発達環境医学分野研究紹介

母親の胎内にいる胎生期から乳幼児期の環境が、子どもの将来の健康や疾病に影響することがわかっています。この概念はDOHaD：Developmental Origins of Health and Diseaseと呼ばれています。また、子どもの健康や疾病に関わる要因には、環境要因と遺伝素因があります。遺伝素因は変えることはできませんが、胎生期と生後の【環境】を改善することで、疾病を予防あるいは軽減できる可能性があります。本研究室では、胎児・子どもがより健やかに発達できるより良い環境つくりを目指した研究を行っています。世界有数の大規模な出生コホート研究（母子10万組）である環境省【子どもの健康と環境に関する全国調査・エコチル調査】など貴重なデータを用いて、研究を遂行中です。エコチル調査は、福島県の方々も参加・協力していただいています。

本分野は2019年秋に新設されたばかりですが、現在は医学博士課程の大学院生達が関連テーマを通して奮闘中です。未来の子どもたちのため、より良い周産期環境つくりのエビデンス構築に興味がある方は、お気軽に相談ください。

 

現在の主なキーワード

 

現在の主な研究テーマ

両親の周産期メンタルヘルスと子どもの神経発達

東日本大震災以降、周産期メンタルヘルスの重要性がますます注目されるようになりました。妊娠中から産後にかけての親のメンタルヘルス不調は、子どもの神経発達や家族全体の健康に大きな影響を及ぼします。しかし、これまでの研究は母親を対象としたものが中心であり、父親に関するエビデンスは十分ではありませんでした。

私たちは、大規模出生コホートであるエコチル調査を用いて、妊娠中から産後にかけての母親および父親のメンタルヘルスやボンディング（親から子への情緒的な絆）が、子どもの神経発達や自閉スペクトラム症などの発達アウトカムに及ぼす影響について研究を進めてきました。

母親については、妊娠中・産後の抑うつ・不安やボンディング障害が子どもの神経発達と関連することを報告しています。また、母親の妊娠中・産後の抑うつ・不安と子どもの自閉スペクトラム症との関連が男女で異なることを世界で初めて報告しました。

父親については、産後うつやボンディング障害が母親と同程度の頻度で認められることを明らかにしました。また、父親のボンディング障害の重要なリスク因子が母親のボンディング障害であることを世界で初めて報告しました。さらに、わが国においても父親の産後うつやボンディング障害が子どもの神経発達と関連することを報告し、父親への早期支援の重要性を提唱しています。

これらの研究成果を基盤として、科学的エビデンスを創出し、その成果の社会実装を推進するとともに、母親だけでなく父親も対象とした周産期メンタルヘルス支援や、子どもの健やかな発達を支える家族全体の支援体制の構築を目指しています。

 

妊婦の医薬品・サプリメント使用と子どもの発達
－わが国独自のエビデンス創出に向けてー

日本では、妊婦の医薬品・サプリメント使用と子どもの発達を疫学的に検証する基盤が存在しなかったために、欧米などの知見に基づいて情報提供が行われているのが現状です。

しかし最近、我々は、妊婦の医薬品使用による先天形態異常発症の感受性が、日本人と欧米では異なる可能性を報告しました。したがって、わが国独自の遺伝素因の違いも考慮した妊婦の医薬品使用と先天性形態異常リスクの関連因子の解明が必要であり、これらの情報に基づいた妊娠中の医薬品選択・用量設定等を考慮した個別化医療が必要です。

また例えば、妊娠初期のバルプロ酸の使用は、神経管閉鎖障害等を引き起こすことが報告されています。しかし、海外の知見では妊娠初期に高用量（≧1000mg/日）のバルプロ酸を使用した場合であっても先天性形態異常の発症率は約25％であり、残りの75％には先天性形態異常は認められていません。その他にも妊娠初期の使用により先天性形態異常リスクを上昇させる医薬品が報告されていますが、その発症率は高くても10％程度です。したがって、異常を発症しない妊婦・胎児の遺伝素因や環境要因を明らかにできれば、妊婦が医薬品を安全に使用できるような環境つくりにつながります。

日本で行われている大規模な出生コホート研究および医療レセプトのデータを解析、わが国独自のエビデンス創出に向けた研究プロジェクトに参画しています。

 

２０１９年以降の主な業績；原著論文

●周産期・乳幼児環境と子どもの神経発達

 

１)

Paternal bonding failure and depression at 1 month postpartum are associated with neurodevelopmental delay in 4-year-old children: An Adjunct Study of the Japan Environment and Children’s Study.

