ObjectiveTo systematically review the association between maternal folate supplementation during pregnancy and the risk of autism spectrum disorder (ASD) in the offspring.MethodsPubMed, EMbase, Web of Science, The Cochrane Library, Scopus, CNKI, WanFang Data, VIP and CBM databases were electronically searched to collect case-control and cohort studies on the association between maternal folate supplementation during pregnancy and the risk of ASD in the offspring from inception to December 2020. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was then performed using RevMan 5.3 and Stata 14.0 software.ResultsA total of 17 studies involving 10 812 cases and 876 241 controls were included. The results of meta-analysis showed that there was no significant association between maternal folate supplementation during pregnancy and the risk of ASD in the offspring in the total population. The subgroup analysis revealed that maternal folate supplementation during pregnancy was statistically associated with a reduced risk of ASD in the offspring in the Asian population (OR=0.71, 95%CI 0.53 to 0.96, P=0.03). However, there were no statistical correlations in European and American populations.ConclusionsCurrent evidence shows that maternal folate supplementation during pregnancy may reduce the risk of ASD in the offspring in the Asian population. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions.