Cost-effectiveness of mandatory folic acid fortification of flours in prevention of neural tube defects: A systematic review

Background: Neural tube defects (NTDs) constitute the most frequent group among congenital malformations and are the main cause of neonatal morbimortality. Folic acid (FA) can reduce the risk of pregnancies affected by NTDs. Objective: We aimed to investigate whether mandatory folic acid (FA) fortification of flours is cost-effective as compared to non-mandatory fortification, and to verify whether FA dosage, cost composition, and the quality of economic studies influence the cost-effectiveness of outcomes. Methods: We conducted a systematic review. The protocol was registered on PROSPERO (CRD 42018115682). A search was conducted using the electronic databases MEDLINE/PubMed, Web of Science, Embase, Scopus, and EBSCO/CINAHL between January 2019 and October 2020 and updated in February 2021. Eligible studies comprised original economic analyses of mandatory FA fortification of wheat and corn flours (maize flours) compared to strategies of non-mandatory fortification in flours and/or use of FA supplements for NTD prevention. The Drummond verification list was used for quality analysis. Results: A total of 7,859 studies were identified, of which 13 were selected. Most (77%; n = 10) studies originated from high-income countries, while three (23%) were from upper-middle-income countries. Results of a cost-effectiveness analysis showed that fortification is cost-effective for NTD prevention, except for in one study in New Zealand. The cost-benefit analysis yielded a median ratio of 17.5:1 (0.98:1 to 417.1:1), meaning that for each monetary unit spent in the program, there would be a return of 17.5 monetary units. Even in the most unfavorable case of mandatory fortification, the investment in the program would virtually payoff at a ratio of 1:0.98. All FA dosages were cost-effective and offered positive health gains, except in one study. The outcomes of two studies showed that FA dosages above 300 μg/100 g have a higher CBA ratio. The studies with the inclusion of “loss of consumer choice” in the analysis may alter the fortification cost-efficacy ratio. Conclusion: We expect the findings to be useful for public agencies in different countries in decision-making on the implementation and/or continuity of FA fortification as a public policy in NTD prevention.