Folic acid to reduce neonatal mortality from neural tube disorders

Abstract

Background Neural 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.Objective To review the evidence for, and estimate the effect of, folic acid fortification/supplementation on neonatal mortality due to NTDs, especially in low-income countries.Methods We 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.Results Meta-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.Discussion Scale-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.Conclusion The evidence supports both folic acid supplementation and fortification as effective in reducing neonatal mortality from NTDs.

Neural tube defects in Latin America and the impact of fortification: a literature review

“…Observational studies reinforce the evidence from clinical trials that have shown conclusively that consumption of staples fortified with folic acid and adequate periconceptional folic acid supplementation reduce the risk of NTD (3,(5)(6)(7) . Currently, all Latin American countries except Venezuela have mandatory fortification legislation and programmes aimed at decreasing conditions related to deficiencies of folic acid and other micronutrients.…”

Stillbirths: how can health systems deliver for mothers and babies?

“…Costs of visits were estimated to be 9% higher in regions with 80-95% coverage, and 24% higher in regions with 95-99% coverage, than were visits in regions with less than 80% coverage. Cost assumptions are detailed in webappendix pp [3][4][5][6][7][8][9][10][11][12][13][14][15] Eff ect estimates refer to the reduction in deaths due to a specifi c cause as a result of intervention-eg, 0·41 for stillbirths due to neural tube defects means that 41% of stillbirths due to neural tube defects could be averted with introduction of folic acid supplementation or fortifi cation. Postnatal interventions are not included so the estimates do not represent the full eff ect on neonatal deaths.…”

Determinants of folate status in pregnant women: results from a national cross-sectional survey in Belgium

“…Several clinical trials have shown that periconceptional supplementation with folic acid reduces the risk of NTD. [6][7][8] Taking supplements (400 mg/day) before conception and during the first trimester of pregnancy may decrease the risk of spina bifida with 72%. 9 In countries like the United States and Canada, the policy of mandatory fortification of flour with folic acid has proved effective in reducing the number of NTD.…”