- Exposure to antiepileptic drugs during pregnancy

linked to adverse outcomes

NEW YORK (Reuters Health) - New research suggests that it is largely the drugs used to treat epilepsy and not the condition itself that increase the risk of adverse pregnancy and birth outcomes.

"Epilepsy is the most common maternal neurologic disorder requiring medical treatment during pregnancy," Dr. Gyri Veiby, of Haukeland University Hospital, Bergen, Norway, and colleagues write. "Risks associated with medical treatment during pregnancy must be weighed against the risk for fetal or maternal complications due to epileptic seizures."

Using data from the population-based Medical Birth Registry of Norway, the researchers examined pregnancy and birth outcome in an unselected population of women with both treated and untreated epilepsy. The study included all births recorded from December 1, 1998, through 2005. The team compared 2861 deliveries by women with epilepsy to 369,267 non-epilepsy deliveries.

Of the 2861 epileptic women, 1900 (66%) did not use antiepileptic drugs during pregnancy. Overall, 961 pregnancies in the epilepsy group were exposed to antiepileptic drugs, mostly as monotherapy. Antiepileptic drugs used included carbamazepine, lamotrigine, valproate, oxcarbazepine, clonazepam, topiramate, phenytoin, phenobarbital, levetiracetam, gabapentin, and vigabatrin.

Infants who were exposed to antiepileptic drugs were more often preterm (p = 0.01), and more often had birth weight <2500 g (p < 0.001), head circumference <2.5 percentile (p < 0.001), and low Apgar score (p = 0.03) compared to non-epilepsy controls, according to the report in the September issue of Epilepsia.

Epilepsy group children were more often transferred to a pediatric ward during the neonatal period. This was especially true in antiepileptic drug-exposed infants. Small-for-gestational-age infants occurred more frequently in infants who were exposed to antiepileptic drugs (p = 0.05) and unexposed infants (p = 0.02) than in controls.

There was no significant difference in the frequency of major congenital malformations between the epilepsy group and the control group (2.8% versus 2.5%, respectively). Significantly higher rates of major congenital malformations and any congenital malformations were found in infants exposed to either valproate or polytherapy.

"Cardiovascular malformations were significantly more common in antiepileptic drug-exposed infants versus controls, and especially for valproate exposure," Dr. Veiby and colleagues explain. "In the untreated epilepsy group there was a higher occurrence of genital malformations."

Neonatal spina bifida was not significantly increased in the epilepsy group compared to the control group. Down syndrome was significantly more common in untreated epilepsy pregnancies compared to controls. Both spina bifida and Down syndrome were major indications for elective pregnancy termination among epileptic women. A higher rate of cesarean section was observed in the epilepsy group, regardless of antiepileptic drug-exposure (p < 0.001).

"Adverse pregnancy and birth outcome in women with epilepsy is mainly confined to antiepileptic drug-exposed pregnancies," the authors conclude, "although some risks are associated also with untreated epilepsy."

Epilepsia 2009;50:2130-2139.