Nutrition/Obesity
Impact of Mandatory Fortification with Folic Acid on Prevalence of Congenital Heart Defects, Neural Tube Defects, and Orofacial Clefts: A Systematic Review and Meta-Analysis Helena Pachón* Kristin Wu Wu Wu Wu Wu Wu Wu Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
Fortification of staple grains with folic acid (FA) has been mandated in 73 countries as of 2025. We conducted a systematic review and meta-analysis of population-based studies that evaluated the association between mandatory FA fortification of wheat flour, maize flour, and/or rice and prevalence of critical congenital heart defects (CHDs), neural tube defects (NTDs) and their 3 subtypes, and orofacial clefts (OFCs) and their 2 subtypes, pre- and post-fortification with FA. We searched PubMed and Embase from inception to October 2021, screened records in duplicate, and extracted data using a standardized form. We estimated pooled prevalence odds ratios (ORs) and 95% confidence intervals (CI) using random-effects models. A total of 26 studies across 9 countries met our inclusion criteria. Five studies reported on any critical CHDs, 18 on NTDs or their subtypes, and 11 on OFCs or their subtypes. We found a non-significant 4% reduction in the odds of any critical CHDs following mandatory FA fortification (OR: 0.96, 95% CI: 0.92, 1.01). A strong protective association was noted for total NTDs (OR: 0.64; 95% CI: 0.57, 0.72), spina bifida (OR: 0.63; 95% CI: 0.53, 0.74), anencephaly (OR: 0.59; 95% CI: 0.51, 0.69), and encephalocele (OR: 0.63; 95% CI: 0.46, 0.85). Associations for total OFCs (OR: 0.90; 95% CI: 0.80, 1.00) and cleft palate (CP) (OR: 1.01; 95% CI: 0.85, 1.20) were non-significant. A protective effect of mandatory FA fortification was found for cleft lip with or without cleft palate (CL/CLP) (OR: 0.93; 95% CI: 0.89, 0.97). Consistent with previous literature, our findings support mandatory FA fortification as an effective population-level strategy to reduce NTDs. Meta-analyses of critical CHDs and OFCs were limited by fewer studies and should be further studied in the future.