
Prenatal folic acid and multivitamin supplementation is associated with a roughly 30% lower risk of autism spectrum disorder (ASD) in children, based on an umbrella review of existing systematic reviews and meta-analyses. Researchers report that the evidence is strong enough to support incorporating folic acid and multivitamin supplementation into routines beginning before conception and continuing through early pregnancy.
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Analysis showed a 30% reduction for folic acid and a 34% reduction for multivitamins - providing 'highly suggestive' support for a protective effect of maternal supplementation.
These findings add to a huge body of existing evidence that improving maternal nutrition before and during pregnancy could significantly reduce the rates of ASD and related conditions in children.
19/11/2025 - Justin Jackson, Medical Xpress
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Researchers from Curtin University in Australia and multiple universities in Ethiopia report that prenatal folic acid and multivitamin supplementation is associated with a roughly 30% lower risk of autism spectrum disorder (ASD) in children, based on an umbrella review of existing systematic reviews and meta-analyses.
Global estimates in the reviewed material place ASD prevalence at up to 1% of children. ASD affects reciprocal social interaction, nonverbal communication, and understanding of social relationships. Co-occurring conditions frequently include epilepsy, depression, anxiety, attention deficit hyperactivity disorder, sleep disturbance, and self-injury.
Previous studies found that both genetic mutations and environmental influences contribute to ASD risk, with prenatal maternal nutrition identified as one modifiable environmental factor. Within that broader category of prenatal maternal nutrition, folic acid and multivitamin supplements are among the most accessible interventions offered to women before and during pregnancy.
Folic acid supports DNA methylation and epigenetic regulation that shape neurodevelopment and supports neural tube formation, processes linked to structural brain development.
Multivitamin preparations typically provide vitamin B12, vitamin D, iodine, and other micronutrients that help maintain immune balance, modulate inflammation, and support neurotransmitter synthesis and amino acid metabolism, creating a nutritional context that may favor optimal fetal brain development and potentially lower ASD risk.
Earlier systematic reviews and meta-analyses that examined maternal prenatal folic acid and multivitamin supplementation in relation to ASD risk reported conflicting findings.
Some reviews reported lower ASD risk among children whose mothers used folic acid and/or multivitamin supplements, while other reviews reported no clear association, with discrepancies attributed to differences in study design, supplement type and dosing, timing and duration of exposure, ASD diagnostic methods, and possible publication or reporting bias.
Those unresolved inconsistencies created a rationale for an umbrella review to synthesize and grade the overall evidence base.
In the study, "The association between maternal prenatal folic acid and multivitamin supplementation and autism spectrum disorders in offspring: An umbrella review," published in PLOS One, researchers conducted an umbrella review to synthesize evidence on the association between prenatal folic acid and/or multivitamin supplementation and ASD risk in offspring.
Eight systematic reviews and meta-analyses met the inclusion criteria and together covered 101 primary studies with 3,029,208 participants. Five of these reviews evaluated maternal folic acid supplementation and three evaluated multivitamin supplementation in relation to ASD in children. Individual reviews included between five and 20 primary studies, with sample sizes ranging from 4,514 to around a million participants.
Across the eight included reviews, six reported an association between prenatal folic acid and/or multivitamin supplementation and reduced ASD risk in offspring. Two reviews, one focusing on folic acid and one on multivitamins, reported no significant association.
Individual pooled estimates in the included reviews ranged from an odds ratio or relative risk of 0.57 to a value of 0.91.
Combined analysis in the umbrella review indicated that maternal prenatal folic acid and/or multivitamin supplementation was associated with a 30% reduced risk of ASD in offspring (pooled relative risk of 0.70 with 95% CI 0.62–0.78 vs. no supplementation.)
Subgroup analysis by supplement type found that prenatal multivitamin supplementation was associated with a 34% reduction in ASD risk. Folic acid supplementation alone was associated with a 30% reduction in ASD risk.
Sensitivity analyses suggested that the overall findings were not driven by any single review. When individual systematic reviews were excluded one at a time, pooled relative risks for the association between maternal prenatal folic acid and multivitamin supplementation and ASD in offspring ranged from 0.67 to 0.72.
Analysis showed a 30% reduction for folic acid and a 34% reduction for multivitamins, each supported by highly suggestive GRADE classifications.
Authors conclude that maternal prenatal folic acid or multivitamin supplementation is associated with reduced ASD risk in children and that current evidence provides highly suggestive support for a protective effect.
Researchers described this pattern as strong enough to support incorporating folic acid and multivitamin supplementation into routines beginning before conception and continuing through early pregnancy.