Nishigori H, Nishigori T, Obara T, Sakurai K, Ishikuro M, Mizuno S, Watanabe Z, Saito M, Ota C, Arima T, Metoki H, Kuriyama S, Yaegashi N.

Infant Ment Health J. 2026;47(3):e70082.

 

2)

Sex-specific associations between maternal prenatal and postnatal psychological distress and autism spectrum disorder in the Japan Environment and Children’s Study.

Nishigori H, Nishigori T, Kyozuka H, Omoto T, Fukuda T, Murata T, Ogata Y, Sato A, Kuraya H, Yasumura S, Hosoya M, Go H, Hashimoto K, Fujimori K; Japan Environment and Children’s Study (JECS) Group.

Sci Rep. 2026;16(1):6899.

 

3)

Association between maternal bonding difficulty and neurodevelopmental delay in children aged 2 to 4 years: the Japan Environment and Children’s Study.

Nishigori T, Nishigori H, Sato A, Ogata Y, Fukuda T, Murata T, Kyozuka H, Yamada M, Chishiki M, Yasumura S, Fujimori K, Hosoya M, Hashimoto K; Japan Environment and Children’s Study (JECS) Group.

J Dev Orig Health Dis. 2026;17:e16.

 

4)

Association between umbilical cord arterial pH and neurodevelopment of offspring at the age of 3 years: The Japan environment and Children’s study.

Kyozuka H, Murata T, Omoto T, Fukuda T, Yasuda S, Takahashi T, Sato A, Ogata Y, Hosoya M, Yasumura S, Hashimoto K, Fujimori K, Nishigori H; Japan Environment and Children’s Study (JECS) Group.

Int J Gynaecol Obstet. 2025;171(1):246-255.

 

5)

Breastfeeding and Children’s Cognitive Development up to the Age of 4 Years: The Japan Environment and Children’s Study.

Nishigori T, Nishigori H, Suzuki T, Fukuda T, Murata T, Kyozuka H, Sato A, Ogata Y, Nagasaka Y, Yasumura S, Fujimori K, Hosoya M, Hashimoto K; Japan Environment and Children’s Study (JECS) Group.

Breastfeed Med. 2024;19(12):911-923.

 

6)

Association between daily breakfast habit during pregnancy and neurodevelopment in 3-year-old offspring: The Japan Environment and Children’s Study.

Imaizumi K, Murata T, Isogami H, Fukuda T, Kyozuka H, Yasuda S, Yamaguchi A, Sato A, Ogata Y, Shinoki K, Hosoya M, Yasumura S, Hashimoto K, Fujimori K, Nishigori H; Japan Environment and Children’s Study (JECS) Group.

Sci Rep. 2024;14(1):6337.

 

7)
Maternal prenatal and postnatal psychological distress trajectories and impact on cognitive development in 4-year-old children: The Japan Environment and Children’s Study.
Nishigori H, Nishigori T, Obara T, Suzuki T, Mori M, Imaizumi K, Murata T, Kyozuka H, Ogata Y, Sato A, Shinoki K, Yasumura S, Hosoya M, Hashimoto K, Fujimori K; Japan Environment and Children’s Study Group.

 J Dev Orig Health Dis. 2023 ;14(6):781-794.

8)
Association of Preconception or Antepartum Maternal Intimate Partner Violence with Autism Spectrum Disorder in 3-Year-Old Offspring: The Japan Environment and Children’s Study.
Isogami H, Murata T, Imaizumi K, Fukuda T, Kanno A, Kyozuka H, Yasuda S, Yamaguchi A, Sato A, Ogata Y, Horiuchi S, Shinohara R, Shinoki K, Hosoya M, Yasumura S, Yamagata Z, Hashimoto K, Fujimori K, Nishigori H; Japan Environment and Children’s Study Group.

J Womens Health (Larchmt). 2024;33(1):80-89.

