Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children
Open accessAbstract
IMPORTANCE: Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders. OBJECTIVE: To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. DESIGN, SETTING, AND PATIENTS: The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity. MAIN OUTCOME MEASURE: Specialist-confirmed diagnosis of ASDs. RESULTS: At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61,042) had autistic disorder, compared with 0.21% (50/24,134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use. CONCLUSIONS AND RELEVANCE: Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.
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The CHARGE finding of an association between low maternal iron intake and ASD was not ratified in a Norwegian birth cohort.
“However, this finding was not ratified in a Norwegian birth cohort [166, 167].”
From The contribution of environmental exposure to the etiology of autism spectrum disorder (2019) · cites this paper as [167]
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 [142]
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 [69]
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- Authors
- Surén, P., Roth, C., Bresnahan, M., Haugen, M., Hornig, M., Hirtz, D., Lie, K. K., Lipkin, W. I., Magnus, P., Reichborn-Kjennerud, T., Schjølberg, S., Smith, G. D., Øyen, A.-S., Susser, E., & Stoltenberg, C.
- Affiliations
- University of London (GB)
- Norwegian Institute of Public Health (NO)
- New York State Psychiatric Institute (US)
- Columbia University (US)
- National Institute of Neurological Disorders and Stroke (US)
- University of Bristol (GB)
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2013-02-13
- Volume
- 309
- Issue
- 6
- Pages
- 570
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC3908544
- OpenAlex
- W2113172416
- Cited by
- 537
- References
- 28
- Citations by year
- 2026: 18 · 2025: 20 · 2024: 33 · 2023: 32 · 2022: 18 · 2021: 29 · 2020: 53 · 2019: 45 · 2018: 42 · 2017: 48 · 2016: 59 · 2015: 47 · 2014: 60 · 2013: 32
- FWCI
- 35.55
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- National Institutes of Health (n01es75558-11-0-1)
- National Institute of Neurological Disorders and Stroke (U01NS047537, NS47537)
- National Institute of Environmental Health Sciences (N01 ES075558, N0-ES-75 558)
- 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, autistic disorder, Asperger syndrome, pervasive developmental disorders, prenatal nutrition, maternal supplementation, neurodevelopmental disorders, fish oil supplements, Norwegian Mother and Child Cohort Study, parity, maternal age at conception, maternal smoking and alcohol use
- MeSH terms
- Adolescent, Child, Child Development Disorders, Pervasive, Child, Preschool, Female, Folic Acid, Humans, Male, Norway, Pregnancy, Pregnancy Trimester, First, Prenatal Care, Prenatal Exposure Delayed Effects, Regression Analysis, Risk, Vitamin B Complex, Cohort Studies, Odds Ratio, Dietary Supplements, Young Adult
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