With careful management, pregnancy ‘does not make seizures worse’

Pregnant women with epilepsy experienced “no meaningful difference” in increased seizure frequency compared with nonpregnant women examined during the same period, according to findings published in The New England Journal of Medicine.

However, the researchers observed a greater rate of dose increases with antiepileptic drugs among pregnant women compared with nonpregnant women.

“I became interested in performing clinical research in this area because I realized we did not have the data needed to counsel our female patients with epilepsy during the reproductive years,” Page B. Pennell, MD, professor of neurology at Harvard Medical School, vice chair of academic affairs in the department of neurology and director of research for the division of epilepsy at Brigham and Women’s Hospital, told Healio Neurology. “With the lack of good data, women were often discouraged from pregnancy because of the unknown risks to themselves and the developing child. In clinic, they and their family members would ask about the risks of pregnancy and if seizures would get worse, and I could not give them an answer based on objective research studies.”

In addition, the last set of guidelines from the American Academy of Neurology — which were published in 2009 — stated that it was not possible to determine if pregnancy made seizures worse “because no study had incorporated an appropriate control group,” Pennell continued.

Pennell and colleagues took this information “into consideration” when they designed the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs, or MONEAD, study. The prospective, observational, multicenter cohort study compared the rate of seizures during pregnancy through the peripartum period (the first 6 weeks after birth; epoch 1) with the rate of seizures during the postpartum period (the ensuing 7.5 months after pregnancy; epoch 2). The researchers enrolled nonpregnant women with epilepsy as controls; these women received similar follow-up over an 18-month period.

The percentage of women who experienced a greater number of seizures that affected their awareness during epoch 1 compared with epoch 2 served as the primary outcome. The researchers also examined alternations in doses of antiepileptic drug medications given in both groups over the first 9 months of epoch 1.

The researchers enrolled 351 pregnant women and 109 controls. They included 299 of 351 pregnant women (85%) and 93 of 109 controls (85%) in the main analysis of seizures that impaired awareness. The analysis of any seizure type included 87% of the women in the two groups (pregnant women, n = 307; nonpregnant women, n = 95). Demographic characteristics, seizure types, antiepileptic medications used and the percentages of participants who were seizure-free in the 9 months before pregnancy or enrollment were similar between the two groups.

The primary outcome occurred in 70 of 299 pregnant women (23%) and in 23 of 93 controls (25%; OR = 0.93; 95% CI, 0.54-1.6). The distribution of the uptick in seizure frequency in epoch 1 compared with epoch 2 was comparable in the two groups within trimesters and according to seizure type.

In epoch 1, at least one seizure that impaired awareness was noted in 87 of 299 pregnant women (29%) and in 29 of 93 controls (31%). In epoch 2, at least one such seizure was reported in 78 of 299 pregnant women (26%) and in 14 of 93 controls (15%). The mean incidence of seizures that impaired awareness, as normalized to a 28-day value and measured as a continuous outcome, was 0.69 seizures in epoch 1 and 0.55 seizures in epoch 2 among pregnant women and 1.4 in epoch 1 and 0.28 in epoch 2 among nonpregnant women. Both pregnant women and controls experienced a higher rate of seizures in epoch 1 compared with epoch 2, with a mean change of 0.14 seizures per 28 days (95% CI, 0.04 to 0.31) and 1.12 seizures per 28 days (95% CI, 1.05 to 3.28), respectively.

Among women with seizures that impaired awareness, Pennell and colleagues reported at least one change in antiepileptic drug dose among 222 of 299 pregnant women (74%) by the time of delivery and in 29 of 93 controls (31%) by 9 months after enrollment (OR = 6.36; 95% CI, 3.82-10.59). In 209 of 299 pregnant women (70%), the dose of an antiepileptic drug was higher by the end of pregnancy than in the period before pregnancy compared with an increase in 22 of 93 controls (24%) during the corresponding period (OR = 7.49; 95% CI, 4.37 to 12.84).

“During pregnancy, women with epilepsy were not more likely to have seizure worsening than a control group of nonpregnant women with epilepsy with similar characteristics. However, the pregnant group was much more likely to have dose increases of their antiseizure medicines during pregnancy,” Pennell said. “It is important to note that this study was observational and did not dictate treatment management.”

However, the findings have clinical implications, she continued.

“It is very helpful that we can now say pregnancy in and of itself does not make seizures worse and put the woman at risk, but that this is in the setting of careful management during pregnancy with dosage adjustments as needed, presumably to adjust for the increased clearance of the antiseizure medicines during pregnancy,” Pennell said.

The researchers are now looking at secondary analyses from this data set to evaluate the patterns of dose adjustments and to see if blood concentrations of antiseizure medicines were related to seizure stability.

“We will also look at other factors that are likely to impact seizure control, such as sleep patterns, neuroactive steroids and stress,” Pennell said. “Future studies should evaluate how pregnant women with epilepsy are managed outside of epilepsy centers and what the maternal and child outcomes are.”