scores of PSAI in boys, whereas no correlation was found in girls. Although 2D/4D negatively correlated with the masculine score in boys and girls, no correlation was observed between 2D/4D and the feminine score. In conclusion, although social factors, such as the existence of brother or sisters, affect dimorphic brain development and behavior in childhood, the present study revealed that the prenatal hormonal environment was an important factor influencing masculine-typical dimorphic brain development and behavior in schoolaged children.
• 子どもを取り巻く環境と健康(第10回) 乳幼児のアレルギーと胎児期・小児期の可塑剤・難燃剤曝露

  荒木 敦子, アイツバマイ ゆふ, 岸 玲子

  公衆衛生 79 12 876 - 881 (株)医学書院 2015年12月 [査読無し][通常論文]
  
• Effects of in utero exposure to polychlorinated biphenyls, methylmercury, and polyunsaturated fatty acids on birth size

  Chihiro Miyashita, Seiko Sasaki, Tamiko Ikeno, Atsuko Araki, Sachiko Ito, Jumboku Kajiwara, Takashi Todaka, Noriyuki Hachiya, Akira Yasutake, Katsuyuki Murata, Tamie Nakajima, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 533 256 - 265 2015年11月 [査読有り][通常論文]
   

  The adverse effects of in utero exposure to polychlorinated biphenyls (PCBs) or methylmercury (MeHg), and the beneficial effects of nutrients from maternal fish intake might have opposing influences on fetal growth. In this study, we assessed the effects of in utero exposure to PCBs and MeHg on birth size in the Japanese population, which is known to have a high frequency of fish consumption. The concentrations of PCBs and polyunsaturated fatty acids in maternal blood, and the total mercury in hair (as a biomarker of MeHg exposure) were measured during pregnancy and at delivery. Maternal intakes of fish (subtypes: fatty and lean) and shellfishes were calculated from a food frequency questionnaire administered at delivery. Newborn anthropometric measurement data were obtained from birth records. The associations between chemical exposures and birth size were analyzed by using multiple regression analysis with adjustment for confounding factors among 367 mother-newborn pairs. The birth weight was 3073 +/- 37 g (mean +/- SD). The incidence of babies small for gestational age (SGA) by weight was 4.9%. The median concentrations of total PCBs and hair mercury were 108 ng/g lipid and 1.41 mu g/g, respectively. There was no overall association between mercury concentrations and birth weight, birth length, chest circumference, and head circumference. We observed that the risk of SGA by weight decreased with increasing mercury concentration in regression analyses with adjustment for polyunsaturated fatty acids. Our results suggest that the beneficial effect of essential nutrition may mask the adverse effects of MeHg on birth size. The concentrations of PCBs had no association with birth size. (C) 2015 Elsevier B.V. All rights reserved.
• The Association of Prenatal Exposure to Perfluorinated Chemicals with Maternal Essential and Long-Chain Polyunsaturated Fatty Acids during Pregnancy and the Birth Weight of Their Offspring: The Hokkaido Study

  Reiko Kishi, Tamie Nakajima, Houman Goudarzi, Sachiko Kobayashi, Seiko Sasaki, Emiko Okada, Chihiro Miyashita, Sachiko Itoh, Atsuko Araki, Tamiko Ikeno, Yusuke Iwasaki, Hiroyuki Nakazawa

  ENVIRONMENTAL HEALTH PERSPECTIVES 123 10 1038 - 1045 2015年10月 [査読有り][通常論文]
   

  BACKGROUND: Fatty acids (FAs) are essential for fetal growth. Exposure to perfluorinated chemicals (PFCs) may disrupt FA homeostasis, but there are no epidemiological data regarding associations of PFCs and FA concentrations.OBJECTIVES: We estimated associations between perfluorooctane sulfonate (PFOS)/perfluoro-octanoate (PFOA) concentrations and maternal levels of FAs and triglyceride (TG) and birth size of the offspring.METHODS: We analyzed 306 mother-child pairs in this birth cohort between 2002 and 2005 in Japan. The prenatal PFOS and PFOA levels were measured in maternal serum samples by liquid chromatography-tandem mass spectrometry. Maternal blood levels of nine FAs and TG were measured by gas chromatography-mass spectrometry and TG E-Test Wako kits, respectively. Information on infants' birth size was obtained from participant medical records.RESULTS: The median PFOS and PFOA levels were 5.6 and 1.4 ng/mL, respectively. In the fully adjusted model, including maternal age, parity, annual household income, blood sampling period, alcohol consumption, and smoking during pregnancy, PFOS but not PFOA had a negative association with the levels of palmitic, palmitoleic, oleic, linoleic, alpha-linolenic, and arachidonic acids (p < 0.005) and TG (p-value = 0.016). Female infants weighed 186.6 g less with mothers whose PFOS levels were in the fourth quartile compared with the first quartile (95% CI: -363.4, -9.8). We observed no significant association between maternal levels of PFOS and birth weight of male infants.CONCLUSIONS: Our data suggest an inverse association between PFOS exposure and polyunsaturated FA levels in pregnant women. We also found a negative association between maternal PFOS levels and female birth weight.
• Association of maternal whole blood fatty acid status during the prenatal period with term birth dimensions: a cross-sectional study

  Xiaofang Jia, Masahiro Tagawa, Hiroshi Yatsuya, Hisao Naito, Yumi Hayashi, Husna Yetti, Seiko Sasaki, Atsuko Araki, Chihiro Miyashita, Tamiko Ikeno, Reiko Kishi, Tamie Nakajima

  JOURNAL OF PERINATAL MEDICINE 43 5 565 - 575 2015年09月 [査読有り][通常論文]
   

  Objective: To investigate selected fatty acid (FA) profiles in maternal whole blood during normal pregnancy and to evaluate their associations with term birth dimensions.Methods: We characterized nine major maternal blood FAs representing four FA families during the second and third trimester of pregnancy, and explored their associations with birth weight, length, and chest or head circumferences by multivariate regression models, using data from 318 mother-newborn pairs of the Hokkaido Study.Results: The absolute and/or relative contents of maternal blood docosahexaenoic acid and arachidonic acid were lowest at 35-41 gestational weeks during pregnancy, as was the essential FA status index. Different from palmitic and stearic acids, palmitoleic and oleic acid contents were higher at 35-41 gestational weeks than those at 23-31 gestational weeks. Three FA components were identified through principal component analysis, and were used in association analysis. Component 3, which was positively and significantly loaded by eicosapentaenoic acid (EPA), was associated with chest circumference [beta=0.281, 95% confidence interval (CI): 0.006, 0.556] at 35-41 gestational weeks (P=0.046). No significant associations were observed for Component 1 and 2 loaded by FAs except EPA.Conclusion: Maternal blood EPA content may have an important influence on infant chest circumference.
• 環境省「エコチル調査」開始3年を経ての集計データの報告と調査予定

  土川 陽子, 西條 泰明, 伊藤 善也, 吉岡 英治, 川西 康之, 堤 裕幸, 遠藤 俊明, 馬場 剛, 小林 正樹, 水上 尚典, 有賀 正, 長 和俊, 白石 秀明, 千石 一雄, 宮本 敏伸, 東 寛, 荒木 敦子, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 岸 玲子

  北海道母性衛生学会誌 44 25 - 30 北海道母性衛生学会 2015年08月 [査読無し][通常論文]
  
• 子どもを取り巻く環境と健康(第5回) 環境化学物質の曝露 短半減期化学物質の曝露実態

  荒木 敦子, アイツバマイ ゆふ, 岸 玲子

  公衆衛生 79 7 485 - 490 (株)医学書院 2015年07月 [査読無し][通常論文]
  
• Comparisons of urinary phthalate metabolites and daily phthalate intakes among Japanese families

  Yu Ait Bamai, Atsuko Araki, Toshio Kawai, Tazuru Tsuboi, Eiji Yoshioka, Ayako Kanazawa, Shi Cong, Reiko Kishi

  INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH 218 5 461 - 470 2015年07月 [査読有り][通常論文]
   

  We measured urinary phthalate metabolites, including di-n-butyl phthalate (DnBP), di-isobutyl phthalate, benzyl butyl phthalate (BBzP), and di(2-ethylhexyl) phthalate (DEHP), from 178 school-aged children and their 284 family members using gas chromatography-mass spectrometry, and we calculated daily phthalate intakes. The highest median levels of phthalate metabolites were for mono-isobutyl phthalate in all participants except schoolchildren, where the highest levels were for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). Comparing the schoolchildren with their parents, the schoolchildren had significantly higher urinary metabolites for MEOHP, mono-(2-ethyl-5-carboxypentyl) phthalate, and EDEHP. Regarding daily intakes, the schoolchildren had significantly higher daily intakes of DnBP, BBzP, and EDEHP. All phthalate metabolite and sums of metabolite levels in the schoolchildren were positively correlated with their mothers' levels, except for MEHP, whereas fathers were less correlated with their children. The DEHP intake in this study was higher than that of most other studies. Moreover, 10% of the children and 3% of the adults exceeded the Reference Dose (RfD) value (20 mu g/kg/day) of the U.S. Environmental Protection Agency, which indicates that it is important to focus on children's DEHP exposure because the children exceeded the RID more than adults among the same families who shared similar exposure sources. Our results will contribute to considerations of the regulations for some phthalates and the actual phthalate exposure levels in the Japanese population. (C) 2015 Elsevier GmbH. All rights reserved.
• Prenatal maternal blood triglyceride and fatty acid levels in relation to exposure to di(2-ethylhexyl)phthalate: a cross-sectional study

  Xiaofang Jia, Yukiko Harada, Masahiro Tagawa, Hisao Naito, Yumi Hayashi, Husna Yetti, Masashi Kato, Seiko Sasaki, Atsuko Araki, Chihiro Miyashita, Tamiko Ikeno, Reiko Kishi, Tamie Nakajima

  ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE 20 3 168 - 178 2015年05月 [査読有り][通常論文]
   

  The hypolipidemic effects of di(2-ethylhexyl)phthalate (DEHP) exposure in humans have not been investigated. And the influences of maternal prenatal DEHP exposure on birth outcomes are not well-known. We aimed to estimate prenatal DEHP exposure in maternal blood, and evaluate its relationships to maternal blood triglyceride (TG) and fatty acid (FA) levels and to birth outcomes.We studied 318 mother-newborn pairs residing in Sapporo, Japan. Blood was taken one time during pregnancy for each mother. Maternal and infant characteristics were obtained from medical records and questionnaire survey. We measured DEHP metabolite, mono(2-ethylhexyl) phthalate (MEHP), along with TG and 9 FAs using maternal blood, and analyzed associations of MEHP level with maternal blood TG/FA levels and infant birth dimensions.Maternal blood TG and palmitoleic/oleic acid levels were higher, but stearic/docosahexaenoic acids and MEHP were lower during late pregnancy. Maternal blood MEHP levels inversely correlated with TG and palmitic/palmitoleic/oleic/linoleic/alpha-linolenic acids. After adjustment for confounders, we found that a tenfold increase in blood MEHP levels correlated with a decrease in TG of 25.1 mg/dl [95 % confidence interval (CI) 4.8-45.3 mg/dl], and similar relations in palmitic (beta = -581.8; 95 % CI -906.5, -257.0), oleic (beta = -304.2; 95 % CI -518.0, -90.5), linoleic (beta = -348.6; 95 % CI -510.6, -186.6), and alpha-linolenic (beta = -6.3; 95 % CI -9.5, -3.0) acids. However, we observed no correlations between maternal blood MEHP levels and infant birth weight, length, chest circumference, or head circumference.Ambient DEHP exposure during pregnancy inversely correlated with maternal blood TG and 4 FA levels, but not birth outcomes.
• 胎児期の母の受動喫煙と児の出生体重に関する最近の研究動向

  小林 澄貴, 荒木 敦子, 佐々木 成子, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 岸 玲子

  北海道公衆衛生学雑誌 28 2 37 - 48 北海道公衆衛生学会 2015年03月 [査読無し][通常論文]
   

  妊娠中の受動喫煙が児の出生体重に及ぼす影響について文献検討をした。検索開始年は絞らず、2014年12月迄に発表された論文について、「Secondhand smoke」「Passive smoking」あるいは「Environmental tobacco smoke」と「Birth weigth」をキーワードとしてand条件としてPubMedで文献検索を行った。内容を精査したうえで、最終的に37編を分析対象とした。36編の論文で質問票が用いられており、バイオマーカーとして血清などを測定した論文は2編のみであった。受動喫煙の評価には、自宅や職場に喫煙者がいる・いないでおこなっているもの、喫煙者の人数でおこなっているものなどさまざまであった。14編が前向きコーホート研究、7編が後ろ向きコーホート研究、11編が横断研究、5編が症例対照研究であった。暴露時期別に評価している論文から、妊娠初期の後半以降(妊娠12週以降)に受動喫煙にさらされると出生体重の減少、低出生体重や早産のリスクの上昇といった報告が多かった。
• Effects of Prenatal Leydig Cell Function on the Ratio of the Second to Fourth Digit Lengths in School-Aged Children

  Takahiko Mitsui, Atsuko Araki, Ayako Imai, Sakiko Sato, Chihiro Miyashita, Sachiko Ito, Seiko Sasaki, Takeya Kitta, Kimihiko Moriya, Kazutoshi Cho, Keita Morioka, Reiko Kishi, Katsuya Nonomura

  PLOS ONE 10 3 e0120636  2015年03月 [査読有り][通常論文]
   

  Prenatal sex hormones can induce abnormalities in the reproductive system and adversely impact on genital development. We investigated whether sex hormones in cord blood influenced the ratio of the second to fourth digit lengths (2D/4D) in school-aged children. Of the 514 children who participated in a prospective cohort study on birth in Sapporo between 2002 and 2005, the following sex hormone levels were measured in 294 stored cord blood samples (135 boys and 159 girls); testosterone (T), estradiol (E), progesterone, LH, FSH, inhibin B, and insulin-like factor 3 (INSL3). A total of 350 children, who were of school age and could be contacted for this survey, were then requested via mail to send black-and-white photocopies of the palms of both the left and right hands. 2D/4D was calculated in 190 children (88 boys and 102 girls) using photocopies and derived from participants with the characteristics of older mothers, a higher annual household income, higher educational level, and fewer smokers among family members. 2D/4D was significantly lower in males than in females (p<0.01). In the 294 stored cord blood samples, T, T/E, LH, FSH, Inhibin B, and INSL3 levels were significantly higher in samples collected from males than those from females. A multivariate regression model revealed that 2D/4D negatively correlated with INSL3 in males and was significantly higher in males with <0.32 ng/mL of INSL3 (p<0.01). No correlations were observed between other hormones and 2D/4D. In conclusion, 2D/4D in school-aged children, which was significantly lower in males than in females, was affected by prenatal Leydig cell function.
• Association between Maternal Exposure to di(2-ethylhexyl) Phthalate and Reproductive Hormone Levels in Fetal Blood: The Hokkaido Study on Environment and Children's Health

  Atsuko Araki, Takahiko Mitsui, Chihiro Miyashita, Tamie Nakajima, Hisao Naito, Sachiko Ito, Seiko Sasaki, Kazutoshi Cho, Tamiko Ikeno, Katsuya Nonomura, Reiko Kishi

  PLOS ONE 9 10 e109039  2014年10月 [査読有り][通常論文]
   

  Prenatal di(2-ethylhexyl) phthalate (DEHP) exposure can produce reproductive toxicity in animal models. Only limited data exist from human studies on maternal DEHP exposure and its effects on infants. We aimed to examine the associations between DEHP exposure in utero and reproductive hormone levels in cord blood. Between 2002 and 2005, 514 pregnant women agreed to participate in the Hokkaido Study Sapporo Cohort. Maternal blood samples were taken from 23-35 weeks of gestation and the concentration of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), was measured. Concentrations of infant reproductive hormones including estradiol (E2), total testosterone (T), and progesterone (P4), inhibin B, insulin-like factor 3 (INSL3), steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone were measured from cord blood. Two hundred and two samples with both MEHP and hormones' data were included in statistical analysis. The participants completed a self-administered questionnaire regarding information on maternal characteristics. Gestational age, birth weight and infant sex were obtained from birth records. In an adjusted linear regression analysis fit to all study participants, maternal MEHP levels were found to be associated with reduced levels of T/E2, P4, and inhibin B. For the stratified analyses for sex, inverse associations between maternal MEHP levels T/E2, P4, inhibin B, and INSL3 were statistically significant for males only. In addition, the MEHP quartile model showed a significant p-value trend for P4, inhibin B, and INSL3 decrease in males. Since inhibin B and INSL3 are major secretory products of Sertoli and Leydig cell, respectively, the results of this study suggest that DEHP exposure in utero may have adverse effects on both Sertoli and Leydig cell development in males, which agrees with the results obtained from animal studies. Comprehensive studies investigating phthalates' exposure in humans, as well as their long-term effects on reproductive development are needed.
• 【ハウスダスト中の汚染物質の健康リスク】 住環境におけるフタル酸エステル類・リン酸トリエステル類の曝露実態と居住者への健康影響

  荒木 敦子, アイツバマイ ゆふ, 岸 玲子

  空気清浄 52 3 170 - 177 (公社)日本空気清浄協会 2014年09月 [査読無し][通常論文]
  
• 専門医のためのアレルギー学講座 環境因子とアレルギー 環境汚染とアレルギーに関する疫学的知見 特に室内空気質に焦点をあてて

  荒木 敦子, アイツバマイ ゆふ, 岸 玲子

  アレルギー 63 8 1075 - 1083 (一社)日本アレルギー学会 2014年09月 [査読無し][通常論文]
  
• 環境省「エコチル調査」開始2年の報告と今後の調査について

  土川 陽子, 西條 泰明, 伊藤 善也, 吉岡 英治, 川西 康之, 堤 裕幸, 遠藤 俊明, 馬場 剛, 小林 正樹, 水上 尚典, 有賀 正, 野々村 克也, 長 和俊, 白石 秀明, 千石 一雄, 宮本 敏伸, 東 寛, 池野 多美子, 荒木 敦子, 宮下 ちひろ, 伊藤 佐智子, 岸 玲子

  北海道母性衛生学会誌 43 37 - 42 北海道母性衛生学会 2014年08月 [査読無し][通常論文]
  
• Exposure to house dust phthalates in relation to asthma and allergies in both children and adults

  Yu Ait Bamai, Eiji Shibata, Ikue Saito, Atsuko Araki, Ayako Kanazawa, Kanehisa Morimoto, Kunio Nakayama, Masatoshi Tanaka, Tomoko Takigawa, Takesumi Yoshimura, Hisao Chikara, Yasuaki Saijo, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 485 153 - 163 2014年07月 [査読有り][通常論文]
   

  Although an association between exposure to phthalates in house dust and childhood asthma or allergies has been reported in recent years, there have been no reports of these associations focusing on both adults and children. We aimed to investigate the relationships between phthalate levels in Japanese dwellings and the prevalence of asthma and allergies in both children and adult inhabitants in a cross-sectional study. The levels of seven phthalates in floor dust and multi-surface dust in 156 single-family homes were measured. According to a self-reported questionnaire, the prevalence of bronchial asthma, allergic rhinitis, allergic conjunctivitis, and atopic dermatitis in the 2 years preceding the study was 4.7%, 18.6%, 7.6%, and 10.3%, respectively. After evaluating the interaction effects of age and exposure categories with generalized liner mixed models, interaction effects were obtained for DiNP and bronchial asthma in adults (P-interaction = 0.028) and for DMP and allergic rhinitis in children (P-Interaction = 0.015). Although not statistically significant, children had higher ORs of allergic rhinitis for DiNP, allergic conjunctivitis for DEHP, and atopic dermatitis for DiBP and BBzP than adults, and liner associations were observed (P-trend < 0.05). On the other hand, adults had a higher OR for atopic dermatitis and DEHP compared to children. No significant associations were found in phthalates levels collected from multi-surfaces. This study suggests that the levels of DMP, DEHP, DiBP, and BBzP in floor dust were associated with the prevalence of allergic rhinitis, conjunctivitis, and atopic dermatitis in children, and children are more vulnerable to phthalate exposure via household floor dust than are adults. The results from this study were shown by cross-sectional nature of the analyses and elaborate assessments for metabolism of phthalates were not considered. Further studies are needed to advance our understanding of phthalate toxicity. (C) 2014 Elsevier B.V. All rights reserved.
• Association of Mechanical Ventilation and Flue Use in Heaters With Asthma Symptoms in Japanese Schoolchildren: A Cross-Sectional Study in Sapporo, Japan

  Shi Cong, Atsuko Araki, Shigekazu Ukawa, Yu Ait Bamai, Shuji Tajima, Ayako Kanazawa, Motoyuki Yuasa, Akiko Tamakoshi, Reiko Kishi

  JOURNAL OF EPIDEMIOLOGY 24 3 230 - 238 2014年05月 [査読有り][通常論文]
   

  Background: Use of fuel heaters is associated with childhood asthma. However, no studies have evaluated the associations of flue use and mechanical ventilation (ventilation) with asthma symptoms in schoolchildren.Methods: This cross-sectional study investigated schoolchildren in grades 1 through 6 (age 6-12 years) in Sapporo, Japan. From November 2008 through January 2009, parents completed questionnaires regarding their home environment and their children's asthma symptoms.Results: In total, 4445 (69.5%) parents of 6393 children returned the questionnaire. After excluding incomplete responses, data on 3874 children (60.6%) were analyzed. The prevalence of current asthma symptoms and ever asthma symptoms were 12.8% and 30.9%, respectively. As compared with electric heaters, current asthma symptoms was associated with use of flued heaters without ventilation (OR = 1.62; 95% CI, 1.03-2.64) and unflued heaters with ventilation (OR = 1.77; 95% CI, 1.09-2.95) or without ventilation (OR = 2.23; 95% CI, 1.31-3.85). Regardless of dampness, unflued heaters were significantly associated with current asthma symptoms in the presence and absence of ventilation.Conclusions: Use of unflued heaters was associated with current asthma symptoms, regardless of dampness. In particular, the prevalence of current asthma symptoms was higher in the absence of ventilation than in the presence of ventilation. Ever asthma symptoms was only associated with use of unflued heaters without ventilation. Consequently, use of fuel heaters, especially those that have no flue or ventilation, deserves attention, as their use might be associated with childhood asthma symptoms.
• Detection and intake assessment of organophosphate flame retardants in house dust in Japanese dwellings

  Shuji Tajima, Atsuko Araki, Toshio Kawai, Tazuru Tsuboi, Yu Ait Bamai, Eiji Yoshioka, Ayako Kanazawa, Shi Cong, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 478 190 - 199 2014年04月 [査読有り][通常論文]
   

  The demand for phosphorus flame retardants (PFRs) has recently increased as an alternative to polybrominated diphenyl ether (PBDE). PFRs have been detected in house dust, but little is known about the concentrations of PFRs in private homes and the effects on human health. We measured the levels of 10 PFRs in indoor floor dust and upper surface dust from 128 Japanese dwellings of families with children in elementary school. The median (min-max) concentrations (mu g/g) of PFRs were as follows: tris(2-butoxyethyl) phosphate (TBOEP), 30.88 (<0.61-936.65); tris(2-chloro-iso-propyl) phosphate (TCIPP), 0.74 (<0.56-392.52); and triphenyl phosphate (TPHP), 0.87 (<0.80-23.35). These values exceeded 50% detection rates, and the rates are median over the LOD in floor dust. The concentrations (wig) of TBOEP 26.55 (<0.61-1933.24), TCIPP 2.23 (<0.56-621.23), TPHP 3.13 (<0.80-27.47), tris(2-chloroethyl) phosphate (TCEP) 1.17 (<0.65-92.22), and tributyl phosphate (TNBP) 0.74 (<036-60.64) exceeded 50% detection rates in the upper surface dust. A significant positive correlation (P<0.05) between the concentrations of TCIPP and TBOEP was shown in floor dust and upper surface dust (n=48). Estimated median and 95th percentile daily intake was calculated for toddlers and elementary school children and was compared with reference dose values (RfD) from the literature. For TBOEP, the estimated 95th percentile intake from floor dust was 14% of RfD for toddlers and 4% for school children. The estimated intake from upper surface dust was somewhat lower. Estimated median intake of TBOEP and median intake for the other PFRs were less than 1% of the RfD. TBOEP, TCIPP and TPHP were the main PFRs in the dust. The median levels of PFRs are well below the RfD values. (C) 2014 Elsevier B.V. All rights reserved.
• 北海道3地区における妊婦の喫煙の実態について 環境省「子どもの環境と健康に関する全国調査(エコチル調査)」北海道ユニットセンター登録者のデータから

  荒木 敦子, 西條 泰明, 伊藤 善也, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 土川 陽子, 田村 菜穂美, 吉岡 英治, 川西 康之, 村林 宏, 岸 玲子, エコチル調査北海道ユニットセンター事務局

  北海道公衆衛生学雑誌 27 2 105 - 113 北海道公衆衛生学会 2014年03月 [査読無し][通常論文]
   

  環境省「エコチル調査」北海道ユニットセンター登録妊婦3901名のデータを基に、妊婦の喫煙の実態について報告した。その結果、喫煙経験者は1941名で、うち妊娠中も喫煙を継続している(喫煙継続)群は5.4%、妊娠中に禁煙した(妊娠中禁煙)群は15.1%、妊娠前から禁煙していた(妊娠前禁煙)群は30.0%であった。喫煙継続群は、妊娠中禁煙群、妊娠前禁煙群と比べ、喫煙開始年齢が早く、収入および学歴が低かった。また、喫煙継続群ではパートナーが喫煙している割合が83.0%と有意に多く、受動喫煙の機会・頻度も多いことが判明した。
• アジア出生コホートコンソーシアム(Birth Cohort Consortium of Asia:BiCCA)の設立と現在の取り組みについて

  岸 玲子, 荒木 敦子

  北海道公衆衛生学雑誌 27 2 191 - 195 北海道公衆衛生学会 2014年03月 [査読無し][通常論文]
  
• Phosphorus flame retardants in indoor dust and their relation to asthma and allergies of inhabitants

  A. Araki, I. Saito, A. Kanazawa, K. Morimoto, K. Nakayama, E. Shibata, M. Tanaka, T. Takigawa, T. Yoshimura, H. Chikara, Y. Saijo, R. Kishi

  Indoor Air 24 1 3 - 15 2014年02月 [査読有り][通常論文]
   

  Organophosphate esters are used as additives in flame retardants and plasticizers, and they are ubiquitous in the indoor environment. Phosphorus flame retardants (PFRs) are present in residential dust, but few epidemiological studies have assessed their impact on human health. We measured the levels of 11 PFRs in indoor floor dust and multi-surface dust in 182 single-family dwellings in Japan. We evaluated their correlations with asthma and allergies of the inhabitants. Tris(2-butoxyethyl) phosphate was detected in all samples (median value: 580 μg/g in floor dust, 111 μg/g in multi-surface dust). Tris(2-chloro-iso-propyl) phosphate (TCIPP) was detected at 8.69 μg/g in floor dust and 25.8 μg/g in multi-surface dust. After adjustment for potential confounders, significant associations were found between the prevalence of atopic dermatitis and the presence of TCIPP and tris(1,3-dichloro-2-propyl) phosphate in floor dust [per log10-unit, odds ratio (OR): 2.43 and 1.84, respectively]. Tributyl phosphate was significantly associated with the prevalence of asthma (OR: 2.85 in floor dust, 5.34 in multi-surface dust) and allergic rhinitis (OR: 2.55 in multi-surface dust). PFR levels in Japan were high compared with values reported previously for Europe, Asia-Pacific, and the USA. Higher levels of PFRs in house dust were related to the inhabitants' health status. © 2013 John Wiley & Sons A/S.
• Associations of phthalate concentrations in floor dust and multi-surface dust with the interior materials in Japanese dwellings

  Yu Ait Bamai, Atsuko Araki, Toshio Kawai, Tazuru Tsuboi, Ikue Saito, Eiji Yoshioka, Ayako Kanazawa, Shuji Tajima, Cong Shi, Akiko Tamakoshi, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 468 147 - 157 2014年01月 [査読有り][通常論文]
   

  Phthalates are widely used as plasticizers in numerous products. However, there has been some concern about the various effects they may have on human health. Thus, household phthalate levels are an important public health issue. While many studies have assessed phthalate levels in house dust, the association of these levels with building characteristics has scarcely been examined. The present study investigated phthalate levels in house dust samples collected from the living areas of homes, and examined associations between these phthalate levels and the interior materials. Dust was collected from two portions of the living area: floor dust from the entire floor surface, and multi-surface dust from objects more than 35 cm above the floor. The levels of seven phthalates were measured using gas chromatography/mass spectrometry in selective ion monitoring mode. Phthalate levels were higher in multi-surface dust than in floor dust Among floor dust samples, those from dwellings with compressed wooden flooring had significantly higher levels of di-iso-butyl phthalate compared to those with other floor materials, while polyvinyl chloride (PVC) flooring was associated with higher di-2-ethylhexyl phthalate (DEHP) levels. Among multi-surface dust samples, higher levels of DEHP and di-iso-nonyl phthalate (DINP) were found in samples from homes with PVC wallpaper than without The number of PVC interior materials was significantly positively correlated with the levels of DEHP and DINP in multi-surface dust. The phthalate levels in multi-surface dust were associated with the interior surface materials, and those in floor dust were directly related to the flooring materials. Our findings show that when using house dust as an exposure assessment, it is very important to note where the samples were collected from. The present report provides useful information about the association between phthalates and dust inside dwellings, which will assist with establishing public health provisions. (C) 2013 Published by Elsevier B.V.
• Epidemiological studies on the environmental pollutants and allergies: Focused on in-door air quality