9)
Nonreassuring fetal status during labor and offspring’s childhood neurodevelopment at 3 years of age: The Japan Environment and Children’s Study.
Murata T, Kyozuka H, Yasuda S, Imaizumi K, Isogami H, Fukuda T, Yamaguchi A, Sato A, Ogata Y, Shinoki K, Hosoya M, Yasumura S, Hashimoto K, Fujimori K, Nishigori H; Japan Environment and Children’s Study Group.

Int J Gynaecol Obstet. 2024;165(1):244-255.

10)
Prenatal folic acid supplement/dietary folate and cognitive development in 4-year-old offspring from the Japan Environment and Children’s Study.
Nishigori H, Nishigori T, Obara T, Suzuki T, Mori M, Imaizumi K, Murata T, Kyozuka H, Ogata Y, Sato A, Shinoki K, Yasumura S, Hosoya M, Hashimoto K, Fujimori K; Japan Environment and Children’s Study Group.
Sci Rep. 2023 ;13(1):9541.

11)
Association between labor duration in singleton spontaneous vaginal deliveries and offspring neurodevelopment: The Japan Environment and Children’s Study.
Murata T, Yasuda S, Kyozuka H, Imaizumi K, Isogami H, Fukuda T, Yamaguchi A, Sato A, Ogata Y, Shinoki K, Hosoya M, Yasumura S, Hashimoto K, Fujimori K, Nishigori H; Japan Environment and Children’s Study Group.
Int J Gynaecol Obstet. 2023;161(3):1097-1101.

12)
Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero.
Nagata A, Masumoto T, Nishigori H, Nakagawa T, Otani S, Kurozawa Y; Japan Environment and Children’s Study Group.
JAMA Netw Open. 2023;6(10): e2339347.

13)
Maternal prenatal psychological distress and motor/cognitive development in two-year-old offspring: The Japan Environment and Children’s Study.
Mori M, Nishigori T, Ogata Y, Suzuki T, Sato A, Murata T, Kyozuka H, Yamaguchi A, Metoki H, Shinohara Y, Takahashi T, Shinoki K, Hosoya M, Fujimori K, Yasumura S, Hashimoto K, Goto A, Nishigori H; Japan Environment and Children’s Study Group.
J Dev Orig Health Dis. 2023 14(3):389-401.

14)
Association between maternal prenatal psychological distress and autism spectrum disorder among 3-year-old children: The Japan Environment and Children’s Study.
Nishigori T, Hashimoto K, Mori M, Suzuki T, Watanabe M, Imaizumi K, Murata T, Kyozuka H, Ogata Y, Sato A, Shinoki K, Yasumura S, Fujimori K, Nishigori H, Hosoya M; Japan Environment and Children’s Study Group.
J Dev Orig Health Dis.  2023;14(1):70-76.

15)
Association between preconception dietary inflammatory index and neurodevelopment of offspring at 3 years of age: The Japan Environment and Children’s Study.
Kyozuka H, Murata T, Fukuda T, Yamaguchi A, Kanno A, Yasuda S, Suzuki D, Takahashi T, Go H, Maeda H, Sato A, Ogata Y, Shinoki K, Hosoya M, Yasumura S, Hashimoto K, Fujimori K, Nishigori H; Japan Environment and Children’s Study Group.
Nutrition. 2022; 102:111708. doi: 10.1016/j.nut.2022.111708.

16)
Maternal folic acid supplement use/dietary folate intake from preconception to early pregnancy and neurodevelopment in 2-year-old offspring: The Japan Environment and Children’s Study.
Suzuki T, Nishigori T, Obara T, Masumoto T, Mori M, Murata T, Kyozuka H, Ogata Y, Sato A, Sanpei M, Takahashi T, Shinoki K, Hosoya M, Fujimori K, Yasumura S, Hashimoto K, Goto A, Nishigori H; Japan Environment and Children’s Study Group.
Br J Nutr. 2022;128(12):2480-2489.

17)
Prenatal folic acid supplementation and autism spectrum disorder in 3-year-old offspring: the Japan Environment and Children’s Study.
Nishigori H, Obara T, Nishigori T, Ishikuro M, Tatsuta N, Sakurai K, Saito M, Sugawara J, Arima T, Nakai K, Mano N, Metoki H, Kuriyama S, Yaegashi N; Japan Environment and Children’s Study Group.
J Matern Fetal Neonatal Med. 2022;35(25):8919-8928.

