NEW ORLEANS – The most commonly used antiepileptic drugs modestly increased the risk of major congenital malformations among prenatally exposed infants in the MONEAD study.
Malformations occurred among 5% of pregnancies exposed to the medications – higher than the 2% background rate – but this was still much lower than the 9%-10% rate associated with valproate.
Overall, however, the message of the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic () study is quite reassuring, at the annual meeting of the American Epilepsy Society. MONEAD is an ongoing, prospective study to determine both maternal outcomes and long-term childhood neurodevelopmental outcomes associated with the use of antiepileptic drugs (AEDs) during pregnancy.
“The rate of malformations was higher than I thought it would be, and higher than the 2% background rate, but it’s still a modest increase and most babies are born completely normal,” Dr. Meador, professor of neurology and neurosciences at Stanford (Calif.) University, said in an interview. “I think the news here is good, and it’s especially reassuring when you put it in the context that, 60 years ago, there were laws that women with epilepsy couldn’t get married, and some states even had laws to sterilize women. I think that’s absurd when most infants born to these women are without malformations and the risk of miscarriage is very low.”
Another positive finding, he said, is that valproate use among pregnant women is now practically nonexistent. Only 1 of 351 pregnant women with epilepsy and just 2 of a comparator group of 109 nonpregnant women with epilepsy were taking it. That’s great news, said Dr. Meador, who also initiated the NEAD (Neurodevelopmental Effects of Antiepileptic Drugs) study in the early 2000s. NEAD determined the drug’s serious teratogenic potential.
In addition to the cohorts of pregnant and nonpregnant women with epilepsy, 105 healthy pregnant women enrolled in the MONEAD study. Women will be monitored during pregnancy and postpartum to measure maternal outcomes and their children will be monitored from birth through age 6 years to measure their health and developmental outcomes.
The study has six primary outcomes, three for the women and three for their children.
- Determine if women with epilepsy have increased seizures during pregnancy and delineate the contributing factors.
- Determine if C-section rate is increased in women with epilepsy and delineate contributing factors.
- Determine if women with epilepsy have an increased risk for depression during pregnancy and the postpartum period and characterize risk factors.
- Determine the long-term effects of in utero AED exposure on verbal intellectual abilities and other neurobehavioral outcomes.
- Determine if small-for-gestational age and other adverse neonatal outcomes are increased.
- Determine if breastfeeding when taking AEDs impairs the child’s ultimate verbal and other cognitive outcomes.
Rates of miscarriage and neonatal malformations were not primary study outcomes, but the descriptive data were collected and are of high interest, Dr. Meador said.