  Atsuko Araki, Yu Ait Bamai, Reiko Kishi

  Japanese Journal of Allergology 63 8 1075 - 1084 2014年 [査読有り][通常論文]
  
• Ten years of progress in the Hokkaido birth cohort study on environment and children's health: cohort profile-updated 2013

  Reiko Kishi, Sachiko Kobayashi, Tamiko Ikeno, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Seiko Sasaki, Emiko Okada, Sumitaka Kobayashi, Ikuko Kashino, Kumiko Itoh, Sonomi Nakajima

  ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE 18 6 429 - 450 2013年11月 [査読有り][通常論文]
   

  The Hokkaido Study on Environment and Children's Health is an ongoing cohort study that began in 2002. The study consists of two prospective birth cohorts, the Sapporo cohort (n = 514) and the Hokkaido large-scale cohort (n = 20,940). The primary goals of this study are to first examine the potential negative effects of perinatal environmental chemical exposures on birth outcomes, including congenital malformations and growth retardation; second, to evaluate the development of allergies, infectious diseases and neurodevelopmental disorders and perform longitudinal observations of the children's physical development to clarify the causal relationship between these outcomes and environmental chemicals; third, to identify individuals genetically susceptible to environmental chemicals; finally, to identify the additive effects of various environmental factors in our daily life, such as secondhand smoke exposure or low folate intake during early pregnancy. In this paper, we introduce our recent progress in the Hokkaido study with a cohort profile updated in 2013. For the last ten years, we followed pregnant women and their offspring, measuring various environmental chemicals, i.e., PCB, OH-PCB and dioxins, PFCs (Perfluorinated Compounds), Organochlorine pesticides, Phthalates, bisphenol A and mercury. We discovered that the concentration of toxic equivalents (TEQ) of dioxin and other specific congeners of PCDF or PCDD have effects on birth weight, infants' neurodevelopment and immune function. There were significant gender differences in these effects; our results suggest that male infants have more susceptibility to those chemical exposures than female infants. Interestingly, we found maternal genetic polymorphisms in AHR, CYP1A1 or GSTs that significantly modified the dioxin concentrations in maternal blood, suggesting different dioxin accumulations in the bodies of individuals with these genotypes, which would lead to different dioxin exposure levels. These genetic susceptibility factors influenced the body size of children born from mothers that either smoked or were passively exposed to tobacco smoke. Further studies investigating the correlation between epigenetics, the effects of intrauterine exposure to environmental chemicals and developmental factors related to health and disease are warranted.
• The relationship between atopic dermatitis and indoor environmental factors: a cross-sectional study among Japanese elementary school children

  Shigekazu Ukawa, Atsuko Araki, Ayako Kanazawa, Motoyuki Yuasa, Reiko Kishi

  INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH 86 7 777 - 787 2013年10月 [査読有り][通常論文]
   

  This study aimed to determine that home environmental factors were associated with atopic dermatitis in Japanese elementary school children.In this cross-sectional study, a total of 4,254 children in 12 public elementary schools in Sapporo city in Hokkaido, Japan were examined. Atopic dermatitis was defined using the International Study of Asthma and Allergies in Childhood questionnaire. The questionnaires also contained 14 questions about the child's home environment. To obtain multivariate-adjusted ORs for atopic dermatitis in relation to the home environment, we controlled for possible confounders including gender, school grade, parental history of allergies, number of siblings, and whether the child was firstborn. The study participants were then divided into two groups according to gender, and a stratified analysis was performed to obtain adjusted ORs for atopic dermatitis in relation to the home environment.The prevalence of atopic dermatitis in our sample was 16.7 %. Using fully adjusted models, the risk factors for atopic dermatitis were found to be the household use of a non-electric heating system without a ventilation duct to the outside (compared to the use of an electric heating system), having visible mould in the house, having a mouldy odour in the house, and condensation on the windowpanes in the house odds ratios (OR 1.25-1.54). In our stratified analysis, having visible mould and having a mouldy odour in the house were relevantly found to be risk factors for boys (OR 1.28-1.64). However, these associations were not found among girls.To improve children's health, further study is needed to corroborate the findings.
• 【化学物質過敏症問題の現状と今後の課題を考える】 いわゆる化学物質過敏症 その国際的動向とアロマテラピーを使った緩和研究

  荒木 敦子, 岸 玲子

  Aroma Research 14 2 111 - 115 フレグランスジャーナル社 2013年05月 [査読無し][通常論文]
  
• 北海道における環境省「エコチル調査」に関する意識調査と広報活動の課題

  荒木 敦子, 尾西 奈江, 中瀬 督久, 伊藤 善也, 西條 泰明, 池野 多美子, 安住 薫, 土川 陽子, 宮下 ちひろ, 伊藤 佐智子, 岸 玲子, エコチル調査北海道ユニットセンター事務局

  北海道公衆衛生学雑誌 26 2 125 - 132 北海道公衆衛生学会 2013年03月 [査読無し][通常論文]
   

  エコチル調査は、子どもの健康に与える環境要因を解明することを目的とし、「胎児期から小児期にかけての化学物質曝露が子どもの健康に大きな影響を与えている」ことを中心仮説としており、全国10万組の親子を対象とした出生コホート調査である。北海道では、札幌、旭川、北見の3地区で調査を進めている。今回、エコチル調査がメディアに露出する前後の道民の認知度・意識を明らかにし、今後の課題について示唆を得る目的で検討を行った。方法は、北海道新聞情報研究所が管理運営する「Doshinインターネット」のモニターを対象とし、エコチル調査の広報を集中的に行った前後の平成24年3月と4月の2回WEBアンケートを実施した。回答者数は1回目が678名、2回目が675名であり、エコチル調査の認知度は1回目14.4%であったが2回目には30.9%に上昇していた。これは、新聞をはじめとしたマスメディアによるPR広告の効果と思われた。今後、エコチル調査への関心を持続させるための課題として、調査の進捗状況など得られた成果を開示していくことが必要と考えられた。
• The feasibility of aromatherapy massage to reduce symptoms of Idiopathic Environmental Intolerance: A pilot study

  Atsuko Araki, Kazuhiko Watanabe, Yoko Eitaki, Toshio Kawai, Reiko Kishi

  COMPLEMENTARY THERAPIES IN MEDICINE 20 6 400 - 408 2012年12月 [査読有り][通常論文]
   

  Objectives: Idiopathic Environmental Intolerance (IEI) is an acquired disorder with multiple recurrent symptoms, which is associated with diverse environmental factors that are tolerated by the majority of people. El is an illness of uncertain aetiology, making it difficult to treat using conventional medicine. Therefore, there is a need for novel therapies to control the symptoms of IEI. The objective of this study was to evaluate the feasibility and impact of aromatherapy massage for individuals with IEI.Design: Non-blinded crossover trial.Setting: IEI patients who attended a clinic in Sapporo city were recruited, and sixteen patients were enrolled. Participants were clinically examined by an experienced medical doctor and met the criteria included in the working definition of IEI disorder.Interventions: During the active period, participants received four one-hour aromatherapy massage sessions every two weeks. During the control period, the participants did not receive any massages.Main outcome measurements: Scores on the IEI-scales trigger checklist, symptoms, life impact, and the State Anxiety Inventory were assessed before and after each period. Short-term mood enhancement was evaluated using the Profiles of Mood Status (POMS) before and after sessions.Results: Due to period effects, evaluation of the results had to be restricted to the first period, and the result showed no effect of intervention. All six sub-scales of the POMS improved after each session (mean score differences: 4.89-1.33, P<0.05).Conclusions: Aromatherapy was well tolerated by subjects with IEI; however, aromatherapy, as applied in this study, did not suggest any specific effects on IEI condition. (C) 2012 Elsevier Ltd. All rights reserved.
• A randomized controlled trial of a Functioning Improvement Tool home-visit program and its effect on cognitive function in older persons

  Shigekazu Ukawa, Hiroki Satoh, Motoyuki Yuasa, Tamiko Ikeno, Tomoko Kawabata, Atsuko Araki, Eiji Yoshioka, Waka Murata, Katsunori Ikoma, Reiko Kishi

  INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY 27 6 557 - 564 2012年06月 [査読有り][通常論文]
   

  Objective: The aim was to determine whether mini mental state examination (MMSE) scores improved in older participants of a Functioning Improvement Tool (FIT) home-visit program. Methods: Two hundred fifty-two participants aged 65 years or older living at home and receiving preventive services or a community long-term care prevention project according to the Japanese social long-term care insurance system were enrolled and randomly assigned to an intervention group (n = 128) or a control group (n = 124). Intervention group subjects received a 60-min FIT home-visit program for 3 months, which included guidance, assistance, and help in writing and teaching calculation in order to complete the FIT. Control subjects did not receive any home visits. Cognitive function was evaluated by MMSE. Analysis of covariance was used to examine the effects of the FIT adjusting for baseline MMSE scores, age, and sex. Results: Fifty-three subjects were excluded because of withdrawal, hospitalization, death, relocation, or missing data of MMSE; 199 subjects (60 men, 139 women; age 78.6 +/- 7.4 years) were analyzed. The baseline MMSE scores did not differ between the intervention and control groups (24.2 +/- 4.3 vs. 24.1 +/- 4.7, p = 0.90). After the study period, the change in the MMSE score was significantly better in the intervention group than in the control group (0.8 +/- 0.3 vs. -0.1 +/- 0.2, p = 0.04). Stratified analyses showed that the intervention strategy was most effective in subjects with mild cognitive decline, with baseline MMSE scores from 18 to 23 points (1.9 +/- 0.5 vs. -0.1 +/- 2.8, p = 0.04). Conclusions: Our FIT home-visit program improved MMSE scores in older participants with mild cognitive decline. Copyright (C) 2011 John Wiley & Sons, Ltd.
• The relationship between exposure to microbial volatile organic compound and allergy prevalence in single-family homes

  Atsuko Araki, Ayako Kanazawa, Toshio Kawai, Yoko Eitaki, Kanehisa Morimoto, Kunio Nakayama, Eiji Shibata, Masatoshi Tanaka, Tomoko Takigawa, Takesumi Yoshimura, Hisao Chikara, Yasuaki Saijo, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 423 18 - 26 2012年04月 [査読有り][通常論文]
   

  Microbial volatile organic compounds (MVOCs) are a type of VOCs produced by microorganisms. Exposure to 1-octen-3-ol, one of the known MVOCs, has been reported to reduce nasal patency and increase nasal lavage myeloperoxidase, eosinophil cationic proteins, and lysozymes in both experimental and field studies. We reported in a previous paper that 1-octen-3-ol exposure at home is associated with mucosal symptoms. In this study, our aim was to investigate the relationship between asthma and allergies and MVOC exposure in single-family homes. The subjects were 624 inhabitants of 182 detached houses in six regions of Japan. Air samples were collected using diffusive samplers, and the concentrations of eight selected MVOCs were analyzed using gas chromatography/mass spectrometry in selected-ion-monitoring mode. Each inhabitant of each of the dwellings was given a self-administered questionnaire. Among the 609 subjects who answered all of the questions about allergies, history of the medical treatment for asthma, atopic dermatitis, allergic rhinitis, and allergic conjunctivitis within the preceding two years was 4.8%, 9.9%, 18.2%, and 7.1%, respectively. A significant association between 1-octen-3-ol (per log(10) unit) and allergic rhinitis odds ratio (OR): 4.10,95% confidence interval (CI): 1.71 to 9.80 and conjunctivitis (OR: 3.54, CI: 1.17 to 10.7) was found after adjusting for age, sex, tobacco, wall-to-wall carpeting, signs of dampness, history of treatment for hay fever, and other potentially relevant environmental factors. No relationships were found between any MVOCs and asthma or atopic dermatitis after the adjustment. The levels of MVOCs and airborne fungi were only weakly correlated. These results are consistent with previous studies that have associated higher levels of 1-octen-3-ol exposure with increased irritation of nasal and ocular mucosae. Although the indoor-air concentrations of 1-octen-3-ol found in this study were relatively low, we conclude that exposure to MVOC may be related to rhinitis and conjunctivitis. (C) 2012 Elsevier B.V. All rights reserved.
• Validation of diffusive mini-samplers for aldehyde and VOC and its feasibility for measuring the exposure levels of elementary school children

  Atsuko Araki, Tazuru Tsuboi, Toshio Kawai, Yu Ait Bamai, Tomoya Takeda, Eiji Yoshioka, Reiko Kishi

  JOURNAL OF ENVIRONMENTAL MONITORING 14 2 368 - 374 2012年02月 [査読有り][通常論文]
   

  Exposure to various chemicals can cause adverse effects to health, such as asthma and allergies, especially in children. Data on personal exposure levels in children are scarce, thus small lightweight diffusive mini-samplers for aldehydes and volatile organic compounds (VOCs) were designed to measure the exposure level of children to these chemicals. The aim of the study was to validate and examine the applicability of these mini-samplers for measuring daily chemical exposure. The diffusive mini-samplers are 20 mm in length, 11 mm in diameter, and 1.67 g in weight. The devices are cylindrically shaped with polytetrafluoroethylene membrane filters placed at each end. To measure aldehydes and acetone, 20 mg of 2,4-dinitrophenylhydrazine was used as an absorbent. To measure VOCs, a carbon molecular sieve was used. The sampling rate for each chemical was determined by parallel sampling with active samplers in a closed exposure bag. The blank levels of the chemicals and the storage stability of the device were tested. The mini-samplers were compared to commercially available diffusive samplers. To examine the applicability of the samplers, 65 elementary school children carried them for 24 h. The sampling rates for formaldehyde, acetaldehyde, and acetone were 20.9, 22.9, and 19.7 mL min(-1), respectively. The limits of quantification (LOQ) for the 24-hour sampling by high-performance liquid chromatography/ultraviolet (HPLC/UV) analysis were 8.3, 7.6, and 8.8 mu g m(-3) for formaldehyde, acetaldehyde, and acetone, respectively. The sampling rates for the 11 VOCs were determined and ranged from 3.3 mL min(-1) for styrene and 2-ethyl-1-hexanol to 11.7 mL min(-1) for benzene. The LOQ for the 24-hour sampling by gas chromatography-mass spectrometry (GC-MS) analysis ranged from 5.9-105.2 mu g m(-3), 1.1-24.7 parts per billion. The storage stability after 5 days ranged from 94.8 to 118.2%. Formaldehyde, acetone, benzene, and toluene were detected above the LOQ in more than 90% of the children, and the median concentrations were 21.7, 20.9, 10.1, and 21.5 mu g m(-3), respectively. This study shows that the diffusive samplers developed were suitable for children to carry and were capable of measuring the children's daily chemical exposure.
• Relationships between mite allergen levels, mold concentrations, and sick building syndrome symptoms in newly built dwellings in Japan

  Y. Saijo, A. Kanazawa, A. Araki, K. Morimoto, K. Nakayama, T. Takigawa, M. Tanaka, E. Shibata, T. Yoshimura, H. Chikara, R. Kishi

  INDOOR AIR 21 3 253 - 263 2011年06月 [査読有り][通常論文]
   

  P>This study investigated the possible relationships between exposures to mite allergen and airborne fungi with sick building syndrome (SBS) symptoms for residents living in newly built dwellings. We randomly sampled 5709 newly built dwellings in six prefectures from northern to southern Japan. A total of 1479 residents in 425 households participated in the study by completing questionnaire surveys and agreeing to environmental monitoring for mite allergen (Der 1), airborne fungi, aldehydes, and volatile organic compounds. Stepwise logistic regression analyses adjusted for confounders were used to obtain odds ratios (OR) of mite allergen and fungi for SBS symptoms. Der 1 had a significantly high OR for nose symptoms. Rhodotorula had a significantly high OR for any symptoms, and Aspergillus had significantly high OR for eye symptoms. However, the total colony-forming units had a significantly low OR for throat and respiratory symptoms. Eurotium had a significantly low OR for skin symptoms. In conclusion, dust-mite allergen levels and indoor airborne Rhodotorula and Aspergillus concentrations may result in SBS symptoms in newly built dwellings. Practical Implications Various factors can cause sick building syndrome symptoms. This study focused on biologic factors such as dust-mite allergen and airborne fungi in newly built dwellings in Japan. Dust-mite allergen levels were significantly associated with higher rates of nose symptoms, airborne Rhodotorula concentrations were significantly associated with higher rates of any symptoms, and Aspergillus concentrations were significantly associated with higher rates of eye symptoms. Measures should be taken to reduce mite allergen levels and fungal concentrations in these dwellings.
• [Variations of indoor environment and the prevalence of sick house syndrome over three-year period in detached houses in Sapporo].

  Araki A, Kanazawa A, Saijo Y, Kishi R

  Nihon eiseigaku zasshi. Japanese journal of hygiene 66 3 589 - 599 3 2011年05月 [査読有り][通常論文]
   

  OBJECTIVES: The purpose of this study was to investigate annual variations in indoor environmental chemical, fungal and dust mite allergen levels, with regards to variations in sick house syndrome (SHS) symptoms over a three-year period. METHODS: Detached houses were randomly selected from a building plan approval application, and a questionnaire survey was conducted in 2003 in Sapporo, Japan. Indoor environmental measurements and a self-administered questionnaires survey were conducted on the selected houses in 2004, 2005 and 2006. The same protocol was used for the three-year period to measure the levels of chemicals, fungi and dust mite allergens. A personal questionnaire to assess SHS was distributed to all inhabitants of the dwellings along with one questionnaire to assess housing characteristics. RESULTS: In 2004, 2005 and 2006, the owners of 104, 64 and 41 houses, respectively, agreed to participate in this study. Forty-one houses and the 127 inhabitants who participated in this three-year survey period were included in the analysis to evaluate the associations between differences in environmental measurements and SHS. The levels of formaldehyde, acetone, toluene, Alternaria and Cladosporium tended to decrease, whereas those of limonene and Aspergillus tended to increase over the three-year period. Increasing levels of Cryptococcus and the dampness index in individual houses correlated with increasing SHS symptom scores in the inhabitants after mutual adjustment. CONCLUSIONS: Although the average levels of chemicals and fungi were relatively low, the results show the relationship between annual variations in indoor environmental measurements and variations in SHS symptom scores.
• 小学生のシックハウス症候群の有訴と自宅の床ダスト中有機リン酸トリエステル類濃度との関連

  竹田 智哉, 荒木 敦子, アイツバマイ ゆふ, 斎藤 育江, 早川 敦司, 吉岡 英治, 金澤 文子, 湯浅 資之, 岸 玲子

  北海道公衆衛生学雑誌 24 2 73 - 84 北海道公衆衛生学会 2011年03月 [査読無し][通常論文]
   

  札幌市の公立小学校に通う児童78名を対象に、自宅居間の床ダスト中における有機リン酸トリエステル類11化合物の測定を行い、シックハウス症候群(SHS)との関連について検討した。SHS有訴群(39名)と非有訴群(39名)とで11化合物の濃度を比較したところ、全ての化合物において有意な群間差は認められなかった。しかし、化合物のうちリン酸トリスブトキシエチルの濃度は、過去に欧米で報告された濃度に比べてかなり高かったことから、健康影響について更なる調査が必要であると考えられた。
• シックハウス症候群研究の最新情報 シックハウス症候群に関する全国疫学研究(その全体像と何がわかったか)

  岸 玲子, 荒木 敦子

  日本衛生学雑誌 66 2 277 - 278 日本衛生学会 2011年02月 [査読無し][通常論文]
  
• Prevalence of Asthma, Atopic Dermatitis, and Rhinitis and MVOC Exposure in Single Family Homes-A Survey in 6 Cities of Japan

  Atsuko Araki, Toshio Kawai, Yoko Eitaki, Ayako Kanazawa, Kanehisa Morimoto, Kunio Nakayama, Eiji Shibata, Masatoshi Tanaka, Tomoko Takigawa, Takesumi Yoshimura, Hisao Chikara, Yasuaki Saijo, Reiko Kishi

  EPIDEMIOLOGY 22 1 S40 - S41 2011年01月 [査読有り][通常論文]
  
• Relationship between selected indoor volatile organic compounds, so-called microbial VOC, and the prevalence of mucous membrane symptoms in single family homes

  Atsuko Araki, Toshio Kawai, Yoko Eitaki, Ayako Kanazawa, Kanehisa Morimoto, Kunio Nakayama, Eiji Shibata, Masatoshi Tanaka, Tomoko Takigawa, Takesumi Yoshimura, Hisao Chikara, Yasuaki Saijo, Reiko Kishi

  SCIENCE OF THE TOTAL ENVIRONMENT 408 10 2208 - 2215 2010年04月 [査読有り][通常論文]
   

  Microorganisms are known to produce a range of volatile organic compounds, so-called microbial VOC (MVOC). Chamber studies where humans were exposed to MVOC addressed the acute effects of objective and/or subjective signs of mucosal irritation However, the effect of MVOC on inhabitants due to household exposure is still unclear The purpose of this epidemiological study was to measure indoor MVOC levels in single family homes and to evaluate the relationship between exposure to them and sick building syndrome (SBS) All Inhabitants of the dwellings were given a self-administered questionnaire with standardized questions to assess their symptoms Air samples were collected and the concentrations of eight selected compounds in indoor air were analyzed by gas chromatography/mass spectrometry selective ion monitoring mode (GC/MS-SIM). The most frequently detected MVOC was 1-pentanol at a detection rate of 78 6% and geometric mean of 060 mu g/m(3). Among 620 participants, 120 (19.4%) reported one or more mucous symptoms; irritation of the eyes, nose, airway, or coughing every week (weekly symptoms), and 30 (4 8%) reported that the symptoms were home-related (home-related symptoms). Weekly symptoms were not associated with any of MVOC. whereas significant associations between home-related mucous symptoms and 1-octen-3-ol (per log(10)-unit: odds ratio (OR) 5 6, 95% confidence interval (Cl) 21 to 14.8) and 2-pentanol (per log(10)-unit OR 2.3, 95% CI 1 0 to 4.9) were obtained after adjustment for gender, age, and smoking. Associations between home-related symptoms and 1-octen-3-ol remained after mutual adjustment. However, concentrations of the selected compounds in indoors were lower than the estimated safety level in animal studies. Thus, the statistically significant association between 1-octen-3-ol may be due to a direct effect of the compounds or the associations may be being associated with other offending compounds. Additional studies are needed to evaluate these possibilities. (C) 2010 Elsevier B.V. All rights reserved
• 【環境リスク】 シックハウス症候群に関する研究の現状と今後の課題

  岸 玲子, 荒木 敦子

  公衆衛生 74 4 295 - 299 (株)医学書院 2010年04月 [査読無し][通常論文]
  
• Association between indoor exposure to semi-volatile organic compounds and building-related symptoms among the occupants of residential dwellings

  A. Kanazawa, I. Saito, A. Araki, M. Takeda, M. Ma, Y. Saijo, R. Kishi

  INDOOR AIR 20 1 72 - 84 2010年02月 [査読有り][通常論文]
   

  P>The aim of this study was to evaluate the levels of semi-volatile compounds (SVOCs) in residential detached houses in Sapporo, Japan, and whether exposure to these SVOCs was associated with the development of building-related symptoms named 'sick house syndrome' (SHS). The definition of SHS is fundamentally the same as that of the sick building syndrome (SBS). The presence of symptoms of SHS was evaluated using a validated self-administered questionnaire. Surveys and samplings of air and house dust in 41 dwellings were performed from October 2006 to January 2007, and 134 occupants responded to questionnaires. Samples were analyzed to quantify the concentrations of eight plasticizers, eleven phosphate triester flame retardants, two alkyl phenols used as anti-oxidants, and one organochlorine synergist called s-421, by gas chromatography-mass spectrometry and gas chromatography-flame photometry. The compounds frequently detected were di-n-butylphthalate, di(2-ethylhexyl)phthalate (DEHP), and dibutylhydroxytoluene in air, and DEHP and tris(2-butoxyethyl)phosphate (TBEP) in dust. Tributylphosphate was strongly and directly associated with mucosal symptoms of SHS; s-421 was also directly associated with mucosal symptoms of SHS. On the contrary, some chemicals such as diethylphthalate and TBEP were inversely associated with SHS. In future studies, we plan to assess these associations in a larger population. Practical Implications This study suggests that it may be possible to reduce building-related symptoms by altering exposure to certain SVOCs, such as tributylphosphate commonly found in ceiling and wall coverings and s-421 used as a synergist for pyrethroids. The association between SHS and s-421 suggested that use of pyrethroid insecticides could elicit symptoms of SHS. However, further studies are necessary to test the associations observed in the present study and to examine whether the SVOCs associated with symptoms are causative agents or simply surrogates for some other factor that is causing the symptoms.
• Diffusive sampling and measurement of microbial volatile organic compounds in indoor air

  A. Araki, Y. Eitaki, T. Kawai, A. Kanazawa, M. Takeda, R. Kishi

  INDOOR AIR 19 5 421 - 432 2009年10月 [査読有り][通常論文]
   

  Microbial volatile organic compounds (MVOC), chemicals emitted from various microorganisms, in indoor air have been of concern in recent years. For large field studies, diffusive samplers are widely used to measure indoor environments. Since the sampling rate of a sampler is a fundamental parameter to calculate concentration, the sampling rates of eight MVOC with diffusive samplers were determined experimentally using a newly developed water-bubbling method: air was supplied to the MVOC-solutions and the vapor collected in an exposure bag, where diffusive and active samplers were placed in parallel for comparison. Correlations between the diffusive and active samplings gave good linear regressions. The sampling rates were 30-35 ml/min and the detection limits were 0.044-0.178 mu g/m3, as determined by GC/MS analysis. Application of the sampling rates in indoor air was validated by parallel sampling of the diffusive and active sampling method. 5% Propan-2-ol/CS(2) was the best solvent to desorb the compounds from absorbents. The procedure was applied to a field study in 41 dwellings. The most frequently detected compounds were hexan-2-one and heptan-2-one, with 97.5% detection rates and geometric mean values of 0.470 and 0.302 mu g/m3, respectively. This study shows that diffusive samplers are applicable to measure indoor MVOC levels.Practical Implications At present, there are still limited reports on indoor Microbial Volatile Organic Compounds (MVOC) levels in general dwellings and occupants' health. Compared with active sampling methods, air sampling using a diffusive sampler is particularly advantageous for use in large field studies due to its smallness, light-size, easy-handling, and cost-effectiveness. In this study, sampling rates of selected MVOC of the diffusive sampler were determined using the water-bubbling method: generating gases by water-bubbling and exposing the diffusive and active samplers at the same time. The obtained sampling rates were validated, and the method was applied to the field study.
• Relationship between sick building syndrome and indoor environmental factors in newly built Japanese dwellings

  Makoto Takeda, Yasuaki Saijo, Motoyuki Yuasa, Ayako Kanazawa, Atsuko Araki, Reiko Kishi

  INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH 82 5 583 - 593 2009年04月 [査読有り][通常論文]
   

  Indoor air contaminants and dampness in dwellings have become important environmental health issues. The aim of this study is to clarify which factors are related to sick building syndrome (SBS) in newly built dwellings at Hokkaido, Japan, through a comprehensive evaluation of the indoor environment and validated sick building symptom questionnaires.The symptoms of 343 residents in 104 detached houses were surveyed by standardized questionnaires, and the concentrations of formaldehyde, acetaldehyde, volatile organic compounds (VOCs), airborne fungi, and dust mite allergen in their living rooms were measured. By summing the presence or absence of the five dampness indicators (condensations, mold growth, moldy odor, high air humidity of the bathroom, water leakage), a dampness index was calculated.SBS symptoms were found in 21.6% of surveyed individuals. In a fully adjusted multivariate logistic regression analysis, the dampness index [odds ratio (OR) = 1.50; 95% confidence interval (CI): 1.06-1.11], log formaldehyde (OR = 23.79, 95% CI: 2.49-277.65), and log alpha-pinene (OR = 2.87, 95% CI: 1.36-6.03) had significantly higher ORs for SBS symptoms. However, other VOCs, airborne fungi, and dust mite allergen did not have significantly higher ORs.Dampness, formaldehyde, and alpha-pinene were significantly related to SBS symptoms in newly built dwellings. We should, therefore, take measures to reduce the chemicals and dampness in dwellings.
• 基礎医学から シックハウス症候群の疫学 最近の知見

  岸 玲子, 竹田 誠, 金澤 文子, 荒木 敦子

  日本医事新報 4370 73 - 76 (株)日本医事新報社 2008年01月 [査読無し][通常論文]
  
• Cloning and expression of a gene encoding N-glycosyltrasferase (ngt) from Saccharothrix aerocolonigenes ATCC39243

  T Ohuchi, A Ikeda-Araki, A Watanabe-Sakamoto, K Kojiri, M Nagashima, M Okanishi, H SUda

  JOURNAL OF ANTIBIOTICS 53 4 393 - 403 2000年04月 [査読有り][通常論文]
   

  In the course of our bioconversion studies on the derivatives of an indolocarbazole, J-104303, Saccharothrix aerocolonigenes ATCC39243 was found to convert J-104303, which was added into the culture medium, to its glycosylated derivative, J-109384. In order to clone the gene having the ability to convert J-104303 to J-109384, a library of Saccharothrix aerocolonigenes ATCC39243 DNA fragments was constructed using Streptomyces lividans TK21 and pIJ702 as host strain and vector, respectively. By examining more than 5,000 transformants, one was found to convert J-104303 to J-109384. Sequence analysis of the inserted DNA fragment revealed an open reading frame with 1,245 base pairs, named ngt. The transformant containing this ngt gene was also found to introduce a D-glucose moiety into 6-N-methylarcyriaflavin C. Furthermore, when ngt was introduced into Streptomyces mobaraensis BA13793, a producer of J-104303, the resulting transformant produced J-109384 directly.
• SECRETORY PRODUCTION OF CHICKEN OVOMUCOID DOMAIN-3 BY ESCHERICHIA-COLI AND ALTERATION OF INHIBITORY SPECIFICITY TOWARD PROTEASES BY SUBSTITUTION OF THE P1 SITE RESIDUE

  S KOJIMA, N FUSHIMI, A IKEDA, KUMAGAI, I, K MIURA

  GENE 143 2 239 - 243 1994年06月 [査読有り][通常論文]
   

  Ovomucoids are commonly present in bird egg white and exhibit inhibitory activity toward various serine proteases. To investigate the structure-function relationship of ovomucoid domain 3, we established a secretory expression system for the chicken ovomucoid domain 3 (OMCHI3)-encoding gene in Escherichia coli by ligating it downstream from the tac promoter and signal peptide of E. coli alkaline phosphatase. E. coli JM105 was transformed with the resulting plasmid and induced with 1 mM isopropyl-beta-D-thiogalactopyranoside (IPTG). The mature OMCHI3 was detected in the culture supernatant, and was purified to homogeneity by three-step chromatography. Amino-acid sequence analysis showed that processing by the signal peptidase was carried out exactly at the expected site. Measurements of circular dichroism spectra and inhibitory activity indicated that OMCHI3 was produced in the properly folded form. Furthermore, site-specific replacement of the Ala residue at the P1 site with Met or Lys resulted in acquisition of inhibitory activity toward chymotrypsin or trypsin, respectively, indicating that the P1 site is the predominant determinant for inhibitory specificity.

