Pre-conception folic acid and multivitamin supplementation for the prevention of Neural Tube Defect: An umbrella Review

Background: 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. These reviews had produced contradictory results, and there had been no umbrella review. Therefore, the objective of this umbrella review is to combine the inconsistent data on the effect of prenatal folic acid and /or multivitamin supplementation for the prevention of NTD in offspring. Methods: 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. Result: Ten SRM with 296,816 study participants were included. The random-effects model analysis from 10 included systematic review and meta-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(95% CI: 0.29, 0.58) (I2 = 93.50%; p <=0·001). In subgroup analysis the pooled effect found to be 0.23(0.09, 0.37) in folic acid group, while this estimate is 0.63(0.53, 0.72) and 0.61(0.46, 0.75) in groups who took multivitamin. The pooled effect of prevention of NTD was found to be 0.50(0.34, 0.66) in SRMs aimed at occurrence prevention (primary prevention) group, while this estimate is 0.20(-0.01, 0.41) among SRMs which aimed at reoccurrence (secondary) prevention, and 0.61(0.46, 0.75) 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 ...