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Epilepsy Drug May Raise Autism Risk in Offspring
Date:12/3/2008

Yet another reason pregnant women should avoid this medication, experts say

WEDNESDAY, Dec. 3 (HealthDay News) -- Women taking the epilepsy drug valproate while pregnant are at increased risk of delivering a child who develops autism.

The British findings, appearing in the Dec. 2 issue of Neurology, add to previous research showing that valproate and other anti-epilepsy drugs can contribute to birth defects (particularly neural tube defects).

"There's a fair amount of early data that indicates, for instance, that valproate may cause neural tube closure problems. That's an indication that valproate affects brain development," said Dr. Michel Berg, medical director of the Strong Epilepsy Center at the University of Rochester Medical Center. "That's an indication that valproate affects brain development. It's not surprising that it might affect other aspects of brain development."

Physicians are already cautious about prescribing valproate and other drugs to pregnant women or women planning to become pregnant, however.

"I don't think this will change practice dramatically," said Dr. Jeffrey P. Brosco, an associate professor of clinical pediatrics at the University of Miami Miller School of Medicine and director of clinical services at the Mailman Center for Child Development in Miami. "This reaffirms that there is a lot of reason to try to avoid this drug if there is another available."

Reassuringly, added Berg, the study did not seem to find a substantial increase in the development of autism spectrum disorders among the children of women who had taken another anti-seizure drug, lamotrigine (brand name Lamictal), while pregnant.

Drugs for this condition have encountered other problems. Previous studies have also found that pregnant women who use the epilepsy drug topiramate (brand name Topamax) alone or in combination with other epilepsy drugs may be increasing their risk of birth defects. And the U.S. Food and Drug Administration recently considered, but eventually rejected, adding a black-box warning that anti-seizure drugs can increase suicidal tendencies in patients.

The current paper is part of an ongoing study by the Liverpool and Manchester Neurodevelopment Group in Britain looking at the effects of anti-epileptic drugs in pregnant women.

The study involved 632 live births from 620 women, 296 of those births to women with epilepsy and 249 of whom took anti-epilepsy drugs at the beginning of the pregnancy.

Controls were 336 live births to women without epilepsy and therefore not taking these medications.

The children were assessed for autism or related conditions at 1, 3 and 6 years of age.

Out of the group of 632 children, nine were diagnosed with autism spectrum disorders and another with features of these disorders, amounting to a total incidence of 1.6 percent.

Seven of the 10 children were born to mothers taking anti-epileptic drugs. Four of the children were exposed to valproate, one to valproate plus lamotrigine, one to phenytoid (Dilantin among other brand names) and one to lamotrigine alone.

Just over 6.3 percent of children exposed to valproate alone have autism spectrum disorders or features of these disorders, a number that's seven times higher than that in the control group.

There is a possibility that more children in the study could be diagnosed with autism or related disorders as time progresses, given that most are still young.

Still, the absolute risk is relatively low. "Ninety-four percent of children exposed to valproate did not go on to have an autism spectrum disorder," Brosco said. "This adds to the evidence that we need to be cautious with every drug we use, especially during pregnancy, when the fetus is sensitive to external influences."

"This is not a strong study and doesn't really definitely make a causal relationship, but obviously it's a good start towards trying to figure out if there are any particular drugs that lead to autism," added Dr. Jane Ripperger-Suhler, an assistant professor of psychiatry and behavioral science and an assistant professor of pediatrics at Texas A&M Health Science Center College of Medicine and a psychiatrist with Scott & White Mental Health Center in Temple.

More information

There's more on autism spectrum disorders at the U.S. National Institute of Mental Health.



SOURCES: Jeffrey P. Brosco, M.D., Ph.D., associate professor, clinical pediatrics, University of Miami Miller School of Medicine, and director, clinical services, Mailman Center for Child Development, Miami; Michel Berg, M.D., neurologist and medical director, Strong Epilepsy Center, University of Rochester Medical Center, New York; Jane Ripperger-Suhler, M.D., assistant professor, psychiatry and behavioral science, and assistant professor, pediatrics, Texas A&M Health Science Center College of Medicine, and psychiatrist, Scott & White Mental Health Center, Temple; Dec. 2, 2008, Neurology


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