Researchers reviewed birth outcomes among almost 4 million babies born in Europe between 1995 and 2005, including almost 100,000 who had major birth defects and 2,680 whose mothers took carbamazepine during the first three months of their pregnancies.
The study was published online today in the journal BMJ Online First.
Risks of Valproic Acid
Valproic acid was linked to a higher risk for several birth defects, including cleft palate, extra fingers and toes, and hypospadia -- a condition in which a male’s urinary opening develops in the wrong part of the penis or in the scrotum.
The new findings bolster recent guidelines from the American Academy of Neurology recommending that women avoid valproic acid, if possible, during pregnancy.
Since switching antiseizure drugs during or just before pregnancy is not recommended, many neurologists try to avoid prescribing valproic acid to their female patients during their childbearing years.
But this is not always possible, says study researcher Lolkje de Jong-van den Berg, who is a professor in pharmacoepidemiology at the University of Groningen in the Netherlands.
“If carbamazepine is effective for controlling seizures it is clearly the best choice,” she tells WebMD. “But this is not always the case. In some cases, valproic acid may be the only effective option.”
She points out that while the relative risk for birth defects is elevated, the overall risk in children born to women who take antiseizure drugs -- including valproic acid -- is still quite low.
Risks vs. Benefits
According to the Spina Bifida Association, about seven babies in 10,000 are born with spina bifida in the U.S.
In the newly reported review, babies exposed to carbamazepine or valproic acid before birth had a 2.6-fold and 7.7-fold increase in risk for the disorder, respectively, compared to babies who had no exposure to antiseizure drugs.
In an editorial published with the study, University of Toronto neurologist and pediatrics professor Irena Nulman, MD, writes that the risks associated with uncontrolled seizures far outweigh the risks associated with epilepsy drugs for most treatment-dependent patients.
“The benefits of seizure control during pregnancy should not be underestimated,” she writes. “For many pregnant women, discontinuing antiseizure drugs is not an option.”
“The good news is, this is a birth defect that can be screened for early in pregnancy and it is one that can be prevented with folic acid,” she tells WebMD. “That is why prepregnancy counseling is so important for women with epilepsy.”