Abstract

Previous reviews explored the association between maternal use of folic acid and multivitamin supplements and risk of Neural Tube Defect (NTD) in children, with no definitive conclusion. Using PRISMA guideline, PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Scopus and Google Scholar which reported the effects of folic acid and/or multivitamin supplementation for the prevention of NTD in offspring were searched. The quality of the included studies was assessed using Assessment of Multiple Systematic Reviews (AMSTAR). A weighted inverse variance random-effects model was applied to find the pooled estimates. The subgroup analysis, heterogeneity, publication bias and sensitivity analysis were also assessed. Ten SRM with 296,816 study participants were included. The random-effects model analysis revealed that, the pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD globally is found to be 0.43( 0.29, 0.58). In subgroup analysis the pooled effect found to be 0.23in folic acid group, while this estimate is 0.63 and 0.61in groups who took multivitamin. The pooled effect of prevention of NTD was found to be 0.50 in SRMs aimed at occurrence prevention group, while this estimate is 0.20) among SRMs which aimed at reoccurrence prevention, and 0.61 among those SRMs aimed to assess the effect folic acid or multivitamin for prevention of both occurrence and re-occurrence. The pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD was found to be 0.45 in SRMs of observational studies, while this estimate is 0.43among SRMs of randomized controlled trials. Prenatal folic acid and /or multivitamin supplementation was associated with a 57% reduction in NTD. Participants who took folic acid supplementation were associated with a slightly higher (77%) percentage of reduction in NTD. An 80% and 50% reduction were observed for re-occurrence and occurrence prevention of NTD. A 57% and 55% reduction of NTD have been found in SRM of RCTs and observational studies. Considering the incorporation of those supplements in NTD prevention strategies during pre-conception period is recommended. More large-scale prospective cohort and RCTs are needed.

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