March 21, 2005 -- The evidence continues to mount against the use of the antiseizure drug valproate during pregnancy.
In two new studies, children born to mothers who took valproate during early pregnancy had higher rates of birth defects and lowered verbal IQ.
These studies join a least a half dozen others implicating valproate in birth defects,valproate in birth defects, and an epilepsy expert tells WebMD that the findings are convincing.
"When you put all of these trials together it is clear that women in their childbearing years should not be using valproate unless there is an absolute need," neurologist Jacqueline French, MD, tells WebMD.
Valproate Very Popular
Valproate, sold under the brand names Depakote, Depakene, and Depacon, is one of the oldest and most widely prescribed antiseizure medications on the market.
In one of the newly published studies, one in 10 children born to women who took valproate had birth defects.
Researcher Diego Wyszynski and colleagues followed 149 women enrolled in a national registry of pregnancy outcomes among users of antiseizure drugs.
The risk of delivering a child with a birth defect was three times higher for women who took valproate during their first trimester of pregnancy than for women taking other antiseizure medications. The risk among valproate users was seven times greater than among the general population.
A study from the U.K. examined IQ scores among children whose mothers took antiseizure drugs while pregnant. A total of 249 children between the ages of 6 and 16 were enrolled in the trial.
Investigators reported that children exposed to valproate in the womb were significantly more likely to have low verbal IQ scores than children exposed to the antiseizure drug Dilantin or children whose mothers took no epilepsy drugs.
Valproate-exposed children were also more likely to have overall IQ scores in the extremely low or mentally impaired range, with 22% falling into this range compared with about a 3% rate in the general population.
No Increase Seen With Lamictal
Finally, a third study examined birth defects among children born to mothers who took the newer epilepsy drug Lamictal.
The study included 414 women who took the drug, either alone or in combination with valproate, during their first trimester of pregnancy between 1992 and 2004.
Roughly 3% of the children born to women who took Lamictal alone had birth defects -- a rate that is similar to that seen in the general population. Four times as many birth defects were reported among women who took Lamictal with valproate.
Several other studies also suggest that newer epilepsy drugs like Lamictal carry a low risk for birth defects. But neurologist Patricia Penovich, MD, tells WebMD that the research is far from conclusive.
"We simply don't have enough information to say with scientific certainty that these newer drugs are safe," she says.
The issue is further complicated by the fact that for many patients with epilepsy, valproate may be the only drug that works to control seizures.
"The most important thing that we can do for a mother is to keep her from having seizures during pregnancy," Penovich says.
French says there is a huge need for new drugs that work as well as valproate without the risks.
"Valproate is very effective for many (types of epilepsy), and there really is not a clear alternative drug for many women at this moment," she says.
But both neurologists agree that too many at-risk women who could control their seizures with other medications are still taking valproate. As many as 15 million prescriptions for antiseizure drugs are written each year to women in their childbearing years.
Folic Acid a Remedy?
There is some evidence that valproate users can lower their risk by taking large amounts of folic acid. It is generally recommended that women who are pregnant or might become pregnant take 400 micrograms of the vitamin. Some experts recommend 10 times that amount for women on the epilepsy drug.
But French says the evidence proving that folic acid can protect babies exposed to valproate in the womb has not materialized.
"Unfortunately, the data haven't shown this to be the case," she says.
Penovich says the risk for the mother and the child can be minimized by carefully planning seizure therapy prior to pregnancy, by supplementing with folate, and by using one seizure drug (rather than numerous drugs) at the lowest and most effective dose.