Prenatal folic acid supplementation and autism spectrum disorder in 3-year-old offspring: the Japan environment and children’s study

The Japan Environment and Children’s Study Group

doi:10.1080/14767058.2021.2007238

Prenatal folic acid supplementation and autism spectrum disorder in 3-year-old offspring: the Japan environment and children’s study

The Japan Environment and Children’s Study Group

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Objective: We evaluated the relationship between prenatal folic acid supplementation and autism spectrum disorder (ASD) in 3-year-old offspring. Methods: We used data from the Japan Environment and Children’s Study, a nationwide prospective birth cohort study. We analyzed the data to determine the association between folic acid supplement use and the incidence of ASD in offspring, and classified participants into three groups based on the time of initiation of folic acid supplementation, as follows: (1) preconception users of folic acid supplements and (2) post-conception users, and (3) non-users. The dietary folate intake of study participants was also classified into three groups (<200 µg, 200 µg to <400 µg, ≥400 µg). Results: Overall, 361 offspring of 96,931 participants with single pregnancies were diagnosed with ASD (0.37%). A total of 7,046 participants (7.3%) used folic acid supplements before conception, 29,984 (30.9%) took them after detection of pregnancy, and 59,901 (61.8%) never received them. Multivariate logistic regression analyses demonstrated no association between prenatal folic acid supplementation and ASD in offspring (preconception use: adjusted odds ratio [AOR], 1.189; 95% confidence interval [CI], 0.819–1.727 and post-conception use: AOR, 1.072; 95% CI, 0.840–1.368); additionally, no association was observed with the use of folic acid supplements and/or multivitamin supplements (preconception use: AOR, 1.273; 95% CI, 0.921–1.760 and post-conception use: AOR, 1.132; 95% CI, 0.885–1.449). Moreover, no significant association was observed in participants with combined prenatal supplement use and dietary folate intake. Conclusions: Maternal use of folic acid supplements from the pre- or post-conception period was not significantly associated with ASD in 3-year-old offspring in Japan. Evaluation of the dietary folate intake from preconception also showed no significant association.

Original language	English
Pages (from-to)	8919-8928
Number of pages	10
Journal	Journal of Maternal-Fetal and Neonatal Medicine
Volume	35
Issue number	25
DOIs	https://doi.org/10.1080/14767058.2021.2007238
Publication status	Published - 2022
Externally published	Yes

Keywords

Japan
Prenatal folic acid supplementation
autism spectrum disorder

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Obstetrics and Gynaecology

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10.1080/14767058.2021.2007238

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@article{1b285d7bc0bb4eef8b972c97ede9db74,

title = "Prenatal folic acid supplementation and autism spectrum disorder in 3-year-old offspring: the Japan environment and children{\textquoteright}s study",

abstract = "Objective: We evaluated the relationship between prenatal folic acid supplementation and autism spectrum disorder (ASD) in 3-year-old offspring. Methods: We used data from the Japan Environment and Children{\textquoteright}s Study, a nationwide prospective birth cohort study. We analyzed the data to determine the association between folic acid supplement use and the incidence of ASD in offspring, and classified participants into three groups based on the time of initiation of folic acid supplementation, as follows: (1) preconception users of folic acid supplements and (2) post-conception users, and (3) non-users. The dietary folate intake of study participants was also classified into three groups (<200 µg, 200 µg to <400 µg, ≥400 µg). Results: Overall, 361 offspring of 96,931 participants with single pregnancies were diagnosed with ASD (0.37%). A total of 7,046 participants (7.3%) used folic acid supplements before conception, 29,984 (30.9%) took them after detection of pregnancy, and 59,901 (61.8%) never received them. Multivariate logistic regression analyses demonstrated no association between prenatal folic acid supplementation and ASD in offspring (preconception use: adjusted odds ratio [AOR], 1.189; 95% confidence interval [CI], 0.819–1.727 and post-conception use: AOR, 1.072; 95% CI, 0.840–1.368); additionally, no association was observed with the use of folic acid supplements and/or multivitamin supplements (preconception use: AOR, 1.273; 95% CI, 0.921–1.760 and post-conception use: AOR, 1.132; 95% CI, 0.885–1.449). Moreover, no significant association was observed in participants with combined prenatal supplement use and dietary folate intake. Conclusions: Maternal use of folic acid supplements from the pre- or post-conception period was not significantly associated with ASD in 3-year-old offspring in Japan. Evaluation of the dietary folate intake from preconception also showed no significant association.",