MISC

• フタル酸ジ(2-エチルヘキシル)代謝物の核内受容体活性プロファイルとHepaRG細胞への曝露影響

  安田彩夏, 村瀬渉, 窪田篤人, 浦丸直人, 奥田勝博, 箱田涼, 池田敦子, 池田敦子, 小島弘幸 衛生薬学・環境トキシコロジー講演要旨集 2023 2023年
• 子どものスクリーンタイムと聴覚・視覚ワーキングメモリーとの関連:北海道スタディ

  田村菜穂美, 山崎圭子, 宮下ちひろ, 池田敦子, 池田敦子, 日景隆, 水田正弘, 大宮学, 竹鼻美月, 赤坂梨莉花, 岸玲子 日本衛生学雑誌(Web) 78 (Supplement) 2023年
• 学童期の子どもの電磁波曝露実態の変化-北海道スタディ

  山崎圭子, 宮下ちひろ, 田村菜穂美, 池田敦子, 池田敦子, 日景隆, 水田正弘, 大宮学, 岸玲子 日本衛生学雑誌(Web) 78 (Supplement) 2023年
• 電波ばく露と小児の健康影響に関する疫学研究のための仰角を考慮した5G周波数帯人体遮蔽特性推定

  敦賀桜, 杉村海渡, 日景隆, 大宮学, 山崎圭子, 宮下ちひろ, 田村奈穂美, 池田敦子, 岸玲子 電子情報通信学会技術研究報告(Web) 123 (72(EMCJ2023 12-28)) 2023年
• Editor’s Focus: Maternal Alcohol Use and Fetal Growth in Japan

  Kazutoshi Cho, Sumitaka Kobayashi, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Yasuaki Saijo, Yoshiya Ito, Kazuo Sengoku, Tsuyoshi Baba, Hisanori Minakami, Yuichi Nakamura, Reiko Kishi, The Japan Environment and Children’s Study Group Pediatric Research 92 (1) 1 -1 2022年07月 [査読無し][招待有り]
   

  掲載論文（責任著者）が、Pediatric Research volume 92 No. 1 July 2022のEditor’s Focusに選出され紹介された。掲載論文：Kazutoshi Cho, Sumitaka Kobayashi, et al. Prenatal alcohol exposure and adverse fetal growth restriction: findings from the Japan Environment and Children's Study. Pediatric Research. 2022; 92: 291-298. https://doi.org/10.1038/s41390-021-01595-3.
• 電波ばく露と青少年の健康影響に関する疫学研究にむけた携帯型ばく露計受信特性に与える人体遮蔽影響評価

  山本康平, 日景隆, 大宮学, 山崎圭子, 池田敦子, 宮下ちひろ, 田村菜穂美, 岸玲子 電子情報通信学会大会講演論文集(CD-ROM) 2022 2022年
• 小児の高周波ばく露ドシメトリを目的とした仰角のある到来平面波に対する人体遮蔽特性推定

  杉村海渡, 山本康平, 日景隆, 山崎恵子, 宮下ちひろ, 田村菜穂美, 荒木敦子, 岸玲子 電気・情報関係学会北海道支部連合大会講演論文集(CD-ROM) 2022 2022年
• 小児の携帯情報端末の使用開始年齢と問題行動の程度との関連-北海道スタディ

  宮下ちひろ, 山崎圭子, 田村菜穂美, 池田敦子, 池田敦子, 福永久典, 日景隆, 水田正弘, 大宮学, 岸玲子 日本衛生学雑誌(Web) 77 (Supplement) 2022年
• 学童期における携帯電話等の電磁波曝露の実態調査-北海道スタディ

  山崎圭子, 田村菜穂美, 宮下ちひろ, 池田敦子, 池田敦子, 福永久典, 日景隆, 水田正弘, 大宮学, 岸玲子 日本衛生学雑誌(Web) 77 (Supplement) 2022年
• 子どものスクリーンタイムおよび問題行動との関連:北海道スタディ

  田村菜穂美, 山崎圭子, 宮下ちひろ, 池田敦子, 池田敦子, 福永久典, 日景隆, 水田正弘, 大宮学, 岸玲子 日本衛生学雑誌(Web) 77 (Supplement) 2022年
• 学童期の高周波ばく露と健康影響の関連性に対する疫学研究を目的とした携帯電話・無線LAN周波数帯における人体遮蔽特性推定

  山本康平, 杉村海渡, 日景隆, 大宮学, 山崎圭子, 宮下ちひろ, 田村奈穂美, 池田敦子, 岸玲子 電子情報通信学会技術研究報告(Web) 122 (40(EMCJ2022 8-13)) 2022年
• 電波ばく露と青少年の健康影響に関する疫学研究を目的とした小児モデルの人体遮蔽特性推定

  杉村海渡, 山本康平, 日景隆, 大宮学, 山崎圭子, 宮下ちひろ, 田村奈穂美, 池田敦子, 岸玲子 電子情報通信学会技術研究報告(Web) 122 (67(EMCJ2022 14-27)) 2022年
• 室内空気中SVOC(準揮発性有機化合物)濃度の実態調査

  金 勲, 稲葉 洋平, 戸次 加奈江, 東 賢一, 林 基哉, 荒木 敦子, アイツバマイ ゆふ, 篠原 直秀, 欅田 尚樹 室内環境学会学術大会講演要旨集 2021年 104 -105 2021年12月
• 一般家庭における短期/長期堆積ダストを活用したSVOCの曝露評価研究1 リン系難燃剤・可塑剤の室内濃度分布と汚染要因の解析

  戸次 加奈江, 池田 敦子, アイツバマイ ゆふ, 稲葉 洋平, 東 賢一, 金 勲, 岸 玲子 室内環境学会学術大会講演要旨集 2021年 100 -101 2021年12月
• 一般家庭における短期/長期堆積ダストを活用したSVOCの曝露評価研究2 子どものハウスダスト中リン系難燃剤・可塑剤の一日摂取量

  池田 敦子, 戸次 加奈江, アイツバマイ ゆふ, 稲葉 洋平, 金 勲, 岸 玲子 室内環境学会学術大会講演要旨集 2021年 102 -103 2021年12月
• 許容濃度等の勧告(2021年度)

  野見山 哲生, 圓藤 吟史, 圓藤 陽子, 河合 俊夫, 岸 玲子, 田中 茂, 長野 嘉介, 那須 民江, 矢野 栄二, 東 賢一, 石竹 達也, 市場 正良, 市原 学, 伊藤 昭好, 岩澤 聡子, 大前 和幸, 奥田 裕計, 加藤 貴彦, 上島 通浩, 苅田 香苗, 川本 俊弘, 日下 幸則, 熊谷 信二, 祖父江 友孝, 竹下 達也, 武林 亨, 原 邦夫, 福島 哲仁, 保利 一, 堀江 正知, 宮内 博幸, 宮川 宗之, 森本 泰夫, 山野 優子, 横山 和仁, 伊藤 由起, 上山 純, 梅田 ゆみ, 佐藤 一博, 諏訪園 靖, 竹内 靖人, 竹内 文乃, 塚原 照臣, 辻 真弓, 内藤 久雄, 中野 真規子, 松本 明子, 山内 武紀, 荒木 敦子, 上野 晋, 奥田 昌之, 各務 竹康, 原田 浩二, 堀口 兵剛, 山本 健也, 日本産業衛生学会許容濃度等に関する委員会(2020年度) 産業衛生学雑誌 63 (5) 179 -211 2021年09月
• 北海道における毒性学研究 胎児期の環境化学物質曝露による出生時の性ホルモンかく乱作用 環境と子どもの健康に関する北海道スタディ

  荒木 敦子, 岸 玲子 環境ホルモン学会研究発表会要旨集 23回 5 -5 2021年09月
• 【COVID-19が流行しない社会を目指す-社会医学・環境衛生学の視点から】環境健康科学の立場からその研究と教育の現状と課題

  荒木 敦子, 宮下 ちひろ, 岸 玲子, 小笠原 克彦 公衆衛生 85 (6) 400 -407 2021年06月 

  ＜文献概要＞ポイント ◆北海道大学環境健康科学研究教育センターは,「環境と健康」分野の研究・教育に取り組んでいる全学共同教育研究施設である.◆大規模な環境疫学研究として,出生コーホートや室内環境と健康に関する研究により,環境化学物質による健康影響について多くの成果を報告している.◆環境と健康は学際的な領域であり,多様な専門性を持つ人材の育成と協力が不可欠である.
• 妊婦の血中フタル酸エステル類と脂肪酸濃度 遺伝環境交互作用の影響 北海道スタディ

  小林 澄貴, 佐田 文宏, 荒木 敦子, 宮下 ちひろ, グウダルジ・ホウマヌ, 那須 民江 日本衛生学雑誌 76 (Suppl.) S155 -S155 2021年03月
• 小児期の肥満傾向と喘鳴リスクの関連:北海道スタディ

  宮下 ちひろ, 小林 澄貴, 荒木 敦子, 伊藤 佐智子, アイツバマイ・ユフ, 山崎 圭子, 岸 玲子 日本衛生学雑誌 76 (Suppl.) S189 -S189 2021年03月
• 北海道のハウスダスト中のフタル酸エステル類及びその代替物質の分析

  稲葉 洋平, 戸次 加奈江, アイツバマイ・ユフ, 荒木 敦子, 岸 玲子 日本衛生学雑誌 76 (Suppl.) S201 -S201 2021年03月
• 電波へのばく露による児の精神神経発達への影響に関する最近の研究動向 文献調査

  山崎 圭子, 荒木 敦子, 田村 菜穂美, 寺岡 友里, 日景 隆, 水田 正弘, 大宮 学, 岸 玲子 北海道公衆衛生学雑誌 34 (2) 14 -21 2021年03月 

  近年、電波ばく露環境は急速に変化していると考えられ、子どもの健康、特に精神神経発達への影響が懸念される。本研究の目的は、胎児期と出生後のばく露による子どもの精神神経発達への影響について先行研究を概観し、今後の研究の方向性を明らかにすることである。胎児期ばく露を扱った7編のうち3編で妊娠中の母の携帯電話使用状況と精神神経発達の間に負の関連が、1編で正の関連が報告されていた。出生後のばく露を扱った22編では、2編を除き、携帯電話使用状況または電波ばく露レベルと精神神経発達との負の関連が報告されていた。今後の研究では、携帯電話や電子機器の使用状況と電波ばく露による影響を独立に検討する必要がある。また、因果関係を考察するために適した前向き研究デザインを用いることが望ましい。さらに電波ばく露の背後にある交絡要因についても慎重に検討する必要がある。(著者抄録)
• 妊婦の血中フタル酸エステル類と脂肪酸濃度 遺伝環境交互作用の影響 北海道スタディ

  小林 澄貴, 佐田 文宏, 荒木 敦子, 宮下 ちひろ, グウダルジ・ホウマヌ, 那須 民江 日本衛生学雑誌 76 (Suppl.) S155 -S155 2021年03月
• 小児期の肥満傾向と喘鳴リスクの関連:北海道スタディ

  宮下 ちひろ, 小林 澄貴, 荒木 敦子, 伊藤 佐智子, アイツバマイ・ユフ, 山崎 圭子, 岸 玲子 日本衛生学雑誌 76 (Suppl.) S189 -S189 2021年03月
• 北海道のハウスダスト中のフタル酸エステル類及びその代替物質の分析

  稲葉 洋平, 戸次 加奈江, アイツバマイ・ユフ, 荒木 敦子, 岸 玲子 日本衛生学雑誌 76 (Suppl.) S201 -S201 2021年03月
• 青年期の高周波ばく露と健康影響の関連性に対する疫学研究を目的とした無線LAN周波数帯における人体遮蔽特性推定

  山本康平, 尾崎龍之介, 日景隆, 山本学, 荒木敦子, 宮下ちひろ, 田村奈穂美, 山崎恵子, 岸玲子 電気・情報関係学会北海道支部連合大会講演論文集(CD-ROM) 2021 2021年
• 【子どもと環境-胎児期・幼少期の環境が与える影響】わが国で最初の出生コホート"環境と子どもの健康に関する北海道スタディ" ライフコースアプローチに基づく成果を中心に

  岸 玲子, 荒木 敦子, 宮下 ちひろ 医学のあゆみ 275 (9) 967 -972 2020年11月 

  わが国ではじめての前向き出生コホート研究"北海道スタディ"を2001年に立ち上げた。現在、幼少期でみられた影響をライフコースアプローチで追跡している。出生後の生活環境を調べ、一番長い追跡の児は17歳である。これまで母体血中の残留性有機汚染物質としてダイオキシン類(PCDD、PCDFなど)、ダイオキシン様ポリ塩化ビフェニル29種類(同族異性体)、有機塩素系農薬、有機フッ素化合物(PFAS)、さらにプラスチック可塑剤DEHPやBPAなどの濃度を測定し、生まれた児の出生体重やアディポカイン、6ヵ月・18ヵ月時のベイリー乳幼児発達検査IIの得点、認知機能、アレルギーや感染症などの免疫系、甲状腺ホルモンや臍帯血の生殖系ホルモン、必須脂肪酸への影響などを認めた。加えて、遺伝的感受性素因や健康影響発現のメカニズムとしてのエピゲノム解析も進めている。今後、将来の疾病発症の早期予測と予防、治療につなげる必要がある。コホートの長期継続とデータの有効活用、これまでの成果を環境・健康政策へ活用する重要性を強く訴えたい。(著者抄録)
• 許容濃度等の勧告(2020年度)

  野見山 哲生, 池田 正之, 圓藤 吟史, 圓藤 陽子, 大前 和幸, 河合 俊夫, 岸 玲子, 小泉 昭夫, 櫻井 治彦, 佐藤 洋, 田中 茂, 田中 正敏, 長野 嘉介, 那須 民江, 矢野 栄二, 市場 正良, 市原 学, 奥田 裕計, 加藤 貴彦, 上島 通浩, 苅田 香苗, 川本 俊弘, 日下 幸則, 熊谷 信二, 祖父江 友孝, 竹下 達也, 武林 亨, 原 邦夫, 福島 哲仁, 保利 一, 宮川 宗之, 森本 泰夫, 山野 優子, 横山 和仁, 東 賢一, 伊藤 由起, 岩澤 聡子, 上野 晋, 上山 純, 梅田 ゆみ, 佐藤 一博, 諏訪園 靖, 竹内 靖人, 塚原 照臣, 角田 正史, 内藤 久雄, 中野 真規子, 原田 浩二, 堀口 兵剛, 松本 明子, 村田 勝敬, 山内 武紀, 石竹 達也, 伊藤 昭好, 竹内 文乃, 堀江 正知, 宮内 博幸, 荒木 敦子, 奥田 昌之, 各務 竹康, 山本 健也, 日本産業衛生学会許容濃度等に関する委員会(2019年度) 産業衛生学雑誌 62 (5) 198 -230 2020年09月
• 胎児期有機フッ素化合物曝露と脂肪酸濃度 遺伝子との相互作用の影響-北海道スタディ

  小林 澄貴, 佐田 文宏, ホウマヌ・グウダルジ, 荒木 敦子, 宮下 ちひろ, 佐々木 成子, 岡田 恵美子, 岩崎 雄介, 那須 民江, 岸 玲子 日本衛生学雑誌 75 (Suppl.) S159 -S159 2020年03月 [査読無し][通常論文]
  
• 電波および携帯電話への胎児期曝露による児の健康影響に関する最近の研究動向 文献調査

  荒木 敦子, 山崎 圭子, 寺岡 友里, 日景 隆, 水田 正弘, 大宮 学, 岸 玲子 日本衛生学雑誌 75 (Suppl.) S172 -S172 2020年03月 [査読無し][通常論文]
  
• 環境と子どもの健康に関する北海道研究(北海道スタディ)からの小児気管支喘息リスクスコア作成

  西條 泰明, 佐藤 遊洋, 吉岡 英治, 小林 澄貴, 宮下 ちひろ, 湊屋 街子, 荒木 敦子, 岸 玲子 日本衛生学雑誌 75 (Suppl.) S199 -S199 2020年03月 [査読無し][通常論文]
  
• 電波曝露と学童期の行動の問題及び認知機能との関連に関する最近の研究動向 文献調査

  山崎 圭子, 荒木 敦子, 寺岡 友里, 日景 隆, 水田 正弘, 大宮 学, 岸 玲子 日本衛生学雑誌 75 (Suppl.) S199 -S199 2020年03月 [査読無し][通常論文]
  
• 胎児期有機フッ素化合物曝露と脂肪酸濃度 遺伝子との相互作用の影響-北海道スタディ

  小林 澄貴, 佐田 文宏, ホウマヌ・グウダルジ, 荒木 敦子, 宮下 ちひろ, 佐々木 成子, 岡田 恵美子, 岩崎 雄介, 那須 民江, 岸 玲子 日本衛生学雑誌 75 (Suppl.) S159 -S159 2020年03月
• 電波および携帯電話への胎児期曝露による児の健康影響に関する最近の研究動向 文献調査

  荒木 敦子, 山崎 圭子, 寺岡 友里, 日景 隆, 水田 正弘, 大宮 学, 岸 玲子 日本衛生学雑誌 75 (Suppl.) S172 -S172 2020年03月
• 環境と子どもの健康に関する北海道研究(北海道スタディ)からの小児気管支喘息リスクスコア作成

  西條 泰明, 佐藤 遊洋, 吉岡 英治, 小林 澄貴, 宮下 ちひろ, 湊屋 街子, 荒木 敦子, 岸 玲子 日本衛生学雑誌 75 (Suppl.) S199 -S199 2020年03月
• 電波曝露と学童期の行動の問題及び認知機能との関連に関する最近の研究動向 文献調査

  山崎 圭子, 荒木 敦子, 寺岡 友里, 日景 隆, 水田 正弘, 大宮 学, 岸 玲子 日本衛生学雑誌 75 (Suppl.) S199 -S199 2020年03月
• 学童期の肥満に関連する要因の検討 北海道スタディ

  湊屋 街子, 宮下 ちひろ, 三浦 りゅう, 荒木 敦子, 岸 玲子 北海道公衆衛生学雑誌 33 (1特別付録) 41 -41 2019年11月
• 「環境化学物質と健康障害の予防」に関するWHO CC(研究協力センター)の取り組みとWHOによる子どもの環境と健康研修モジュールの紹介

  荒木 敦子, 湊屋 街子, 岸 玲子 北海道公衆衛生学雑誌 33 (1特別付録) 50 -50 2019年11月
• 許容濃度等の勧告(2019年度)

  武林 亨, 池田 正之, 圓藤 陽子, 圓藤 吟史, 大前 和幸, 河合 俊夫, 岸 玲子, 小泉 昭夫, 櫻井 治彦, 佐藤 洋, 田中 茂, 田中 正敏, 長野 嘉介, 那須 民江, 矢野 栄二, 市場 正良, 市原 学, 奥田 裕計, 加藤 貴彦, 上島 通浩, 苅田 香苗, 川本 俊弘, 日下 幸則, 熊谷 信二, 祖父江 友孝, 竹下 達也, 野見山 哲生, 原 邦夫, 福島 哲仁, 保利 一, 宮川 宗之, 森本 泰夫, 山野 優子, 横山 和仁, 東 賢一, 伊藤 由起, 岩澤 聡子, 上野 晋, 上山 純, 梅田 ゆみ, 佐藤 一博, 諏訪園 靖, 竹内 靖人, 塚原 照臣, 角田 正史, 内藤 久雄, 中野 真規子, 原田 浩二, 堀口 兵剛, 松本 明子, 村田 勝敬, 山内 武紀, 石竹 達也, 伊藤 昭好, 竹内 文乃, 堀江 正知, 宮内 博幸, 荒木 敦子, 奥田 昌之, 各務 竹康, 山本 健也, 日本産業衛生学会許容濃度等に関する委員会(2018年度) 産業衛生学雑誌 61 (5) 170 -202 2019年09月
• WHO研究協力センターとしての環境化学物質と健康障害の予防に関する取り組み

  荒木敦子, 湊屋街子, 岸玲子 産業衛生学雑誌 61 (臨増) 588 -588 2019年05月22日 [査読無し][通常論文]
  
• 小児における排尿習慣の確立と脳の性分化

  守屋 仁彦, 西村 陽子, 中村 美智子, 今 雅史, 橘田 岳也, 荒木 敦子, 宮下 ちひろ, 伊藤 佐智子, 長 和俊, 三井 貴彦, 村井 祥代, 岸 玲子, 篠原 信雄 日本泌尿器科学会総会 107回 OP -071 2019年04月 [査読無し][通常論文]
  
• アジアにおける有機フッ素化合物の胎児期曝露が及ぼす児の健康影響

  伊藤佐智子, 荒木敦子, 宮下ちひろ, 岸玲子 北海道公衆衛生学雑誌 32 (2) 43‐54 -54 2019年03月31日 [査読無し][通常論文]
   

  有機フッ素化合物(Perfluoroalkyl Substances:PFASs)は、その撥水性・撥油性から、界面活性剤、食品パッケージなどに使われてきたが、残留性や生物蓄積性を示す。近年、アジア地域では急速に工業化・経済発展が進み、PFASsの製造や廃棄物処理などの問題に直面している。世界的なPFOS、PFOAの製造規制後も、代替の長炭素鎖または短炭素鎖PFASsの製造が続いている。本総説では、PFASsの胎児期曝露と児の健康を検討したアジアの知見を整理し、今後の研究課題を探ることを目的とした。2018年11月までに発表された論文をPubMedにて検索を行い、出生コホートを中心とした27編についてPFASsの曝露濃度および子どもの健康に与える影響をまとめた。欧米諸国と比較して日本、台湾、韓国、中国での胎児期PFOS曝露濃度は同等および低かったが、出生体格、甲状腺ホルモン値、アレルギー・感染症、神経行動発達、性ホルモン・ステロイドホルモン値に影響を及ぼす可能性があることが明らかになった。しかし、アウトカムによっては結果が一致していないもの、また報告数が限られているものもあった。今後の課題として、生産量が増加している短・長炭素鎖のPFASsによる影響評価を行うことに加え、幼少期の健康影響がいつまで続くのか、コホートを追跡することが必要である。さらに、PFASs曝露によって攪乱された出生時の甲状腺や性ホルモン値が、その後の神経行動発達、思春期にどのように影響していくのかを明らかにすることが、PFASsの健康影響に対する生化学的な機序を明らかにすることにつながると考えられる。(著者抄録)
• アジアにおける有機フッ素化合物の胎児期曝露が及ぼす児の健康影響

  伊藤 佐智子, 荒木 敦子, 宮下 ちひろ, 岸 玲子 北海道公衆衛生学雑誌 32 (2) 43 -54 2019年03月 [査読無し][通常論文]
   

  有機フッ素化合物(Perfluoroalkyl Substances:PFASs)は、その撥水性・撥油性から、界面活性剤、食品パッケージなどに使われてきたが、残留性や生物蓄積性を示す。近年、アジア地域では急速に工業化・経済発展が進み、PFASsの製造や廃棄物処理などの問題に直面している。世界的なPFOS、PFOAの製造規制後も、代替の長炭素鎖または短炭素鎖PFASsの製造が続いている。本総説では、PFASsの胎児期曝露と児の健康を検討したアジアの知見を整理し、今後の研究課題を探ることを目的とした。2018年11月までに発表された論文をPubMedにて検索を行い、出生コホートを中心とした27編についてPFASsの曝露濃度および子どもの健康に与える影響をまとめた。欧米諸国と比較して日本、台湾、韓国、中国での胎児期PFOS曝露濃度は同等および低かったが、出生体格、甲状腺ホルモン値、アレルギー・感染症、神経行動発達、性ホルモン・ステロイドホルモン値に影響を及ぼす可能性があることが明らかになった。しかし、アウトカムによっては結果が一致していないもの、また報告数が限られているものもあった。今後の課題として、生産量が増加している短・長炭素鎖のPFASsによる影響評価を行うことに加え、幼少期の健康影響がいつまで続くのか、コホートを追跡することが必要である。さらに、PFASs曝露によって攪乱された出生時の甲状腺や性ホルモン値が、その後の神経行動発達、思春期にどのように影響していくのかを明らかにすることが、PFASsの健康影響に対する生化学的な機序を明らかにすることにつながると考えられる。(著者抄録)
• 学童の尿中リン酸トリエステル類代謝物濃度と尿中炎症関連マーカーとの関連

  アイツバマイ ゆふ, Bastiaensen Michiel, 荒木 敦子, Houman Goudarzi, 今野 哲, 伊藤 佐智子, 宮下 ちひろ, Covaci Adrian, 岸 玲子 日本衛生学雑誌 74 (Suppl.) S116 -S116 2019年02月 [査読無し][通常論文]
  
• 胎児期の環境化学物質への混合曝露による児の性ホルモンへの影響

  荒木 敦子, 宮下 ちひろ, 伊藤 佐智子, 三井 貴彦, ホウマヌ・ゴウダルジ, 長 和俊, 守屋 仁彦, 那須 民江, 岩崎 雄介, 堀 就英, 梶原 淳睦, 篠原 信雄, 岸 玲子 日本衛生学雑誌 74 (Suppl.) S122 -S122 2019年02月 [査読無し][通常論文]
  
• 胎児期の有機塩素系農薬曝露と3.5歳の児の問題行動の関連 北海道スタディ

  山崎 圭子, 荒木 敦子, 中島 そのみ, 宮下 ちひろ, 池野 多美子, 伊藤 佐智子, 湊屋 街子, 水谷 太, 苣木 洋一, 岸 玲子 日本衛生学雑誌 74 (Suppl.) S123 -S123 2019年02月 [査読無し][通常論文]
  
• 胎児期の喫煙曝露と学童期の子どもの体格 北海道スタディ

  湊屋 街子, 宮下 ちひろ, 荒木 敦子, 岸 玲子 日本衛生学雑誌 74 (Suppl.) S141 -S141 2019年02月 [査読無し][通常論文]
  
• 環境と子どもの健康に関する北海道研究(北海道スタディ)からの小児肥満リスクスコア作成

  西條 泰明, 伊藤 善也, 佐藤 遊洋, 吉岡 英治, 宮下 ちひろ, 湊屋 街子, 荒木 敦子, 岸 玲子 日本衛生学雑誌 74 (Suppl.) S157 -S157 2019年02月 [査読無し][通常論文]
  
