Detection of maternal serum unmetabolized folic acid following multivitamin and mineral supplementation with or without folic acid after 12 weeks’ gestation: a randomized controlled trial

Abstract

ABSTRACTBackgroundPregnant women are advised to take folic acid supplements before conception and during the first three months of pregnancy. Many women continue folic acid supplementation throughout pregnancy, and concerns have been raised about associations between excess folic acid intake and adverse child health outcomes. Unmetabolized folic acid (UMFA) is found in serum at higher folic acid intakes and has been proposed as a biomarker for excess folic acid intake.ObjectiveTo determine if removing folic acid from prenatal multivitamin and mineral supplements after 12 weeks of pregnancy reduces concentrations of serum UMFA at 36 weeks’ gestation.DesignA double-blind, parallel-group, randomized controlled trial. Women with a singleton pregnancy 12-16-weeks’ gestation were randomly assigned to a multi-micronutrient supplement containing no folic acid (intervention) or 800 µg folic acid/day (control) from enrolment until 36 weeks’ gestation. Maternal serum was analyzed for UMFA and secondary outcomes of red blood cell and serum folate at 36 weeks’ gestation.ResultsUMFA was detected in most of the 103 randomized women (86% >limit of detection). However, only 12% (n=11/90) of serum samples were above the limit of quantification (0.55 nmol/L), preventing analysis of UMFA concentrations. Fewer women had detectable UMFA in the no folic acid group compared to the 800 µg folic acid group (72% [n=33/46] vs. 98% [n=43/44]; p = 0.001). Maternal serum and red blood cell folate concentrations were lower in the no folic acid intervention group compared to the control group (median 23.2 vs. 49.3 nmol/L, 1335 vs. 1914 nmol/L, respectively; p< 0.,001) and no woman was classified as folate deficient.ConclusionsRemoving folic acid from prenatal multivitamin and mineral supplements reduced the number of women with detectable UMFA at 36 weeks’ gestation, however, differences in UMFA concentration between treatment groups were not quantifiable.