Pregnancy, folic acid, and antiseizure medication

BackgroundAlthough some antiseizure medications (ASMs) are teratogenic, most people with epilepsy need treatment in pregnancy. The risk of ASM fetotoxicity may be mitigated with folic acid. High-dose folic acid supplementation has traditionally been recommended before and during gestation despite little evidence of efficacy and safety for this patient group. Several studies have investigated the potential benefits and risks of folic acid supplements.ObjectiveTo provide an updated overview of the risks, benefits, and rationale for use of folic acid supplementation in relation to pregnant people of childbearing age using ASM.Materials and methodsThis is a narrative review based on an unstructured literature search of PubMed. We also scrutinized neurological and obstetrical guidelines.ResultsAntiseizure medication can decrease folate concentrations. In children exposed to ASM prenatally, those born to persons using folic acid supplements periconceptionally had lower risk of adverse neurodevelopment and preterm birth. It remains unclear whether the risk for congenital malformations can be equally alleviated. In studies of the general population, high plasma folate concentrations and/or high-dose folic acid supplements were associated with adverse neurodevelopmental outcomes. This has not been seen in children of mothers with epilepsy. However, an increased cancer risk has been found in children of mothers with epilepsy using high-dose folic acid supplements in pregnancy.ConclusionThe optimal folic acid dose is not clear for persons of childbearing potential with epilepsy using ASM. Both low and excess folate status during pregnancy have been associated with adverse neurodevelopment. We propose an individual folic acid supplement dose that should be titrated based on maternal plasma folate concentrations during pregnancy.