• 学童の尿中リン酸トリエステル類代謝物濃度と尿中炎症関連マーカーとの関連

  アイツバマイ ゆふ, Bastiaensen Michiel, 荒木 敦子, Houman Goudarzi, 今野 哲, 伊藤 佐智子, 宮下 ちひろ, Covaci Adrian, 岸 玲子 日本衛生学雑誌 74 (Suppl.) S116 -S116 2019年02月 [査読無し][通常論文]
  
• 胎児期の環境化学物質への混合曝露による児の性ホルモンへの影響

  荒木 敦子, 宮下 ちひろ, 伊藤 佐智子, 三井 貴彦, ホウマヌ・ゴウダルジ, 長 和俊, 守屋 仁彦, 那須 民江, 岩崎 雄介, 堀 就英, 梶原 淳睦, 篠原 信雄, 岸 玲子 日本衛生学雑誌 74 (Suppl.) S122 -S122 2019年02月 [査読無し][通常論文]
  
• 胎児期の有機塩素系農薬曝露と3.5歳の児の問題行動の関連 北海道スタディ

  山崎 圭子, 荒木 敦子, 中島 そのみ, 宮下 ちひろ, 池野 多美子, 伊藤 佐智子, 湊屋 街子, 水谷 太, 苣木 洋一, 岸 玲子 日本衛生学雑誌 74 (Suppl.) S123 -S123 2019年02月 [査読無し][通常論文]
  
• 胎児期の喫煙曝露と学童期の子どもの体格 北海道スタディ

  湊屋 街子, 宮下 ちひろ, 荒木 敦子, 岸 玲子 日本衛生学雑誌 74 (Suppl.) S141 -S141 2019年02月 [査読無し][通常論文]
  
• 環境と子どもの健康に関する北海道研究(北海道スタディ)からの小児肥満リスクスコア作成

  西條 泰明, 伊藤 善也, 佐藤 遊洋, 吉岡 英治, 宮下 ちひろ, 湊屋 街子, 荒木 敦子, 岸 玲子 日本衛生学雑誌 74 (Suppl.) S157 -S157 2019年02月 [査読無し][通常論文]
  
• 胎児期有機フッ素化合物濃度と出生体重との関連:異物代謝酵素遺伝型の修飾による影響―北海道スタディ

  小林澄貴, 佐田文宏, 佐田文宏, 荒木敦子, 宮下ちひろ, 佐々木成子, 坂晋, 岩崎雄介, 岸玲子 日本疫学会学術総会講演集(Web) 29th 133 (WEB ONLY) 2019年01月30日 [査読無し][通常論文]
  
• 学術研究からの少子化対策 日本衛生学会からの提言に向けて 日本衛生学会における少子化対策提言に向けて 日本衛生学会少子化対策ワーキンググループによるとりまとめ

  野村 恭子, 苅田 香苗, 荒木 敦子, 西岡 笑子, 武藤 剛, 岩井 美幸, 錦谷 まりこ, 井上 まり子, 鶴ヶ野 しのぶ, 北野 尚美, 辻 真弓, 飯島 佐知子, 上田 佳代, 上島 通浩, 山縣 然太郎, 坂田 清美, 伊木 雅之, 柳澤 裕之, 加藤 昌志, 横山 和仁, 小泉 昭夫, 大槻 剛巳 日本衛生学雑誌 74 1of5 -5of5 2019年 

  日本衛生学会では、少子化対策ワーキンググループを設置し、少子化対策シンポジウムを開催し、この問題について様々な角度から議論を重ねてきた。主にそのシンポジウムにおける学術的知見を次の様にまとめた。1)未婚化、晩婚化に対する社会環境整備、2)労働衛生領域における環境整備、3)職場の少子化対策、4)環境化学物質による性成熟、生殖能力への影響、5)社会環境および親のストレスと小児の健全な育ちに関する包括的な研究、として述べた。
• 胎児期の受動喫煙曝露が正期産のSmall-for-gestational-age（SGA）に及ぼす影響：前向き出生コーホート研究（北海道スタディ）

  小林澄貴, 佐田文宏, 花岡知之, チチローラ・ブライモー, 伊藤久美子, 田村菜穂美, 荒木敦子, 伊藤佐智子, 宮下ちひろ, 岸玲子 北海道公衆衛生学雑誌 33 (2) 10 -12 2019年 [査読無し][招待有り]
   

  妊娠後期の受動喫煙曝露が正期産のSmall-for-gestational-age(SGA)に及ぼす影響について検討した。北海道内40産科病院で調査協力を依頼し同意が得られた妊婦20788名を対象に、前向き出生コホート研究を実施した。妊娠8ヵ月時に母体血漿を採取し、高感度酵素免疫測定法を用いてコチニン値を測定、SGAは日本小児科学会の在胎期間別出生時体格基準値に従って判定した。ROC曲線下面積は0.554〜0.557を示し、母体血漿コチニンのカットオフ値は3.03ng/mLであった。コチニン値<3.03ng/mLの妊婦と比較して、コチニン値≧3.03ng/mLの妊婦が正期産のSGA児を産むオッズ比は2.44倍高かった。また、能動および受動喫煙曝露されていない妊婦と比較して、受動喫煙のみ曝露された妊婦が正期産のSGA児を産むオッズ比は2.28倍高かった。妊娠後期における妊婦の受動喫煙曝露であっても、能動喫煙曝露と同様に正期産のSGA児を産むリスクがあることが明らかになった。
• 小児における排尿習慣の確立と脳の性分化

  守屋仁彦, 西村陽子, 西村陽子, 中村美智子, 今雅史, 橘田岳也, 荒木敦子, 宮下ちひろ, 伊藤佐智子, 長和俊, 三井貴彦, 村井祥代, 岸玲子, 篠原信雄 日本泌尿器科学会総会(Web) 107th ROMBUNNO.OP‐071 (WEB ONLY) -071 2019年 [査読無し][通常論文]
  
• 学術研究からの少子化対策 日本衛生学会からの提言に向けて 日本衛生学会における少子化対策提言に向けて 日本衛生学会少子化対策ワーキンググループによるとりまとめ

  野村 恭子, 苅田 香苗, 荒木 敦子, 西岡 笑子, 武藤 剛, 岩井 美幸, 錦谷 まりこ, 井上 まり子, 鶴ヶ野 しのぶ, 北野 尚美, 辻 真弓, 飯島 佐知子, 上田 佳代, 上島 通浩, 山縣 然太郎, 坂田 清美, 伊木 雅之, 柳澤 裕之, 加藤 昌志, 横山 和仁, 小泉 昭夫, 大槻 剛巳 日本衛生学雑誌 74 1of5 -5of5 2019年 [査読無し][通常論文]
   

  日本衛生学会では、少子化対策ワーキンググループを設置し、少子化対策シンポジウムを開催し、この問題について様々な角度から議論を重ねてきた。主にそのシンポジウムにおける学術的知見を次の様にまとめた。1)未婚化、晩婚化に対する社会環境整備、2)労働衛生領域における環境整備、3)職場の少子化対策、4)環境化学物質による性成熟、生殖能力への影響、5)社会環境および親のストレスと小児の健全な育ちに関する包括的な研究、として述べた。
• エコチル調査北海道ユニットセンターの進捗状況と,2歳までの喘鳴および湿疹の有病割合に関する報告

  荒木敦子, 西條泰明, 伊藤善也, AIT BAMAI Yu, 宮下ちひろ, 伊藤佐智子, 小林澄貴, 湊屋街子, 山崎圭子, 三浦りゅう, 吉岡英治, 川西康之, 村林宏, 佐藤遊洋, 岸玲子 日本内分泌かく乱化学物質学会研究発表会要旨集 21st 100 -100 2018年12月 [査読無し][通常論文]
  
• エコチル調査北海道ユニットセンターの進捗状況と、2歳までの喘鳴および湿疹の有病割合に関する報告

  荒木 敦子, 西條 泰明, 伊藤 善也, アイツバマイ ゆふ, 宮下 ちひろ, 伊藤 佐智子, 小林 澄貴, 湊屋 街子, 山崎 圭子, 三浦 りゅう, 吉岡 英治, 川西 康之, 村林 宏, 佐藤 遊洋, 岸 玲子 環境ホルモン学会研究発表会要旨集 21回 100 -100 2018年12月 [査読無し][通常論文]
  
• エコチル調査北海道ユニットセンターの進捗状況と、2歳までの喘鳴および湿疹の有病割合に関する報告

  荒木 敦子, 西條 泰明, 伊藤 善也, アイツバマイ ゆふ, 宮下 ちひろ, 伊藤 佐智子, 小林 澄貴, 湊屋 街子, 山崎 圭子, 三浦 りゅう, 吉岡 英治, 川西 康之, 村林 宏, 佐藤 遊洋, 岸 玲子 環境ホルモン学会研究発表会要旨集 21回 100 -100 2018年12月 [査読無し][通常論文]
  
• 室内ダスト中リン酸トリエステル類とその尿中代謝物濃度と学童の喘鳴・アレルギー症状との関連 札幌市学童調査

  荒木 敦子, アイツバマイ ゆふ, Bastiaensen Michiel, Van den Eede Nele, 河合 俊夫, 坪井 樹, Ketema Rahel Mesfin, Covaci Adrian, 岸 玲子 北海道公衆衛生学雑誌 32 (1特別付録) 66 -66 2018年10月 [査読無し][通常論文]
  
• 許容濃度等の勧告(2018年度)

  武林 亨, 池田 正之, 圓藤 陽子, 圓藤 吟史, 大前 和幸, 河合 俊夫, 岸 玲子, 小泉 昭夫, 櫻井 治彦, 佐藤 洋, 田中 茂, 田中 正敏, 長野 嘉介, 那須 民江, 矢野 栄二, 市場 正良, 市原 学, 奥田 裕計, 加藤 貴彦, 上島 通浩, 苅田 香苗, 川本 俊弘, 日下 幸則, 熊谷 信二, 祖父江 友孝, 竹下 達也, 野見山 哲生, 原 邦夫, 福島 哲仁, 保利 一, 宮川 宗之, 森本 泰夫, 山野 優子, 横山 和仁, 東 賢一, 伊藤 由起, 岩澤 聡子, 上野 晋, 上山 純, 梅田 ゆみ, 佐藤 一博, 諏訪園 靖, 竹内 靖人, 塚原 照臣, 角田 正史, 内藤 久雄, 中野 真規子, 原田 浩二, 堀口 兵剛, 松本 明子, 村田 勝敬, 山内 武紀, 石竹 達也, 伊藤 昭好, 竹内 文乃, 堀江 正知, 宮内 博幸, 荒木 敦子, 奥田 昌之, 各務 竹康, 山本 健也, 日本産業衛生学会許容濃度等に関する委員会(2017年度) 産業衛生学雑誌 60 (5) 116 -148 2018年09月 [査読無し][通常論文]
  
• 学術研究からの少子化対策-日本衛生学会からの提言に向けて 環境化学物質による次世代の性ホルモンへの影響

  荒木 敦子, 伊藤 佐智子, 宮下 ちひろ, 湊屋 街子, 岸 玲子 日本衛生学雑誌 73 (3) 313 -321 2018年09月 [査読無し][通常論文]
   

  環境化学物質による内分泌撹乱作用により、体内のホルモン濃度は撹乱されると考えられる。また、環境化学物質により、女性では、第二次性徴、生理不順、妊孕性の低下、不妊、子宮内膜症等の疾患に、男性では精子の質の低下や不妊への影響が示唆されている。環境化学物質による次世代の性腺への影響について、以下の項目に分けて概説した。1)「環境と子供の健康に関する北海道スタディ」の紹介、2)環境化学物質曝露と児の性ホルモンへの影響、3)代替物質と複合曝露、について述べた。
• ヒトマクロファージ様THP‐1細胞の遺伝子発現に及ぼす核内受容体アゴニストの曝露影響

  小島弘幸, 武内伸治, 室本竜太, 岸玲子, 荒木敦子 日本免疫毒性学会学術年会講演要旨集 25th 98 2018年08月 [査読無し][通常論文]
  
• これまでの環境リスクとこれからの環境リスク わが国で初めての本格的な出生コーホート研究から見た環境化学物質の濃度レベルと次世代影響

  岸玲子, 荒木敦子 保健医療科学 67 (3) 292‐305 2018年08月 [査読無し][通常論文]
  
• 【これまでの環境リスクとこれからの環境リスク】 わが国で初めての本格的な出生コーホート研究から見た環境化学物質の濃度レベルと次世代影響

  岸 玲子, 荒木 敦子 保健医療科学 67 (3) 292 -305 2018年08月 [査読無し][通常論文]
   

  シーア・コルボーンらにより「Our stolen future(邦訳「奪われし未来」)」が出版された1996年頃から、各国で環境化学物質の内分泌かく乱作用など次世代影響に関心が高まった。日本でも我々は2001年から厚生労働科学研究により「環境と子どもの健康に関する北海道スタディ:先天異常・発達・アレルギー」として2つのコーホートを立ち上げた。コーホートの1つは北海道全域の産科の協力により器官形成期に同意を得て、母20,926人のベースライン採血を行い、出生アウトカムを観察し、その児を学童期、思春期と追跡している。他の一つは妊娠中後期に母514人の同意を得て児の詳細な精神神経発達を観察している。この研究は我が国で初めての本格的な出生コーホートで、16年に渡って追跡し、現在までに100編を超える原著論文が出ている。コーホート研究の最近の成果を見るとPCB・ダイオキシン類、有機フッ素化合物、有機塩素系農薬など半減期の長いPOPsでは母の曝露濃度が体格、甲状腺機能、性ホルモンに影響を与え、生後の神経発達、感染症アレルギー等にも影響を与えた。近年、使用量が増加しているプラスチック可塑剤やBPAなど短半減期物質と肥満や発達障害等の関係についても検討を開始している。日本では過去に高濃度の水銀曝露で水俣病が、またダイオキシン類曝露でカネミライスオイル事故が引きおこされた。一方、本研究における比較的低濃度レベルの曝露でも、比較的高い人と低い人では影響の差が検出された。北海道スタディは当初から環境遺伝交互作用に着目し、SNPs解析によって喫煙やカフェインなど環境要因に感受性が高いハイリスク群を発見してきた。またエピゲノム解析では、環境化学物質の濃度と関連したメチル化への影響や、出生体重など発育に影響するCpGサイトを介在分析で明らかにできた。近年は世界的にDOHaD仮説(Developmental origin of health and Diseases、疾病の胎児期・幼少時期起源説)が重要になっているので、今後は広く小児疾患への環境要因として捉えることが必要になる。環境疫学では正確な曝露測定に基づくリスク評価を行い、科学的な成果を環境政策に活かすことが重要である。実際に、北海道スタディは環境省エコチル研究のモデルにもなり、計画設計時から協力している。また日本、韓国、台湾の3つのコーホートの主任研究者が協力してBiCCA(Birth Cohort Consortium of Asia)を設立し、現在15か国で29の出生コーホートが参加して活動をしている。今後のリスク評価でも国際共同研究が数多く進展するであろう。(著者抄録)
• 小型携帯サンプラーを用いた学童の化学物質曝露と自宅環境中濃度との関連

  荒木敦子, 河合俊夫, 坪井樹, アイツバマイ ゆふ, 岸玲子 産業衛生学雑誌 60 (臨増) 416 -416 2018年05月16日 [査読無し][通常論文]
  
• 【住環境における健康リスク要因とそのマネジメント】 室内環境中のハウスダストによる健康影響

  荒木 敦子, アイツバマイ ゆふ, ラヘル・メスフィン・ケテマ, 岸 玲子 日本衛生学雑誌 73 (2) 130 -137 2018年05月 [査読無し][通常論文]
   

  2003年より室内環境と居住者の健康に関する疫学研究を実施し、ダスト中のダニアレルゲン、微生物由来成分、準揮発性有機化合物を測定してきた。これら疫学研究の結果から、特にハウスダストに焦点を当て、健康影響としてシックハウス症候群やアレルギー症状との関連について概説した。最後に、ダストを用いた曝露評価の課題について述べた。
• 【小児環境保健疫学研究のパラダイム】 2万人規模の出生コーホートと、500人規模の小コーホートからなる北海道スタディが目指してきたもの 環境と子どもの健康 先天異常・発達・アレルギーの15年におよぶ経験と成果

  岸 玲子, 荒木 敦子, 宮下 ちひろ, 伊藤 佐智子, 湊屋 街子, 小林 澄貴, 山崎 圭子, アイツバマイ ゆふ, 三浦 りゅう, 田村 菜穂美 日本衛生学雑誌 73 (2) 164 -177 2018年05月 [査読無し][通常論文]
   

  2001年より胎児期からの環境曝露影響を前向きに研究する「環境と子供の健康に関する北海道スタディー」を立ち上げた。これは2万人規模と500人規模の大小2つの前向きコーホートから構成されている。1)北海道スタディーの背景と目的、特徴、2)追跡の時系列デザインと測定項目、3)北海道スタディーでこれまでに得られた成果、4)北海道スタディーの今後の課題と提言、について概説した。
• 【住環境における健康リスク要因とそのマネジメント】 科学的エビデンスに基づく『新シックハウス症候群に関する相談と対策マニュアル(改訂新版)』を作成して

  岸 玲子, 吉野 博, 荒木 敦子, 西條 泰明, 東 賢一, 河合 俊夫, 大和 浩, 大澤 元毅, 柴田 英治, 田中 正敏, 増地 あゆみ, 湊屋 街子, アイツバマイ ゆふ 日本衛生学雑誌 73 (2) 116 -129 2018年05月 [査読無し][通常論文]
   

  科学的エビデンスに基づく「新シックハウス症候群に関する相談と対策マニュアル(改訂新版)」を作成したので紹介した。このマニュアルでは、近年震災や豪雨等の災害に伴って入居者が増えている仮設住宅の問題や、地球温暖化による熱中症と室内環境などの最近の問題、電磁過敏症に関する系統的レビューについて記載した。また、快適で健康な建物を実現する上で必要な基礎的な理論、設計の考え方と方法、建物の使い方、設備の調整の方法や扱い方についても解説した。
• 【住環境における健康リスク要因とそのマネジメント】 室内環境中のハウスダストによる健康影響

  荒木 敦子, アイツバマイ ゆふ, ラヘル・メスフィン・ケテマ, 岸 玲子 日本衛生学雑誌 73 (2) 130 -137 2018年05月 [査読無し][通常論文]
   

  2003年より室内環境と居住者の健康に関する疫学研究を実施し、ダスト中のダニアレルゲン、微生物由来成分、準揮発性有機化合物を測定してきた。これら疫学研究の結果から、特にハウスダストに焦点を当て、健康影響としてシックハウス症候群やアレルギー症状との関連について概説した。最後に、ダストを用いた曝露評価の課題について述べた。
• 【小児環境保健疫学研究のパラダイム】 2万人規模の出生コーホートと、500人規模の小コーホートからなる北海道スタディが目指してきたもの 環境と子どもの健康 先天異常・発達・アレルギーの15年におよぶ経験と成果

  岸 玲子, 荒木 敦子, 宮下 ちひろ, 伊藤 佐智子, 湊屋 街子, 小林 澄貴, 山崎 圭子, アイツバマイ ゆふ, 三浦 りゅう, 田村 菜穂美 日本衛生学雑誌 73 (2) 164 -177 2018年05月 [査読無し][通常論文]
   

  2001年より胎児期からの環境曝露影響を前向きに研究する「環境と子供の健康に関する北海道スタディー」を立ち上げた。これは2万人規模と500人規模の大小2つの前向きコーホートから構成されている。1)北海道スタディーの背景と目的、特徴、2)追跡の時系列デザインと測定項目、3)北海道スタディーでこれまでに得られた成果、4)北海道スタディーの今後の課題と提言、について概説した。
• 胎児期の有機フッ素化合物曝露が7歳のアレルギーに及ぼす影響 北海道スタディ

  アイツバマイ ゆふ, 荒木 敦子, 宮下 ちひろ, 岡田 恵美子, 樫野 郁子, グウダルジ・ホウマヌ, 松浦 英幸, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S225 -S225 2018年03月 [査読無し][通常論文]
  
• 尿中リン酸とトリエステル類と児の喘息・アレルギーとの関連 札幌市学童調査

  荒木 敦子, アイツバマイ ゆふ, バスチャンセン・ミキエル, ファンデンイーデ・ネール, ケテマ・ラヘル, 伊藤 佐智子, 宮下 ちひろ, コバチ・アドリアン, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S234 -S234 2018年03月 [査読無し][通常論文]
  
• 胎児期の有機塩素系農薬曝露が3.5歳の児の知的機能に及ぼす影響 北海道スタディ

  山崎 圭子, 荒木 敦子, 中島 そのみ, 宮下 ちひろ, 池野 多美子, 伊藤 佐智子, 湊屋 街子, 水谷 太, 苣木 洋一, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S235 -S235 2018年03月 [査読無し][通常論文]
  
• 胎児期の両親の喫煙と幼児期におけるADHD症状の関連

  湊屋 街子, 伊藤 佐智子, 小林 澄貴, 山崎 圭子, 宮下 ちひろ, 荒木 敦子, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S243 -S243 2018年03月 [査読無し][通常論文]
  
• 胎児期のPCB類曝露による児のH19・LINE-1のDNAメチル化への影響 北海道スタディ

  小林 澄貴, 佐田 文宏, 宮下 ちひろ, 三浦 りゅう, ゴウダルジ・ホウマヌ, 荒木 敦子, 梶原 淳睦, 堀 就英, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S243 -S243 2018年03月 [査読無し][通常論文]
  
• 両親の教育歴と児のSmall for gestational ageとの媒介要因分析 北海道スタディ

  田村 菜穂美, 花岡 知之, 伊藤 久美子, 伊藤 佐智子, 宮下 ちひろ, 荒木 敦子, 小笠原 克彦, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S244 -S244 2018年03月 [査読無し][通常論文]
  
• 両親の教育歴と児のSmall for gestational ageとの媒介要因分析:北海道スタディ

  田村菜穂美, 田村菜穂美, 花岡知之, 伊藤久美子, 伊藤久美子, 伊藤佐智子, 宮下ちひろ, 荒木敦子, 小笠原克彦, 小笠原克彦, 岸玲子 日本衛生学雑誌(Web) 73 (Supplement) S244 2018年03月 [査読無し][通常論文]
  
• 尿中リン酸トリエステル類と児の喘息・アレルギーとの関連―札幌市学童調査

  荒木敦子, アイツバマイ ゆふ, バスチャンセン ミキエル, ファンデンイーデ ネール, ケテマ ラヘル, ケテマ ラヘル, 伊藤佐智子, 宮下ちひろ, コバチ アドリアン, 岸玲子 日本衛生学雑誌(Web) 73 (Supplement) S234 2018年03月 [査読無し][通常論文]
  
• 胎児期の有機フッ素化合物曝露が7歳のアレルギーに及ぼす影響 北海道スタディ

  アイツバマイ ゆふ, 荒木 敦子, 宮下 ちひろ, 岡田 恵美子, 樫野 郁子, グウダルジ・ホウマヌ, 松浦 英幸, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S225 -S225 2018年03月 [査読無し][通常論文]
  
• 尿中リン酸トリエステル類と児の喘息・アレルギーとの関連 札幌市学童調査

  荒木 敦子, アイツバマイ ゆふ, バスチャンセン・ミキエル, ファンデンイーデ・ネール, ケテマ・ラヘル, 伊藤 佐智子, 宮下 ちひろ, コバチ・アドリアン, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S234 -S234 2018年03月 [査読無し][通常論文]
  
• 胎児期の有機塩素系農薬曝露が3.5歳の児の知的機能に及ぼす影響 北海道スタディ

  山崎 圭子, 荒木 敦子, 中島 そのみ, 宮下 ちひろ, 池野 多美子, 伊藤 佐智子, 湊屋 街子, 水谷 太, 苣木 洋一, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S235 -S235 2018年03月 [査読無し][通常論文]
  
• 胎児期の両親の喫煙と幼児期におけるADHD症状の関連

  湊屋 街子, 伊藤 佐智子, 小林 澄貴, 山崎 圭子, 宮下 ちひろ, 荒木 敦子, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S243 -S243 2018年03月 [査読無し][通常論文]
  
• 胎児期のPCB類曝露による児のH19・LINE-1のDNAメチル化への影響 北海道スタディ

  小林 澄貴, 佐田 文宏, 宮下 ちひろ, 三浦 りゅう, ゴウダルジ・ホウマヌ, 荒木 敦子, 梶原 淳睦, 堀 就英, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S243 -S243 2018年03月 [査読無し][通常論文]
  
• 両親の教育歴と児のSmall for gestational ageとの媒介要因分析 北海道スタディ

  田村 菜穂美, 花岡 知之, 伊藤 久美子, 伊藤 佐智子, 宮下 ちひろ, 荒木 敦子, 小笠原 克彦, 岸 玲子 日本衛生学雑誌 73 (Suppl.) S244 -S244 2018年03月 [査読無し][通常論文]
  
• マタニティヨガ実践と切迫早産,早産との関連に関する検討(エコチル調査北海道追加調査)

  川西 康之, 岸 玲子, 吉岡 英治, 西條 泰明, 吉田 貴彦, 宮本 敏伸, 千石 一雄, 伊藤 善也, 伊藤 佐智子, 宮下 ちひろ, 荒木 敦子 日本産科婦人科学会雑誌 70 (2) 787 -787 2018年02月 [査読無し][通常論文]
  
• マタニティヨガ実践と切迫早産,早産との関連に関する検討(エコチル調査北海道追加調査)

  川西 康之, 岸 玲子, 吉岡 英治, 西條 泰明, 吉田 貴彦, 宮本 敏伸, 千石 一雄, 伊藤 善也, 伊藤 佐智子, 宮下 ちひろ, 荒木 敦子 日本産科婦人科学会雑誌 70 (2) 787 -787 2018年02月 [査読無し][通常論文]
  
• 胎児期ダイオキシン類曝露による第二次性徴への影響 環境と子供の健康北海道スタディ

  宮下 ちひろ, 荒木 敦子, 三井 貴彦, 伊藤 佐智子, 梶原 淳睦, 堀 就英, 長 和俊, 守屋 仁彦, 篠原 信雄, 岸 玲子 北海道公衆衛生学雑誌 31 (1特別付録) 46 -46 2017年11月 [査読無し][通常論文]
  
• 胎児期ダイオキシン類曝露による第二次性徴への影響 環境と子供の健康北海道スタディ

  宮下 ちひろ, 荒木 敦子, 三井 貴彦, 伊藤 佐智子, 梶原 淳睦, 堀 就英, 長 和俊, 守屋 仁彦, 篠原 信雄, 岸 玲子 北海道公衆衛生学雑誌 31 (1特別付録) 46 -46 2017年11月 [査読無し][通常論文]
  
• ヒトマクロファージ様THP‐1細胞の遺伝子発現に及ぼすDEHP及びMEHPの曝露影響

  小島弘幸, 武内伸治, 室本竜太, 岸玲子, 荒木敦子 日本免疫毒性学会学術年会講演要旨集 24th 93 2017年08月 [査読無し][通常論文]
  
• 室内空気とダスト中の化学物質と居住者の健康 (特集 室内空気汚染の低減対策と規制の動向)

  アイツバマイ ゆふ, 荒木 敦子, 岸 玲子 環境技術 46 (7) 372 -377 2017年07月
• 住環境における健康リスク要因とそのマネジメント 科学的エビデンスに基づく「シックハウス症候群相談マニュアル改訂版」の作成について

  岸 玲子, 東 賢一, 西條 泰明, 柴田 英治, 田中 正敏, 河合 俊夫, 大和 浩, 吉野 博, 大澤 元毅, 増地 あゆみ, 荒木 敦子, アイツバマイ ゆふ, 湊屋 街子 日本衛生学雑誌 72 (Suppl.) S138 -S138 2017年03月 [査読無し][通常論文]
  
• 住環境における健康リスク要因とそのマネジメント 室内環境中のハウスダストによる健康影響

  荒木 敦子, アイツバマイ ゆふ, 岸 玲子 日本衛生学雑誌 72 (Suppl.) S138 -S138 2017年03月 [査読無し][通常論文]
  
• 胎児期有機フッ素化合物曝露と臍帯血中アディポカイン濃度の関係 北海道スタディ

  湊屋 街子, 伊藤 佐智子, 宮下 ちひろ, 荒木 敦子, 佐々木 成子, 岩崎 雄介, 岸 玲子 日本衛生学雑誌 72 (Suppl.) S198 -S198 2017年03月 [査読無し][通常論文]
  
• 胎児期BPA曝露による7歳までの喘鳴・アトピー性皮膚炎への影響 北海道スタディ

  アイツバマイ ゆふ, 宮下 ちひろ, 荒木 敦子, 湊屋 街子, 山本 潤, 松村 徹, 佐々木 成子, 岸 玲子 日本衛生学雑誌 72 (Suppl.) S198 -S198 2017年03月 [査読無し][通常論文]
  
• ダイオキシン類の胎児期曝露による児のアレルギーへの影響 北海道スタディ

  宮下 ちひろ, 荒木 敦子, 伊藤 佐智子, 湊屋 街子, 小林 澄貴, アイツバマイ ゆふ, 梶原 淳睦, 戸高 尊, 岸 玲子 日本衛生学雑誌 72 (Suppl.) S199 -S199 2017年03月 [査読無し][通常論文]
  
