Study Finds Anticonvulsant Drug Poses Greater Birth-defect Risk Than Suspected

"The basic message for women who take valproate is to plan ahead if they want to have children. Discuss the risks with their physician and consider taking alternative drugs," says Lewis Holmes, MD, chief of the Genetics and Teratology Unit at MassGeneral Hospital for Children, director of the registry and senior author of the Neurology paper.

Sold in the U.S. under the brand names Depakote and Depakene, valproate is used to treat seizures, migraines and such psychiatric disorders as bipolar disorder. Earlier studies have suggested a potential risk of birth defects, primarily neural tube defects such as spina bifida, but none had definitively established the level of risk and the types of malformations that most frequently occur.

The North American AED Pregnancy Registry was established in 1996 and has enrolled more than 4,000 women who took anticonvulsant drugs during pregnancy. The current study analyzed information from 149 women who took only valproate while pregnant during the years 1997 to 2003. Of those 149 women, 16 had infants with major birth defects. Three infants had spina bifida, and a wide variety of malformations was seen in the others, including developmental delays.

While the risk level among women taking valproate was 10.7 percent, the risk for women in the registry who took other anticonvulsants as single-drug therapy was only 2.9 percent. In a comparison group of infants whose mothers had not taken an anticonvulsant drug, the frequency of major malformations in infants born to women at Brigham and Women's Hospital was 1.6 percent.

"This is the first indication to many neurologists that they should focus on more than the risk of spina bifida with this drug," says Holmes. "Many physicians have just advised their patients taking valproate to make sure to take folic acid to prevent neural tube defects; but the women in our study who had children with spinal bifida or other malformations had all taken the recommended dose of folic acid." Holmes is a professor of Pediatrics at Harvard Medical School.

Co-authors of the Neurology report are first author Diego Wyszynski, MD, PhD, of Boston University School of Medicine and Public Health; Maya Nambisian, MPH, and Triptaa Surve, MPH, of Harvard Medical School; Caitlin Reilly Smith, MPH, of the MGH, and Rachel Alsdorf of Boston University.