North American Antiepileptic Drug Pregnancy Registry Depakote Study

Pregnancy registries were developed as a way assess the potential risks to a fetus associated with exposure to anticonvulsant drugs in utero. Since its introduction in 1997, the North American Antiepileptic Drug (AED) Pregnancy Registry has enrolled 6,456 women taking anticonvulsant drugs while pregnant. The registry hopes to be able to shed some light on the connection between anti-epileptic drug use and major congenital malformations among infants exposed to the drugs in utero.

According to the registry’s founders, the North American Antiepileptic Drug Pregnancy Registry was developed in order to better understand the risks of birth defects associated with anti-epileptic drug treatment, and more importantly, to systematically study the range of birth defects resulting from use of each anti-epileptic drug. Women are enrolled in the pregnancy registry by simply calling the registry, and are subsequently interviewed three separate times: at the time of enrollment, after seven month’s gestation, and between eight and twelve weeks after the expected delivery date.

Depakote and Anitepileptic Drug Study Findings

According to a study conducted for publication in the North American Antiepileptic Drug Pregnancy Registry, the use of valproate, the active ingredient in Depakote, during the first trimester of pregnancy significantly increases an infant’s risk of developing major congenital malformations. Furthermore, researchers found that the risk of birth defects among infants exposed to valproate in utero was significantly higher than the risk among infants whose mothers took other anti-epileptic drugs while pregnant. The malformations associated with valproate use included pulmonary atresia, spina bifida, developmental delay, heart defects, hypospadias, and microcephaly.

In the past, experts believed that taking folic acid supplements before and during pregnancy could prevent up to 70% of all birth defects. However, in this study in particular, the mothers of all sixteen infants that were born with congenital abnormalities took either folic acid supplements or multivitamins containing folic acid during pregnancy. In fact according to researchers, “the three cases with spina bifida were among the 106 [valproate]-exposed women who took the daily recommended amount of folic acid.”

The findings of this study are in agreement with several previous studies which determined not only that valproate was associated with adverse outcomes, but that these malformations occur more frequently among infants exposed to valproate than other anti-epileptic drugs. Unfortunately, even women who consume the recommended level of folic acid during pregnancy are at risk of giving birth to children with major congenital malformations resulting from their use of anticonvulsant drugs during pregnancy.

Quotations From This Depakote and Antiepileptic Study

“One notable and new finding in our study was the occurrence in two infants of pulmonary atresia, a severe heart defect. The suggested increased frequency of craniosynostosis, especially metopic synostosis, was validated.”

“There was a fourfold increased risk for having an offspring with a major birth defect for VPA-exposed women compared with those taking other AEDs.”

“The risk for women taking [valproate] VPA of having a baby with a [neural tube defect] NTD is about 2 to 5%. Thus, in our sample of 149 VPA-exposed women, two to eight infants with NTD would be expected and three were observed.”

Every anticonvulsant drug studied in human pregnancies, to date, including phenobarbital, phenytoin, carbamazepine, and valproate, has been shown to be teratogenic,” which is defined as the potential for a drug to cause fetal malformation.

Resource Links to This Depakote Study

http://www2.massgeneral.org/aed/index.htm

http://www2.massgeneral.org/aed/articles/Neurology2005.pdf

http://www2.massgeneral.org/aed/articles/Neurology2008.pdf