Previous research indicates that most women with epilepsy are dependent on treatment with antiepileptic drugs (AEDs) throughout their pregnancy to prevent epileptic seizures. AED therapy during pregnancy, however, has been associated with impaired neurodevelopment and behavioral disorders in offspring.
“Poor verbal abilities in early childhood may have consequences for academic achievement, mental health, behavior, and social life both during the school years and into adulthood,” says Dr. Elisabeth Synnøve Nilsen Husebye, PhD-candidate. “There is growing evidence of a positive association between maternal folate status during pregnancy and neurodevelopmental outcome in offspring in studies from the general population, but the relationship between maternal folate status during pregnancy and the verbal abilities in the offspring has not been examined previously in children of mothers with epilepsy.”
For a study published in Neurology, Husebye and colleagues examined the effect of maternal folic acid supplementation and concentrations of maternal plasma folate and AED on language delay in AED-exposed children of mothers with epilepsy.
A total of 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy were surveyed. Maternal plasma folate and maternal plasma and umbilical cord AED concentrations were measured in blood samples from gestational weeks 17 to 19 and immediately after birth. Language development at 18 and 36 months was also evaluated.
For those with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratio (OR) for language delay in AED-exposed children when compared with controls at 18 months was 3.9, and at 36 months was 4.7. When folic supplementation was used, the corresponding ORs for language delay were 1.7 and 1.7, respectively. The positive effect of folic acid supplement use on language delay in AED-exposed children was significant only when supplementation was used from 4 weeks before pregnancy through the end of the first trimester.
“Folic acid supplement use early in pregnancy appears to have a preventative effect on language delay associated with in utero AED exposure,” says Husebye. “Higher maternal valproate concentrations significantly correlated with a lower language score at age 18 months.”
Husebye E, Gilhus N, Riedel B, et al. Verbal abilities in children of mothers with epilepsy: Association to maternal folate status. Neurology. 2018;91(9):e811-e821. Available at