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Cited by 408Folate and B Vitamins ResearchAutism Spectrum Disorder ResearchPharmacological Effects and Toxicity Studies

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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

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Schmidt, Rebecca J, Tancredi, Daniel J, Ozonoff, Sally, Hansen, Robin L, Hartiala, Jaana, Allayee, Hooman, Schmidt, Linda C, Tassone, Flora, Hertz-Picciotto, Irva·2012·The American Journal of Clinical Nutrition
DOI 10.3945/ajcn.110.004416PMC PMC3374734
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Abstract

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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  1. 1996, Food standards: amendment of standards of identity for enriched grain products to require addition of folic acid, Fed Regist, 61, 8781
  2. Sparrow SS, Balla DA, Cicchetti DV. Vineland Adaptive Behavior Scales: interview edition, expanded form manual. Circle Pines, MN: American Guidance Services Inc, 1984.
  3. Schmidt, 2011, Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism, Epidemiology, 22, 476, 10.1097/EDE.0b013e31821d0e30 · DOI · Paper page

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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)
ORCID
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)
DOI
10.3945/ajcn.110.004416
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
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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