Maternal and umbilical cord plasma concentrations of antiseizure medications: Results from the observational MONEAD study

Objective: Unanticipated changes in antiseizure medication (ASM) exposure can lead to subtherapeutic or toxic medication concentrations in the mother and unnecessary drug exposure for the fetus. The objectives of this study were to characterize ASM concentrations in mother's and cord blood at delivery in women with epilepsy (PWWE). Methods: The analysis included PWWE (aged 14–45 years) from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study who were on ASM monotherapy or polytherapy at delivery. Women with an intelligence quotient < 70, major medical illness, substance use, and poor treatment adherence were excluded. Blood samples were collected from the mother and umbilical cord on the day of delivery. The ratio of umbilical cord to maternal plasma concentration at birth was used as a measure of fetal in utero exposure. Pearson correlation coefficients were calculated to determine the degree of correlation between ASM maternal and cord plasma concentrations. A p-value of <.05 was deemed to be significant. Results: Data from 207 infants included eight pairs of twins (104 females and 103 males) born to 199 women (140 on monotherapy and 59 on polytherapy), yielding 305 paired maternal and umbilical cord ASM concentrations. Significant correlation was observed between umbilical cord and maternal plasma concentrations for total and unbound carbamazepine, total and unbound carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam, total and unbound oxcarbazepine, and zonisamide. The mean ratios (SD) of umbilical cord plasma concentration to maternal plasma concentration were as follows: carbamazepine =.84 (.18), unbound carbamazepine = 1.15 (.47), carbamazepine-10,11-epoxide =.87 (.18), unbound carbamazepine epoxide = 1.17 (.36), gabapentin = 1.56 (.28), lacosamide =.96 (.29), levetiracetam = 1.1 (.53), lamotrigine =.92 (.26), oxcarbazepine = 1.01 (.22), unbound oxcarbazepine = 1.1 (.46), topiramate =.98 (.38), valproic acid = 1.03 (.85), unbound valproic acid =.73 (.74), and zonisamide =.93 (.12). Significance: Umbilical cord to maternal ASM concentration ratios were close to 1.0, indicating placental passage of ASMs. Gabapentin had the highest ratio, suggesting possible accumulation of drug. Additional studies are needed for infrequently prescribed ASMs.