• 殺虫用途の農薬への曝露とADHDを中心とした神経発達障害との関連についての疫学研究動向

  西原 進吉, 荒木 敦子, 宮下 ちひろ, 山崎 圭子, 岸 玲子 北海道公衆衛生学雑誌 30 (2) 27 -40 2017年03月 [査読無し][通常論文]
   

  我が国では神経発達障害の子どもが増加傾向にある。近年、殺虫用途等で使用される農薬への曝露がその一因であるとも考えられている。そこで、本稿では、胎児期、乳幼児期、学童期における農薬曝露と、注意欠如/多動性障害を中心とした神経発達への影響に関する近年の研究動向について検討を行うことを目的とした。医学文献データベースPubMedを用いて、有機塩素系、有機リン系、ピレスロイド系、カーバメイト系、ネオニコチノイド系農薬と、注意欠如・多動性障害、不注意、多動、神経発達、行動発達を検索用語として、文献検索を行った。得られた176編の論文から、農薬と神経発達に直接関係する疫学論文40編に焦点をあてて検討した。その結果、有機リン系農薬については、胎児期曝露の影響がみられること、生後曝露の影響は一貫しないこと、有機塩素系農薬についても、胎児期曝露の影響を示す報告が多いことが示された。一方、ピレスロイド系農薬では、胎児期よりも出生後の影響が強い可能性が示唆された。カーバメイト系農薬については、胎児期曝露の影響が示唆されたが、論文数は2編のみであった。ネオニコチノイド系農薬については報告が1編のみであった。精神発達においては、検索内容に関する評価項目が多岐にわたり、また、影響が表出する年齢も異なる可能性があることから、農薬曝露と精神発達の関連についての研究報告数は、現状では不十分であり、さらなる研究の蓄積が望まれる。(著者抄録)
• 「シックハウス症候群に関する相談マニュアル改訂新版」の作成 公衆衛生分野での活用に向けて

  荒木 敦子, アイツバマイ ゆふ, 西條 泰明, 湊屋 街子, 吉野 博, 東 賢一, 河合 俊夫, 大和 浩, 大澤 元毅, 柴田 英治, 田中 正敏, 増地 あゆみ, 岸 玲子 北海道公衆衛生学雑誌 30 (1特別付録) 55 -55 2016年10月 [査読無し][通常論文]
  
• 最近のDOHaD研究のトピックスと地域を基盤とする研究 環境省「子どもの健康と環境に関する全国調査(エコチル調査)」 北海道ユニットセンター・旭川サブユニットの参加者プロファイル

  西條 泰明, 川西 康之, 吉岡 英治, 伊藤 俊弘, 伊藤 善也, 伊藤 佐智子, 宮下 ちひろ, 荒木 敦子, 岸 玲子 日本衛生学雑誌 71 (Suppl.) S168 -S168 2016年05月 [査読無し][通常論文]
  
• ダイオキシン類異性体の曝露が胎生期の性ホルモンに与える影響 北海道スタディ

  宮下 ちひろ, 荒木 敦子, 三井 貴彦, 伊藤 佐知子, 佐々木 成子, 戸高 尊, 梶原 淳睦, 長 和俊, 野々村 克也, 岸 玲子 日本衛生学雑誌 71 (Suppl.) S192 -S192 2016年05月 [査読無し][通常論文]
  
• DEHP曝露による胎生期ステロイドホルモンプロファイルへの影響 北海道スタディ

  荒木 敦子, グウダルジ・ホウマヌ, 三井 貴彦, 那須 民江, 宮下 ちひろ, 伊藤 佐智子, 佐々木 成子, 長 和俊, 野々村 克也, 岸 玲子 日本衛生学雑誌 71 (Suppl.) S192 -S192 2016年05月 [査読無し][通常論文]
  
• FLG変異とフタル酸エステル曝露による児のADへの影響 北海道スタディ

  アイツバマイ ゆふ, 荒木 敦子, 乃村 俊史, 河合 俊夫, 坪井 樹, 叢 石, 宮下 ちひろ, 池野 多美子, 清水 宏, 岸 玲子 日本衛生学雑誌 71 (Suppl.) S192 -S192 2016年05月 [査読無し][通常論文]
  
• 母の喫煙曝露と胎児発育との関連 遺伝的なハイリスクについて 北海道スタディ

  小林 澄貴, 佐田 文宏, 佐々木 成子, Braimoh TitilolaSerifat, 荒木 敦子, 宮下 ちひろ, Goudarzi Houman, 小林 祥子, 岸 玲子 日本衛生学雑誌 71 (Suppl.) S193 -S193 2016年05月 [査読無し][通常論文]
  
• 胎児期の有機塩素系農薬曝露が母児の甲状腺ホルモンに及ぼす影響 北海道スタディ

  山崎 圭子, 宮下 ちひろ, 伊藤 佐智子, 荒木 敦子, 小林 祥子, 水谷 太, 苣木 洋一, 岸 玲子 日本衛生学雑誌 71 (Suppl.) S194 -S194 2016年05月 [査読無し][通常論文]
  
• 児の出生時体格に妊婦の喫煙とAHR、CYP1A1、XRCC1遺伝子型の組合せが影響する―北海道スタディ

  小林澄貴, 佐田文宏, 佐々木成子, チチローラ・セリファト・ブライモー, 荒木敦子, 宮下ちひろ, ホウマヌ・ゴウダルジ, 小林祥子, 岸玲子 北海道医学雑誌 91 81 2016年 [査読無し][通常論文]
  
• 前向きコーホート研究に基づく先天異常,免疫アレルギーおよび小児発達障害のリスク評価と環境化学物質に対する遺伝的感受性の解明 胎児期有機フッ素化合物曝露影響の臍帯血網羅的エピゲノム解析

  岸玲子, 荒木敦子, 宮下ちひろ, 佐々木成子, 石塚真由美, 小林祥子, 三浦りゅう, 安住薫, 中澤裕之 前向きコーホート研究に基づく先天異常、免疫アレルギーおよび小児発達障害のリスク評価と環境化学物質に対する遺伝的感受性の解明 平成27年度 総括・分担研究報告書 168‐185 2016年 [査読無し][通常論文]
  
• 妊娠初期における就労女性の有害物質の取扱いが児の流・死産に及ぼす影響

  小林 澄貴, 宮下 ちひろ, 荒木 敦子, 池野 多美子, 伊藤 佐智子, Goudarzi Houman, 花岡 知之, 岸 玲子 北海道公衆衛生学雑誌 29 (1特別付録) 25 -25 2015年11月 [査読無し][通常論文]
  
• 胎児期ダイオキシン類曝露による臍帯血中性ホルモンへの影響 環境と子供の健康北海道スタディ

  宮下 ちひろ, 荒木 敦子, 三井 貴彦, 伊藤 佐知子, 佐々木 成子, 戸高 尊, 梶原 淳睦, 長和 俊, 野々村 克也, 岸 玲子 北海道公衆衛生学雑誌 29 (1特別付録) 26 -26 2015年11月 [査読無し][通常論文]
  
• 胎児期ビスフェノールA曝露による臍帯血中のアディポカイン、出生体重、子どもの体重への影響 北海道スタディ

  湊屋 街子, 佐々木 成子, 荒木 敦子, 宮下 ちひろ, 山本 潤, 松村 徹, 岸 玲子 北海道公衆衛生学雑誌 29 (1特別付録) 27 -27 2015年11月 [査読無し][通常論文]
  
• 北海道のエコチル調査の集計結果 生後2歳までの食物アレルギーの頻度および食品の摂食状況について

  アイツバマイ ゆふ, 西條 泰明, 伊藤 善也, 村林 宏, 吉岡 英治, 川西 康之, 水上 尚典, 有賀 正, 長和 俊, 白石 秀明, 千石 一雄, 宮本 敏伸, 東 寛, 堤 裕幸, 遠藤 俊明, 馬場 剛, 小林 正樹, 荒木 敦子, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 土川 陽子, 湊屋 街子, 小林 澄貴, 山崎 圭子, 西原 進吉, 田村 菜穂美, 岸 玲子 北海道公衆衛生学雑誌 29 (1特別付録) 36 -36 2015年11月 [査読無し][通常論文]
  
• エコチル調査北海道ユニットセンター旭川サブユニット参加者における母体基本属性および周産期転帰と、その全国データとの比較

  川西 康之, 西條 泰明, 伊藤 善也, 中木 良彦, 吉岡 英治, 伊藤 俊弘, 吉田 貴彦, 宮本 敏伸, 千石 一雄, 東 寛, 土川 陽子, 宮下 ちひろ, 荒木 敦子, 岸 玲子 北海道公衆衛生学雑誌 29 (1特別付録) 41 -41 2015年11月 [査読無し][通常論文]
  
• Effects of maternal AHR, CYP1A1 and GSTM1 polymorphisms and dioxins on infant birth size

  Kobayashi S, Miyashita C, Sasaki S, Araki A, Sata F, Ban S, Kajiwara J, Todaka T, Kishi R 27th conference of the International Society of Environmental Epidemiology: ISEE 2015 Abstracts 2015年08月 [査読無し][通常論文]
  
• 母体への環境化学物質曝露と胎児期ホルモン環境が身体的変化に与える影響 第2指/第4指比との関連性について

  三井 貴彦, 荒木 敦子, 宮下 ちひろ, 橘田 岳也, 守屋 仁彦, 長 和俊, 森岡 圭太, 伊藤 佐智子, 篠原 信雄, 岸 玲子, 野々村 克也 日本生殖医学会雑誌 60 (3) 196 -196 2015年07月 [査読無し][通常論文]
  
• 胎児期における男性ホルモンへの曝露が小児期の脳の性分化に与える影響について

  三井 貴彦, 荒木 敦子, 伊藤 佐智子, 宮下 ちひろ, 橘田 岳也, 守屋 仁彦, 長 和俊, 森岡 圭太, 篠原 信雄, 岸 玲子, 野々村 克也 泌尿器外科 28 (5) 1011 -1011 2015年05月 [査読無し][通常論文]
  
• 北海道スタディ出生コホートを用いたアレルギー疾患とフィラグリン遺伝子変異の関連解析

  乃村 俊史, 竹田 真依, 鈴木 翔多朗, 清水 宏, 荒木 敦子, 宮下 ちひろ, 池野 多美子, 佐々木 成子, 岸 玲子, 秋山 真志 角化症研究会記録集 29 12 -15 2015年03月 [査読無し][通常論文]
  
• 臍帯血ビスフェノールA濃度と児のIGF2 DNAメチル化との関連 北海道スタディ

  小林 祥子, 安住 薫, 佐々木 成子, 松村 徹, 山本 潤, 石塚 真由美, 宮下 ちひろ, 池野 多美子, 荒木 敦子, 岸 玲子 日本衛生学雑誌 70 (Suppl.) S173 -S173 2015年03月 [査読無し][通常論文]
  
• ダイオキシン類曝露と胎児発育との関連 遺伝的なリスクについて 北海道スタディ

  小林 澄貴, 宮下 ちひろ, 佐々木 成子, 荒木 敦子, 佐田 文宏, 坂 晋, 梶原 淳睦, 戸高 尊, 岸 玲子 日本衛生学雑誌 70 (Suppl.) S181 -S181 2015年03月 [査読無し][通常論文]
  
• 胎児期MEHP曝露による神経行動発達への影響 北海道スタディ

  湊屋 街子, 佐々木 成子, 中島 そのみ, 那須 民江, 後藤 裕子, 宮下 ちひろ, 荒木 敦子, 小林 澄貴, 池野 多美子, 岸 玲子 日本衛生学雑誌 70 (Suppl.) S182 -S182 2015年03月 [査読無し][通常論文]
  
• 有機塩素系農薬への胎児期曝露による児の性ホルモン濃度への影響 北海道スタディ

  荒木 敦子, 宮下 ちひろ, 金澤 文子, 伊藤 佐智子, 三井 貴彦, 佐々木 成子, 水谷 太, 苣木 洋一, 野々村 克也, 岸 玲子 日本衛生学雑誌 70 (Suppl.) S182 -S182 2015年03月 [査読無し][通常論文]
  
• 有機塩素系農薬が乳幼児の免疫に与える影響 環境と子どもの健康北海道スタディー

  宮下 ちひろ, 金澤 文子, 佐々木 成子, 池野 多美子, 荒木 敦子, 伊藤 佐智子, 小林 祥子, 水谷 太, 苣木 洋一, 岸 玲子 日本衛生学雑誌 70 (Suppl.) S183 -S183 2015年03月 [査読無し][通常論文]
  
• 胎児期の有機塩素系農薬曝露が6ヵ月児の精神運動発達に及ぼす影響 北海道スタディ

  山崎 圭子, 宮下 ちひろ, 中島 そのみ, 池野 多美子, 荒木 敦子, 伊藤 佐智子, 小林 祥子, 水谷 太, 苣木 洋一, 岸 玲子 日本衛生学雑誌 70 (Suppl.) S183 -S183 2015年03月 [査読無し][通常論文]
  
• 児の出生体重と母親の社会経済要因との関連についての疫学研究 北海道スタディ

  田村 菜穂美, 伊藤 久美子, 花岡 知之, 喜多 歳子, 西原 進吉, 宮下 ちひろ, 荒木 敦子, 小笠原 克彦, 岸 玲子 日本衛生学雑誌 70 (Suppl.) S190 -S190 2015年03月 [査読無し][通常論文]
  
• 第2指・第4指比(2D/4D比)に影響を及ぼす遺伝要因の検討

  佐田 文宏, 江藤 亜紀子, 金谷 泰宏, 三井 貴彦, 荒木 敦子, 岸 玲子, 野々村 克也 日本衛生学雑誌 70 (Suppl.) S220 -S220 2015年03月 [査読無し][通常論文]
  
• マタニティヨガの周産期予後改善効果に関する研究

  川西 康之, 中木 良彦, 伊藤 俊弘, 吉岡 英治, 吉田 貴彦, 伊藤 善也, 宮下 ちひろ, 荒木 敦子, 岸 玲子, 千石 一雄, 西條 泰明 北海道産科婦人科学会会誌 59 (1) 206 -207 2015年03月 [査読無し][通常論文]
  
• 前向きコーホート研究に基づく先天異常,免疫アレルギーおよび小児発達障害のリスク評価と環境化学物質に対する遺伝的感受性の解明 胎児期ダイオキシンPCBs曝露が児の臍帯血DNAメチル化に及ぼす影響

  岸玲子, 荒木敦子, 梶原淳睦, 佐々木成子, 石塚真由美, 小林祥子, 安住薫, 小林澄貴, 蜂谷紀之, 安武章, 戸高尊 前向きコーホート研究に基づく先天異常、免疫アレルギーおよび小児発達障害のリスク評価と環境化学物質に対する遺伝的感受性の解明 平成26年度 総括・分担研究報告書 134 -143 2015年 [査読無し][通常論文]
  
• 環境省「エコチル調査」北海道ユニットセンターにおけるこれまでの活動報告

  荒木 敦子, 伊藤 善也, 西條 泰明, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 土川 陽子, 田村 菜穂美, 湊屋 街子, 吉岡 英治, 川西 康之, 村林 宏, 岸 玲子 環境ホルモン学会研究発表会要旨集 17回 65 -65 2014年12月 [査読無し][通常論文]
  
• さい帯血と血液のダイオキシン及びPCB類の組成比較

  梶原 淳睦, 戸高 尊, 平川 博仙, 宮下 ちひろ, 伊藤 佐智子, 佐々木 成子, 荒木 敦子, 岸 礼子 環境ホルモン学会研究発表会要旨集 17回 69 -69 2014年12月 [査読無し][通常論文]
  
• 胎児期の有機塩素系農薬が小児アレルギー発症に与える影響 環境と子どもの健康北海道スタディ

  宮下 ちひろ, 金澤 文子, 池野 多美子, 荒木 敦子, 伊藤 佐智子, 小林 澄貴, 湊屋 街子, Goudarzi Houman, 小林 祥子, 田村 菜穂美, 水谷 太, 苣木 洋一, 岸 玲子 北海道公衆衛生学雑誌 28 (1特別付録) 44 -44 2014年12月 [査読無し][通常論文]
  
• 胎児期の母の受動喫煙が児の出生時体格に及ぼす影響 遺伝環境交互作用について

  小林 澄貴, 佐々木 成子, 佐田 文宏, 宮下 ちひろ, 池野 多美子, 荒木 敦子, 岸 玲子 北海道公衆衛生学雑誌 28 (1特別付録) 45 -45 2014年12月 [査読無し][通常論文]
  
• 北海道3地区における妊婦の食習慣・運動習慣の実態について 環境省「子どもの健康と環境に関する全国調査(エコチル調査)」 北海道ユニットセンター登録者のデータから

  湊屋 街子, 西條 泰明, 伊藤 善也, 荒木 敦子, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 小林 澄貴, 土川 陽子, 田村 菜穂美, 吉岡 英治, 川西 康之, 村林 宏, 岸 玲子, エコチル調査北海道ユニットセンター事務局 北海道公衆衛生学雑誌 28 (1特別付録) 57 -57 2014年12月 [査読無し][通常論文]
  
• 生殖次世代影響の疫学研究における生体内短半減期物質の評価 フタル酸エステル類の胎児期曝露による次世代影響に関する疫学研究

  荒木 敦子, 岸 玲子 日本衛生学雑誌 69 (Suppl.) S143 -S143 2014年05月 [査読無し][通常論文]
  
• PFOS・PFOAの胎児期曝露が与える児の出生時性ホルモン濃度への影響

  伊藤 佐智子, 荒木 敦子, 宮下 ちひろ, 中澤 裕之, 三井 貴彦, 長 和俊, 佐々木 成子, 池野 多美子, 野々村 克也, 岸 玲子 日本衛生学雑誌 69 (Suppl.) S196 -S196 2014年05月 [査読無し][通常論文]
  
• 児の出生体重と母親の社会経済要因との関連についての疫学研究

  田村 菜穂美, 伊藤 久美子, 小林 澄貴, 岡田 恵美子, 喜多 歳子, ホウマヌ・ゴウダルジ, 宮下 ちひろ, 荒木 敦子, 池野 多美子, 岸 玲子 日本衛生学雑誌 69 (Suppl.) S204 -S204 2014年05月 [査読無し][通常論文]
  
• DEHPへの胎児期曝露による児の性ホルモン濃度への影響

  荒木 敦子, 三井 貴彦, 宮下 ちひろ, 那須 民江, 伊藤 佐智子, 佐々木 成子, 長 和俊, 池野 多美子, 野々村 克也, 岸 玲子 日本衛生学雑誌 69 (Suppl.) S211 -S211 2014年05月 [査読無し][通常論文]
  
• 胎児期ビスフェノールA曝露による臍帯血中性ホルモン濃度への影響

  佐々木 成子, 山本 潤, 荒木 敦子, 伊藤 佐智子, 宮下 ちひろ, 三井 貴彦, 長 和俊, 野々村 克也, 松村 徹, 岸 玲子 日本衛生学雑誌 69 (Suppl.) S215 -S215 2014年05月 [査読無し][通常論文]
  
• 母体への環境化学物質曝露と胎児期ホルモン環境が身体的変化に与える影響 第2指/第4指比との関連性について

  三井 貴彦, 荒木 敦子, 宮下 ちひろ, 今井 紋子, 佐藤 早基子, 橘田 岳也, 守屋 仁彦, 長 和俊, 森岡 圭太, 伊藤 佐智子, 岸 玲子, 野々村 克也 日本泌尿器科学会総会 102回 472 -472 2014年04月 [査読無し][通常論文]
  
• 妊婦の受動喫煙が児の出生時体格へ及ぼす影響：遺伝的なハイリスク群について―環境と子どもの健康に関する北海道スタディ―

  小林澄貴, 佐々木成子, 佐田文宏, 宮下ちひろ, 池野多美子, 荒木敦子, 岸玲子 北海道小児保健研究会会誌 35 -39 2014年 [査読無し][通常論文]
  
• 前向きコーホート研究に基づく先天異常,免疫アレルギーおよび小児発達障害のリスク評価と環境化学物質に対する遺伝的感受性の解明 胎児期の環境化学物質曝露が児のIGF2/H19メチル化に及ぼす影響

  安住薫, 岸玲子, 佐々木成子, 石塚真由美, 梶原淳睦, 宮下ちひろ, 池野多美子, 荒木敦子, 小林祥子, 小林澄貴, 中澤裕之, 那須民江, 蜂谷紀之, 安武章 前向きコーホート研究に基づく先天異常、免疫アレルギーおよび小児発達障害のリスク評価と環境化学物質に対する遺伝的感受性の解明 平成25年度 総括・分担研究報告書 71 -79 2014年 [査読無し][通常論文]
  
• 胎児のホルモン環境に影響を及ぼす要因の検討 ホルモン関連遺伝子多型と臍帯血ホルモン濃度

  佐田 文宏, 江藤 亜紀子, 荒木 敦子, 三井 貴彦, 金谷 泰宏, 岸 玲子, 野々村 克也 環境ホルモン学会研究発表会要旨集 16回 170 -170 2013年12月 [査読無し][通常論文]
  
• 札幌市128軒のハウスダスト中リン酸トリエステル類濃度と小学生のアレルギー疾患との関連

  多島 秀司, 荒木 敦子, 河合 俊夫, 坪井 樹, アイツバマイ ゆふ, 叢 石, 吉岡 英治, 岸 玲子 北海道公衆衛生学雑誌 27 (1特別付録) 44 -44 2013年11月 [査読無し][通常論文]
  
• 札幌市内小学生の自宅における暖房、および機械換気の有無と児童の喘息

  叢 石, 荒木 敦子, 鵜川 重和, アイツバマイ ゆふ, 多島 秀司, 金澤 文子, 湯浅 資之, 玉腰 暁子, 岸 玲子 北海道公衆衛生学雑誌 27 (1特別付録) 45 -45 2013年11月 [査読無し][通常論文]
  
• 尿中フタル酸代謝物濃度とハウスダスト中フタル酸エステル濃度との関連 札幌市児童における調査

  アイツバマイ ゆふ, 荒木 敦子, 河合 俊夫, 坪井 樹, 多島 秀司, 叢 石, 湯浅 資之, 金澤 文子, 玉腰 暁子, 岸 玲子 北海道公衆衛生学雑誌 27 (1特別付録) 47 -47 2013年11月 [査読無し][通常論文]
  
• 北海道3地区における妊婦の喫煙率および喫煙開始年齢について 環境省「子どもの環境と健康に関する全国調査(エコチル調査)」より

  荒木 敦子, 西條 泰明, 伊藤 善也, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 土川 陽子, 吉岡 英治, 川西 康之, 村林 宏, 岸 玲子 北海道公衆衛生学雑誌 27 (1特別付録) 52 -52 2013年11月 [査読無し][通常論文]
  
• マタニティヨガの周産期予後改善効果に関する研究(エコチル調査北海道追加調査)

  川西 康之, 中木 良彦, 伊藤 俊弘, 吉岡 英治, 吉田 貴彦, 伊藤 善也, 池野 多美子, 荒木 敦子, 岸 玲子, 西條 泰明 日本公衆衛生学会総会抄録集 72回 366 -366 2013年10月 [査読無し][通常論文]
  
• マタニティヨガの周産期予後改善効果に関する研究

  川西 康之, 中木 良彦, 伊藤 俊弘, 吉岡 英治, 吉田 貴彦, 伊藤 善也, 宮下 ちひろ, 荒木 敦子, 岸 玲子, 千石 一雄, 西條 泰明 北日本産科婦人科学会総会・学術講演会プログラム・抄録集 61回 100 -100 2013年09月 [査読無し][通常論文]
  
• GC/MSによるヒトの尿中2-エチルヘキサノールの定量 フタル酸ジエステル類評価としての無水フタル酸可塑剤・難燃剤曝露と小児の健康影響

  河合 俊夫, 坪井 樹, 荒木 敦子, アイツバマイ ゆふ, 岸 玲子 産業衛生学雑誌 55 (臨増) 439 -439 2013年05月 [査読無し][通常論文]
  
• 札幌市の小学生4,500名を対象とした住環境とアトピー性皮膚炎に関する調査

  鵜川 重和, 荒木 敦子, 金澤 文子, 湯浅 資之, 岸 玲子 北海道醫學雜誌 = Acta medica Hokkaidonensia 88 (2) 95 -95 2013年04月01日 [査読無し][通常論文]
  
• フタル酸エステル尿中代謝物の同時測定方法の開発可塑剤難燃剤曝露と小児の健康影響(1)

  坪井 樹, 河合 俊夫, 荒木 敦子, アイツバマイ ゆふ, 岸 玲子 日本衛生学雑誌 68 (Suppl.) S159 -S159 2013年03月 [査読無し][通常論文]
  
• アレルギーとダスト中フタル酸エステル濃度 可塑剤・難燃剤曝露と小児の健康影響(3)

  アイツバマイ ゆふ, 荒木 敦子, 坪井 樹, 河合 俊夫, 多島 秀司, 叢 石, 吉岡 英治, 玉腰 暁子, 岸 玲子 日本衛生学雑誌 68 (Suppl.) S159 -S159 2013年03月 [査読無し][通常論文]
  
• フタル酸ジエステル類評価としての無水フタル酸可塑剤・難燃剤曝露と小児の健康影響(2)

  河合 俊夫, 坪井 樹, 荒木 敦子, アイツバマイ ゆふ, 岸 玲子 日本衛生学雑誌 68 (Suppl.) S204 -S204 2013年03月 [査読無し][通常論文]
  
• 児童の尿中フタル酸代謝物濃度とアレルギー 可塑剤、難燃剤の小児への健康影響(4)

  荒木 敦子, 坪井 樹, 河合 俊夫, アイツバマイ ゆふ, 多島 秀司, 叢 石, 鵜川 重一, 吉岡 英治, 岸 玲子 日本衛生学雑誌 68 (Suppl.) S204 -S204 2013年03月 [査読無し][通常論文]
  
• ハウスダスト中フタル酸エステルと住環境との関連

  アイツバマイゆふ, 荒木敦子, 河合俊夫, 坪井樹, 斎藤育江, 吉岡栄治, 金澤文子, 多島秀司, 叢石, 玉腰暁子, 岸玲子 北海道医学雑誌 88 (6) 2013年 [査読無し][通常論文]
  
• 可塑剤・難燃剤の曝露評価手法の開発と小児アレルギー・リスク評価への応用 尿中2-エチル-1-ヘキサノールの分析方法と測定事例

  河合 俊夫, 坪井 樹, 荒木 敦子, アイツバマイゆふ, 岸 玲子 産業衛生学雑誌 55 (1) 36 -36 2013年01月 [査読無し][通常論文]
  
• 戸建て住宅における微生物由来揮発性有機化合物曝露と居住者のアレルギーとの関連

  荒木 敦子, 金沢 文子, 河合 俊夫, 永滝 陽子, 森本 兼曩, 中山 邦夫, 柴田 英治, 田中 正敏, 瀧川 智子, 吉村 健清, 力 寿雄, 西條 泰明, 岸 玲子 北海道醫學雜誌 = Acta medica Hokkaidonensia 87 (6) 286 -286 2012年11月01日
• 小学生の住宅におけるハウスダスト中のエンドトキシンならびにβ-グルカン量とアレルギー性疾患に関する研究

  叢 石, 荒木 敦子, アイツバマイ ゆふ, 竹田 智哉, 早川 敦司, 吉岡 英治, 多島 秀司, 鵜川 重和, 玉腰 暁子, 岸 玲子 北海道公衆衛生学雑誌 26 (1特別付録) 33 -33 2012年11月 [査読無し][通常論文]
  
• ハウスダスト中に含まれるリン酸トリエステル類の濃度と住居環境

  多島 秀司, 荒木 敦子, 坪井 樹, 河合 俊夫, 斎藤 育江, アイツバマイ ゆふ, 竹田 智哉, 鵜川 重和, 吉岡 英治, 岸 玲子 北海道公衆衛生学雑誌 26 (1特別付録) 34 -34 2012年11月 [査読無し][通常論文]
  
• 環境省「エコチル調査」に関する意識調査と広報活動の課題

  荒木 敦子, 尾西 奈江, 中瀬 督久, 岸 玲子, エコチル調査北海道ユニットセンター事務局 北海道公衆衛生学雑誌 26 (1特別付録) 38 -38 2012年11月 [査読無し][通常論文]
  
• 札幌市の小学生4500名を対象とした住環境と喘息、アトピー性皮膚炎に関する調査

  鵜川 重和, 荒木 敦子, 金澤 文子, 湯浅 資之, 吉岡 英治, 岸 玲子 日本公衆衛生学会総会抄録集 71回 333 -333 2012年10月 [査読無し][通常論文]
  
• シックハウス症候群研究最近の動向 シックハウス症候群に関する全国規模の疫学研究 化学物質、湿度環境、生物学的要因

  荒木 敦子, 西條 泰明, 田中 正敏, 瀧川 智子, 吉村 健清, 森本 兼曩, 柴田 英治, 河合 俊夫, 斎藤 育江, 岸 玲子 日本衛生学雑誌 67 (2) 232 -232 2012年02月 [査読無し][通常論文]
  
