Epilepsy drug in pregnancy linked to autism risk, study finds
Women taking the epilepsy drug valproate (Depakote) while pregnant are at increased risk of having children with autism and other developmental problems, according to a small British study.
Valproate is prescribed for epilepsy as well as certain psychiatric disorders and migraines. Other studies have shown its use during pregnancy is associated with birth defects and, more recently, lower IQ in school-age children.
The American Academy of Neurology advises against valproate use during pregnancy, and some experts believe it should not be used by women of childbearing age.
"Women for whom valproate is a treatment option should discuss the risks and benefits of this drug with their doctor prior to pregnancy, to ensure that their health and that of the potential child is optimized," said Rebecca Bromley, a clinical psychologist and research associate at the University of Liverpool, who led the new study.
"Planning a pregnancy in collaboration with your doctor is important if you are taking antiepileptic drugs," she added. And evidence suggests the damage to the fetus occurs early in pregnancy, according to the study.
But women should not alter their medication without talking to their doctor, she noted.
For the study, published online Jan. 30 in the Journal of Neurology, Neurosurgery & Psychiatry, Bromley's team collected data on more than 500 pregnant women between 2000 and 2004. About half had epilepsy, of whom all but 34 took medicine to control their seizures.
The drugs they took included carbamazepine (Tegretol), valproate and lamotrigine (Lamictal), the researchers noted.
Of the 415 children for whom data was available, 19 were diagnosed with a developmental problem by age 6 years. Three of them also had a physical handicap.
Twelve of these children had an autism spectrum disorder, and one was also diagnosed with attention-deficit/hyperactivity disorder (ADHD), the researchers found.
Three children had ADHD alone and four had dyspraxia, a condition causing poor physical coordination and clumsiness.
These neurodevelopmental problems were far more common among children whose mothers had epilepsy (7.46 percent) compared with those whose mothers didn't have the seizure disorder (1.87 percent). And they were detected more often among children whose mothers took valproate by itself or in combination with other drugs, the study authors found.
Twelve percent of the children of mothers who took valproate alone had developmental problems as did 15 percent of those whose mothers took valproate along with other medications, the researchers reported.
Also, the likelihood of a neurodevelopmental disorder appeared to increase with higher doses of valproate, they noted.
Overall, children exposed to valproate alone or with other drugs were six times and 10 times more likely to be diagnosed with a developmental problem, respectively, compared with children of mothers who did not have epilepsy, the study authors said.
In addition, boys were three times more likely to be diagnosed with a developmental disorder than girls.
Children with autism have trouble with communication and social interactions, and its incidence is increasing.
Bromley said she hopes to continue the research in larger studies.
Meanwhile, children exposed to valproate in the womb should be monitored, the authors said. However, "it is important to stress that not every child is affected," Bromley said.
"Exposure to the drug is associated with an increase in the level of risk, but we do not yet understand the mechanism behind the association," she added.
Other experts said that valproate is overused.
"There is still a lot of valproate being used in women of childbearing age, probably more than we should be using," said Dr. Kimford Meador, a professor of neurology at Emory University School of Medicine in Atlanta.
Valproate is known to increase the risk of birth defects in higher doses, Meador said. "It is the antiepileptic drug that has the most risk for developmental disorders," he added.
"We have a lot of alternate drugs that can be tried," he said.
Only half of the prescriptions for valproate in the United States are for epilepsy; the rest are for psychiatric disorders and migraines, he noted.
Dr. Orrin Devinsky, director of the epilepsy center at NYU Langone Medical Center in New York City, agreed that valproate use should be limited.
"The increased risk of poor neurodevelopmental outcomes, including autism, must be viewed in light of the similarly increased risk of major congenital malformations," Devinsky said.
Together, he added, these risks "should make every doctor treating a woman of childbearing age with valproate make sure it is truly essential."
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