The Effect of Maternal Folic Acid Supplementation on Neurodevelopmental Disorders in Offspring: An Umbrella Review of Systematic Reviews and Meta-Analyses.

This large review looked at whether taking folic acid during pregnancy might protect children from autism, ADHD, and other developmental challenges. The research suggests folic acid supplements may reduce the risk of autism by about one-third and slightly lower ADHD and behavioral problems. However, the quality of the research was generally poor, so we can't be completely confident in these results. The good news is that folic acid is already recommended during pregnancy to prevent serious birth defects, so these potential benefits are a bonus.

This umbrella review examined 23 systematic reviews and meta-analyses investigating maternal folic acid supplementation and neurodevelopmental disorders in children. The analysis found potential protective effects, with supplementation associated with reduced odds of autism spectrum disorder (OR 0.66), ADHD (OR 0.86), and behavioral problems (OR 0.75). However, no significant associations were found for motor, intellectual/cognitive, or language development outcomes. The review noted substantial methodological limitations, with 50% of included studies rated as very low quality and only 36.37% achieving high or moderate quality.

Despite evidence limitations, the authors suggest supplementation guidelines remain justified due to established benefits for neural tube defect prevention.

While evidence quality is limited, folic acid supplementation during pregnancy may provide neurodevelopmental benefits beyond established neural tube defect prevention. Current supplementation guidelines remain justified. Practitioners should counsel patients that potential neurodevelopmental benefits are promising but require further high-quality research for confirmation.

Major methodological concerns with 50% of included studies rated as very low quality. Evidence certainty was low across outcomes. Systematic reviews showed inconsistent conclusions for most outcomes. The review relied on non-randomized studies, which limits causal inferences.

: Maternal folic acid supplementation is recommended to prevent neural tube defects (NTDs), yet its influence on offspring neurodevelopmental disorders (NDDs) remains uncertain. This umbrella review aims to evaluate whether maternal folic acid supplementation before and/or during pregnancy affects the risk of NDDs.We conducted a systematic search in MEDLINE, Cochrane Library, EMBASE, PubMed, and Web of Science from inception to 30 June 2025, to identify systematic reviews (SRs) and meta-analyses (MAs) that synthesized evidence from non-randomized studies on maternal folic acid supplementation and NDDs. Methodological quality was assessed using the AMSTAR-2 assessment and evidence certainty using the GRADE framework.A total of 23 SRs/MAs were included, of which 14 did not perform meta-analysis. Most included SRs/MAs were methodologically limited, with 50.00% rated as very low quality and only 36.37% achieving high or moderate quality.

MAs indicated a protective effect of supplementation, with odds ratio (OR) of 0.66 (95% confidence interval (CI): 0.55-0.79) for autism spectrum disorder (ASD), 0.86 (95% CI: 0.78-0.95) for attention-deficit/hyperactivity disorder (ADHD), and 0.75 (95% CI: 0.63-0.91) for behavioral problems. No significant associations were found for motor, intellectual/cognitive, or language development. SRs reported inconsistent conclusions across most outcomes.In summary, maternal folic acid supplementation may reduce the risk of ASD, ADHD, and behavioral problems in offspring. Although the current evidence is of low quality, supplementation guidelines are justified by the well-established benefits for NTDs.

Further research is required to address remaining uncertainties.