keywords = "Japan, Prenatal folic acid supplementation, autism spectrum disorder",

author = "{The Japan Environment and Children{\textquoteright}s Study Group} and Hidekazu Nishigori and Taku Obara and Toshie Nishigori and Mami Ishikuro and Nozomi Tatsuta and Kasumi Sakurai and Masatoshi Saito and Junichi Sugawara and Takahiro Arima and Kunihiko Nakai and Nariyasu Mano and Hirohito Metoki and Shinichi Kuriyama and Nobuo Yaegashi",

note = "Funding Information: This study was funded by the Ministry of the Environment, Japan. The findings and conclusions of this article are solely the responsibility of the authors, and do not represent the official views of the Ministry of the Environment. The authors are grateful to all the participants of the study. The members of the JECS Group, as of 2020 include: Michihiro Kamijima (principal investigator, Nagoya City University, Nagoya, Japan), Shin Yamazaki (National Institute for Environmental Studies, Tsukuba, Japan), Yukihiro Ohya (National Center for Child Health and Development, Tokyo, Japan), Reiko Kishi (Hokkaido University, Sapporo, Japan), Nobuo Yaegashi (Tohoku University, Sendai, Japan), Koichi Hashimoto (Fukushima Medical University, Fukushima, Japan), Chisato Mori (Chiba University, Chiba, Japan), Shuichi Ito (Yokohama City University, Yokohama, Japan), Zentaro Yamagata (University of Yamanashi, Chuo, Japan), Hidekuni Inadera (University of Toyama, Toyama, Japan), Takeo Nakayama (Kyoto University, Kyoto, Japan), Hiroyasu Iso (Osaka University, Suita, Japan), Masayuki Shima (Hyogo College of Medicine, Nishinomiya, Japan), Youichi Kurozawa (Tottori University, Yonago, Japan), Narufumi Suganuma (Kochi University, Nankoku, Japan), Koichi Kusuhara (University of Occupational and Environmental Health, Kitakyushu, Japan), and Takahiko Katoh (Kumamoto University, Kumamoto, Japan). Publisher Copyright: {\textcopyright} 2021 Informa UK Limited, trading as Taylor & Francis Group.",

year = "2022",

doi = "10.1080/14767058.2021.2007238",

language = "English",

volume = "35",

pages = "8919--8928",

journal = "Journal of Maternal-Fetal and Neonatal Medicine",

issn = "1476-7058",

publisher = "Informa Healthcare",

number = "25",

}

TY - JOUR

T1 - Prenatal folic acid supplementation and autism spectrum disorder in 3-year-old offspring

T2 - the Japan environment and children’s study

AU - The Japan Environment and Children’s Study Group

AU - Nishigori, Hidekazu

AU - Obara, Taku

AU - Nishigori, Toshie

AU - Ishikuro, Mami

AU - Tatsuta, Nozomi

AU - Sakurai, Kasumi

AU - Saito, Masatoshi

AU - Sugawara, Junichi

AU - Arima, Takahiro

AU - Nakai, Kunihiko

AU - Mano, Nariyasu

AU - Metoki, Hirohito

AU - Kuriyama, Shinichi

AU - Yaegashi, Nobuo

N1 - Funding Information: This study was funded by the Ministry of the Environment, Japan. The findings and conclusions of this article are solely the responsibility of the authors, and do not represent the official views of the Ministry of the Environment. The authors are grateful to all the participants of the study. The members of the JECS Group, as of 2020 include: Michihiro Kamijima (principal investigator, Nagoya City University, Nagoya, Japan), Shin Yamazaki (National Institute for Environmental Studies, Tsukuba, Japan), Yukihiro Ohya (National Center for Child Health and Development, Tokyo, Japan), Reiko Kishi (Hokkaido University, Sapporo, Japan), Nobuo Yaegashi (Tohoku University, Sendai, Japan), Koichi Hashimoto (Fukushima Medical University, Fukushima, Japan), Chisato Mori (Chiba University, Chiba, Japan), Shuichi Ito (Yokohama City University, Yokohama, Japan), Zentaro Yamagata (University of Yamanashi, Chuo, Japan), Hidekuni Inadera (University of Toyama, Toyama, Japan), Takeo Nakayama (Kyoto University, Kyoto, Japan), Hiroyasu Iso (Osaka University, Suita, Japan), Masayuki Shima (Hyogo College of Medicine, Nishinomiya, Japan), Youichi Kurozawa (Tottori University, Yonago, Japan), Narufumi Suganuma (Kochi University, Nankoku, Japan), Koichi Kusuhara (University of Occupational and Environmental Health, Kitakyushu, Japan), and Takahiko Katoh (Kumamoto University, Kumamoto, Japan). Publisher Copyright: © 2021 Informa UK Limited, trading as Taylor & Francis Group.

