The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutr

Reliable folate status data for women of reproductive age (WRA) to assess global risk for neural tube defects (NTDs) are needed. We focus on a recent recommendation by the World Health Organization that a specific “optimal” red blood cell (RBC) folate concentration be used as the sole indicator of NTD risk within a population and discuss how to best apply this guidance to reach the goal of assessing NTD risk globally. We also emphasize the importance of using the microbiologic assay (MBA) as the most reliable assay for obtaining comparable results for RBC folate concentration across time and countries, the need for harmonization of the MBA through use of consistent key reagents and procedures within laboratories, and the requirement to apply assay‐matched cutoffs for folate deficiency and insufficiency. To estimate NTD risk globally, the ideal scenario would be to have country‐specific population‐based surveys of RBC folate in WRA determined utilizing a harmonized MBA, as was done in recent studies in Guatemala and Belize. We conclude with guidance on next steps to best navigate the road map toward the goal of generating reliable folate status data on which to assess NTD risk in WRA in low‐ and middle‐income countries.

Background/Objectives: The folate Recommended Daily Allowance (RDA) for pregnant women is 600 μg/day dietary folate equivalents, which is equivalent to approximately 400 μg folic acid. Many prenatal supplements contain much higher doses of folic acid. The body’s ability to reduce synthetic folic acid to the metabolically active form may be exceeded with high levels of supplementation. The objective of this double-blinded randomized controlled intervention trial was to determine changes in unmetabolized folic acid and other biomarkers of folate and one-carbon metabolism in maternal and cord blood in response to a folic acid dose commonly found in prenatal supplements (800 μg/day) compared to the dose equivalent of the RDA (400 μg/day). Methods: Healthy pregnant women were randomized and provided supplements from their first prenatal visit (<12 weeks gestation) through delivery. Maternal blood was collected at baseline and delivery. Umbilical cord blood from the mothers was collected at delivery. Results: A repeated measures analysis of variance revealed that there was a significant group supplemental dose effect (p = 0.0225) on serum unmetabolized folic acid concentration in mothers but no difference in cord blood unmetabolized folic acid concentrations between groups. Mixed effects analysis found a significant overall effect of pre-pregnancy BMI (p = 0.0360) and length of previous folic acid supplementation (p = 0.0281) on serum folate concentrations. No treatment effect was seen in RBC folate concentrations. Choline concentrations were higher in cord blood from the 800 μg/day group compared to the 400 μg/day group, but there was no group effect in maternal choline concentrations. Conclusions: The results indicate that folic acid dose during pregnancy affects certain folate and one-carbon biomarkers, and these effects are not consistent between maternal and cord blood. Potential long-term effects of these results on both mothers and offspring are unknown and merit further investigation.