Optimizing the Pharmacology of Periconceptional and Prenatal Multivitamin Supplementation

It is highly recommended for women to take multivitamin/mineral supplements during the periconceptional and prenatal periods. Studies have confirmed that taking prenatal multivitamins prevents maternal iron deficiency anemia, and reduces the risk for neural tube defects (NTDs). To date, research aimed at optimizing the use of multivitamins before and during pregnancy has been minimal. My thesis focused on two challenges of periconceptional and prenatal multivitamin supplementation. The first challenge was gastrointestinal (GI) adverse events such as nausea and constipation which may be attributed to iron content and tablet size. Pregnant women are highly susceptible to GI adverse events since 80% experience nausea and vomiting of pregnancy. A prospective, randomized, controlled, open-label study was conducted to investigate whether a low-iron, small-tablet prenatal multivitamin can reduce GI adverse events, and improve supplement tolerability and adherence, relative to a high-iron, small-tablet prenatal multivitamin. We determined that low iron dose did not produce a significant difference, while small tablet size could be considered an important factor. Moreover, our results confirmed that adherence was poor in pregnant women. We were prompted to identify determinants which could predict adherence to prenatal multivitamins. Our retrospective study determined that predictors of adherence are rooted in women’s prior experiences with multivitamin use. The second challenge we addressed was achieving adequate blood folate concentrations for prevention of NTDs. If adherence is poor, standard dosing of 0.4-1 mg folic acid may not produce the blood folate concentrations needed in women prior to conception. We investigated the pharmacokinetics of 5 mg folic acid. Our prospective, parallel, open-labeled study, comparing a single dose of 5 mg to 1.1 mg folic acid, confirmed that folic acid follows linear (proportional) pharmacokinetics. However, our prospective, randomized, controlled, open-labeled, multiple-dose study determined that repeated use of folic acid at these 2 doses followed non-linear pharmacokinetics. Nevertheless, our data confirmed that 5 mg folic acid can produce higher blood folate concentrations, with a faster rate, which can counter the effect of poor adherence. In conclusion, optimal use of prenatal multivitamins requires improvements in supplement tolerability, adherence, and pharmacokinetics which depend on supplement formulations, and individualized assessment and counseling.Ph