Approximately 500,000 women suffer from epilepsy in the US. For those that are pregnant, what can we do to help mitigate the risk of seizure? And how can we manage this risk during the course of pregnancy?
Written by Andrew Wilner, MD, FACP, FAAN
In the United States, approximately 500,000 women suffer from epilepsy (Harden and Sethi 2008). Treatment usually requires one or more antiseizure drugs (ASDs), but there’s been a long-standing question among neurology specialists regarding seizure frequency during pregnancy… a question that Dr. Page Pennell, who’s an expert in managing women with epilepsy, addresses in her recent paper in the New England Journal of Medicine (Pennell et al., 2020).
Factors That Impact Seizure Frequency in Pregnancy
Before we dive into Dr. Pennell’s research, let’s explore why some women experience more seizures during pregnancy.
One explanation is that women may stop ASDs because they fear that their medication may harm the fetus. This concern is not unfounded. However, the risk of teratogenicity must be weighed against the risk of seizures, which can lead to injury and death of both the mother and fetus.
In addition, low ASD serum levels during pregnancy risk breakthrough seizures. For example, morning sickness and vomiting may lower serum drug levels. Other physiologic changes in pregnancy that can lower ASD levels include increased volume of distribution, increased renal clearance, increased hepatic metabolism, and decreased gut motility. There is considerable variation between individuals, making it difficult to predict ASD levels in a particular patient.
A third explanation is that hormonal changes during pregnancy may affect seizure frequency as estrogen is proconvulsant and progesterone anticonvulsant. Sleep deprivation, which is common in pregnancy and the post-partum period, may also lower the seizure threshold.
Lastly, the occurrence of epileptic seizures is rarely predictable; some women may have seizures during pregnancy that they would have had anyway due to the natural course of the disease.
Does Pregnancy Increase the Risk of Seizures?
To answer this question, Dr. Pennell and colleagues performed a prospective, observational, parallel-group, 18-month, multicenter cohort study of 351 pregnant women with epilepsy compared to 109 women with epilepsy who were not pregnant. All of the women were expertly managed at one of 20 epilepsy centers.
While 23 percent of the pregnant women had a seizure increase during pregnancy, so did 25 percent of controls during the same time period. Antiseizure drug dose changes were far more frequent in pregnant women (74 percent) than in controls (31 percent). Levetiracetam and lamotrigine were the most commonly prescribed ASDs in both groups. Drug levels of both of these medications may change dramatically during pregnancy.
This study demonstrated that pregnant women with epilepsy can achieve seizure control similar to controls. One caveat is that epilepsy specialists followed these women closely and frequently adjusted ASD doses. It is unclear whether pregnant women with epilepsy treated by non-specialists would experience such reassuring results.
Considerations for Neurology Specialists Caring for Pregnant Epileptic Patients
As with any medication taken during gestation, there is a concern for fetal malformations with most if not all ASDs. However, valproate products (valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and generic products exhibit the highest documented risk of congenital malformations and developmental delay compared to other ASDs.
Consequently, except under highly unusual circumstances, neurology specialists should not prescribe valproate products during pregnancy or in women of childbearing potential (Harden and Sethi 2008). If physicians must use valproate, they should prescribe the lowest effective dose.
Because of the many physiologic changes during pregnancy, neurology specialists should also frequently monitor ASD levels (Reisinger et al., 2013). Specifically, two drugs often prescribed to women with epilepsy, lamotrigine (Lamictal) and levetiracetam (Keppra), may undergo significant clearance changes during pregnancy that lower ASD serum levels leading to breakthrough seizures (Reisinger et al. 2013). For example, levetiracetam clearance may increase more than 200 percent during pregnancy.
The Importance of Seizure Control During Pregnancy
Seizure control during pregnancy requires a delicate balancing act. To control seizures, ASD levels should be high. To prevent teratogenicity, ASD levels should be low. Dr. Pennell’s research reveals that pregnancy need not increase seizures. But to protect the health of the mother and fetus, seizure control during pregnancy is paramount.
Harden CL, Sethi NK. Epileptic disorders in pregnancy: an overview. Curr Opin Obstet Gynecol 20:557-562.
Herzog AG, Mandle HB, Cahill KE et al. Predictors of unintended pregnancy in women with epilepsy. Neurology 2017;88:728-733.
Pennell PB, French JA, May RC et al. Changes in seizure frequency and antiepileptic therapy during pregnancy. NEJM 2020;383:2547-56.
Reisinger TL, Newman M, Loring DW et al. Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy. Epilepsy Behav 2013;29(1):13-18.