Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy

Abstract

Background: Among women with epilepsy, studies regarding changes in seizure frequency during pregnancy have been limited by the lack of an appropriate nonpregnant comparator group to provide data on the natural course of seizure frequency in both groups.

Methods: In this prospective, observational, multicenter cohort study, we compared the frequency of seizures during pregnancy through the peripartum period (the first 6 weeks after birth) (epoch 1) with the frequency during the postpartum period (the following 7.5 months after pregnancy) (epoch 2). Nonpregnant women with epilepsy were enrolled as controls and had similar follow-up during an 18-month period. The primary outcome was the percentage of women who had a higher frequency of seizures that impaired awareness during epoch 1 than during epoch 2. We also compared changes in the doses of antiepileptic drugs that were administered in the two groups during the first 9 months of epoch 1.

Results: We enrolled 351 pregnant women and 109 controls with epilepsy. Among the 299 pregnant women and 93 controls who had a history of seizures that impaired awareness and who had available data for the two epochs, seizure frequency was higher during epoch 1 than during epoch 2 in 70 pregnant women (23%) and in 23 controls (25%) (odds ratio, 0.93; 95% confidence interval [CI], 0.54 to 1.60). During pregnancy, the dose of an antiepileptic drug was changed at least once in 74% of pregnant women and in 31% of controls (odds ratio, 6.36; 95% CI, 3.82 to 10.59).

Conclusions: Among women with epilepsy, the percentage who had a higher incidence of seizures during pregnancy than during the postpartum period was similar to that in women who were not pregnant during the corresponding epochs. Changes in doses of antiepileptic drugs occurred more frequently in pregnant women than in nonpregnant women during similar time periods. (Funded by the National Institutes of Health; MONEAD ClinicalTrials.gov number, NCT01730170.).

