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

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 access
Schmidt, Rebecca J, Tancredi, Daniel J, Ozonoff, Sally, Hansen, Robin L, Hartiala, Jaana, Allayee, Hooman, Schmidt, Linda C, Tassone, Flora +1 more·2012·The American Journal of Clinical Nutrition
DOI 10.3945/ajcn.110.004416PMC PMC3374734
Open this paper in CoChat — free accountOpen PDF

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3945/ajcn.110.004416

Cites

69 of 69 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Studies indicate prenatal vitamin supplementation close to delivery might reduce the risk of autism in offspring, with folate receiving considerable attention.

    “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]

  • 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.

    “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]

  • Negative confounding by nutrients in fruits and vegetables could counterbalance pesticide toxicity, given evidence that folate reduces autism risk.

    “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]

  • Periconceptional folic acid is associated with reduced risk of autism spectrum disorder.

    “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]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 70 references couldn’t be matched to a known paper.

Research works printed but not linked: 6

  1. US Food and Drug Administration. Food standards: amendment of standards of identity for enriched grain products to require addition of folic acid. Fed Regist 1996;61:8781-97.
  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 RJ, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ, Tassone F, Hertz-Picciotto I. Prenatal vitamins, one-carbon me- tabolism gene variants, and risk for autism. Epidemiology 2011;22: 476-85.
  4. Christensen B, Arbour L, Tran P, Leclerc D, Sabbaghian N, Platt R, Gilfix BM, Rosenblatt DS, Gravel RA, Forbes P, et al. Genetic poly- morphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube de- fects. Am J Med Genet 1999;84:151-7.
  5. Van den Veyver IB. Genetic effects of methylation diets. Annu Rev Nutr 2002;22:255-82.
  6. Dror DK, Allen LH. Effect of vitamin B12 deficiency on neuro- development in infants: current knowledge and possible mechanisms. Nutr Rev 2008;66:250-5.

Cited by

Sorted by citations

Related

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 › Medicine › Rheumatology › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review