Sex Steroid Hormone Serum Concentrations in Pregnant Women with Epilepsy in MONEAD
Paula Voinescu1, Page Pennell2, Alison Pack3, Elizabeth Gerard4, Laura Kalayjian5, Angela Birnbaum6, Carrie Brown7, Alice Henning7, Kimford Meador8
1Neurology, Brigham and Women's Hospital, 2University of Pittsburgh School of Medicine, 3Neurological Institute, Columbia University, 4Northwestern University, 5University of Southern California, 6University of Minnesota, 7Emmes, 8Stanford University School of Medicine
Objective:
Compare sex steroid hormone (SSH) serum concentrations in pregnant women with epilepsy (PWWE) on enzyme-inducing (EI) antiseizure medications (ASMs) to PWWE on non-EIASMs or no ASM.
Background:
SSH concentrations dramatically increase throughout pregnancy. They and their neuroactive steroid metabolites may influence fetal neurodevelopment and seizure control in PWWE. EIASMs alter SSH concentrations in the non-pregnant state. This secondary analysis aims to evaluate this effect in PWWE.
Design/Methods:
Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) is a prospective, observational, multi-center study of PWWE, enrolled <20 weeks gestation. Serum progesterone, estradiol, and estrone concentrations were measured at enrollment, trimesters two and three and delivery. Some participants had multiple samples in the second and/or third trimesters. Participants were categorized into the EIASM group if on at least one EIASM (carbamazepine, oxcarbazepine, topiramate, felbamate, phenobarbital, phenytoin, clobazam, perampanel) or non-EIASM group if not using any EIASM. We compared demographics with chi-squared and independent T-tests and calculated SSH distributions.
Results:
Samples were available in 30 PWWE on EIASMs and 169 PWWE on non-EIASM regimens (1st trimester n=10, 52; 2nd trimester n=37, 240; 3rd trimester n=30, 188; delivery n=8, 39, respectively). There were no differences between groups for race/ethnicity, marital status, income, IQ, but EIASM users were less educated and younger (mean: 28.0 years (95%CI: 26.1, 29.9) vs. 31.3 (30.5, 32.0). Progesterone and estradiol concentrations did not appear different between groups at any pregnancy stage. Estrone concentrations for the EIASM group appeared consistently lower, most notably in the second [median: 1572pg/mL (IQR: 621, 2690) vs 3030 (1820, 5040)] and third trimesters [3025 (1460, 4510) vs 5095 (3605, 7025)].
Conclusions:
EIASM regimens in PWWE did not notably affect progesterone and estradiol concentrations. However, estrone concentrations were lower in the second and third trimesters. Future studies will include investigation of potential implications for maternal and child outcomes.