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Seizure Risk in Pregnancy Highest With Frontal Lobe Epilepsy

— Changes in antiepileptic drug metabolism during pregnancy may play a role

MedpageToday

NEW ORLEANS -- About half of women with frontal lobe epilepsy experienced more frequent seizures during pregnancy, researchers reported here.

"Women with frontal lobe epilepsy have the highest risk for seizure worsening during pregnancy -- even with adequate therapeutic dose monitoring -- and need close monitoring during this vulnerable period of their life," said Paula Voinescu, MD, PhD, of Brigham and Women's Hospital in Boston, at the annual meeting of the .

"Similarly to prior reports, we found that the risk for seizure worsening during pregnancy is higher in women with focal compared to women with generalized epilepsy, and women with frontal lobe epilepsy had a significantly higher risk," Voinescu told MedPage Today.

Seizures during pregnancy can increase the risk of miscarriage and the risk of distress and neurodevelopmental delays for the baby, Voinescu said. Concerns about seizure worsening stem not just from physiologic changes during pregnancy, but changes in the metabolism of common antiepileptic drugs, explained Jacqueline French, MD, of the NYU Comprehensive Epilepsy Center in New York City, who was not involved with the research.

"The two drugs of greatest concern are lamotrigine (Lamictal) and levetiracetam (Keppra)," French told MedPage Today. "A woman with epilepsy may require a several-fold increase in drug dosage to maintain consistent exposure."

In addition, "several sources have demonstrated increases in mortality during pregnancy in women with epilepsy and there is a suspicion this may be related to sudden unexplained death, which typically results from generalized tonic clonic convulsion, or other seizure worsening," French noted.

In the study, Voinescu and co-authors looked at prospectively collected data from 114 pregnancies in 99 women who were followed at Brigham and Women's from 2013 to 2018. They analyzed seizure frequency during three periods: 9 months before pregnancy, during pregnancy, and 9 months postpartum.

Overall, women on polytherapy had higher odds of seizure worsening during pregnancy than women on monotherapy (OR 8.36, 95% CI 2.07-33.84; P=0.0029).

Women with generalized epilepsy had lower odds of seizure worsening in pregnancy compared with women with focal epilepsy, although a reverse trend emerged in the postpartum months that did not reach statistical significance. Among women with focal epilepsy, those with frontal focal epilepsy had the highest rate of seizure worsening in pregnancy, even after adjusting for polytherapy (OR 8.40, 95% CI 2.06-34.20; P=0.0030).

Seizures were more frequent during pregnancy than in the 9-month pre-pregnancy period in:

  • 5.5% of women with generalized epilepsy
  • 22.6% of women with focal epilepsy
  • 53% of women with frontal lobe epilepsy

Seizures were more frequent during the postpartum than in the 9-month pre-pregnancy period in:

  • 12.12% of women with generalized epilepsy
  • 7.14% of women with focal epilepsy
  • 20% of women with frontal lobe epilepsy

In women with frontal epilepsy, seizure worsening was most likely to begin in the second trimester of pregnancy. It wasn't clear why seizures grew worse in pregnant women with frontal lobe epilepsy because the level of medication in their blood was considered adequate, Voinescu noted.

In future work, Voinescu and colleagues plan to evaluate the influence of anti-epileptic drugs and specific timing on seizure control during pregnancy and postpartum. Subsequent studies should also include measures of sleep, which may contribute to the differences found among epilepsy types, they added.

Disclosures

The researchers reported relationships with the American Brain Foundation, the American Epilepsy Society, the Epilepsy Foundation, the Karger Fund, and Sunovion.

Primary Source

American Epilepsy Society

Voinescu P, et al "Variations in seizure frequency during pregnancy and postpartum by epilepsy type" AES 2018: abstract 3.236.