Conflict of interest statement

Dr. French reports receiving consulting fees, steering committee fees, and advisory board fees, all paid to the Epilepsy Study Consortium (TESC), consulting fees, and travel support from Adamas, consulting fees, paid to TESC, from Anavex, Athenen Therapeutics, BioMotiv, BioXcel Therapeutics, Bloom Science, Bridge Valley Ventures, Eliem, Engrail, Epitel, Idorsia, Ionis, Johnson & Johnson Pharmaceuticals, Mend Neuroscience, Shire, SpringWorks Therapeutics, Sofinnova, Stoke, Vyera, and Xeris, consulting fees, paid to TESC, and travel support from Arvelle Therapeutics, consulting fees, fees for trial development, and training fees, all paid to TESC, from Axcella Health, grant support, paid to NYU Langone Medical Center, consulting fees, advisory board fees, and fees for training, all paid to NYU Langone Medical Center, travel support from Biogen, consulting fees and advisory board fees, all paid to TESC, from Blackfynn, Cerebral Therapeutics, and Redpin Therapeutics, grant support, paid to NYU Langone Medical Center, and consulting fees, paid to TESC, from Cavion, consulting fees, paid to TESC, and travel support from Cerevel and Crossject, consulting fees, fees for trial development, fees for training, and reviewer fees, all paid to TESC, from CuroNZ, consulting fees and advisory board fees, all paid to TESC, from Eisai, consulting fees, paid to TESC, from Encoded, Epiminder, Fortress Biotech, Greenwich Biosciences, Janssen, Knopp Biosciences, Merck, Neurocrine Biosciences, Passage Bio, Praxis, Supemus Pharmaceuticals, and West Therapeutic Development, grant support, paid to NYU Langone Medical Center, consulting fees, fees for trial development, reviewer fees, and training fees, all paid to TESC, and travel support from Engage Therapeutics, advisory board fees, consulting fees, fees for training, and reviewer fees, all paid to TESC, from GW Pharmaceuticals, consulting fees, advisory board fees, all paid to TESC, and travel support from Lundbeck, consulting fees, reviewer fees, and fees for trial development, all paid to TESC, from Marinus, consulting fees, paid to TESC, and travel support from NeuCyte, grant support, paid to NYU Langone Medical Center, from Neurelis and the National Institute of Neurological Disorders and Stroke, consulting fees, advisory board fees, fees for trial development, and fees for serving as a principal investigator, all paid to TESC, and travel support from Otsuka Pharmaceutical, grant support, paid to NYU Langone Medical Center, consulting fees, advisory board fees, fees for trial development, all paid to TESC, and travel support from Ovid, consulting fees, advisory board fees, and trial development, all paid to TESC, from Pfizer, consulting fees, advisory board fees, steering committee fees, all paid to TESC, and travel support from Sage, grant support, paid to NYU Langone Medical Center, consulting fees, fees for trial development, training fees, all paid to TESC, and travel support from SK Life Science, consulting fees and training fees, all paid to TESC, from Sunovion, consulting fees, advisory board fees, reviewer fees, and fees for trial development, all paid to TESC, from Takeda Pharmaceuticals International, grant support, paid to NYU Langone Medical Center, advisory board fees, consulting fees, fees for serving as clinical director, all paid to TESC, and travel support from UCB, consulting fees, steering committee fees, reviewer fees, all paid to TESC, and travel support from Xenon Pharmaceuticals, grant support, paid to NYU Langone Medical Center, consulting fees, paid to TESC, and travel support form Zogenix, and advisory board fees, consulting fees, and reviewers fees, all paid to TESC, from Zynerba; Dr. Gerard, receiving lecture fees from Greenwich Biosciences and serving as trial principal investigator for Sunovion Pharmaceuticals and Xenon; Dr. Penovich, receiving consulting fees from Engage Therapeutics and LVIS, consulting and lecture fees from Neurelis, advisory board fees and fees for serving on a speakers bureau from SK Life Sciences and UCB Pharma, fees for serving on a speakers bureau from Eisai, and lecture fees from Aquestive Therapeutics; Dr. Miller, receiving grant support, paid to his institution, from Medtronic, SK Life Sciences, and Xenon Pharma, holding patent US 9,522,081 on methods and devices for brain cooling for treatment or prevention of epileptic seizures, and patent US 8,591,562 B2 on methods and devices for brain cooling; Dr. Birnbaum, receiving grant support, paid to her institution, from Supernus Pharmaceuticals, holding patent US9770407B2 on parenteral carbamazepine formulation, licensed to Lundbeck, and patent EP12150783A on novel parenteral carbamazepine formulations, licensed to Lundbeck; and Dr. Meador, receiving grant support, paid to his institution, and travel support from Eisai. No other potential conflict of interest relevant to this article was reported.

Copyright © 2020 Massachusetts Medical Society.

Figures

Figure 1.. Study Design.

Among both pregnant and nonpregnant (control) women who were enrolled in the study, the primary outcome was determined by the incidence of seizures that impaired awareness during epoch 1 as compared with epoch 2. Among pregnant women, enrollment (visit 1) occurred at a gestational age of 20 weeks or less. Visits during the second and third trimesters were scheduled between 21 and 27 weeks and between 30 and 36 weeks, respectively. When the first visit occurred within the second trimester, the next visit was separated by at least 4 weeks.

Figure 2.. Enrollment and Outcomes.

Study participants could have more than one reason for lack of eligibility or nonenrollment. In the two groups, among the reasons for withdrawal from the study were scheduling conflicts, transportation issues, pregnancy in the control group, and loss to follow-up.

Figure 3.. Changes in Seizure Frequency and Antiepileptic-Drug Dose.

Panel A shows the changes in the frequency of seizures that impaired awareness during epoch 1 as compared with epoch 2 in pregnant women and in controls (odds ratio for an increase in seizure frequency during pregnancy, 0.93; 95% confidence interval [CI], 0.54 to 1.60). Panel B shows the changes in the dose of an antiepileptic drug by the time of delivery in pregnant women and by 9 months after enrollment in controls (odds ratio for a change in dose during pregnancy, 6.36; 95% CI, 3.82 to 10.59).