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Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study
Open accessAbstract
Background Periconceptional folate is essential for proper neurodevelopment.Objective Maternal folic acid intake was examined in relation to the risk of autism spectrum disorder (ASD) and developmental delay (DD).Design Families enrolled in the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study from 2003 to 2009 were included if their child had a diagnosis of ASD (n = 429), DD (n = 130), or typical development (TD; n = 278) confirmed at the University of California Davis Medical Investigation of Neurodevelopmental Disorders Institute by using standardized clinical assessments. Average daily folic acid was quantified for each mother on the basis of dose, brands, and intake frequency of vitamins, supplements, and breakfast cereals reported through structured telephone interviews.Results Mean (±SEM) folic acid intake was significantly greater for mothers of TD children than for mothers of children with ASD in the first month of pregnancy (P1; 779.0 ± 36.1 and 655.0 ± 28.7 μg, respectively; P < 0.01). A mean daily folic acid intake of ≥600 μg (compared with <600 μg) during P1 was associated with reduced ASD risk (adjusted OR: 0.62; 95% CI: 0.42, 0.92; P = 0.02), and risk estimates decreased with increased folic acid (P-trend = 0.001). The association between folic acid and reduced ASD risk was strongest for mothers and children with MTHFR 677 C>T variant genotypes. A trend toward an association between lower maternal folic acid intake during the 3 mo before pregnancy and DD was observed, but not after adjustment for confounders.Conclusions Periconceptional folic acid may reduce ASD risk in those with inefficient folate metabolism. The replication of these findings and investigations of mechanisms involved are warranted.
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“Studies indicate prenatal vitamin supplementation close to delivery might reduce the risk of autism in offspring, with folate (vitamin, B9, folic acid, folacin) receiving considerable attention [231–233].”
From The contribution of environmental exposure to the etiology of autism spectrum disorder (2019) · cites this paper as [232]
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“Diverse environmental factors have been implicated as risk factors for ASD, including maternal stress and drug use, paternal age, nutritional status, hormones, and environmental chemicals [ 14 , 25–29 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [26]
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“Another attenuating influence may be negative confounding by nutrients in the fruit and vegetables that contribute pesticides, which could counter-balance the toxic impact of the pesticide given some evidence that nutrients like folate are associated with reduced risk for autism.”
From Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence (2014) · cites this paper as [141]
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“as expected given that periconceptional folic acid is associated with reduced ASD risk (35, 69)”
From Maternal Intake of Supplemental Iron and Risk of Autism Spectrum Disorder (2014) · cites this paper as [35]
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Metadata
- Authors
- Schmidt, R. J., Tancredi, D. J., Ozonoff, S., Hansen, R. L., Hartiala, J., Allayee, H., Schmidt, L. C., Tassone, F., & Hertz-Picciotto, I.
- Affiliations
- University of California, Davis (US)
- University of Southern California (US)
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 96
- Issue
- 1
- Pages
- 80-89
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC3374734
- OpenAlex
- W2156287076
- Cited by
- 408
- References
- 70
- Citations by year
- 2026: 21 · 2025: 17 · 2024: 22 · 2023: 19 · 2022: 14 · 2021: 29 · 2020: 35 · 2019: 34 · 2018: 33 · 2017: 35 · 2016: 42 · 2015: 28 · 2014: 42 · 2013: 30 · 2012: 7
- FWCI
- 26.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Environmental Protection Agency (R-829388, R-833292, 829388)
- National Institutes of Health
- National Institute of Mental Health (T32MH073124)
- National Institute of Environmental Health Sciences (P01-ES-11269, R01-ES015359-03S1, R01ES015359, P01ES011269)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12-HD051958-06, K12HD051958)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- periconceptional period, autism spectrum disorder, developmental delay, MTHFR 677 C>T polymorphism, folate metabolism, brain development, prenatal supplementation
- MeSH terms
- California, Developmental Disabilities, Child Development Disorders, Pervasive, Child, Preschool, Diet, Female, Folic Acid, Folic Acid Deficiency, Food, Fortified, Humans, Infant, Male, Pregnancy, Pregnancy Complications, Pregnancy Trimester, First, Risk, Confounding Factors, Epidemiologic, Case-Control Studies, Dietary Supplements, Polymorphism, Single Nucleotide, Maternal Nutritional Physiological Phenomena, Methylenetetrahydrofolate Reductase (NADPH2), Genetic Association Studies
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