“During pregnancy, seizures affect not only the woman with epilepsy, but also her unborn child. They may lead to miscarriages, and they may affect the health and neurodevelopment of the baby,” Paula E. Voinescu, MD, PhD, explains. “Yet, antiseizure medications need to be thoroughly weighed because they may carry developmental risks as well. During the postpartum period, physical and emotional stressors may lower one’s seizure threshold and women may need more medication(s), while the baby’s exposure may continue through breastfeeding.”
For a study published in Neurology, Dr. Voinescu and colleagues examined whether greater seizure frequency in pregnancy and the postpartum period is affected by epilepsy type, seizure location, and antiseizure medications. “Being able to identify the women at risk for seizure worsening and monitoring them closer is important for optimal pregnancy outcomes,” Dr. Voinescu notes.
The researchers used a longitudinal, prospective database to obtain data on pregnant women with epilepsy at a single center. They determined baseline seizure frequency for 9 months prior to conception and whether seizure frequency increased in pregnancy—calculated for every 4-week interval of pregnancy—and the postpartum period. Data were available for 99 patients who had a total of 114 pregnancies between 2013 and 2018.
Focal Epilepsies Associated With Greatest Risk for Increased Seizure Activity
“Women with focal epilepsy have an increased chance of seizure worsening during pregnancy than women with generalized epilepsy,” says Dr. Voinescu. “Our finding that, among patients with focal epilepsy, those with frontal epilepsy are at a dramatically increased risk for seizure worsening despite sufficient therapeutic dose monitoring, is novel.”
Specifically, greater seizure frequency was reported among 21.1% of pregnancies in women with focal epilepsies versus 5.3% of pregnancies in women with generalized epilepsy (OR, 4.70; 95% CI, 1.00-22.00). For women with focal epilepsy, greater seizure frequency was seen more often in frontal lobe epilepsy (OR, 8.00; 95% CI, 2.19-29.21). Dr. Voinescu and colleagues saw no difference in seizure worsening during the postpartum period for women with focal versus generalized epilepsy or frontal versus other focal epilepsy types.
“In plotting the number of pregnancies with heightened seizure frequency for each 4-week interval of pregnancy, we noted a trend for more patients with frontal lobe epilepsy to experience seizure worsening starting at the 20-week age of gestation (Figure),” Dr. Voinescu says. “The meaning of this finding still needs to be investigated. Clinically, this suggests that women may be more vulnerable in the second half of their pregnancy.”
Predictors of Seizure Worsening & Directions for Future Research
Physicians treating pregnant patients with focal epilepsy “should be aware that these women may benefit from closer monitoring,” Dr. Voinescu notes.
“Polytherapy and lack of preconception seizure freedom are additional predictors for an increased likelihood of seizure worsening in pregnancy,” she continues. “Both of these clinical factors may be signals for refractory epilepsy, and these are patients who require closer monitoring as well.”
Women with focal epilepsy—particularly frontal lobe epilepsy—may also require more aggressive medication management, given that the risk for seizure worsening in these patients is higher, according to Dr. Voinescu.
The study notes that frontal lobe seizures often disrupt sleep, and that sleep deprivation may be contributing to the differences the researchers saw. However, the improvement seen in the postpartum period among patients with these types of seizures “goes against this explanation,” and future studies should include measures of sleep.
“Objective measures of how sleep and hormonal factors influence seizures are still lacking,” Dr. Voinescu says. “To be able to improve seizure outcomes during pregnancy for women with frontal lobe epilepsy, studies to investigate the factors driving the observed seizure worsening are necessary.”