• Hannah Blencowe, Simon Cousens, Bernadette Modell, and Joy Lawn.
• London School of Hygiene and Tropical Medicine, London, UK. hblencowe@gmail.com
• Int J Epidemiol. 2010 Apr 1;39 Suppl 1:i110-21.

BackgroundNeural tube defects (NTDs) remain an important, preventable cause of mortality and morbidity. High-income countries have reported large reductions in NTDs associated with folic acid supplementation or fortification. The burden of NTDs in low-income countries and the effectiveness of folic acid fortification/supplementation are unclear.ObjectiveTo review the evidence for, and estimate the effect of, folic acid fortification/supplementation on neonatal mortality due to NTDs, especially in low-income countries.MethodsWe conducted systematic reviews, abstracted data meeting inclusion criteria and evaluated evidence quality using adapted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Where appropriate, meta-analyses were performed.ResultsMeta-analysis of three randomized controlled trials (RCTs) of folic acid supplementation for women with a previous pregnancy with NTD indicates a 70% [95% confidence interval (CI): 35-86] reduction in recurrence (secondary prevention). For NTD primary prevention through folic acid supplementation, combining one RCT with three cohort studies which adjusted for confounding, suggested a reduction of 62% (95% CI: 49-71). A meta-analysis of eight population-based observational studies examining folic acid food fortification gave an estimated reduction in NTD incidence of 46% (95% CI: 37-54). In low-income countries an estimated 29% of neonatal deaths related to visible congenital abnormalities are attributed to NTD. Assuming that fortification reduces the incidence of NTDs, but does not alter severity or case-fatality rates, we estimate that folic acid fortification could prevent 13% of neonatal deaths currently attributed to congenital abnormalities in low-income countries.DiscussionScale-up of periconceptional supplementation programmes is challenging. Our final effect estimate was therefore based on folic acid fortification data. If folic acid food fortification achieved 100% population coverage the number of NTDs in low-income countries could be approximately halved.ConclusionThe evidence supports both folic acid supplementation and fortification as effective in reducing neonatal mortality from NTDs.

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