Optimizing periconceptional folic acid supplementation: Steady‐state folate pharmacokinetics in pregnancy (LB416)

Abstract

Background: Folic acid supplementation before and during pregnancy reduces the risk of neural tube defects. Although previous studies have investigated folate status in non‐pregnant women of childbearing age, steady‐state folate pharmacokinetics have never been evaluated in pregnant women to inform healthcare recommendations regarding the timing of prenatal multivitamin supplementation.Objective: To compare the steady‐state periconceptional and gestational RBC and plasma folate levels in pregnant women who supplement daily with prenatal multivitamins containing 1.1mg (regular dose) vs. 5mg (high dose) folic acid.Methods: 37 women, between 18‐45 years of age, who were early in pregnancy or trying to conceive, and were not previously taking folic acid‐containing supplements, were enrolled in this open‐label, 2‐arm, randomized clinical trial after obtaining informed consent. Participants were randomly assigned to take either 1.1mg or 5mg of folic acid‐containing prenatal multivitamins daily till 30 weeks gestational age (g.a.). Plasma and RBC folate levels were measured at baseline, and at 6, 12 and 30 weeks of gestation using a competitive‐binding receptor assay.Results: RBC folate levels significantly increased in both groups from baseline during pregnancy (p<0.0005). Sustained significant increase in RBC folate was observed in the 5mg group over the course of pregnancy between 6 and 30 weeks gestation, and between 12 and 30 weeks gestation (p<0.0001 and p<0.001), whereas a significant increase in RBC folate concentrations was observed in the 1.1mg group only between g.a.12 to g.a.30 (p<0.05). Plasma folate increased in both groups from baseline to 6 weeks gestation, and then decreased over the course of pregnancy between 6 and 30 weeks gestation, but the decrease was not statistically significant. Plasma levels at 30 weeks gestation in both groups were comparable to their respective baseline levels.Conclusion: The pharmacokinetics of folate in pregnancy are different than among healthy, non‐pregnant adult women. Despite supplementation over an extended period of time, steady‐state does not seem to be achieved in either group. The decrease in plasma folate in pregnancy may have clinical relevance for women with poor folate status, and may reflect the increased folate demands during pregnancy.Grant Funding Source: Duchesnay Inc.