Download Risks for a variety of different birth defects are increased after early

Risks for a variety of different birth defects are increased after early
pregnancy use of the antiepileptic drug valproic acid.
This week researchers of the EUROCAT-Antiepileptic-Study Working Group
published in the New England Journal of Medicine results of a study about the risks of
specific birth defects after first trimester valproic acid use. Exposure in the first trimester has
the potential to cause birth defects because this is the period when the major organs are
developing. Their study used a dataset including 98,075 livebirths, stillbirths, or terminations
with malformations from a population of 3.8 million births in 14 European countries 19952005. A significantly increased risk was reported for a variety of specific birth defects with
first trimester exposure to valproic acid compared with no antiepileptic drug use. The risk of
having a baby with one of the following birth defects - spina bifida (incomplete closure of the
vertebral column), atrial septal defect (defect in the tissue that divides the right and left atria
of the heart), cleft palate (fissure or opening in the roof of the mouth) hypospadias
(abnormally placed urinary opening in males), polydactyly (supernumerary fingers or toes)
craniosynostosis (premature fusion of fibrous sutures in an infant skull) and limb reduction
(failure of the complete formation of the arm or leg) - was 2-12 times greater for mothers
exposed to valproic acid during pregnancy compared to mothers with no antiepileptic drug
use during pregnancy.
The study also compared the use of valproic acid with the use of other antiepileptic
drugs and found similar results, suggesting that valproic acid has higher risks associated with
birth defects compared to other antiepileptic drugs.
In general about 2% of all births have major birth defects of the types studied by
the researchers, and it has been known for some time that this proportion can be two to three
times higher associated with antiepileptic drug use. Although the relative risks of several birth
defects were increased after 1st trimester exposure of valproic acid, it should be recognized
that the risks of these specific birth defects are still low, ranging from 1 to 7 per 1,000
exposed pregnancies.
These findings provide further support for the recommendations of the American
Academy of Neurology to avoid valproic acid, if possible, in pregnant women. Since
switching drugs during or just before pregnancy is difficult, the risks associated with valproic
acid use should be routinely considered in choosing therapy for women of childbearing
potential.