Study finds anticonvulsant drug poses
greater birth-defect risk than suspected
Risk with valproate four time greater
than with alternative medications
BOSTON - March 21, 2005 - Use of the anticonvulsant drug
valproate during pregnancy may pose a significantly great risk of
birth defects than does use of other antiseizure medications. In
the March 22 issue of Neurology, researchers from the North
American AED (Antiepileptic Drug) Pregnancy Registry at Massachusetts
General Hospital (MGH) report that women taking valproate alone
had a fourfold increased risk of having a child with a major malformation,
compared with the risk among women taking other anticonvulsants.
"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.
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
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.
The largest hospital-based pregnancy registry of any kind, the North
American AED Pregnancy Registry is supported by grants from Abbott
Laboratories, Elan Pharmaceuticals, GlaxoSmithKline, Novartis, Ortho-McNeil
and Pfizer Pharmaceuticals. More information is available at www.aedpregnancyregistry.org
or by calling toll-free 888-233-2334.
MassGeneral Hospital for Children, the pediatric service of
Massachusetts General Hospital, is the oldest provider of pediatric
services in Boston. It is consistently listed in the U.S. News
and World Report Guide to America's Best Hospitals and was ranked
number 17 in the 2004 edition. Through its growing network of community-based
facilities and pediatricians, the hospital's excellent care is conveniently
accessible to families throughout the region.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $450 million
and major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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