PY - 2022

Y1 - 2022

N2 - Objective: We evaluated the relationship between prenatal folic acid supplementation and autism spectrum disorder (ASD) in 3-year-old offspring. Methods: We used data from the Japan Environment and Children’s Study, a nationwide prospective birth cohort study. We analyzed the data to determine the association between folic acid supplement use and the incidence of ASD in offspring, and classified participants into three groups based on the time of initiation of folic acid supplementation, as follows: (1) preconception users of folic acid supplements and (2) post-conception users, and (3) non-users. The dietary folate intake of study participants was also classified into three groups (<200 µg, 200 µg to <400 µg, ≥400 µg). Results: Overall, 361 offspring of 96,931 participants with single pregnancies were diagnosed with ASD (0.37%). A total of 7,046 participants (7.3%) used folic acid supplements before conception, 29,984 (30.9%) took them after detection of pregnancy, and 59,901 (61.8%) never received them. Multivariate logistic regression analyses demonstrated no association between prenatal folic acid supplementation and ASD in offspring (preconception use: adjusted odds ratio [AOR], 1.189; 95% confidence interval [CI], 0.819–1.727 and post-conception use: AOR, 1.072; 95% CI, 0.840–1.368); additionally, no association was observed with the use of folic acid supplements and/or multivitamin supplements (preconception use: AOR, 1.273; 95% CI, 0.921–1.760 and post-conception use: AOR, 1.132; 95% CI, 0.885–1.449). Moreover, no significant association was observed in participants with combined prenatal supplement use and dietary folate intake. Conclusions: Maternal use of folic acid supplements from the pre- or post-conception period was not significantly associated with ASD in 3-year-old offspring in Japan. Evaluation of the dietary folate intake from preconception also showed no significant association.

AB - Objective: We evaluated the relationship between prenatal folic acid supplementation and autism spectrum disorder (ASD) in 3-year-old offspring. Methods: We used data from the Japan Environment and Children’s Study, a nationwide prospective birth cohort study. We analyzed the data to determine the association between folic acid supplement use and the incidence of ASD in offspring, and classified participants into three groups based on the time of initiation of folic acid supplementation, as follows: (1) preconception users of folic acid supplements and (2) post-conception users, and (3) non-users. The dietary folate intake of study participants was also classified into three groups (<200 µg, 200 µg to <400 µg, ≥400 µg). Results: Overall, 361 offspring of 96,931 participants with single pregnancies were diagnosed with ASD (0.37%). A total of 7,046 participants (7.3%) used folic acid supplements before conception, 29,984 (30.9%) took them after detection of pregnancy, and 59,901 (61.8%) never received them. Multivariate logistic regression analyses demonstrated no association between prenatal folic acid supplementation and ASD in offspring (preconception use: adjusted odds ratio [AOR], 1.189; 95% confidence interval [CI], 0.819–1.727 and post-conception use: AOR, 1.072; 95% CI, 0.840–1.368); additionally, no association was observed with the use of folic acid supplements and/or multivitamin supplements (preconception use: AOR, 1.273; 95% CI, 0.921–1.760 and post-conception use: AOR, 1.132; 95% CI, 0.885–1.449). Moreover, no significant association was observed in participants with combined prenatal supplement use and dietary folate intake. Conclusions: Maternal use of folic acid supplements from the pre- or post-conception period was not significantly associated with ASD in 3-year-old offspring in Japan. Evaluation of the dietary folate intake from preconception also showed no significant association.

KW - Japan

KW - Prenatal folic acid supplementation

KW - autism spectrum disorder

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DO - 10.1080/14767058.2021.2007238

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ER -

Prenatal folic acid supplementation and autism spectrum disorder in 3-year-old offspring: the Japan environment and children’s study

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