Anti-epileptic drug linked to birth defects, fetal deaths
By KEVIN SPURGAITIS
TORONTO — There’s new evidence valproic acid poses a higher risk for fetal death and birth defects than other widely used anti-epileptic drugs.
The Neurodevelopmental Effects of Anti-epileptic Drugs (NEAD) study focused on 333 mother-child pairs during pregnancy across 25 centres in the United States and the United Kingdom. Its primary aim was to look at the possible long-term cognitive behavioural effects of monotherapy involving carbamazepine, lamotrigine, phenytoin or valproic acid.
“We provided very compelling evidence valproate poses an increased risk. . . . It’s now factual, and not just conjectural,” said Dr. Kimford Meador, the lead author and a professor of neurology at the University of Florida. “It comes on the heels of several preceding (studies) in which anatomical malformations have been noted to be greater with valproate than other drugs.”
The frequency of serious adverse pregnancy outcomes, including fetal death and major congenital malformations, was 20.3% in women taking valproate, compared with 10.7% for phenytoin, 8.2% for carbamazepine and 1% for lamotrigine. Analysis of individual outcomes revealed fetal death rates did not differ significantly between groups, but major congenital malformations were more common in children of valproate users.
The risk increased with higher dosages of valproate. The average dose for those with serious adverse outcomes was 1,268 mg per day, while the average dose for those without malformations was 844 mg per day.
“The majority of babies born to women with epilepsy are normal. We’re just working to increase the number of children that come out normal,” Dr. Meador said, adding that valproate should no longer be used by women of childbearing age as a “drug of first choice.”
Dr. Donald Weaver, president of Epilepsy Canada and a professor at Dalhousie University’s school of biomedical engineering in Halifax, said the NEAD study’s findings are “not surprising” given previous anecdotal evidence implicating valproate in some birth defects.
“There have been a whole lot of anticonvulsant drugs that have come out over the last 20 years. It’s hard to get a handle on all of them,” said Dr. Weaver.
He continued: “Having epilepsy is not in any way an impediment to having a healthy pregnancy. Nonetheless, all anticonvulsants should be used with caution by women of childbearing age. Physicians and people involved have to make them aware of the risks and help them take appropriate precautions. One of these precautions is minimizing the use of valproic acid during pregnancy.”
Dr. Meador agreed. “Because valproate will continue to be an important treatment option for women who cannot use other epilepsy drugs, clinicians have an absolute obligation to tell their patients about the effects of this medication on children.”
However, he also warned women with more than mild epilepsy not to stop their medication without consulting their MD.
“It’s always like being between a rock and a hard place, because the control of the seizures must be balanced with the risk of the drug.”
The study was published in the Aug. 8 issue of Neurology and was funded by the U.S. National Institutes of Health and the U.K. Epilepsy Research Foundation. Pregnant women taking epilepsy drugs are being asked to join the North American Pregnancy Registry, which is seeking additional information on the risks associated with pregnant women taking valproate. Women can sign up for the North American Pregnancy Registry by calling toll-free 1-888-233-2334.
Originally published in the Medical Post, September 2006
