Epilepsy and Pregnancy

Abstract

Purpose of review: Seizure disorders are the most frequent major neurologic complication in pregnancy, affecting 0.3% to 0.8% of all gestations. Women of childbearing age with epilepsy require special care related to pregnancy. This article provides up-to-date information to guide practitioners in the management of epilepsy in pregnancy.

Recent findings: Ongoing multicenter pregnancy registries and studies continue to provide important information on issues related to pregnancy in women with epilepsy. Valproate poses a special risk for malformations and cognitive/behavioral impairments. A few antiseizure medications pose low risks (eg, lamotrigine, levetiracetam), but the risks for many antiseizure medications remain uncertain. Although pregnancy rates differ, a prospective study found no difference in fertility rates between women with epilepsy who were attempting to get pregnant and healthy controls. During pregnancy, folic acid supplementation is important, and a dose greater than 400 mcg/d during early pregnancy (ie, first 12 weeks) is associated with better neurodevelopmental outcome in children of women with epilepsy. Breastfeeding is not harmful and should be encouraged in women with epilepsy even when they are on antiseizure medication treatment.

Summary: Women with epilepsy should be counseled early and regularly about reproductive health. Practitioners should discuss the risks of various obstetric complications; potential anatomic teratogenicity and neurodevelopmental dysfunction related to fetal antiseizure medication exposure; and a plan of care during pregnancy, delivery, and postpartum. Women with epilepsy should also be reassured that the majority of pregnancies are uneventful.

FIGURE 2–1

Changes in seizure frequency and antiseizure medication dose. A, Changes in the frequency of seizures that impair awareness in women during pregnancy as compared with postpartum and during equivalent time periods for nonpregnant women. B, Changes in the dose or medication of an antiseizure medication by the time of delivery in pregnant women and by 9 months after enrollment for nonpregnant women. ASM = antiseizure medication. Modified with permission from Pennell PB, et al, N Engl J Med.

FIGURE 2–2

Risk of major congenital malformations associated with antiseizure medication exposure. Pooled data from a meta-analysis of antiseizure monotherapy showed that the malformation prevalence associated with antiseizure medication is 1.47% for gabapentin, 1.77% for levetiracetam, 2.39% for oxcarbazepine, 4.28% for topiramate, 4.93% for carbamazepine, 6.26% for phenytoin, 7.10% for phenobarbital, 8.49% for primidone, and 10.93% for valproate. ^aThe sample size for gabapentin-exposed cases is small. Data from Weston J, et al, Cochrane Database Syst Rev.

FIGURE 2–3

Neurodevelopmental outcome in children associated with antiseizure medication exposure in women with epilepsy. A significantly lower IQ was found in children of women with epilepsy treated with valproate than in children of women with epilepsy taking carbamazepine, lamotrigine, or phenytoin. Similar effects were also observed for other antiseizure medications such as phenobarbital. Data from the UK Epilepsy and Pregnancy Register showed that prenatal exposure to levetiracetam and to piramate was not found to be associated with reductions in child cognitive abilities.

FIGURE 2–4

Projected decrease of antiseizure medication concentrations during pregnancy if no dose changes are made. Data from Tomson T, et al, Epileptic Disord.