"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."
Researchers are also learning that effects of AEDs in offspring may not be so instant. "We are recognizing that we need to not only be concerned about birth defects from the AEDs, but also about cognitive effects later in the child's life," says Dr. Pennell. "At two years of age, we are realizing some of these children are experiencing speech delays, delays in walking and difficulties with fine motor skills. This study should help us notice the subtle differences in a child's ability to learn, and it should help us understand how to best care for pregnant women and their children." The NEAD study looks at the child's actual IQ vs. its predicted IQ based on parental testing.
The researchers are expanding this study to examine how AEDs cross into the fetus and exactly how much of the medications are absorbed (see next release). They also hope to follow all children in the study until they are six-years-old.
"Women with epilepsy who are considering pregnancy must weigh the option of staying on their medications during pregnancy or coming off of them," Dr. Pennell explains. "In many cases, the risk of seizures is clearly higher than the risk of medications. In epileptic mothers, most AEDs are paramount, simply because seizures during pregnancy can cause traumatic injuries to the fetus, fetal distress, miscarriages, and premature labor. Patients should always talk with their doctor before becoming pregnant to discuss which treatment plan is best for them. The NEAD study will help us determine the different risks between AEDs on the market today and the safest medications to prescribe to epileptic mothers during fetal development."