Prenatal Folic Acid Supplements and Offspring’s Autism Spectrum Disorder: A Meta-Analysis and Meta-Regression
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We systematically reviewed the evidence on the association between maternal folic acid supplementation and the risk of offspring’s autism spectrum disorders (ASD). A total of 10 studies with 23 sub-studies (9795 ASD cases) were included. Folic acid supplementation during early pregnancy was associated with a lower risk of offspring’s ASD [OR 0.57, 95% CI 0.41–0.78]. The consumption of a daily amount of at least 400 μg folic acid from dietary sources and supplements, was associated with a reduced risk of offspring ASD [OR 0.55, 95% CI 0.36–0.83]. Critical effective maternal folic acid supplementation strategies, such as intake timing and intake dosage, may aid the reduction in the risk of offspring ASD. This meta-analysis provided new insights for the prevention of offspring’s ASD.
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Inadequate intake of essential micronutrients-including iron, folate, iodine, vitamin A, and vitamin D-can profoundly affect cellular processes such as DNA synthesis, epigenetic regulation, and organogenesis.
“While much focus has been placed on maternal overnutrition and gestational diabetes mellitus, inadequate intake of essential micronutrients—including iron, folate, iodine, vitamin A, and vitamin D—can profoundly affect cellular processes such as DNA synthesis, epigenetic regulation, and organogenesis [86,87,88].”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [88]
The Introduction (page unavailable) says folate is involved in DNA synthesis and methylation, and the Discussion (page unavailable) says fetal brain development is sensitive to nutritional deficiency. The paper does not establish the claimed cellular effects for iron, iodine, vitamins A and D, or address organogenesis. (LLM, conf=0.88)
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- Authors
- Liu, X., Zou, M., Sun, C., Wu, L., & Chen, W.-X.
- Affiliations
- Harbin Medical University (CN)
- Guangzhou Women and Children Medical Center (CN)
- Corresponding author
- Wu, Lijie
- Chen, Wen-Xiong
- Venue
- Journal of Autism and Developmental Disorders
- Published
- 2021-03-20
- Volume
- 52
- Issue
- 2
- Pages
- 522-539
- ISSN
- 0162-3257 (ISSN-L)
- 1573-3432
- PMC
- PMC8813730
- OpenAlex
- W3137998533
- Cited by
- 58
- References
- 89
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 15 · 2023: 11 · 2022: 6 · 2021: 4
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Autism and Developmental Disorders (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Science and Technology Department of Guangdong Province of China (2016A020215019)
- the fund from Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center (YIP-2018-049)
- the key projects fund of Ministry of science and technology of China (2016YFC1306205)
- Science and technology project of Guangzhou Municipal Health Commission (2019A011028)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- folic acid supplementation, autism spectrum disorder, prenatal nutrition, maternal supplementation, early pregnancy, dietary folic acid, dosage
- MeSH terms
- Autism Spectrum Disorder, Diet, Female, Folic Acid, Humans, Pregnancy, Vitamins, Dietary Supplements
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