Epilepsy Drug Linked to Birth Defects

Use of valproate should be limited, researchers say

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By Randy Dotinga
HealthDay Reporter

TUESDAY, Aug. 8, 2006 (HealthDay News) -- A new study adds to evidence that women of child-bearing age should avoid an epilepsy drug that could cause birth defects.

Researchers who followed more than 300 pregnant mothers found that about 20 percent of those who took the drug valproate had miscarriages or babies who suffered from birth defects.

The rates of problems were significantly lower among women who took three other epilepsy drugs to control seizures.

Doctors have been suspicious about the effects of epilepsy drugs on pregnant women for about 40 years, said study lead author Dr. Kimford Meador, professor of neurology at the University of Florida and a fellow at the American Academy of Neurology.

"By the 1990s, it was pretty clear that women taking multiple anti-convulsive drugs had increased risks," he said.

It has become routine to prescribe just one drug to women with epilepsy, but there still seemed to be a risk, according to Meador.

In the new study, Meador and his colleagues examined the records of 333 American and British pregnant women who took epilepsy drugs between 1999 and 2004.

The researchers found that fetal death or serious birth defects occurred in 20 percent of the women who took valproate. Other problem rates were 11 percent for phenytoin, 8 percent for carbamazepine and 1 percent for lamotrigine.

The four drugs are also known by their U.S. brand names Depacon (valproate), Dilantin (phenytoin), Tegretol (carbamazepine) and Carbatrol (carbamazepine), and Lamictal (lamotrigine).

The study findings were published in the Aug. 8 issue of the journal Neurology.

The good news, according to Meador, is that more than 90 percent of all the pregnant women who took the drugs gave birth to normal children. Still, "their risk is elevated against the general population," in which defects occur in about 2 percent to 3 percent of births.

Why is valproate, which is also used to treat some psychological disorders, so hazardous? The answer isn't clear, but Meador speculated that the drug may form molecules that bind to DNA and proteins in the body, adversely affecting the developing fetus.

What should doctors and pregnant mothers with epilepsy do?

Dr. Gholam Motamedi, an assistant professor of neurology at Georgetown University who was part of the large study group that contributed to the new research, said use of valproate should be limited. However, the research "provides evidence that perhaps at lower doses, and when there is no better option, valproate may not be that bad and can be used at lower doses," he added.

Motamedi said it's important to note that the study only looked at a small number of women, and there are newer anti-epilepsy drugs that were not included in the research.

Future research will determine the full extent of birth defects, such as possible cognitive and development problems that only show up later in life, he said.

More information

Pregnant women who take epilepsy drugs are asked to join the Antiepileptic Drug Pregnancy Registry.

SOURCES: Kimford J. Meador, M.D., The Melvin Greer Professor of Neurology, department of neurology, University of Florida, Gainesville; Gholam Motamedi, M.D., assistant professor of neurology, Georgetown University Medical Center, Washington, D.C.; Aug. 8, 2006, Neurology

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