• 札幌市小学生の喘息・鼻結膜炎有訴と自宅環境および気中VOC・MVOC濃度

  荒木 敦子, アイツバマイ ゆふ, 河合 俊夫, 坪井 樹, 竹田 智哉, 多島 秀司, 鵜川 重和, 叢 石, 吉岡 英治, 岸 玲子 日本衛生学雑誌 67 (2) 285 -285 2012年02月 [査読無し][通常論文]
  
• 小学生のシックハウス症候群の有訴と床ダスト中有機リン酸トリエステル類濃度との関係

  多島 秀司, 荒木 敦子, 斎藤 育江, 河合 俊夫, 坪井 樹, アイツバマイ ゆふ, 竹田 智哉, 吉岡 英治, 鵜川 重和, 岸 玲子 日本衛生学雑誌 67 (2) 285 -285 2012年02月 [査読無し][通常論文]
  
• ヒトの出産前後における血液DEHP代謝物濃度の解析

  田川 雅大, 内藤 久雄, 林 由美, 川野 愛子, 佐々木 成子, 荒木 敦子, 小林 澄貴, 岸 玲子 日本衛生学雑誌 67 (2) 303 -303 2012年02月 [査読無し][通常論文]
  
• 室内空気質中フタル酸エステル類曝露とアレルギーへの影響

  アイツバマイ ゆふ, 荒木 敦子, 岸 玲子 Endocrine Disrupter News Letter 15 (1) 2 -2 2012年
• 自宅空気中化学物質濃度とシックハウス症候群に関する調査研究 札幌市小学生を対象として

  荒木 敦子, アイツバマイ ゆふ, 坪井 樹, 河合 俊夫, 竹田 智哉, 早川 敦司, 吉岡 英治, 多島 秀司, 叢 石, 鵜川 重和, 岸 玲子 北海道公衆衛生学雑誌 25 (1特別付録) 50 -50 2011年11月 [査読無し][通常論文]
  
• 自宅住環境とアトピー性皮膚炎に関する調査 札幌市の小学生4,500名を対象として

  鵜川 重和, 荒木 敦子, 金澤 文子, 湯浅 資之, アイツバマイ ゆふ, 吉岡 英治, 叢 石, 多島 秀司, 岸 玲子 北海道公衆衛生学雑誌 25 (1特別付録) 51 -51 2011年11月 [査読無し][通常論文]
  
• 小学生の住宅におけるハウスダスト中のエンドトキシンならびにβ-グルカン量と住宅特徴に関する調査

  叢 石, 荒木 敦子, アイツバマイ ゆふ, 竹田 智哉, 早川 敦司, 吉岡 英治, 多島 秀司, 鵜川 重和, 岸 玲子 北海道公衆衛生学雑誌 25 (1特別付録) 54 -54 2011年11月 [査読無し][通常論文]
  
• 札幌市戸建住宅における3年の室内環境とシックハウス症候群有訴の変化

  荒木 敦子, 金澤 文子, 西條 泰明, 岸 玲子 日本衛生学雑誌 66 (3) 589 -599 2011年05月 [査読無し][通常論文]
   

  札幌市戸建住宅における3年の室内環境とシックハウス症候群有訴の変化について検討した。調査対象住宅は2004年、2005年、2006年、それぞれ104軒、64軒、41軒で、調査を3年継続した住宅は41軒であった。40軒は木造建築で、41軒の築年の平均は2.3±1.5年であった。全室あるいは居間に換気システムが導入されていたのは24軒であったが、2006年には、このうち6軒は換気システムを使用していなかった。芳香剤および防虫剤を利用する住宅は2006年にはほぼ半減した。ホルムアルデヒドは毎回の調査ですべての住宅から検出したが、経年的な減少傾向を認めた。Aspergillus属の総真菌数に占める割合は低いものの、2006年は2004年、2005年に比べて有意に増加していた。Der1の検出率はいずれの年も78%以上であった。SHS症状は、いずれの年も鼻症状の訴えが最も多かった。
• シックハウス症状解明のための超小型、軽量、拡散型サンプラーの開発 VOC測定用サンプラー

  坪井 樹, 河合 俊夫, 乾谷 正樹, 住野 公昭, 荒木 敦子, 岸 玲子 産業衛生学雑誌 53 (臨増) 413 -413 2011年05月 [査読無し][通常論文]
  
• シックハウス症状解明のための超小型、軽量、拡散型サンプラーの開発 アルデヒド測定用サンプラー

  河合 俊夫, 坪井 樹, 乾谷 正樹, 荒木 敦子, 住野 公昭, 岸 玲子 産業衛生学雑誌 53 (臨増) 414 -414 2011年05月 [査読無し][通常論文]
  
• 微生物由来VOCによる室内空気室汚染の実情と健康影響

  荒木 敦子, 岸 玲子 日本衛生学雑誌 66 (2) 368 -368 2011年02月 [査読無し][通常論文]
  
• 札幌市小学生のシックハウス症候群有訴と自宅の気中化学物質濃度

  荒木 敦子, アイトバマイ ゆふ, 竹田 智哉, 河合 俊夫, 坪井 樹, 早川 敦司, 吉岡 英治, 岸 玲子 日本衛生学雑誌 66 (2) 388 -388 2011年02月 [査読無し][通常論文]
  
• シックハウス症候群の原因解明のための全国規模の疫学研究―化学物質および真菌・ダニ等による健康影響の評価と対策―グルカンとシックハウス症候群との関連についての文献調査

  岸玲子, 湯浅資之, 金澤文子, 小林澄貴, 荒木敦子, 宮下ちひろ シックハウス症候群の原因解明のための全国規模の疫学研究-化学物質及び真菌・ダニ等による健康影響の評価と対策 平成20-22年度 総合研究報告書 194 -201 2011年 [査読無し][通常論文]
  
• シックハウス症候群の原因解明のための全国規模の疫学研究―化学物質および真菌・ダニ等による健康影響の評価と対策―学校の室内空気質と生徒におけるシックビル症候群(SBS)の関係についての海外の文献調査

  岸玲子, 湯浅資之, 荒木敦子, 宮下ちひろ, 金澤文子, 小林澄貴 シックハウス症候群の原因解明のための全国規模の疫学研究-化学物質及び真菌・ダニ等による健康影響の評価と対策 平成20-22年度 総合研究報告書 191 -193 2011年 [査読無し][通常論文]
  
• 室内環境汚染物質51物質の分析・測定技術

  坪井 樹, 永滝 陽子, 河合 俊夫, 住野 公昭, 荒木 敦子, 大前 和幸, 岸 玲子 産業衛生学雑誌 52 (臨増) 431 -431 2010年05月 [査読無し][通常論文]
  
• 喫煙者の有無別にみた室内環境化学物質濃度とシックハウス症候群の自覚症状

  アイトバマイ ゆふ, 荒木 敦子, 西條 泰明, 森本 兼曩, 中山 邦夫, 瀧川 智子, 田中 正敏, 柴田 英治, 吉村 健清, 力 寿雄 日本衛生学雑誌 65 (2) 309 -309 2010年04月 [査読無し][通常論文]
  
• シックハウス関連物質の活性炭脱着率に関する基礎的検討

  永滝 陽子, 坪井 樹, 河合 俊夫, 清水 英佑, 大前 和幸, 荒木 敦子, 岸 玲子 産業衛生学雑誌 52 (1) 52 -53 2010年01月 [査読無し][通常論文]
  
• 札幌市小学生を対象としたシックハウス症候群の有訴率と関連要因に関する調査

  荒木 敦子, 湯浅 資之, 金澤 文子, 岸 玲子 北海道公衆衛生学雑誌 23 (1特別付録) 69 -69 2009年11月 [査読無し][通常論文]
  
• 全国6地域の一般住宅におけるシックハウス症候群の実態と原因の解明 (第5報)室内空気質中Microbial VOC類の濃度と症状との関係

  荒木 敦子, 河合 俊夫, 永滝 陽子, 金澤 文子, 竹田 誠, 森本 兼曩, 中山 邦夫, 柴田 英治, 田中 正敏, 瀧川 智子, 吉村 健清, 力 寿雄, 岸 玲子 日本衛生学雑誌 64 (2) 355 -355 2009年03月 [査読無し][通常論文]
  
• シックハウス症候群の原因解明のための全国規模の疫学研究―化学物質及び真菌・ダニ等による健康影響の評価と対策―グルカンとシックハウス症候群との関連についての文献調査

  岸玲子, 湯浅資之, 金澤文子, 小林澄貴, 荒木敦子, 宮下ちひろ シックハウス症候群の原因解明のための全国規模の疫学研究-化学物質及び真菌・ダニ等による健康影響の評価と対策 平成20年度 総括・分担研究報告書 142 -149 2009年 [査読無し][通常論文]
  
• シックハウス症候群の原因解明のための全国規模の疫学研究―化学物質及び真菌・ダニ等による健康影響の評価と対策―学校の室内空気質と生徒におけるシックビル症候群(SBS)の関係についての海外の文献調査

  岸玲子, 湯浅資之, 荒木敦子, 宮下ちひろ, 金澤文子, 小林澄貴 シックハウス症候群の原因解明のための全国規模の疫学研究-化学物質及び真菌・ダニ等による健康影響の評価と対策 平成20年度 総括・分担研究報告書 69 -71 2009年 [査読無し][通常論文]
  
• 札幌市新築戸建住宅における3年間の室内環境変化

  荒木 敦子, 金澤 文子, 竹田 誠, 西條 泰明, 岸 玲子 北海道公衆衛生学雑誌 22 (1特別付録) 112 -112 2008年11月 [査読無し][通常論文]
  
• 全国6地域の一般住宅におけるシックハウス症候群の実態と原因の解明(第4報) 室内空気質中Microbial VOC類の濃度と住環境との関係

  荒木 敦子, 河合 俊夫, 永滝 陽子, 竹田 誠, 金澤 文子, 森本 兼曩, 中山 邦夫, 柴田 英治, 田中 正敏, 瀧川 智子, 吉村 健清, 力 寿雄, 岸 玲子 日本衛生学雑誌 63 (2) 356 -356 2008年03月 [査読無し][通常論文]
  
• 札幌市一般住宅におけるフタル酸エステル、リン酸トリエステルによる室内汚染 実態解明とシックハウス症候群との関連

  金澤 文子, 斎藤 育江, 荒木 敦子, 竹田 誠, 矢口 久美子, 岸 玲子 日本衛生学雑誌 63 (2) 357 -357 2008年03月 [査読無し][通常論文]
  
• ミニサンプラーを用いた室内空気中可塑剤、難燃剤、殺虫剤等の一斉分析法

  斎藤 育江, 大貫 文, 矢口 久美子, 上原 眞一, 金澤 文子, 竹田 誠, 荒木 敦子, 岸 玲子 環境ホルモン学会研究発表会要旨集 10回 75 -75 2007年12月 [査読無し][通常論文]
  
• 新規シックハウス関連物質(MVOC)の測定法について

  竹田 誠, 河合 俊夫, 永滝 陽子, 荒木 敦子, 金澤 文子, 岸 玲子 産業衛生学雑誌 49 (6) 242 -243 2007年11月 [査読無し][通常論文]
  
• 一般住宅における微生物由来有機化合物(MVOC)測定法の確立と実態調査

  竹田 誠, 河合 俊夫, 永滝 陽子, 荒木 敦子, 金澤 文子, 岸 玲子 産業衛生学雑誌 (80回CD-ROM抄録集) P3092 -P3092 2007年04月 [査読無し][通常論文]
  
• 全国6地域の一般住民におけるシックハウス症候群の実態と原因の解明(第3報) 戸建住宅の室内環境要因と症状の地域差

  岸 玲子, 西條 泰明, 荒木 敦子, 田中 正敏, 柴田 英治, 森本 兼曩, 中山 邦夫, 瀧川 智子, 吉村 健清, 力 寿雄 日本衛生学雑誌 62 (2) 433 -433 2007年03月 [査読無し][通常論文]
  
• 札幌市一般住宅におけるフタル酸エステル、リン酸トリエステル、殺虫剤による室内汚染の実態

  金沢 文子, 斎藤 育江, 竹田 誠, 荒木 敦子, 馬 明月, 瀬戸 博, 岸 玲子 日本衛生学雑誌 62 (2) 435 -435 2007年03月 [査読無し][通常論文]
  

書籍等出版物

• プレコンセプションケア

  (担当:分担執筆範囲:10 環境要因の生殖と次世代への影響 児への長期的影響)
  メジカルビュー社 2024年04月 (ISBN: 9784758321402)
• 室内環境の事典 : 快適で健康な暮らしを支える科学

  室内環境学会 (担当:分担執筆範囲:5-16 シックハウス症候群（SHS） ［池田敦子］)
  朝倉書店 2023年09月 (ISBN: 9784254266528) xiii, 439, 7p, 図版8p
• Indoor environmental quality and health risk toward healthier environment for all

  Kishi, Reiko, Norbäck, Dan, Araki, Atsuko 
  Springer 2020年 (ISBN: 9789813291843) viii, 333 p.

講演・口頭発表等

• Mixture Chemical Exposure in Utero and Boys Reproductive Hormone Levels at Birth: the Hokkaido Study  [通常講演]

  Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Takahiko Mitsui, Houman Goudarzi, Kazutoshi Cho, Kimihiko Moriya, Tamie Nakajima, Yusuke Iwasaki, Tsuguhide Hori, Junboku Kajiwara, Nobuo Shinohara, Reiko Kish

  ISESISEE-AC2019 2019年11月 口頭発表（一般）
• The Hokkaido Study on Environment and Children’s Health: Overview of the study and collaborations with cohorts in Asia  [招待講演]

  Atsuko Araki, Chihiro Miyashita, Machiko Minatoya, Reiko Kishi

  ISESISEE-AC2019 2019年11月 シンポジウム・ワークショップパネル（公募）
• Capacity building and increasing awareness on environmental chemical exposures and prevention of their hazards  [招待講演]

  Atsuko Araki, Machiko Minatoya, Reiko Kishi

  Pacific Basin Consortium Conference 2019 2019年09月 口頭発表（招待・特別）
• Exposure to organophosphate esters in Japan: associations among their concentrations in house dust, urinary metabolite levels, and allergie  [通常講演]

  Atsuko Araki, Yu Ait Bamai, Reiko Kishi

  ISESISIAQ-2019 2019年08月 シンポジウム・ワークショップパネル（公募）
• Organohosphate flame retardants in house dust and their association with school children’s asthma and allergies  [通常講演]

  Atsuko Araki, Yu Ait Bamai, Toshio kawai, Tazuru Tsuboi, Reiko Kishi

  ISEE/ES AC2018 2018年 Taipei, Taiwan
• Mixed phthalate ester and phosphate flame retardant exposure and asthma and allergies in school children:  [通常講演]

  Atsuko Araki, Yu Ait Bamai, Michiel Bastiaensen, Nele van den Eede, Toshio Kawai, Tazuru Tsuboi, Sachiko Itoh, Chihiro Miyashita, Adrian Covaci, Reiko Kishi

  ISESISEE-2018 2018年 Ottawa, Canada
• ダイオキシン類の胎児期曝露による児のアレルギーへの影響 北海道スタディ  [通常講演]

  宮下 ちひろ, 荒木 敦子, 伊藤 佐智子, 湊屋 街子, 小林 澄貴, アイツバマイ ゆふ, 梶原 淳睦, 戸高 尊, 岸 玲子

  日本衛生学雑誌 2017年03月
• 胎児期BPA曝露による7歳までの喘鳴・アトピー性皮膚炎への影響 北海道スタディ  [通常講演]

  アイツバマイ ゆふ, 宮下 ちひろ, 荒木 敦子, 湊屋 街子, 山本 潤, 松村 徹, 佐々木 成子, 岸 玲子

  日本衛生学雑誌 2017年03月
• 住環境における健康リスク要因とそのマネジメント 室内環境中のハウスダストによる健康影響  [通常講演]

  荒木 敦子, アイツバマイ ゆふ, 岸 玲子

  日本衛生学雑誌 2017年03月
• 胎児期有機フッ素化合物曝露と臍帯血中アディポカイン濃度の関係 北海道スタディ  [通常講演]

  湊屋 街子, 伊藤 佐智子, 宮下 ちひろ, 荒木 敦子, 佐々木 成子, 岩崎 雄介, 岸 玲子

  日本衛生学雑誌 2017年03月
• 住環境における健康リスク要因とそのマネジメント 科学的エビデンスに基づく「シックハウス症候群相談マニュアル改訂版」の作成について  [通常講演]

  岸 玲子, 東 賢一, 西條 泰明, 柴田 英治, 田中 正敏, 河合 俊夫, 大和 浩, 吉野 博, 大澤 元毅, 増地 あゆみ, 荒木 敦子, アイツバマイ ゆふ, 湊屋 街子

  日本衛生学雑誌 2017年03月
• Urinary biomonitoring of organophosphate flame retardants in Japanese children and correlations with house dust concentrations  [通常講演]

  Bastiaensen M, Van den Eede N, Araki A, Ait Bamai Y, Kishi R, Covaci A

  Dioxin2017 2017年 Vancouver, Canada
• Phthalates and organophosphate flame retardants in house dust and their relation to asllergies and oxidative stress marker 8-OHdG: the Hokkaido Study  [通常講演]

  Atsuko Araki, Yu Ait Bamai, Toshio Kawai, Tzuru Tsuboi, Chihiro Miyashita, Reiko Kishi

  ISES2017 2017年 Research Traiangle Park, NC, USA
• 室内環境中のハウスダストによる健康影響  [通常講演]

  荒木敦子, アイツバマイゆふ, 岸玲子

  第87回日本衛生学会総会 2017年 宮崎
• ヒトマクロファージ様THP-1細胞の遺伝子発現に及ぼすDEHP及びMEHPの曝露影響  [通常講演]

  小島弘幸, 武内伸治, 室本竜太, 岸玲子, 荒木敦子

  第24回日本免疫毒性学会学術年会 2017年 十和田市
• 「シックハウス症候群に関する相談マニュアル改訂新版」の作成 公衆衛生分野での活用に向けて  [通常講演]

  荒木 敦子, アイツバマイ ゆふ, 西條 泰明, 湊屋 街子, 吉野 博, 東 賢一, 河合 俊夫, 大和 浩, 大澤 元毅, 柴田 英治, 田中 正敏, 増地 あゆみ, 岸 玲子

  北海道公衆衛生学雑誌 2016年10月
• 胎児期の有機塩素系農薬曝露が母児の甲状腺ホルモンに及ぼす影響 北海道スタディ  [通常講演]

  山崎 圭子, 宮下 ちひろ, 伊藤 佐智子, 荒木 敦子, 小林 祥子, 水谷 太, 苣木 洋一, 岸 玲子

  日本衛生学雑誌 2016年05月
• FLG変異とフタル酸エステル曝露による児のADへの影響 北海道スタディ  [通常講演]

  アイツバマイ ゆふ, 荒木 敦子, 乃村 俊史, 河合 俊夫, 坪井 樹, 叢 石, 宮下 ちひろ, 池野 多美子, 清水 宏, 岸 玲子

  日本衛生学雑誌 2016年05月
• 母の喫煙曝露と胎児発育との関連 遺伝的なハイリスクについて 北海道スタディ  [通常講演]

  小林 澄貴, 佐田 文宏, 佐々木 成子, Braimoh TitilolaSerifat, 荒木 敦子, 宮下 ちひろ, Goudarzi Houman, 小林 祥子, 岸 玲子

  日本衛生学雑誌 2016年05月
• DEHP曝露による胎生期ステロイドホルモンプロファイルへの影響 北海道スタディ  [通常講演]

  荒木 敦子, グウダルジ・ホウマヌ, 三井 貴彦, 那須 民江, 宮下 ちひろ, 伊藤 佐智子, 佐々木 成子, 長 和俊, 野々村 克也, 岸 玲子

  日本衛生学雑誌 2016年05月
• ダイオキシン類異性体の曝露が胎生期の性ホルモンに与える影響 北海道スタディ  [通常講演]

  宮下 ちひろ, 荒木 敦子, 三井 貴彦, 伊藤 佐知子, 佐々木 成子, 戸高 尊, 梶原 淳睦, 長 和俊, 野々村 克也, 岸 玲子

  日本衛生学雑誌 2016年05月
• 最近のDOHaD研究のトピックスと地域を基盤とする研究 環境省「子どもの健康と環境に関する全国調査(エコチル調査)」 北海道ユニットセンター・旭川サブユニットの参加者プロファイル  [通常講演]

  西條 泰明, 川西 康之, 吉岡 英治, 伊藤 俊弘, 伊藤 善也, 伊藤 佐智子, 宮下 ちひろ, 荒木 敦子, 岸 玲子

  日本衛生学雑誌 2016年05月
• “Symposium-S2-09 Early life exposure to environmental endocrine disruptors and the related effects in children and adolescence” Prenatal Di(2-ethylhexyl) phthalate Exposure and Reproductive Hormone in Cord Blood ? The Hokkaido Study  [通常講演]

  Atsuko Araki, Reiko Kishi

  ISEE-ISES AC2016 2016年 Sapporo, Japan
• Prenatal exposure to organochlorine pesticides and reproductive hormones in fetal blood: The Hokkaido Study  [通常講演]

  Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Takahiko Mitsui, Futoshi Mizutani, Yoichi Chisaki, Seiko Sasaki, Kazutoshi Cho, Katsuya Nonomura, Reiko Kishi

  ISEE2016 2016年 Rome, Italy
• Prenatal exposure to organochlorine pesticides and steroid hormones profiles in fetal blood-the Hokkaido Study  [通常講演]

  tsuko Araki, Chihiro Miyashita, Takahiko Mitsui, Houman Goudarzi, Sachiko Itoh, Futoshi Mizutani, Youichi Chisaki, Seiko Sasaki, Kimihiko Moriya, Kazutoshi Cho, Nobuo Shinohara, Katsuya Nonomura, Reiko Kishi

  PPToX V 2016年 Kitakyusyu, Japan
• Association between prenatal phthalates and BPA exposures and fatal adipokines and birth size: the Hokkaido Study on Environment and Children’s Health  [通常講演]

  Machiko Minatoya, Atsuko Araki, Chihiro Miyashita, Jun Yamamoto, Yu Onoda, Toru Matsumura, Reiko Kishi

  PPToX V 2016年 Kitakyusyu, Japan
• 産業衛生の現場で役立つ「シックハウス症候群に関する相談マニュアル改訂新版」の作成  [通常講演]

  荒木敦子, 西條泰明, アイツバマイゆふ, 湊屋街子, 吉野博, 東賢一, 河合俊夫, 大和浩, 大澤元毅, 柴田英治, 田中正敏, 増地あゆみ, 岸玲子

  第96回 北海道医学大会 産業衛生分科会 2016年 札幌
• シックハウス症候群に関する相談マニュアル改訂新版」の作成‐公衆衛生分野での活用に向けて‐  [通常講演]

  荒木敦子, アイツバマイゆふ, 西條泰明, 湊屋街子, 吉野博, 東賢一, 河合俊夫, 大和浩, 大澤元毅, 柴田英治, 田中正敏, 増地あゆみ, 岸玲子

  第68回 北海道公衆衛生学会 2016年 札幌
• エコチル調査北海道ユニットセンター旭川サブユニット参加者における母体基本属性および周産期転帰と、その全国データとの比較  [通常講演]

  川西 康之, 西條 泰明, 伊藤 善也, 中木 良彦, 吉岡 英治, 伊藤 俊弘, 吉田 貴彦, 宮本 敏伸, 千石 一雄, 東 寛, 土川 陽子, 宮下 ちひろ, 荒木 敦子, 岸 玲子

  北海道公衆衛生学雑誌 2015年11月
• 北海道のエコチル調査の集計結果 生後2歳までの食物アレルギーの頻度および食品の摂食状況について  [通常講演]

  アイツバマイ ゆふ, 西條 泰明, 伊藤 善也, 村林 宏, 吉岡 英治, 川西 康之, 水上 尚典, 有賀 正, 長和 俊, 白石 秀明, 千石 一雄, 宮本 敏伸, 東 寛, 堤 裕幸, 遠藤 俊明, 馬場 剛, 小林 正樹, 荒木 敦子, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 土川 陽子, 湊屋 街子, 小林 澄貴, 山崎 圭子, 西原 進吉, 田村 菜穂美, 岸 玲子

  北海道公衆衛生学雑誌 2015年11月
• 胎児期ビスフェノールA曝露による臍帯血中のアディポカイン、出生体重、子どもの体重への影響 北海道スタディ  [通常講演]

  湊屋 街子, 佐々木 成子, 荒木 敦子, 宮下 ちひろ, 山本 潤, 松村 徹, 岸 玲子

  北海道公衆衛生学雑誌 2015年11月
• 胎児期ダイオキシン類曝露による臍帯血中性ホルモンへの影響 環境と子供の健康北海道スタディ  [通常講演]

  宮下 ちひろ, 荒木 敦子, 三井 貴彦, 伊藤 佐知子, 佐々木 成子, 戸高 尊, 梶原 淳睦, 長和 俊, 野々村 克也, 岸 玲子

  北海道公衆衛生学雑誌 2015年11月
• 妊娠初期における就労女性の有害物質の取扱いが児の流・死産に及ぼす影響  [通常講演]

  小林 澄貴, 宮下 ちひろ, 荒木 敦子, 池野 多美子, 伊藤 佐智子, Goudarzi Houman, 花岡 知之, 岸 玲子

  北海道公衆衛生学雑誌 2015年11月
• 母体への環境化学物質曝露と胎児期ホルモン環境が身体的変化に与える影響 第2指/第4指比との関連性について  [通常講演]

  三井 貴彦, 荒木 敦子, 宮下 ちひろ, 橘田 岳也, 守屋 仁彦, 長 和俊, 森岡 圭太, 伊藤 佐智子, 篠原 信雄, 岸 玲子, 野々村 克也

  日本生殖医学会雑誌 2015年07月
• 胎児期における男性ホルモンへの曝露が小児期の脳の性分化に与える影響について  [通常講演]

  三井 貴彦, 荒木 敦子, 伊藤 佐智子, 宮下 ちひろ, 橘田 岳也, 守屋 仁彦, 長 和俊, 森岡 圭太, 篠原 信雄, 岸 玲子, 野々村 克也

  泌尿器外科 2015年05月
• マタニティヨガの周産期予後改善効果に関する研究  [通常講演]

  川西 康之, 中木 良彦, 伊藤 俊弘, 吉岡 英治, 吉田 貴彦, 伊藤 善也, 宮下 ちひろ, 荒木 敦子, 岸 玲子, 千石 一雄, 西條 泰明

  北海道産科婦人科学会会誌 2015年03月
• 第2指・第4指比(2D/4D比)に影響を及ぼす遺伝要因の検討  [通常講演]

  佐田 文宏, 江藤 亜紀子, 金谷 泰宏, 三井 貴彦, 荒木 敦子, 岸 玲子, 野々村 克也

  日本衛生学雑誌 2015年03月
• 児の出生体重と母親の社会経済要因との関連についての疫学研究 北海道スタディ  [通常講演]

  田村 菜穂美, 伊藤 久美子, 花岡 知之, 喜多 歳子, 西原 進吉, 宮下 ちひろ, 荒木 敦子, 小笠原 克彦, 岸 玲子

  日本衛生学雑誌 2015年03月
• 胎児期の有機塩素系農薬曝露が6ヵ月児の精神運動発達に及ぼす影響 北海道スタディ  [通常講演]

  山崎 圭子, 宮下 ちひろ, 中島 そのみ, 池野 多美子, 荒木 敦子, 伊藤 佐智子, 小林 祥子, 水谷 太, 苣木 洋一, 岸 玲子

  日本衛生学雑誌 2015年03月
• 有機塩素系農薬が乳幼児の免疫に与える影響 環境と子どもの健康北海道スタディー  [通常講演]

  宮下 ちひろ, 金澤 文子, 佐々木 成子, 池野 多美子, 荒木 敦子, 伊藤 佐智子, 小林 祥子, 水谷 太, 苣木 洋一, 岸 玲子

  日本衛生学雑誌 2015年03月
• 有機塩素系農薬への胎児期曝露による児の性ホルモン濃度への影響 北海道スタディ  [通常講演]

  荒木 敦子, 宮下 ちひろ, 金澤 文子, 伊藤 佐智子, 三井 貴彦, 佐々木 成子, 水谷 太, 苣木 洋一, 野々村 克也, 岸 玲子

  日本衛生学雑誌 2015年03月
• 胎児期MEHP曝露による神経行動発達への影響 北海道スタディ  [通常講演]

  湊屋 街子, 佐々木 成子, 中島 そのみ, 那須 民江, 後藤 裕子, 宮下 ちひろ, 荒木 敦子, 小林 澄貴, 池野 多美子, 岸 玲子

  日本衛生学雑誌 2015年03月
• ダイオキシン類曝露と胎児発育との関連 遺伝的なリスクについて 北海道スタディ  [通常講演]

