Tuesday, March 21, 2023
This activity is intended for obstetricians/gynecologists/women's health clinicians, critical care clinicians, emergency medicine clinicians, family medicine/primary care clinicians, neurologists, nurses, pharmacists, and other members of the health care team who treat and manage pregnant women with seizure disorders.
The goal of this activity is to compare the frequency of seizures during pregnancy through the peripartum period with frequency during the postpartum period, based on the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study, a prospective, observational, multicenter cohort study including sites across the United States.
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CME / CE Released: 2/24/2021
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Managing pregnant women with epilepsy requires balancing the need for stable seizure control against the potential adverse events (AEs) of antiepileptic drugs (AEDs) on fetal development. Studies of changes in seizure frequency during pregnancy have been limited the lack of an appropriate nonpregnant comparator group.
This prospective US cohort study using a nonpregnant control group compared seizure frequency during pregnancy and the peripartum period with postpartum frequency.
Women with epilepsy do not have an increased seizure rate during pregnancy provided their medication levels are carefully monitored, a new study suggests.
The study showed very similar fluctuations in seizure rates in women with epilepsy during pregnancy and the peripartum period compared with that of a group of matched nonpregnant controls.
"[P]regnancy in and of itself does not increase seizures in women with epilepsy in the setting of recognition of increased drug clearance and increased medication dosing as needed," lead author Page Pennell, MD, professor of neurology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Medical News.
"This is very much a reassuring result," Dr Pennell added. "Women with epilepsy are generally scared about pregnancy. While many want to start a family, they don't want to risk their seizures getting worse, which has been a concern. Our results show that they don't have to worry about that, that their risk is no different to that of nonpregnant controls as long as they have their medication levels monitored."
"Women with epilepsy were being discouraged from starting a family as it was thought seizures worsened during pregnancy and could be hard to control, but there has been very little research on this," Dr Pennell noted. "While we now have newer safer epilepsy medications for use during pregnancy, there has been concern that they may not be as effective in controlling seizures during pregnancy."
The current National Institutes of Health-funded study compared seizure frequency during pregnancy through the peripartum period (first 6 weeks after birth; epoch 1) with frequency during the postpartum period (following 7.5 months; epoch 2) in 351 women with epilepsy from 20 clinical sites across the United States. The control group included 109 nonpregnant women with epilepsy matched for age, race, seizure type and frequency, and medication.
The most commonly used medications were lamotrigine and levetiracetam.
The primary outcome was the percentage of women with higher frequency of seizures that impaired awareness during epoch 1 vs epoch 2.
Among 299 pregnant women and 93 controls with history of seizures that impaired awareness and available data for both epochs, seizure frequency was higher during epoch 1 vs epoch 2 in 70 pregnant women (23%) and in 23 controls (25%) (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.54-1.60).
"The 2 groups had an almost identical increase in seizure frequency during epoch 1," Dr Pennell commented. "The increases seen in epoch 1 versus epoch 2 fit with the natural variability of seizure frequency, as we can see from the control group."
Seizure improvements were reported by 14% of pregnant women and 11% of controls during epoch 1 compared with epoch 2.
"Very few previous studies have followed women with epilepsy during pregnancy in this much detail, and this is the first study that we know of that has included a control group," Dr Pennell noted.
"Without the control group, we could have thought that it was the pregnancy that was causing increased seizures in some of the women, but we saw almost identical results in the control group."
In addition, 74% of the pregnancy group had a medication change during pregnancy compared with 31% of controls, and the vast majority of these involved medication increases (70% vs 24%, respectively).
Dr Pennell explained that during recent years there has been increased awareness among neurologists to monitor AED levels in pregnancy because of increased clearance of many medicines. During pregnancy, liver enzymes are upregulated and renal blood flow increases, leading to increased drug metabolism and clearance.
AEDs tend to have a very tight therapeutic window and levels can fall below those needed for a therapeutic effect, so dose increases are often needed.
"This is another important message from our study, as...one third of women in the US are treated in primary care settings and do not regularly see a neurologist. Primary care doctors also need to [monitor AED blood levels] during pregnancy," Dr Pennell added.
Grants from the National Institute of Neurological Disorders and Stroke supported the study. Dr Pennell has disclosed no relevant financial relationships.
N Engl J Med. Published online December 23, 2020.[1]
