Abstracts

Rationale:
Antiseizure medication (ASM) concentrations can change drastically during pregnancy and return to preconception levels after birth, leading to subtherapeutic or toxic medication exposure to the mother and/or fetus. There is a dearth of systemic studies characterizing gestation-related and postpartum changes in ASM concentrations with very little to no representation of newer ASMs. The objective of this study was to characterize changes in ASM concentrations during pregnancy and postpartum in pregnant women with epilepsy (PWWE). ASM analyses included lamotrigine (LTG), levetiracetam (LEV), total carbamazepine (CBZ), unbound CBZ (CBZ-U), CBZ-10,11-epoxide (CBZ-E), oxcarbazepine (OXC), unbound OXC (OXC-U), zonisamide (ZNS) and topiramate (TPM) in women enrolled in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.
Method:
In MONEAD we recruited both PWWE and non-pregnant women with epilepsy (NPWWE) between the ages of 14-45 years. Exclusion criteria included IQ < 70, major medical illness, substance use, poor treatment adherence, and gestational weeks < = 20 (PWWE). An electronic daily diary app was used to track seizures and ASM dosing and adherence, and dosing was verified at each study visit. Seven study visits with blood sample collections occurred for both cohorts: 3-4 during pregnancy and over 9 months postpartum for PWWE and 7 over 24 months for NPWWE. Women on ASM monotherapy or in combination with a noninteracting ASM were considered for this analysis. To characterize differences in the dose normalized concentrations (DNC) during pregnancy compared to postpartum within the PWWE cohort, a repeated measures ANOVA was used with Tukey’s post-hoc test. Alpha level of significance for all models was 5%. Results324 PWWE (LTG=162, LEV=151, ZNS=22, OXC=20, CBZ=18, TPM=15) were included in this analysis. A majority (70%) of women were on monotherapy. DNCs for LTG, LEV, CBZ, OXC, OXC-U and ZNS DNCs were significantly lower during pregnancy (3rd trimester) compared to postpartum visits in the PWWE cohort (Table 1). There were no significant differences in DNC for TPM, CBZ-E, or CBZ-U. Additionally, LTG DNCs were also found to be significantly lower (20%, p< 0.001) during the 2nd and 3rd trimester compared to 1st trimester. However, the same was not identified for the remaining study ASMs.
Conclusion:
Women with epilepsy on LTG, LEV, CBZ, OXC, and ZNS on average experienced a significant decrease in DNCs during pregnancy when compared to postpartum levels within the PWWE – reinforcing the need for increasing doses during pregnancy and supporting therapeutic drug monitoring. In addition, women on LTG experienced a significant drop in DNCs throughout pregnancy with the lowest DNCs occurring in the 3rd trimester - indicating that women on LTG might require more than one dose change during pregnancy.
Funding:
:NINIDS and NICHD U01-NS038455, U01-NS050659 and 2U01-NS038455. University of Minnesota’s Doctoral Dissertation Fellowship.