  小林 澄貴, 宮下 ちひろ, 佐々木 成子, 荒木 敦子, 佐田 文宏, 坂 晋, 梶原 淳睦, 戸高 尊, 岸 玲子

  日本衛生学雑誌 2015年03月
• 臍帯血ビスフェノールA濃度と児のIGF2 DNAメチル化との関連 北海道スタディ  [通常講演]

  小林 祥子, 安住 薫, 佐々木 成子, 松村 徹, 山本 潤, 石塚 真由美, 宮下 ちひろ, 池野 多美子, 荒木 敦子, 岸 玲子

  日本衛生学雑誌 2015年03月
• 北海道スタディ出生コホートを用いたアレルギー疾患とフィラグリン遺伝子変異の関連解析  [通常講演]

  乃村 俊史, 竹田 真依, 鈴木 翔多朗, 清水 宏, 荒木 敦子, 宮下 ちひろ, 池野 多美子, 佐々木 成子, 岸 玲子, 秋山 真志

  角化症研究会記録集 2015年03月
• “Symposium-S17-Phthalate Diester Exposure and Systematic Health Effects” Allergic disease in relation to phthalates in house dust and urine  [通常講演]

  Atsuko Araki, Yu Ait Bamai, Reiko Kishi

  ISEE2015 2015年 Sao Paolo, Brazil
• 胎児期ビスフェノールA曝露影響に関する臍帯血DNA網羅的メチル化解析??北海道スタディ  [通常講演]

  第4回日本DOHaD研究学術集会 2015年 東京
• 北海道3地区における妊婦の食習慣・運動習慣の実態について 環境省「子どもの健康と環境に関する全国調査(エコチル調査)」 北海道ユニットセンター登録者のデータから  [通常講演]

  湊屋 街子, 西條 泰明, 伊藤 善也, 荒木 敦子, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 小林 澄貴, 土川 陽子, 田村 菜穂美, 吉岡 英治, 川西 康之, 村林 宏, 岸 玲子, エコチル調査北海道ユニットセンター事務局

  北海道公衆衛生学雑誌 2014年12月
• 胎児期の母の受動喫煙が児の出生時体格に及ぼす影響 遺伝環境交互作用について  [通常講演]

  小林 澄貴, 佐々木 成子, 佐田 文宏, 宮下 ちひろ, 池野 多美子, 荒木 敦子, 岸 玲子

  北海道公衆衛生学雑誌 2014年12月
• 胎児期の有機塩素系農薬が小児アレルギー発症に与える影響 環境と子どもの健康北海道スタディ  [通常講演]

  宮下 ちひろ, 金澤 文子, 池野 多美子, 荒木 敦子, 伊藤 佐智子, 小林 澄貴, 湊屋 街子, Goudarzi Houman, 小林 祥子, 田村 菜穂美, 水谷 太, 苣木 洋一, 岸 玲子

  北海道公衆衛生学雑誌 2014年12月
• さい帯血と血液のダイオキシン及びPCB類の組成比較  [通常講演]

  梶原 淳睦, 戸高 尊, 平川 博仙, 宮下 ちひろ, 伊藤 佐智子, 佐々木 成子, 荒木 敦子, 岸 礼子

  環境ホルモン学会研究発表会要旨集 2014年12月
• 環境省「エコチル調査」北海道ユニットセンターにおけるこれまでの活動報告  [通常講演]

  荒木 敦子, 伊藤 善也, 西條 泰明, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 土川 陽子, 田村 菜穂美, 湊屋 街子, 吉岡 英治, 川西 康之, 村林 宏, 岸 玲子

  環境ホルモン学会研究発表会要旨集 2014年12月
• 胎児期ビスフェノールA曝露による臍帯血中性ホルモン濃度への影響  [通常講演]

  佐々木 成子, 山本 潤, 荒木 敦子, 伊藤 佐智子, 宮下 ちひろ, 三井 貴彦, 長 和俊, 野々村 克也, 松村 徹, 岸 玲子

  日本衛生学雑誌 2014年05月
• DEHPへの胎児期曝露による児の性ホルモン濃度への影響  [通常講演]

  荒木 敦子, 三井 貴彦, 宮下 ちひろ, 那須 民江, 伊藤 佐智子, 佐々木 成子, 長 和俊, 池野 多美子, 野々村 克也, 岸 玲子

  日本衛生学雑誌 2014年05月
• 児の出生体重と母親の社会経済要因との関連についての疫学研究  [通常講演]

  田村 菜穂美, 伊藤 久美子, 小林 澄貴, 岡田 恵美子, 喜多 歳子, ホウマヌ・ゴウダルジ, 宮下 ちひろ, 荒木 敦子, 池野 多美子, 岸 玲子

  日本衛生学雑誌 2014年05月
• PFOS・PFOAの胎児期曝露が与える児の出生時性ホルモン濃度への影響  [通常講演]

  伊藤 佐智子, 荒木 敦子, 宮下 ちひろ, 中澤 裕之, 三井 貴彦, 長 和俊, 佐々木 成子, 池野 多美子, 野々村 克也, 岸 玲子

  日本衛生学雑誌 2014年05月
• 生殖次世代影響の疫学研究における生体内短半減期物質の評価 フタル酸エステル類の胎児期曝露による次世代影響に関する疫学研究  [通常講演]

  荒木 敦子, 岸 玲子

  日本衛生学雑誌 2014年05月
• 母体への環境化学物質曝露と胎児期ホルモン環境が身体的変化に与える影響 第2指/第4指比との関連性について  [通常講演]

  三井 貴彦, 荒木 敦子, 宮下 ちひろ, 今井 紋子, 佐藤 早基子, 橘田 岳也, 守屋 仁彦, 長 和俊, 森岡 圭太, 伊藤 佐智子, 岸 玲子, 野々村 克也

  日本泌尿器科学会総会 2014年04月
• Association between Maternal Exposure to Di(2-Ethylhexyl) Phthalate and Sex Hormone Levels in Fetal Blood  [通常講演]

  Atsuko Araki, Takahiko Mitsui, Chihiro Miyashita, Tamie Nakajima, Seiko Sasaki, Tamiko Ikeno, Kazutoshi Cho, Sachiko Ito, Katsuya Nonomura, Reiko Kishi

  ISEE2014 2014年 Seattle, WA, USA
• Effect of PFOS and PFOA Exposure in Utero on Reproductive Hormones Levels at Birth  [通常講演]

  Sachiko Itoh, Atsuko Araki, Chihiro Miyashita, Hiroyuki Nakazawa, Takahiko Mitsui, Kazutoshi Cho, Seiko Sasaki, Tamiko Ikeno, Katsuya Nonomura, Reiko Kishi

  ISEE2014 2014年 Seattle, WA, USA
• Exposure to House Dust Phthalates in Relation to Asthma and Allergies in Both Children and Adults  [通常講演]

  Yu Ait Bamai, Eiji Shibata, Ikue Saito, Atsuko Araki, Ayako Kanazawa, Kanehisa Morimoto, Kunio Nakayama, Masatoshi Tanaka, Tomoko Takigawa, Kanesumi Yoshimura, Hisao Chikara, Yasuaki Saijo, Reiko Kishi

  ISEE2014 2014年 Seattle, WA, USA
• Exposure to Perfluoroalkyl Chemicals and Neurodevelopment at 6 Months of Age  [通常講演]

  Houman Goudarzi, Tamiko Ikeno, Sachiko Kobayashi, Atsuko Araki, Chihiro Miyashita, Seiko Sasaki, Sonomi Nakajima, Hiroyuki Nakazawa, Reiko Kish

  ISEE2014 2014年 Seattle, WA, USA
• The Effects of Perfluoroalkyl Acids (Pfaas) Exposure in Utero on IGF2/H19 DNA Methylation in Cord Blood  [通常講演]

  Sachiko Kobayashi, Kaoru Azumi, Seiko Sasaki, Mayumi Ishizuka, Hiroyuki Nakazawa, Emiko Okada, Sumitaka Kobayashi, Houman Goudarzi, Sachiko Itoh, Chihiro Miyashita, Tamiko Ikeno, Atsuko Araki, Reiko Kishi

  ISEE2014 2014年 Seattle, WA, USA
• Perinatal PFAAs Exposure Cause Various Health Outcomes on Offspring Including Effects on Reproductive and Thyroid Hormones: The Hokkaido Study  [通常講演]

  Reiko Kishi, Atsuko Araki, Sachiko Itoh, Chihiro Miyashita, Houman Goudarzi, Sachiko Kobayashi, Seiko Sasaki, Ikuko Kashino, H Nakazawa, Tamie Nakajima, Takahiko Mitsui, Katsuya Nonomura

  PPToX IV 2014年 Boston, MA, USA
• Hokkaido Study on Environment and Children’s Health: Cohort profile and findings of perinatal Perfluoroalkyl acid (PFAAs)exposure and various health outcomes  [通常講演]

  Reiko Kishi, Atsuko Araki

  ISEE-AC2014 2014年 Shanghai, Chaina
• Prenatal bisphenol A exposure and birth outcomes: The Hokkaido Study  [通常講演]

  Machiko Minatoya, Seiko Sasaki, Sonomi Nakajima, Jun Yamamoto, Atsuko Araki, Sachiko Itoh, Chihiro Miyashita, Toru Matsumura, Katsuya Nonomura, Takahiko Mitsui, Kazutoshi Cho, Reiko Kishi

  ISEE-AC2014 2014年 Shanghai, Chaina
• 胎児のホルモン環境に影響を及ぼす要因の検討 ホルモン関連遺伝子多型と臍帯血ホルモン濃度  [通常講演]

  佐田 文宏, 江藤 亜紀子, 荒木 敦子, 三井 貴彦, 金谷 泰宏, 岸 玲子, 野々村 克也

  環境ホルモン学会研究発表会要旨集 2013年12月
• 北海道3地区における妊婦の喫煙率および喫煙開始年齢について 環境省「子どもの環境と健康に関する全国調査(エコチル調査)」より  [通常講演]

  荒木 敦子, 西條 泰明, 伊藤 善也, 池野 多美子, 宮下 ちひろ, 伊藤 佐智子, 土川 陽子, 吉岡 英治, 川西 康之, 村林 宏, 岸 玲子

  北海道公衆衛生学雑誌 2013年11月
• 尿中フタル酸代謝物濃度とハウスダスト中フタル酸エステル濃度との関連 札幌市児童における調査  [通常講演]

  アイツバマイ ゆふ, 荒木 敦子, 河合 俊夫, 坪井 樹, 多島 秀司, 叢 石, 湯浅 資之, 金澤 文子, 玉腰 暁子, 岸 玲子

  北海道公衆衛生学雑誌 2013年11月
• 札幌市内小学生の自宅における暖房、および機械換気の有無と児童の喘息  [通常講演]

  叢 石, 荒木 敦子, 鵜川 重和, アイツバマイ ゆふ, 多島 秀司, 金澤 文子, 湯浅 資之, 玉腰 暁子, 岸 玲子

  北海道公衆衛生学雑誌 2013年11月
• 札幌市128軒のハウスダスト中リン酸トリエステル類濃度と小学生のアレルギー疾患との関連  [通常講演]

  多島 秀司, 荒木 敦子, 河合 俊夫, 坪井 樹, アイツバマイ ゆふ, 叢 石, 吉岡 英治, 岸 玲子

  北海道公衆衛生学雑誌 2013年11月
• マタニティヨガの周産期予後改善効果に関する研究(エコチル調査北海道追加調査)  [通常講演]

  川西 康之, 中木 良彦, 伊藤 俊弘, 吉岡 英治, 吉田 貴彦, 伊藤 善也, 池野 多美子, 荒木 敦子, 岸 玲子, 西條 泰明

  日本公衆衛生学会総会抄録集 2013年10月
• マタニティヨガの周産期予後改善効果に関する研究  [通常講演]

  川西 康之, 中木 良彦, 伊藤 俊弘, 吉岡 英治, 吉田 貴彦, 伊藤 善也, 宮下 ちひろ, 荒木 敦子, 岸 玲子, 千石 一雄, 西條 泰明

  北日本産科婦人科学会総会・学術講演会プログラム・抄録集 2013年09月
• GC/MSによるヒトの尿中2-エチルヘキサノールの定量 フタル酸ジエステル類評価としての無水フタル酸可塑剤・難燃剤曝露と小児の健康影響  [通常講演]

  河合 俊夫, 坪井 樹, 荒木 敦子, アイツバマイ ゆふ, 岸 玲子

  産業衛生学雑誌 2013年05月
• 児童の尿中フタル酸代謝物濃度とアレルギー 可塑剤、難燃剤の小児への健康影響(4)  [通常講演]

  荒木 敦子, 坪井 樹, 河合 俊夫, アイツバマイ ゆふ, 多島 秀司, 叢 石, 鵜川 重一, 吉岡 英治, 岸 玲子

  日本衛生学雑誌 2013年03月
• フタル酸ジエステル類評価としての無水フタル酸可塑剤・難燃剤曝露と小児の健康影響(2)  [通常講演]

  河合 俊夫, 坪井 樹, 荒木 敦子, アイツバマイ ゆふ, 岸 玲子

  日本衛生学雑誌 2013年03月
• アレルギーとダスト中フタル酸エステル濃度 可塑剤・難燃剤曝露と小児の健康影響(3)  [通常講演]

  アイツバマイ ゆふ, 荒木 敦子, 坪井 樹, 河合 俊夫, 多島 秀司, 叢 石, 吉岡 英治, 玉腰 暁子, 岸 玲子

  日本衛生学雑誌 2013年03月
• フタル酸エステル尿中代謝物の同時測定方法の開発可塑剤難燃剤曝露と小児の健康影響(1)  [通常講演]

  坪井 樹, 河合 俊夫, 荒木 敦子, アイツバマイ ゆふ, 岸 玲子

  日本衛生学雑誌 2013年03月
• Phthalate metabolites in urine and their relation to allergies in school children -Exposure assessment to plasticizer and flame retardants (3)-  [通常講演]

  Atsuko Araki, Toshio Kawai, Tazuru Tsuboi, Yu Ait Bamai, Eiji Yoshioka, Shuji Tajima, Cong Shi, Shigekazu Ukawa, Reiko Kishi

  ISEE-ISES-ISIAQ 2013 2013年 Basel, Switzerland
• Biological monitoring of environments exposure to DEHP by urine analysis for 2-Ethyl-1-hexanol. Environment and Health - Bridging South, North, East and West Conference of ISEE, ISES and ISIAQ. Basel, Switzerland.  [通常講演]

  Kawai Toshio, Tsuboi Tazuru, Araki Atsuko, Bamai Ait Yu, Kishi Reiko

  ISEE-ISES-ISIAQ 2013 2013年 Basel, Switzerland
• Maternal exposure to DEHP and sex hormone levels in cord blood  [通常講演]

  Atsuko Araki, Takahiko Mitsui, Chihiro Miyashita, Masahiro Tagawa, Tamie Nakajima, Seiko Sasaki, Tamiko Ikeno, Sachiko Itoh, Emiko Okada, Kazutoshi Cho, Katsuya Nonomura, Reiko Kishi

  DOHaD2013 2013年 Singapore
• 可塑剤・難燃剤の曝露評価手法の開発と小児アレルギー・リスク評価への応用 尿中2-エチル-1-ヘキサノールの分析方法と測定事例  [通常講演]

  河合 俊夫, 坪井 樹, 荒木 敦子, アイツバマイゆふ, 岸 玲子

  産業衛生学雑誌 2013年01月
• 環境省「エコチル調査」に関する意識調査と広報活動の課題  [通常講演]

  荒木 敦子, 尾西 奈江, 中瀬 督久, 岸 玲子, エコチル調査北海道ユニットセンター事務局

  北海道公衆衛生学雑誌 2012年11月
• ハウスダスト中に含まれるリン酸トリエステル類の濃度と住居環境  [通常講演]

  多島 秀司, 荒木 敦子, 坪井 樹, 河合 俊夫, 斎藤 育江, アイツバマイ ゆふ, 竹田 智哉, 鵜川 重和, 吉岡 英治, 岸 玲子

  北海道公衆衛生学雑誌 2012年11月
• 小学生の住宅におけるハウスダスト中のエンドトキシンならびにβ-グルカン量とアレルギー性疾患に関する研究  [通常講演]

  叢 石, 荒木 敦子, アイツバマイ ゆふ, 竹田 智哉, 早川 敦司, 吉岡 英治, 多島 秀司, 鵜川 重和, 玉腰 暁子, 岸 玲子

  北海道公衆衛生学雑誌 2012年11月
• 札幌市の小学生4500名を対象とした住環境と喘息、アトピー性皮膚炎に関する調査  [通常講演]

  鵜川 重和, 荒木 敦子, 金澤 文子, 湯浅 資之, 吉岡 英治, 岸 玲子

  日本公衆衛生学会総会抄録集 2012年10月
• ヒトの出産前後における血液DEHP代謝物濃度の解析  [通常講演]

  田川 雅大, 内藤 久雄, 林 由美, 川野 愛子, 佐々木 成子, 荒木 敦子, 小林 澄貴, 岸 玲子

  日本衛生学雑誌 2012年02月
• 小学生のシックハウス症候群の有訴と床ダスト中有機リン酸トリエステル類濃度との関係  [通常講演]

  多島 秀司, 荒木 敦子, 斎藤 育江, 河合 俊夫, 坪井 樹, アイツバマイ ゆふ, 竹田 智哉, 吉岡 英治, 鵜川 重和, 岸 玲子

  日本衛生学雑誌 2012年02月
• 札幌市小学生の喘息・鼻結膜炎有訴と自宅環境および気中VOC・MVOC濃度  [通常講演]

  荒木 敦子, アイツバマイ ゆふ, 河合 俊夫, 坪井 樹, 竹田 智哉, 多島 秀司, 鵜川 重和, 叢 石, 吉岡 英治, 岸 玲子

  日本衛生学雑誌 2012年02月
• シックハウス症候群研究最近の動向 シックハウス症候群に関する全国規模の疫学研究 化学物質、湿度環境、生物学的要因  [通常講演]

  荒木 敦子, 西條 泰明, 田中 正敏, 瀧川 智子, 吉村 健清, 森本 兼曩, 柴田 英治, 河合 俊夫, 斎藤 育江, 岸 玲子

  日本衛生学雑誌 2012年02月
• Phthalate in house dust and tis relation to sick building syndrome and allergic symptoms.  [通常講演]

  Reiko Kishi, Atsuko Araki, Ikue Saito, Eiji Shibata, Ayako Kanazawa, Kanehisa Morimoto, Kunio Nakayama, Masatoshi Tanaka, Tomoko Takigawa, Takesumi Yoshimura, Hisao Chikara, Yasuaki Saijo

  ICOH2012 2012年 Cancun, Mexico
• Determination of phthalate metabolites in urine of children and their family -Exposure assessment to plasticizer and flame retardants and their risk on children (3)-  [通常講演]

  Atsuko Araki, Toshio Kawai, Tazuru Tsuboi, Yu Ait Bamai, Tomoya Takeda, Eiji Yoshioka, Shuji Tajima, Shigekazu Ukawa, Cong Shi, Reiko Kishi

  ISES2012 2012年 Seattle, WA, USA
• Determination of human urinary metabolites of five phthalate by gas chromatography-mass spectrometry -Exposure assessment to plastisizer and flame retardants and their risk on children (1)-  [通常講演]

  Tsuboi Tazuru, Toshio Kawai, Atsuko Araki, Yu Ait Bamai, Reiko Kishi

  ISES2012 2012年 Seattle, WA, USA
• Phthalic anhydride as a marker of total uptake of phthalate diesters -Exposure assessment to plastisizer and flame retardants and their risk on children (2)-  [通常講演]

  Toshio Kawai, Tsuboi Tazuru, Atsuko Araki, Yu Ait Bamai, Reiko Kishi

  ISES2012 2012年 Seattle, WA, USA
• Research plan for 7 year-old survey of the Hokkaido Stud  [通常講演]

  Atsuko Araki, Chihiro Miyashita, Tamiko Ikeno, Seiko Sasaki, Shuji Tajima, Yu Ait Bamai, Cong Shi, Shigekazu Ukawa, Toshio Kawai, Tazuru Tsuboi, Emiko Okada, Reiko Kishi

  BiCCA2012 2012年 Taipei, Taiwan
• 小学生の住宅におけるハウスダスト中のエンドトキシンならびにβ-グルカン量と住宅特徴に関する調査  [通常講演]

  叢 石, 荒木 敦子, アイツバマイ ゆふ, 竹田 智哉, 早川 敦司, 吉岡 英治, 多島 秀司, 鵜川 重和, 岸 玲子

  北海道公衆衛生学雑誌 2011年11月
• 自宅住環境とアトピー性皮膚炎に関する調査 札幌市の小学生4,500名を対象として  [通常講演]

  鵜川 重和, 荒木 敦子, 金澤 文子, 湯浅 資之, アイツバマイ ゆふ, 吉岡 英治, 叢 石, 多島 秀司, 岸 玲子

  北海道公衆衛生学雑誌 2011年11月
• 自宅空気中化学物質濃度とシックハウス症候群に関する調査研究 札幌市小学生を対象として  [通常講演]

  荒木 敦子, アイツバマイ ゆふ, 坪井 樹, 河合 俊夫, 竹田 智哉, 早川 敦司, 吉岡 英治, 多島 秀司, 叢 石, 鵜川 重和, 岸 玲子

  北海道公衆衛生学雑誌 2011年11月
• 札幌市戸建住宅における3年の室内環境とシックハウス症候群有訴の変化  [通常講演]

  荒木 敦子, 金澤 文子, 西條 泰明, 岸 玲子

  日本衞生學雜誌 2011年05月 

  Objectives: The purpose of this study was to investigate annual variations in indoor environmental chemical, fungal and dust mite allergen levels, with regards to variations in sick house syndrome (SHS) symptoms over a three-year period. Methods: Detached houses were randomly selected from a building plan approval application, and a questionnaire survey was conducted in 2003 in Sapporo, Japan. Indoor environmental measurements and a self-administered questionnaires survey were conducted on the selected houses in 2004, 2005 and 2006. The same protocol was used for the three-year period to me...
• シックハウス症状解明のための超小型、軽量、拡散型サンプラーの開発 アルデヒド測定用サンプラー  [通常講演]

  河合 俊夫, 坪井 樹, 乾谷 正樹, 荒木 敦子, 住野 公昭, 岸 玲子

  産業衛生学雑誌 2011年05月
• シックハウス症状解明のための超小型、軽量、拡散型サンプラーの開発 VOC測定用サンプラー  [通常講演]

  坪井 樹, 河合 俊夫, 乾谷 正樹, 住野 公昭, 荒木 敦子, 岸 玲子

  産業衛生学雑誌 2011年05月
• 札幌市小学生のシックハウス症候群有訴と自宅の気中化学物質濃度  [通常講演]

  荒木 敦子, アイトバマイ ゆふ, 竹田 智哉, 河合 俊夫, 坪井 樹, 早川 敦司, 吉岡 英治, 岸 玲子

  日本衛生学雑誌 2011年02月
• 微生物由来VOCによる室内空気室汚染の実情と健康影響  [通常講演]

  荒木 敦子, 岸 玲子

  日本衛生学雑誌 2011年02月
• Organophosphate triesters in house dust and its relation to allergic symptoms.  [通常講演]

  Atsuko Araki, Tomoya Takeda, Ayako Kanazawa, Ikue Saito, Kanehisa Morimoto, Kunio Nakayama, Eiji Shibata, Masatoshi Tanaka, Tomoko Takigawa, Takesumi Yoshimura, Hisao Chikara, Yasuaki Saijo, Reiko Kishi

  ISEE2011 2011年 Barcelona, Spain
• Validation and feasibility study of the developed small diffusive sampers for aldehyde and VOC in elementary school children  [通常講演]

  Atsuko Araki, Toshio Kawai, Tazuru Tsuboi, Yu Ait Bamai, Tomoya Takeda, Eiji Yoshioka, Reiko Kishi

  7th AIRMON 2011年 Loen, Norway
• 室内環境汚染物質51物質の分析・測定技術  [通常講演]

  坪井 樹, 永滝 陽子, 河合 俊夫, 住野 公昭, 荒木 敦子, 大前 和幸, 岸 玲子

  産業衛生学雑誌 2010年05月
• 喫煙者の有無別にみた室内環境化学物質濃度とシックハウス症候群の自覚症状  [通常講演]

  アイトバマイ ゆふ, 荒木 敦子, 西條 泰明, 森本 兼曩, 中山 邦夫, 瀧川 智子, 田中 正敏, 柴田 英治, 吉村 健清, 力 寿雄

  日本衛生学雑誌 2010年04月
• Prevalence of asthma, atopic dermatitis, and rhinitis and MVOC exposure in single family homes ?a survey in six cities of Japan-  [通常講演]

  Atsuko Araki, Toshio Kawai, Yoko Eitaki, Ayako Kanazawa, Kanehisa Morimoto, Kunio Nakayama, Eiji Shibata, Masatoshi Tanaka, Tomoko Takigawa, Takesumi Yoshimura, Hisashi Chikara, Yasuaki Saijo, Reiko Kishi

  ISEE-ISES 2010 2010年 Seoul, Korea
• シックハウス関連物質の活性炭脱着率に関する基礎的検討  [通常講演]

  永滝 陽子, 坪井 樹, 河合 俊夫, 清水 英佑, 大前 和幸, 荒木 敦子, 岸 玲子

  産業衛生学雑誌 2010年01月
• 札幌市小学生を対象としたシックハウス症候群の有訴率と関連要因に関する調査  [通常講演]

  荒木 敦子, 湯浅 資之, 金澤 文子, 岸 玲子

  北海道公衆衛生学雑誌 2009年11月
• 全国6地域の一般住宅におけるシックハウス症候群の実態と原因の解明 (第5報)室内空気質中Microbial VOC類の濃度と症状との関係  [通常講演]

  荒木 敦子, 河合 俊夫, 永滝 陽子, 金澤 文子, 竹田 誠, 森本 兼曩, 中山 邦夫, 柴田 英治, 田中 正敏, 瀧川 智子, 吉村 健清, 力 寿雄, 岸 玲子

  日本衛生学雑誌 2009年03月
• 札幌市新築戸建住宅における3年間の室内環境変化  [通常講演]

  荒木 敦子, 金澤 文子, 竹田 誠, 西條 泰明, 岸 玲子

  北海道公衆衛生学雑誌 2008年11月
• 全国6地域の一般住宅におけるシックハウス症候群の実態と原因の解明 : 第4報 室内空気質中 Microbial VOC 類の濃度と住環境との関係  [通常講演]

  荒木 敦子, 河合 俊夫, 永滝 陽子, 竹田 誠, 金澤 文子, 森本 兼曩, 中山 邦夫, 柴田 英治, 田中 正敏, 瀧川 智子, 吉村 健清, 力 寿雄, 岸 玲子

  日本衞生學雜誌 2008年03月
• 札幌市一般住宅におけるフタル酸エステル、リン酸トリエステルによる室内汚染 : 実態解明とシックハウス症候群との関連  [通常講演]

  金澤 文子, 斎藤 育江, 荒木 敦子, 竹田 誠, 矢口 久美子, 岸 玲子

  日本衞生學雜誌 2008年03月
• Aromatherapy massage benefit patient with idiopathic environmental intolerance in short term mood changes: A pilot study.  [通常講演]

  Atsuko Araki, Kazuhiko Watanabe, Yoko Eitaki, Toshio Kawai, Reiko Kishi

  10th International Congress of Behavioral Medicine 2008年 Tokyo, Japan
• ミニサンプラーを用いた室内空気中可塑剤、難燃剤、殺虫剤等の一斉分析法  [通常講演]

  斎藤 育江, 大貫 文, 矢口 久美子, 上原 眞一, 金澤 文子, 竹田 誠, 荒木 敦子, 岸 玲子

  環境ホルモン学会研究発表会要旨集 2007年12月
• 8.新規シックハウス関連物質(MVOC)の測定法について(一般口演,第34回有機溶剤中毒研究会,地方会・研究会記録)  [通常講演]

  竹田 誠, 河合 俊夫, 永滝 陽子, 荒木 敦子, 金澤 文子, 岸 玲子

  産業衛生学雑誌 2007年11月
• 新規シックハウス関連物質(MVOC)の測定法について  [通常講演]

  竹田 誠, 河合 俊夫, 永滝 陽子, 荒木 敦子, 金澤 文子, 岸 玲子

  産業衛生学雑誌 2007年11月
• 一般住宅における微生物由来有機化合物(MVOC)測定法の確立と実態調査  [通常講演]

  竹田 誠, 河合 俊夫, 永滝 陽子, 荒木 敦子, 金澤 文子, 岸 玲子

  産業衛生学雑誌 2007年04月
• 全国6地域の一般住民におけるシックハウス症候群の実態と原因の解明(第3報) 戸建住宅の室内環境要因と症状の地域差  [通常講演]

  岸 玲子, 西條 泰明, 荒木 敦子, 田中 正敏, 柴田 英治, 森本 兼曩, 中山 邦夫, 瀧川 智子, 吉村 健清, 力 寿雄

  日本衛生学雑誌 2007年03月
• 全国6地域の一般住宅におけるシックハウス症候群の実態と原因の解明 : 第3報 戸建住宅の室内環境要因と症状の地域差  [通常講演]

