WEDNESDAY, June 9 (HealthDay News) -- The offspring of women who
took the epilepsy drug valproic acid during the first trimester of
pregnancy are much more likely to have serious births defects
affecting the brain, heart and limbs, a new study finds.
Babies whose mothers took valproic acid during the first
trimester were 12.7 times more likely to have spina bifida, in
which the spinal cord and backbone fail to develop or close
properly, compared to babies whose mothers did not take the
Babies whose mothers took valproic acid were also 2.5 times more
likely to have an atrial septal defect (a heart defect); about five
times as likely to have a cleft palate (a defect of the upper lip
and roof of the mouth) or hypospadias (a penis abnormality); more
than twice as likely to be born with an extra digit on the hand
(polydactyly); and nearly seven times more likely to have
craniosynostosis (premature fusion of the skull during fetal
development that restricts skull and brain growth).
While valproic acid (brand names include Depakene and Depakote)
was associated with a higher relative risk of the six birth
defects, the absolute risk of having a baby with any of the defects
remains small, the researchers noted. For example, the risk of
having a baby with spina bifida was 0.6 percent, or six in 1,000,
among women who took the drug compared to five in 1,000 of babies
born to mothers who didn't take any epilepsy medication.
Yet given mounting evidence of the risks of valproic acid to
fetuses, researchers urged women of childbearing age to try other
drugs to control their seizures.
"These findings provide further evidence to avoid valproic acid, if possible, in pregnant women and [for doctors] to discuss with girls and women of childbearing potential the risk of the drug for the unborn child," said senior study author Lolkje T.W. de Jong-van den Berg, of the University of Groningen in the Netherlands.
Dr. Kimford Meador, a professor of neurology at Emory University
in Atlanta, echoed that warning.
"This drug should not be used as a first-line drug for epilepsy in women of childbearing age," Meador said. "There are multiple types of malformations that can be associated with valproic acid."
The review is published in the June 10 issue of the
New England Journal of Medicine.
In the review, researchers first looked at eight studies that
included nearly 1,600 births and identified some 14 birth defects
that seemed to be much more common among the children of women who
took valproic acid early in pregnancy.
Researchers then took that information and analyzed data from a
large European study that included nearly 4 million births and
98,000 birth defects. They found women who took valproic acid in
early pregnancy had two to 12 times the risk of having a baby with
one of six specific birth defects compared to women who took no
epilepsy drugs. The findings were similar when birth defect rates
among those taking valproic acid were compared to the rates for
women who took other epilepsy drugs, leading researchers to
conclude it was the valproic acid, not some other epilepsy drug,
that was to blame.
Among those who took valproic acid during early pregnancy, the
chances of having a baby with any of the defects was less than 1
percent -- cleft palate (0.3 percent), hypospadias (0.7 percent),
polydactyly (0.2 percent), craniosynostosis (0.1 percent).
Previous research has also linked valproic acid to spina bifida,
other birth defects and cognitive problems in children, Meador
noted. In April 2009, Meador was the lead author of a study that
appeared in the
New England Journal of Medicine that linked exposure to
valproic acid in the womb to lower IQ scores in children at age
The American Academy of Neurology recommends avoiding the use of
valproic acid in pregnant women, according to background
information in the article. Yet since up to half of pregnancies are
unplanned, according to the study, all women of childbearing age
should be warned about the dangers, researchers said.
Despite such concerns, valproic acid is often still prescribed,
Meador said. In 2006, valproic acid was the second most commonly
prescribed epilepsy drug, he noted.
Valproic acid is also prescribed to prevent migraines and for
bipolar disorder, he added.
Despite the risks, valproic acid can be a very effective drug
and may be the best choice for some patients whose seizures are not
well-controlled by other medications, Meador said.
National Institute of Neurological Disorders and
Stroke has more on epilepsy.