Maternal and fetal implications of anticonvulsive therapy during pregnancy

Seizure disorders represent the most frequent neurologic disorders in pregnancy, affecting 0.4% to 0.8% of patients and an estimated 1.1 million women of childbearing age in the United States. Approximately 85% of seizure disorders are idiopathic, whereas 15% are acquired as a result of metabolic disorders, space occupying lesions, infections, or trauma. Epilepsy is defined as the tendency for recurrent seizure activity (two or more) unprovoked by any known insult. A seizure can be defined as a paroxysmal disorder of the central nervous system in which abnormal neuronal discharge occurs, with or without the loss of consciousness.(10) Idiopathic seizures can be classified as partial or generalized. Partial seizures originate from a focal area in the brain and may or may not progress secondarily to involve the entire brain. Ln contrast, generalized seizures involve the entire brain from the outset. Pregnancy can have variable effects on seizure frequency. Yerby and Devinsky(45) reviewed 30 studies evaluating this subject. They found that in the recent reports 5% to 25% of gravidas experience an increase in seizure frequency, whereas 60% to 85% experience no change. Epilepsy may increase the risk of pregnancy to both mother and fetus. The literature evaluating the effects of epilepsy on pregnancy is somewhat conflicting. Wilhelm and colleagues(42) in a case control study compared 98 pregnancies complicated by epilepsy to controls. They confirmed the findings of Nelson and Ellenberg from 1982(35) suggesting a two- to threefold increase in the incidence of preeclampsia, cesarean delivery, preterm delivery, low birth weight, congenital malformations, and perinatal mortality. Other studies,(21, 26) however, have been unable to demonstrate an increase in the rates of perinatal mortality, preeclampsia, preterm labor, or cesarean delivery. Management of pregnant patients with seizure disorders may be challenging and requires cooperation among the obstetrician, perinatalogist, neurologist, and patient. The effects of epilepsy on pregnancy, the effects of antiepileptic medication on both mother and fetus, and the changes in pharmacokinetics of antiseizure medication during pregnancy require a multidisciplinary team approach to optimize outcome. Preconceptionally, one can evaluate the maternal neurologic status and explore the need for continued therapy. If ongoing anticonvulsive treatment is deemed necessary, the most appropriate medication should be used, the lowest effective daily dose should be determined, and the medication should be administered in divided doses. Discontinuation of an anticonvulsive medication should only be considered prior to pregnancy. Supplemental folate administration may minimize the risk of anomalies, primarily neural tube defects, Fortunately, despite the risks, most women with seizure disorders will experience an uneventful pregnancy and a normal outcome.