Antiepileptic Drugs in Pregnant Woman: Determining Fetal Cognition Risks

Family planning is especially challenging for women with epilepsy.

The Epilepsy Foundation reports most women with epilepsy can and do become pregnant, but they face small, manageable risks. Although experts universally agree most women with epilepsy require continued treatment with antiepileptic drugs (AEDs) throughout their pregnancies, one concern is the risk these drugs present to the developing child.

A recent article published in Epilepsy Research discussed AEDs and their potential teratogenic effects, particularly those cognitive in nature.

The authors from the Department of Neurology and Neurological Sciences at Stanford University reminded readers that concerns known since the late 1960s about AED use during pregnancy include fetal malformations. At that time, the most commonly prescribed AEDs were phenytoin, phenobarbital, and primidone. Clinicians reported harelip, cleft palate, congenital heart lesions, and minor skeletal abnormalities in some children of epileptic mothers who had continued AED therapy through pregnancy.

By the 1980s, researchers’ attention was redirected to cognitive outcomes of offspring exposed to AEDs in utero. While their findings were inconsistent, due to complicated or poorly planned study designs, some agents were clearly associated with negative cognitive impact.

More recently, the FDA has required pregnancy registries for pregnant women who have epilepsy, and the result has been a better data pool. Studies have confirmed that valproate poses the greater risk of cognitive impairment in children, and should thus be avoided.

The results of good human trials suggest lamotrigine, levetiracetam, and carbamazepine are unlikely to cause cognitive deficits. Inconclusive or no information is available for other AEDs.

Animal research is still needed to screen for the cognitive effects of prenatal exposure to many untested AEDs, and it must be followed by human trials to provide a degree of certainty. The current study authors indicated clinicians must rely on the pharmaceutical pipeline to produce new agents that have fewer harmful effects and may prevent or reverse AED therapy’s effect on cognition.