  岸 玲子, 西條 泰明, 荒木 敦子, 田中 正敏, 柴田 英治, 森本 兼曩, 中山 邦夫, 瀧川 智子, 吉村 健清, 力 寿雄

  日本衞生學雜誌 2007年03月
• 札幌市一般住宅におけるフタル酸エステル、リン酸トリエステル、殺虫剤による室内汚染の実態  [通常講演]

  金沢 文子, 斎藤 育江, 竹田 誠, 荒木 敦子, 馬 明月, 瀬戸 博, 岸 玲子

  日本衞生學雜誌 2007年03月

所属学協会

• International Society of Exposure Science   International Society for Environmental Epidemiology   北海道公衆衛生学会   室内環境学会   日本産業衛生学会   日本衛生学会   The Pacific Basin Consortium for Environment and Health (PBC)   The International Commission on Occupational Health (ICOH)   

共同研究・競争的資金等の研究課題

• 化学物質の次世代影響-出生から青年期の脂質代謝やエピゲノムの作用機序

  日本学術振興会：科学研究費助成事業

  研究期間 : 2023年04月 -2026年03月 

  代表者 : 宮下 ちひろ, 池田 敦子, 田村 菜穂美, 山口 健史, 惠 淑萍
• 化学物質による青年期の生殖機能、抑うつ、NCDsへの影響：分子機構の解明を含めて

  日本学術振興会：科学研究費助成事業

  研究期間 : 2022年04月 -2026年03月 

  代表者 : 岸 玲子, 齊藤 卓弥, 池田 敦子, 山崎 圭子, 田村 菜穂美, 山口 健史, 宮下 ちひろ, 伊藤 佐智子, アイツバマイ ゆふ, 小林 澄貴
• 学童期の子どものピレスロイド系農薬への曝露と発達障がいとの関連

  日本学術振興会：科学研究費助成事業

  研究期間 : 2023年04月 -2026年03月 

  代表者 : 西原 進吉, 池田 敦子, 小林 澄貴
• 有機フッ素化合物および新規類縁化合物の曝露実態と児の免疫系への健康影響の解明

  日本学術振興会：科学研究費助成事業

  研究期間 : 2022年04月 -2025年03月 

  代表者 : アイツバマイ ゆふ, 池田 敦子, 宮下 ちひろ, 岸 玲子, 山口 健史
• 環境化学物質曝露による有害作用：ヒト疫学研究と動物実験による機序解明

  日本学術振興会：科学研究費助成事業 基盤研究(A)

  研究期間 : 2021年04月 -2025年03月 

  代表者 : 荒木 敦子, 小島 弘幸, 増田 秀幸, 池中 良徳, Goudarzi Houman, POUDEL KRITIKA, 中村 明枝, アイツバマイ ゆふ

   

  疫学研究では、「北海道スタディ」に参加する9-11歳の前思春期児から収集した血漿を用いて、購入したBio-Plex200 multiplexアッセイシステムによりTh1/Th2関連サイトカイン17種類およびエオタキシン、糖尿病マーカー10種類およびアディポネクチンとアディプシンを約420検体測定した。同様に、9-11歳の学童339人の血漿を用いて、独自に開発した内標準物質による定量LC/MS分析法を利用し、血中各種コレステリルエステル（CE）11化合物の濃度測定を行った。なお、CE濃度が他のパラメーター、例えば性別や年齢、体格と関連性については現在解析中である。一般集団の子どもにおけるT2バイオマーカー（総IgE、好酸球、呼気中一酸化窒素（FeNO））の基準値を求めた。喘鳴、鼻結膜炎、湿疹といったアレルギー症状に加えて、性別（男児）と喫煙がT2バイオマーカー値を説明していた。 リン酸トリエステル類曝露とT2バイオマーカーである血中総IgE、好酸球、FeNO、および表現型としての喘鳴、湿疹、鼻結膜炎の症状との関連を解析し、リン酸トリエステル類ΣTBOEPとΣTPHP濃度が高いと喘息、好酸球およびFeNOのリスクが高くなることが明らかになった。 妊娠ICRマウスに、水（対照群）、PFOA 0.3 mg/kg（低用量群）及びPFOA 3 mg/kg（高用量群）を妊娠期間中経口曝露した。それぞれ出生後７日目の仔マウス肝臓からmRNAを採取した。GeneChip解析を用いた網羅的遺伝子発現解析を行い、PFOA投与量に応じて変動遺伝子数の上昇を認めた。また、高用量群マウスから生まれた仔マウスの肝臓は肥大しており、PFOAが胎盤や母乳を介して仔に影響したと考えられた。
• 学童期の有機リン・ネオニコチノイド系農薬曝露と子どもの注意および抑制機能との関連

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2021年04月 -2025年03月 

  代表者 : 山崎 圭子, 荒木 敦子, 須山 聡, 伊藤 佐智子

   

  本研究では、出生前向きコホート「北海道スタディ」の参加児を対象に、7歳時に採取・保存した尿中の有機リン・ネオニコチノイド系農薬曝露と、13歳時の認知機能およびADHD傾向との関連について解析する。有機リン・ネオニコチノイド系農薬への曝露評価は、既に採取済みの7歳時尿検体6000件のうち、ERPデータを得た参加者の検体を測定する。有機リン 6代謝物（DMP, DEP, DMTP, DMDTP, DETP, DEDTP）、ネオニコチノイド 7物質（ジノテフラン、ニテンピラム、チアメトキサム、クロチアニジン、イミダクロピリド、チアクリプリド、アセミタプリド）を、LC-MS/MSを用いて測定する。アウトカムとして事象関連脳電位（Event related brain potential: ERP）の測定およびADHD質問票を実施する。ERP測定時に用いるGo/No-go課題は注意および行動抑制機能の評価を行うための標準的な課題である。これにより記録されるERPとして、注意の容量を反映するP300、心的な反応抑制や反応の判断を反映するN2、運動反応の抑制を反映するNo-go P3が出現する。これらERPの振幅、潜時、頭皮上分布に調査票により評価するADHD傾向をアウトカムとする。本研究は、総体としてのADHD傾向よりも、それを構成する個々の認知機能に着目し、その測度として、生物学的な基盤を持つ脳波のERPを用いている。ADHD症状を個別の認知機能の面から解釈し、不全を起こしている機能を特定することにより、療育方法の改善にも寄与する可能性がある。当該年度にはこれらを踏まえ、アウトカムとなるERP測定およびADHD調査票の回収を中心に研究を進めた。
• Potential role of club cell secretory protein (CC16) in development of obese asthma: findings from a birth cohort and animal studies

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2020年04月 -2023年03月 

  代表者 : Goudarzi Houman, 荒木 敦子, 今野 哲

   

  1) Adult asthma cohort):BMI was significantly and monotonously associated with reduced circulating CC16 levels in adult asthmas patients. Also, CC16 was inversely associated with sputum eosinophils and blood periostin. Patients with the lowest tertile of serum CC16 levels at baseline had a -14.3 mL decline in FEV1 than those with the highest tertile over five years of follow-up (p for trend = 0.031). 2) Population 2 (birth cohort): Ongoing. 3) Animal study: The percentage of CC16-cells was reduced in the small airways of mice with obesity. In addition, serum CC16 levels were significantly lower in obese mice than in non-obese control mice. However, the serum levels of SP-A and SP-D, other products of club cells, did not vary between obese and non-obese control mice.
• 胎児期環境の神経発達障害と脳の性分化および肥満への影響解明：出生コーホート研究

  日本学術振興会：科学研究費助成事業 基盤研究(A)

  研究期間 : 2019年04月 -2023年03月 

  代表者 : 岸 玲子, 荒木 敦子, 小林 澄貴, 齊藤 卓弥, 湊屋 街子, 山崎 圭子, 中島 そのみ, 宮下 ちひろ, 白石 秀明, アイツバマイ ゆふ, 三浦 りゅう

   

  本研究は、出生コーホート研究で保存された母体血・臍帯血および学童期から思春期に採取した児の尿を用いて、胎児期および生後の環境化学物質曝露が児のアレルギー、神経行動発達、第二次性徴等のアウトカムへ及ぼす影響についてリスク評価を行うことを目的とした。 令和3年度は、出生コーホートの参加者について11歳で第二次性徴に関する調査票1182件、12歳で小学校の学校健診記録から転記する身長体重調査票1236件、15歳で中学校の身長体重調査票1440件、17歳調査1787件を発送した。回収数は11歳812件（回収率68.7.％）、12歳771件（回収率62.4％）、15歳815件（回収率56.5％）、17歳855件（47.8％）であった。生後のアウトカム評価として、これまでの質問票調査によるアレルギー、神経行動発達、第二次性徴の評価を行った。脳波調査では、有機フッ素化合物（PFAS）の胎児期曝露が児の認知機能に関連する可能性を検討した。妊娠初期母体血清中のフタル酸7代謝物と第二次性徴発来のタイミングおよび、成長や肥満などの体格との解析を実施した。
• 農薬曝露による子どもの神経発達リスクの解明－遺伝子多型(SNPs)解析を用いて－

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2019年04月 -2022年03月 

  代表者 : 西原 進吉, 荒木 敦子, 小林 澄貴

   

  近年、発達障害の子どもが増加傾向にある中、農薬への曝露がその一因である可能性が指摘されている。しかしながら、農薬への曝露が、子どもの神経発達に与える健康影響を検討した研究は極めて少ない。 本研究では、児の尿を用いて、有機リン、ネオニコチノイド等の農薬や代謝物の濃度を測定する。加えて、これらの曝露濃度と神経発達スコアとの関連を検討し、農薬曝露が神経発達に与える影響を明らかにする。出生時に採取された臍帯血からDNAを抽出し、代謝関連遺伝子多型（SNPs）を解析することで、上記農薬曝露に対して脆弱な集団の存在を解明する。最終的には、このような個人差を考慮に入れた評価モデルの構築を目指す。 R1年度末までに、農薬やその代謝物をを測定する尿検体、および、アウトカムを評価するための情報（Conners3P，ADHD-RS）は収集済みである。また、その中で今回の研究で測定するための検体候補もピックアップ済みである。具体的には、2003年から2009年に生まれ、2017年11月までに8歳に到達した児の中で、妊娠初期に収集されたベースライン調査票、産後の新生児個票、7歳時点での尿検体、8歳時のアウトカム調査票、および、DNA抽出用の臍帯血の検体が揃う1537名から、ランダムに抽出されたサブコホート287名の検体を測定検体として選定した。 R2年度は、上記のピックアップした尿検体中の農薬やその代謝物濃度について、LC/MS/MS法を用いて測定し、アウトカムとの関連を解析する。
• 有機フッ素化合物の第二次性徴への影響解明ー出生コホートと細胞アッセイ系による研究

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2018年04月 -2022年03月 

  代表者 : 荒木 敦子, 小島 弘幸, 小林 澄貴, 守屋 仁彦, 池中 良徳, 宮下 ちひろ, 岸 玲子, アイツバマイ ゆふ

   

  北海道スタディに参加者504名の母体血清中のPFOS/PFOA濃度と臍帯血中の性ホルモン濃度、臍帯血中DNAのCYP17A1、CYP19A1、HSD3B1、HSD3B2、HSD17B1、HSD17B3遺伝子にある12か所の一塩基多型(SNPs)を解析した。PFOS濃度とHSD17B1（rs676387およびrs2675531）遺伝型との交互作用がDHEA/A-dione濃度と関連を示した。HSD17B1遺伝型で層別解析したところ、HSD17B1(rs676387)-GG/GA型ではPFOS濃度が2倍増えるとDHEA/A-dioneは0.115（95%CI: -0.294, 0.065）減少したのに対し、AA型では0.476（-0.276, 0.979）増加した。HSD17B1(rs2676531)-CC/CT型ではPFOS濃度が2倍増えるとDHEA/A-dioneは0.138（95%CI: -0.335, 0.060）減少したのに対し、TT型では0.535（0.013, 1.057）増加した。児のHSD17B1遺伝型は、母体血清PFOS濃度と児の性ホルモン濃度との関連に違いを及ぼす可能性が示唆された。 in vitro細胞アッセイ系を用いてPFAS11化合物のpregnane X receptor(PXR)、constitutive androstane receptor(CAR)、peroxisome proliferators-activated receptor(PPAR)α、PPARβ、PPARγの各種ヒト核内受容体に対するアゴニスト活性を調べた。PFOA及びPFNAが高用量でPPARalpha;アゴニスト活性を示したが、PXR・CAR・PPARalpha,PPARganmaに対するアゴニスト活性は認められなかった。また、PFASsの遺伝子発現に及ぼす影響評価として、ヒト血中濃度の高いPFOA及びPFNAをそれぞれヒト肝細胞株に曝露してmRNAを採取した。
• 環境・遺伝・エピゲノム交互作用のコホート縦断的解明：学童期肥満の早期予防へ

  日本学術振興会：科学研究費助成事業 挑戦的研究(萌芽)

  研究期間 : 2019年06月 -2021年03月 

  代表者 : 岸 玲子, 荒木 敦子, 小林 澄貴, 三浦 りゅう, 湊屋 街子, 宮下 ちひろ, 川野 佐智子

   

  小学６年生時の肥満度が20以上（日本小児内分泌学会）の肥満傾向児218名、および肥満傾向でない児282名、合計500名のケースサブコホート集団を対象とした。７歳児の受動喫煙は小児肥満のリスク要因であったが、妊婦（母）の喫煙とは関係がなかった。小児肥満の有無によって臍帯血DNAメチル化率に差異があるCpGを抽出することを目的に、児の性別で層別化したロバスト線形回帰、および経験ベイズ法を用いて解析した。従属変数には臍帯血DNA約85万CpGのエピゲノム網羅的メチル化（EPIC）データ、独立変数に小児肥満の有無、母の出産時年齢、学歴、および細胞組成を投入した。多重比較を考慮しFDR q < 0.05を有意水準にした。全体および男児では肥満と関連するCpGサイトは抽出されなかったが、女児で小児肥満と関連する5か所のCpGが抽出された（HECW1：cg15299402、UTS2：cg26405913、INF2：cg02878289、MIR200A：cg25101291、EXT1：cg14779140）。これまでに小児肥満とDNAメチル化の関連を検討した先行研究は限られており本研究で抽出されたCpGおよび遺伝子は先行研究の結果と一致しなかった（Kresovich et al 2017, Kupers et al 2019, Yang et al 2018）。欧米人が対象であるため日本の結果は一致しなかったと思われる。一方、DNAメチル化と出生体重や喫煙との関連を検討した研究では、男女合わせた解析でHECW1およびINF2は児の出生体重(Kupers et al 2019)や胎盤形成（KYB et al 2018）、および胎児期の喫煙（Juubert et al 2016）の関連が報告されている。本研究では女児のみの解析では臍帯血DNAメチル化と小児肥満が関連した。小児肥満発生機序に関与するエピゲノム修飾には男女差があることが示唆された。
• 胎児期POPs曝露の甲状腺機能攪乱作用が児のADHD症状へ与える影響の解明

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2018年04月 -2021年03月 

  代表者 : 川野 佐智子, 荒木 敦子, 山崎 圭子, 須山 聡, 岸 玲子

   

  甲状腺ホルモン合成には、主に土台となる蛋白質のサイログロブリン（Tg）とヨウ素化酵素である甲状腺ペルオキシダーゼ（TPO）が大きく関わっている。橋本病等の自己免疫性甲状腺疾患では、これらの自己抗体である抗TPO抗体(TPOAb)、抗Tg抗体（TgAb）が産生され、自己の甲状腺細胞を攻撃することで甲状腺ホルモン産生が低下する。そこで本研究では出生前向きコホート「環境と子どもの健康に関する北海道スタディ（以下、北海道スタディ）」を用いて、妊娠中のPOPs曝露が母児抗甲状腺抗体値の攪乱により甲状腺ホルモン濃度を変化させ、児のADHD症状へ影響するかを明らかにすることで、近年増加傾向にあるADHD症状のメカニズム解明への糸口を示し、予防対策および治療法への道を切り拓くことを目的とする。H31年度は、H30年度に母体血および臍帯血中TPOAb、TgAb濃度を測定した母児のうち、既存のコホートの母体血中有機フッ素化合物（Per- and poly-alkylfluorosubstances: PFAS）濃度のデータを有する701組の母児を対象に、PFASと児のTSH、FT3、FT4、TPOAb、TgAb値との関連を解析した。母の抗体値を基に抗体有/無の2グループに分けて層別解析したところ、抗体無のグループにおいて、男児では母体血中PFASが高いと男児のTSHが高く、FT3、TgAbが有意に低かった。女児ではPFASが高いとFT3が高く、TSHが低かった。抗体有のグループにおいて、男児では母のPFASが高いとTSHが低かった。女児ではFT4が低く、TgAbが高かった。これらの結果から、胎児期のPFAS曝露を及ぼす児の甲状腺攪乱作用は、母親の抗甲状腺抗体値によって異なる可能性が示唆された。
• 環境化学物質の第二次性徴・神経行動発達・アレルギーへの影響：分子メカニズムの解明

  日本学術振興会：科学研究費助成事業 基盤研究(A)

  研究期間 : 2016年04月 -2019年03月 

  代表者 : 岸 玲子, 荒木 敦子, 宮下 ちひろ, 中島 そのみ, 花岡 知之, 山崎 圭子, 小林 澄貴, 湊屋 街子, 有賀 正, 齊藤 卓弥, 鈴川 晶夫, 梶原 淳睦, 佐田 文宏, 西條 泰明, 吉岡 英治

   

  胎児期および生後の環境化学物質曝露が児の神経行動発達や第二次性徴等へ及ぼす影響を単一および複合曝露によるリスク評価を行い、環境-遺伝交互作用も検討した。児の尿中MEHP濃度は2012-2017年の間で有意な減少を認めた。胎児期フタル酸エステル類およびBPA曝露は、MECPP が5歳の児の問題行動のリスク増加を示し、MnBP, MiBP, MEHPが女児のみで第二次性徴開始月齢の早発を認めた。環境化学物質の複合曝露による性ホルモン値の有意な変動が認められ, MEHPとPFOSの寄与が大きかった。児のエストロゲン受容体1型のXbaI遺伝子型において右手の2D:4D比の低下が見られた。
• 出生コホート調査における親子のスキンシップ頻度の実態および、その関連要因の解明

  日本学術振興会：科学研究費助成事業 若手研究(B)

  研究期間 : 2015年04月 -2019年03月 

  代表者 : 川西 康之, 西條 泰明, 吉岡 英治, 岸 玲子, 荒木 敦子, 伊藤 善也

   

  本研究は、幼児期の母子のスキンシップ頻度尺度の開発と、その関連要因を明らかにすることを目的とした。環境省「子どもの健康と環境に関する全国調査(エコチル調査)」の追加調査として、子供が3.5～4歳の北海道ユニットセンター参加者に自記式質問票調査を実施し、因子分析を行った。結果4因子「愛情表出的かかわり、文化的かかわり、アクティブなかかわり、見つめ合い」を抽出。このスキンシップスコア４因子16項目(16-80点)を目的変数として、産後一ヶ月までのデータを説明変数とした重回帰分析を行った。結果、出産歴、非妊時BMI、近しい人と連絡をとる頻度、相談できる親族や友人の数が、有意に関連していた。
• 前向き出生コホート研究によるADHDの病態関連バイオマーカーの解明

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2016年04月 -2018年03月 

  代表者 : 岸 玲子, 荒木 敦子, 齊藤 卓弥, 三浦 りゅう, 山崎 圭子, アイツバマイ ゆふ, 小林 澄貴

   

  本研究は、胎児期の環境化学物質曝露が注意欠陥/多動性障害（ADHD）発症に至る機序の1つとして、DNAメチル化変化に注目し、臍帯血 DNAの45万ヶ所メチル化部位（CpG部位）の網羅的解析を行った。有機フッ素化合物、フタル酸エステル類、ビスフェノールAの胎児期曝露について、多重比較補正後も統計学的に有意に関連するメチル変化部位を特定した。 ６歳のADHD-RS調査票で見いだされたADHD疑い群（n=245）とコントロール群（n=317）の臍帯血DNAを用いて、網羅的解析で明らかとなった曝露に起因するCpG部位を次世代シークエンサーにより解析し、メチル変化とADHDとの関連を検討している。
• 児のエピゲノム変化に影響する母のダイオキシン類曝露と遺伝子との交互作用の解明

  日本学術振興会：科学研究費助成事業 若手研究(B)

  研究期間 : 2016年04月 -2018年03月 

  代表者 : 小林 澄貴, 宮下 ちひろ, 荒木 敦子

   

  出生前向きコホートを用いて、ダイオキシン類代謝・解毒酵素関連(AHR、CYP1A1、CYP1A2、CYP1A2、GSTM1)遺伝子型による胎児期ダイオキシン類曝露と児の発育に関わる3つの遺伝子領域（インスリン様成長因子[IGF-2、H19]および転移因子[LINE-1]）のエピゲノム変化との関連への影響を検討した。いすれの遺伝子型においても胎児期の母のダイオキシン類曝露と児のIGF-2、H19、およびLINE-1メチル化率との関連に有意な違いは見られなかった。胎児期の母のダイオキシン類濃度と児のメチル化率との関連に母のダイオキシン類代謝関連受容体や酵素の遺伝子型の違いが影響しないと考えられた。
• 学童のアトピー性皮膚炎発症へのFLG遺伝子変異と環境化学物質曝露によ る影響解明

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2015年04月 -2018年03月 

  代表者 : 荒木 敦子, 小島 弘幸, 乃村 俊史, 宮下 ちひろ, 岸 玲子, 清水 宏, 小林 澄貴, 湊屋 街子, アイツバマイ ゆふ, 伊藤 佐智子, 武内 伸治, 浦丸 直人, 奥田 勝博, 竹田 真衣, 河合 俊夫

   

  FLG変異の有無と環境化学物質曝露によるアレルギー発症や酸化ストレスマーカー8-OHdGへの影響を検討した。FLG変異保有割合は、アレルギーのケース群と対照群で統計学的有意差は認めなかった。ダスト中DINP濃度が高いと湿疹のオッズ比が上昇、特にFLG変異のない群で認められた。8OH-dGによるフタル酸エステル類曝露とアレルギーの介在効果は認められなかった。ヒトマクロファージ様細胞株にDEHPとMEHPを曝露し、マイクロアレイ網羅的遺伝子発現解析では、MEHP曝露がTLR4やIL2などの免疫応答に関わる受容体の遺伝子発現上昇が認められ、MEHPと核内受容体PPARαとの親和性が認められた。
• メンデル無作為化解析による胎児期環境リスク評価と遺伝・環境交互作用

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2015年04月 -2018年03月 

  代表者 : 佐田 文宏, 岸 玲子, 荒木 敦子, 野々村 克也, 三井 貴彦, 小林 澄貴

   

  母親の妊娠中の能動・受動喫煙、カフェイン摂取及びPCB・ダイオキシン類の曝露と代謝・DNA修復酵素、受容体をコードする遺伝子の遺伝子多型が、児の発育、特に、出生時体重、頭囲、Kaup指数に及ぼす遺伝‐環境交互作用を原著論文として出版し、学術雑誌に発表した。 また、DOHaD関連疫学研究の動向、特に、最近のゲノムワイド関連研究、エピゲノムワイド関連研究とともにメンデル無作為化解析を含む出生ゲノムコホート研究の現況と今後の課題を総説として学術雑誌に発表した。 さらに、DOHaD疫学セミナーという勉強会を開始し、DOHaD概念に基づく疫学研究の紹介や啓発活動にも力を入れた。
• フタル酸エステル類への胎児期および学童期曝露が第二次性徴初来に与える影響解明

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2014年04月 -2017年03月 

  代表者 : 荒木 敦子, 岸 玲子, アイツバマイ ゆふ, 三井 貴彦, 池野 多美子, Goudarzi Houman, 伊藤 佐智子, 宮下 ちひろ

   

  フタル酸エステル類はプラスチック製品の可塑剤として添加される物質で、内分泌かく乱作用が懸念される。しかし、疫学研究で胎児期曝露による児の第二次性徴発来への影響に関する報告はほとんどなかった。本研究では胎児期DEHP曝露と児の第二次性徴発来への影響に、出生時の性ホルモンが介在するかを検討した。北海道スタディ札幌コ-ホートに参加する児から、第二次性徴に関して150件（45.6％）の回答を得た。胎児期のフタル酸エステルDEHP曝露が高いと男児の第二次性徴発来を有意に遅らせることが明らかになった。一方、その影響は出生時の性ホルモンを介在しておらず、メカニズムの背景には性ホルモン以外の要因が示唆された。
• 前向き出生コホート研究による化学物質の次世代影響並びに環境遺伝交互作用の解明

  日本学術振興会：科学研究費助成事業 基盤研究(A)

  研究期間 : 2013年04月 -2016年03月 

  代表者 : 岸 玲子, 池野 多美子, 荒木 敦子, 宮下 ちひろ, 中島 そのみ, 佐々木 成子, 花岡 知之, 梶原 淳睦, 松浦 英幸, 室橋 春光, 白石 秀明, 佐田 文宏, 西條 泰明, 吉岡 英治, 安住 薫, 安住 薫

   

  母児20000組を対象とした北海道内40産院コホートで、妊娠中の化学物質、特に喫煙・ダイオキシン類・有機フッ素化合物に対する曝露と、学童期までの児の発育、神経行動発達および免疫アレルギーとの関連を検討した。妊娠中の化学物質曝露が(1) PPARβ遺伝子多型を介して血清脂質に、(2) 母のDNA修復（XRCC1）遺伝子多型を介して児の出生体重に、(3) 児のIGF2のDNAメチル化に、そして(4) 1.5歳児の神経行動発達に影響することを明らかにした。加えて、学童期のADHDに関するリスク要因が検討され、妊娠中の飲酒や喫煙がリスクとなることが明らかにされた。
• 出生コーホートを用いた７歳児のアトピー性皮膚炎に関する環境要因と遺伝要因の解明

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2012年04月 -2015年03月 

  代表者 : 荒木 敦子, 乃村 俊史, 岸 玲子, 清水 宏, 佐々木 成子, アイツバマイ ゆふ, 多島 秀司, 鵜川 重和, 叢 石, 多島 秀司

   

  アトピー性皮膚炎(AD)の環境要因として自宅のダニアレルゲンや化学物質曝露、遺伝的素因のフィラグリンFLG遺伝子の変異、さらにこれらの要因を複合的に明らかにすることを目的とした。研究対象は出生コーホート北海道スタディの7歳児で、1,064名のうち約10%が変異を保有し、国内外の先行研究と同程度であった。FLG変異があることが、2歳・4歳時のADのオッズ比をそれぞれ1.6倍・1.5倍上昇させたが、7歳時では有意な上昇を認めなかった。環境要因では、ハウスダスト中の化学物質DiNP濃度が高いことが児のADのオッズ比を1.3倍上げ、FLG変異で層別すると、変異がない群でオッズ比を1.45倍上げた。
• コーホート内症例対照研究による学童期発達障害発症の環境リスク要因と予防策の解明

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2012年04月 -2015年03月 

  代表者 : 池野 多美子, 室橋 春光, 白石 秀明, 佐々木 成子, 岸 玲子, 荒木 敦子, 安住 薫

   

  2万人規模の出生コーホート参加者8歳児を対象に、注意欠如多動性障害(ADHD)発症の環境リスク要因を明らかにすることを目的とした。1)8歳児2,545名でADHD症状得点への喫煙曝露の影響を解析した結果、胎児期喫煙曝露より学童期の養育環境や母の抑うつが影響していた。2) Conners3の各指標から症例と対照計179名に対しWISC-Ⅳ検査など対面調査を実施した。3) 統計学パワーが最大になるよう計算した390名(症例:対照＝1：2）のうちADHD疑い群138名を含む200名分について、神経伝達関連遺伝子(DRD4、DAT1など)と脳由来神経栄養因子(BDNF)の SNPs解析を行った。
• 出生コホート研究による環境化学物質の次世代影響ならびに環境遺伝交互作用の解明

  日本学術振興会：科学研究費助成事業 基盤研究(A)

  研究期間 : 2010年04月 -2014年03月 

  代表者 : 岸 玲子, 吉岡 英治, 佐々木 成子, 室橋 春光, 中島 そのみ, 白石 秀明, 安住 薫, 池野 多美子, 荒木 敦子, 花岡 知之, 梶原 淳睦, 斉藤 貢一, 佐田 文宏, 西條 泰明, 伊藤 佐智子, 宮下 ちひろ

   

  妊婦514名とその児を対象とした1産院コホートで、ベースライン時、1歳半、3歳半、7歳児の両親または児の食習慣・生活習慣や育児環境などを詳細に調べた。児の神経行動発達検査は、生後6か月と1歳半にBSID-II、3歳半にK-ABC、3歳7か月にCBCL、7歳にWISC-III、CBCLなどを実施した。環境化学物質として母体血および母乳中のダイオキシン･PCB異性体類、母体血中PFOS/PFOA等を測定した。