Maternal folic acid and multivitamin supplementation: International clinical evidence with considerations for the prevention of folate-sensitive birth defects

More evidence is available for maternal intake, absorption, distribution, tissue specific concentrations, and pregnancy outcomes with folic acid (fortification/supplementation) during preconception – first trimester. This Quality Improvement prevention review used expert guidelines/opinions, systematic reviews, randomized control trials/controlled clinical trials, and observational case control/case series studies, published in English, from 1990 to August 2021. Optimization for an oral maternal folic acid supplementation is difficult because it relies on folic acid dose, type of folate supplement, bio-availability of the folate from foods, timing of supplementation initiation, maternal metabolism/genetic factors, and many other factors. There is continued use of high dose pre-food fortification ‘RCT evidenced-based’ folic acid supplementation for NTD recurrence pregnancy prevention. Innovation requires preconception and pregnancy use of ‘carbon one nutrient’ supplements (folic acid, vitamin B12, B6, choline), using the appropriate evidence, need to be considered. The consideration and adoption of directed personalized approaches for maternal complex risk could use serum folate testing for supplementation dosing choice. Routine daily folic acid dosing for low-risk women should consider a multivitamin with 0.4 mg of folic acid starting 3 months prior to conception until completion of breastfeeding. Routine folic acid dosing or preconception measurement of maternal serum folate (after 4–6 weeks of folate supplementation) could be considered for maternal complex risk group with genetic/medical/surgical co-morbidities. These new approaches for folic acid oral supplementation are required to optimize benefit (decreasing folate sensitive congenital anomalies; childhood morbidity) and minimizing potential maternal and childhood risk.