First-trimester exposure to the antiepileptic drug valproate increases the risk of major congenital malformation, particularly neural tube defects and facial clefts, according to recent guidelines developed by the American Academy of Neurology (AAN) and the American Epilepsy Society (AES).1-3 The guidelines recommend that women who have epilepsy avoid taking valproate during pregnancy.
“Good evidence shows that valproate is linked to an increased risk for fetal malformations and decreased thinking skills in children, whether used by itself or with other medications,” said lead guideline author Cynthia Harden, MD, director of the Epilepsy Division at the University of Miami’s Miller School of Medicine and member of the AAN.
The guidelines also suggest that, if possible, women who have epilepsy avoid taking more than one epilepsy drug during pregnancy because the use of multiple antiseizure medications increases the risk of birth defects.
In addition, the guidelines recommend that physicians avoid prescribing the epilepsy drugs phenytoin and phenobarbital during pregnancy. When a fetus is exposed to one of these drugs, cognitive development may be impaired.
Safe pregnancy is likely—if no seizures occur
Aside from the risks known to be associated with valproate, phenytoin, phenobarbital, and polytherapy, pregnancy in women who have well-controlled epilepsy appears to be relatively safe.
“Overall, what we found should be very reassuring to every woman with epilepsy planning to become pregnant,” said Harden.
“These guidelines show that women with epilepsy are not at a substantially increased risk of having a cesarean section, late-pregnancy bleeding, or premature contractions or premature labor and delivery. Also, if a woman is seizure-free 9 months before she becomes pregnant, it’s likely that she will not have any seizures during the pregnancy.”
However, a just-published study suggests that the presence of seizures during pregnancy confers some degree of risk, according to data from Yi-Hua Chen, PhD, and colleagues, of Taipei Medical University and General Cathay Hospital in Taiwan.4
Chen and associates performed a retrospective cross-sectional study that linked two nationwide population-based data sets from Taiwan. The study focused on 1,016 women who had epilepsy and who delivered singleton infants from 2001 to 2003; these women had been diagnosed with epilepsy within 2 years prior to their index delivery. Women who had epilepsy were further stratified into two groups: those who did and those who did not have seizures during pregnancy. They were compared with 8,128 women who had no chronic disease.
Women who experienced seizures during pregnancy were more likely to give birth to preterm, small, or low-birth-weight babies than were women who did not have epilepsy. In addition, women who experienced seizures during pregnancy were more likely to give birth to a small-for-gestational-age infant than were women who had epilepsy but who did not have seizures.
Some previous studies had reported a link between adverse pregnancy outcomes and a mother’s epilepsy, but others found no association, Chen and colleagues observed.
“Our study further illuminates these conflicting data to suggest that it is the seizures themselves that seem to contribute greatly to the increased risk of infants being delivered preterm, of low birthweight, and small for gestational age. For women who remained seizure-free throughout pregnancy, null or mild risk was identified, compared with unaffected women,” they wrote.
- It is estimated that approximately 500,000 women of childbearing age in the United States have epilepsy, and that 3 to 5 of every 1,000 births are to women who have epilepsy.
- Most people who have epilepsy have well-controlled seizures and are otherwise healthy.
- The birth rate in women who have epilepsy is slightly lower than it is in women who do not have the disease.10
- Most women who have epilepsy have uneventful pregnancies and deliver healthy infants with no complications.11
- Epilepsy can be associated with reproductive endocrine disorders, including polycystic ovary syndrome, hypothalamic amenorrhea, or functional hyperprolactinemia, possibly through the effects of antiepileptic drugs.12
- The children of women who have idiopathic epilepsy have a slightly elevated risk ( 13
As a safeguard, measure blood levels
of antiseizure drugs
The guidelines from the AAN and AES recommend that pregnant women who have epilepsy consider having their blood tested regularly.