18)
Preconception folic acid supplementation use and the occurrence of neural tube defects in Japan: A nationwide birth cohort study of the Japan Environment and Children’s Study.
Nishigori H, Obara T, Nishigori T, Ishikuro M, Sakurai K, Hoshiai T, Saito M, Fujiwara I, Arima T, Nakai K, Kuriyama S, Mano N, Metoki H, Yaegashi N; Japan Environment & Children’s Study Group.
Congenit Anom (Kyoto). 2019;59(4):110-117.

 

●周産期メンタルヘルス

1)

Paternal bonding failure and depression at 1 month postpartum are associated with neurodevelopmental delay in 4-year-old children: An Adjunct Study of the Japan Environment and Children’s Study.

Nishigori H, Nishigori T, Obara T, Sakurai K, Ishikuro M, Mizuno S, Watanabe Z, Saito M, Ota C, Arima T, Metoki H, Kuriyama S, Yaegashi N.

Infant Ment Health J. 2026;47(3):e70082.

 

2)

Sex-specific associations between maternal prenatal and postnatal psychological distress and autism spectrum disorder in the Japan Environment and Children’s Study.

Nishigori H, Nishigori T, Kyozuka H, Omoto T, Fukuda T, Murata T, Ogata Y, Sato A, Kuraya H, Yasumura S, Hosoya M, Go H, Hashimoto K, Fujimori K; Japan Environment and Children’s Study (JECS) Group.

Sci Rep. 2026;16(1):6899.

 

3)

Association between maternal bonding difficulty and neurodevelopmental delay in children aged 2 to 4 years: the Japan Environment and Children’s Study.

Nishigori T, Nishigori H, Sato A, Ogata Y, Fukuda T, Murata T, Kyozuka H, Yamada M, Chishiki M, Yasumura S, Fujimori K, Hosoya M, Hashimoto K; Japan Environment and Children’s Study (JECS) Group.

J Dev Orig Health Dis. 2026;17:e16.

 

4)

Trajectories of paternal depression symptoms from 1 to 6 months postpartum and associated factors: An Adjunct Study of the Japan Environment and Children’s Study.

Suzuki T, Nishigori T, Obara T, Sakurai K, Ishikuro M, Hamada H, Watanabe Z, Saito M, Ota C, Arima T, Metoki H, Kuriyama S, Yaegashi N, Nishigori H.

Infant Ment Health J. 2026;47(1):e70047.

 

5)
Factors associated with new onset of father-to-infant bonding failure from 1 to 6 months postpartum: an adjunct study of the Japan environment and children’s study.
Suzuki T, Nishigori T, Obara T, Mori M, Sakurai K, Ishikuro M, Hamada H, Saito M, Sugawara J, Arima T, Metoki H, Kuriyama S, Goto A, Yaegashi N, Nishigori H.
Soc Psychiatry Psychiatr Epidemiol. 2023;58(11):1603-1624.

6)
Maternal prenatal psychological distress and motor/cognitive development in two-year-old offspring: The Japan Environment and Children’s Study.
Mori M, Nishigori T, Ogata Y, Suzuki T, Sato A, Murata T, Kyozuka H, Yamaguchi A, Metoki H, Shinohra Y, Takahashi T, Shinoki K, Hosoya M, Fujimori K, Yasumura S, Hashimoto K, Goto A, Nishigori H; Japan Environment and Children’s Study Group.
J Dev Orig Health Dis 2023 ;14(3):389-401.

7)
Association between maternal prenatal psychological distress and autism spectrum disorder among 3-year-old children: The Japan Environment and Children’s Study.
Nishigori T, Hashimoto K, Mori M, Suzuki T, Watanabe M, Imaizumi K, Murata T, Kyozuka H, Ogata Y, Sato A, Shinoki K, Yasumura S, Fujimori K, Nishigori H, Hosoya M; Japan Environment and Children’s Study Group.
J Dev Orig Health Dis. 2023;14(1):70-76.

