Food Fortification With Folic Acid for Prevention of Spina Bifida and Anencephaly: The Need for a Paradigm Shift in Evidence Evaluation for Policy-Making.

Context-specific evidence evaluation is advocated in modern epidemiology to support public health policy decisions, avoiding excessive reliance on experimental study designs. Here we present the rationale for a paradigm shift in evaluation of the evidence derived from independent studies, as well as systematic reviews and meta-analyses of observational studies, applying Hill's criteria (including coherence, plausibility, temporality, consistency, magnitude of effect, and dose-response) to evaluate food fortification as an effective public health intervention against folic acid-preventable (FAP) spina bifida and anencephaly (SBA). A critical appraisal of evidence published between 1983 and 2020 supports the conclusion that food fortification with folic acid prevents FAP SBA. Policy-makers should be confident that with mandatory legislation, effective implementation, and periodic evaluation, food fortification assures that women of reproductive age will safely receive daily folic acid to significantly reduce the risk of FAP SBA. Current evidence should suffice to generate the political will to implement programs that will save thousands of lives each year in over 100 countries.