Association of maternal prenatal folic acid intake with subsequent risk of autism spectrum disorder in children: A systematic review and meta-analysis.

Background: A number of studies have explored the link of antenatal folic acid (FA) intake with autism spectrum disorder (ASD) in children, with inconsistent findings. Therefore, we conducted a systematic review and meta-analysis of relevant studies to elucidate the actual association between maternal FA intake during the prenatal period and the risk of ASD in offspring.

Methods: PubMed, EMBASE, PsycINFO, Scopus, Web of Science, and Cochrane Library were searched up to June 7, 2018, without language restriction. The random-effects model was applied to summarize results. The adjusted odds ratios (ORs) and hazard ratios (HRs) were pooled separately.

Results: Eight observational studies (a total of 13 reports; 840,776 children and 7127 cases) were included. FA intake was mainly estimated from self-report of mothers or available databases. The results of overall analysis from 6 studies (9 reports) combined by OR and 2 studies (4 reports) presenting HR showed that the likelihoods of ASD in offspring whose mothers were prenatally exposed to FA did not vary significantly compared with those in offspring of mothers without such exposure (OR = 0.91, 95% CI: 0.73-1.13 and HR = 0.66, 95% CI: 0.38-1.17, respectively). Further analysis revealed that the primary outcome of the meta-analysis was stable regardless of the study design, and not unduly affected by any single report. Additionally, no publication bias was observed, and the findings of overall analysis were in agreement with those of subgroup analyses.

Conclusions: This study does not provide support for the association between maternal FA intake during the prenatal period and the reduced risk of ASD in children. However, in view of the types and limited number of studies in the literature, more investigation is needed to confirm the findings of this meta-analysis.