8)
Validation of the Mother-to-Infant Bonding Scale for Infant Maltreatment by Mothers at One Month Postpartum: An Adjunct Study of the Japan Environment and Children’s Study.
Nishigori T, Obara T, Metoki H, Sakurai K, Mori M, Suzuki T, Ishikuro M, Tatsuta N, Saito M, Sugawara J, Arima T, Nakai K, Kuriyama S, Yaegashi N, Nishigori H.
JMA J. 2022;5(3):366-369.

9)
Gestational weight gain and risk factors for postpartum depression symptoms from the Japan Environment and Children’s Study: a prospective cohort study.
Yamaguchi A, Kyozuka H, Kanno A, Murata T, Fukuda T, Yasuda S, Hosoya M, Yasumura S, Kuse M, Sato A, Ogata Y, Hashimoto K, Nishigori H, Fujimori K; Japan Environment and Children’s Study (JECS) Group.
J Affect Disord. 2021; 283:223-228.

10)
The delivery of a placenta/fetus with high gonadal steroid production contributes to postpartum depressive symptoms.
Kikuchi S, Kobayashi N, Watanabe Z, Ono C, Takeda T, Nishigori H, Yaegashi N, Arima T, Nakai K, Tomita H.
Depress Anxiety. 2021;38(4):422-430

11)
The prevalence and risk factors for postpartum depression symptoms of fathers at one and 6 months postpartum: an adjunct study of the Japan Environment & Children’s Study.
Nishigori H, Obara T, Nishigori T, Metoki H, Mizuno S, Ishikuro M, Sakurai K, Hamada H, Watanabe Z, Hoshiai T, Arima T, Nakai K, Kuriyama S, Yaegashi N; Miyagi Regional Center of Japan Environment & Children’s Study Group.
J Matern Fetal Neonatal Med. 2020;33(16):2797-2804.

12)
Mother-to-infant bonding failure and intimate partner violence during pregnancy as risk factors for father-to-infant bonding failure at 1 month postpartum: an adjunct study of the Japan Environment and Children’s Study.
Nishigori H, Obara T, Nishigori T, Metoki H, Mizuno S, Ishikuro M, Sakurai K, Hamada H, Watanabe Z, Hoshiai T, Arima T, Nakai K, Kuriyama S, Yaegashi N; Miyagi Regional Center of Japan Environment & Children’s Study Group.
J Matern Fetal Neonatal Med. 2020;33(16):2789-2796.

13)
Preconception dysmenorrhea as a risk factor for psychological distress in pregnancy: The Japan Environment and Children’s Study.
Watanabe Z, Nishigori H, Tanoue K, Tanaka K, Iwama N, Satoh M, Murakami T, Nishigori T, Mizuno S, Sakurai K, Ishikuro M, Obara T, Tatsuta N, Saito M, Tachibana M, Fujiwara I, Arima T, Takeda T, Kuriyama S, Nakai K, Yaegashi N, Metoki H; Japan Environment & Children’s Study Group.
J Affect Disord. 2019; 245:475-483.

 

●妊婦の医薬品・サプリメント使用

 

１)

Benzodiazepine exposure during early pregnancy and risk of miscarriage: dose-response, half-life classification, and individual agents.

Ishikawa T, Sakai T, Iwama N, Obara R, Morishita K, Adomi M, Kunitoki T, Noda A, Ishikuro M, Kikuchi S, Kobayashi N, Tomita H, Saito M, Nishigori H, Kuriyama S, Mano N, Obara T.

Arch Womens Ment Health. 2026 May 23;29(3):86.

 

2)

Inclination of antidepressant medication continuation during pregnancy between 2012 and 2023 in Japan: A cohort study.

Ishikawa T, Sakai T, Noda A, Kikuchi S, Kobayashi N, Tomita H, Nishigori H, Kuriyama S, Mano N, Obara T.

J Affect Disord. 2025;374:640-645.

 

3)

Association between exposure to atypical antipsychotics during pregnancy and risk of miscarriage.

Ishikawa T, Sakai T, Iwama N, Obara R, Morishita K, Adomi M, Noda A, Ishikuro M, Kikuchi S, Kobayashi N, Tomita H, Saito M, Nishigori H, Kuriyama S, Mano N, Obara T.

