Preliminary data show that babies of epileptic mothers who take antiepileptic drugs (AEDs) during pregnancy absorb the medication to substantial degrees in utero, and some of these babies may develop birth defects, other disabilities or even die. Although the majority of children born to mothers with epilepsy are normal, researchers believe some of these babies are at an increased risk for birth defects or developmental delays. The findings of this nationwide study, still preliminary, were presented at the American Academy of Neurology in San Francisco, CA, on April 28th.
"Newborns of women with epilepsy have a four to seven percent risk of birth defects, compared to the two to three percent risk of the general population, and we think some antiepileptic medications may be to blame," says Page Pennell, MD, associate professor of neurology, Emory University School of Medicine, Atlanta, GA. "While the outcomes are many times positive, a small number of babies born to epileptic mothers who took AEDs during pregnancy have congenital heart defects, neural tube defects (spina bifida) or cleft lip and palate."
Epilepsy is a chronic medical condition produced by temporary changes in the electrical function of the brain, causing seizures that affect awareness, movement, and/or sensation. One percent of the population has epilepsy at any given time. Mothers with epilepsy are three times as likely as non-epileptic women to give birth to children with epilepsy. Epilepsy can be treated with drugs, surgery or special diets. Of those treatments, antiepileptic drug therapy is the most common and usually the first to be tried on a patient.
In this five-year study, called the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, some of the most commonly prescribed seizure-control drugs are being tested to determine if they have a negative, lasting impact on the developing brains of fetuses when mothers take them while pregnant. The four medications being studied are carbamazepine (Tegretol, Tegretol-XR, Carbatrol), lamotrigine (Lamictal), phenytoin (Dilantin) and valproate (Depakote).
In the study, funded by the National Institutes of Health, nearly 350 mother/child pairs were enrolled at 28 centers in the U.S. and U.K. Emory enrolled 29 pairs. With over a year left in the study to record and analyze the effects of the drugs, researchers are already seeing significant data related to complications with these medications. The percentages of children with birth defects, developmental disabilities or death for each AED were as follows: carbamazepine 10 percent, lamotrigine two percent, phenytoin seven percent, and valproate 28 percent.
"While our numbers are still preliminary, we are learning that some of the newer AEDs, like lamotrigine, cause less harm to the child, while it looks like others cause more damage," says Dr. Pennell, who is leading the NEAD study at Emory University. " We will have to wait until the study is complete, however, to know exactly which medications are best for fetal development."
In a follow-up study also reported at the AAN meeting, he researchers found that there was a progressive increase in the clearance (breakdown) of valproate during pregnancy compared to preconception and after delivery, meaning mothers needed higher doses of medications because of their metabolic changes. The greatest clearance was during the third trimester, where clearance doubled compared to preconception levels (preconception 14.0 mg/L, trimester one - 18.6 mg/L, trimester two - 22.1 mg/L, trimester three - 30.2 mg/L, after delivery - 19.2 mg/L). This means that in the third trimester, more medication was needed to control seizures in the mother which meant the fetuses were getting the larger doses of valproate, too.