Acta Psychiatr Scand. 2024 ;150(6):562-572.

 

4)

Combination of taking neuropsychiatric medications and psychological distress in pregnant women, with behavioral problems in children at 2 years of age: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Takahashi I, Obara T, Kikuchi S, Kobayashi N, Obara R, Noda A, Ohsawa M, Ishikawa T, Mano N, Nishigori H, Ueno F, Shinoda G, Murakami K, Orui M, Ishikuro M, Tomita H, Kuriyama S.

PCN Rep. 2024;3(3): e226.

 

5)
Safety evaluation of the use of calcineurin inhibitor to prenatal and postpartum women in Japan from a health administrative database.
Yashima K, Noda A, Ishikawa T, Matsuzaki F, Miyakoda K, Nishigori H, Mano N, Obara T.
J Neonatal Perinatal Med. 2023;16(3):461-473.

6)
Prenatal folic acid supplement/dietary folate and cognitive development in 4-year-old offspring from the Japan Environment and Children’s Study.
Nishigori H, Nishigori T, Obara T, Suzuki T, Mori M, Imaizumi K, Murata T, Kyozuka H, Ogata Y, Sato A, Shinoki K, Yasumura S, Hosoya M, Hashimoto K, Fujimori K; Japan Environment and Children’s Study Group.
Sci Rep. 2023 ;13(1):9541.

7)
Maternal folic acid supplement use/dietary folate intake from preconception to early pregnancy and neurodevelopment in 2-year-old offspring: The Japan Environment and Children’s Study.
Suzuki T, Nishigori T, Obara T, Masumoto T, Mori M, Murata T, Kyozuka H, Ogata Y, Sato A, Sanpei M, Takahashi T, Shinoki K, Hosoya M, Fujimori K, Yasumura S, Hashimoto K, Goto A, Nishigori H; Japan Environment and Children’s Study Group.
Br J Nutr. 2022;128(12):2480-2489.

8)
Development and validation of claims-based algorithms to identify pregnancy based on data from a university hospital in Japan.
Tajima K, Ishikawa T, Noda A, Matsuzaki F, Morishita K, Inoue R, Iwama N, Nishigori H, Sugawara J, Saito M, Obara T, Mano N.
Curr Med Res Opin. 2022;38(9):1651-1654.

9)
Validity of Administrative Data for Identifying Birth-Related Outcomes with the End Date of Pregnancy in a Japanese University Hospital.
Tajima K, Ishikawa T, Matsuzaki F, Noda A, Morishita K, Inoue R, Iwama N, Nishigori H, Sugawara J, Saito M, Obara T, Mano N.
Int J Environ Res Public Health. 2022;19(8):4864

10)
Risk of major congenital malformations associated with first-trimester exposure to propulsives: A health administrative database study in Japan.
Ishikawa T, Obara T, Akazawa M, Noda A, Oyanagi G, Morishita K, Miyakoda K, Nishigori H, Kawame H, Yaegashi N, Kuriyama S, Mano N.
Pharmacoepidemiol Drug Saf. 2022;31(2):196-205.

11)
Folic acid prescribed to prenatal and postpartum women who are also prescribed antiepileptic drugs in Japan: Data from a health administrative database.
Ishikawa T, Obara T, Jin K, Nishigori H, Miyakoda K, Akazawa M, Nakasato N, Yaegashi N, Kuriyama S, Mano N.
Birth Defects Res. 2020;112(16):1224-1233.

12)
Antidepressant prescriptions for prenatal and postpartum women in Japan: A health administrative database study.
Ishikawa T, Obara T, Kikuchi S, Kobayashi N, Miyakoda K, Nishigori H, Tomita H, Akazawa M, Yaegashi N, Kuriyama S, Mano N.
J Affect Disord. 2020; 264:295-303.

13)
Examination of the prescription of antiepileptic drugs to prenatal and postpartum women in Japan from a health administrative database.
Ishikawa T, Obara T, Jin K, Nishigori H, Miyakoda K, Suzuka M, Ikeda-Sakai Y, Akazawa M, Nakasato N, Yaegashi N, Kuriyama S, Mano N.
Pharmacoepidemiol Drug Saf. 2019;28(6):804-811.