Valproate in pregnancy associated with several congenital malformations

January 01, 0001

Valproate in pregnancy associated with several congenital malformations

These Dutch authors studied the association between the use of valproic acid in the first trimester of pregnancy and congenital malformations. They identified 14 malformations from prior cohort studies that were significantly more common among the offspring of women who had received valproic acid during the first trimester. They then assessed the associations between use of valproic acid during the first trimester and these 14 malformations by performing a case-control study with the use of the European Surveillance of Congenital Anomalies (EUROCAT) antiepileptic-study database, which is derived from population-based congenital-anomaly registries. The data set included 98,075 live births, stillbirths, or terminations with malformations among 3.8 million births in 14 European countries from 1995 through 2005.

They found: "Exposure to valproic acid monotherapy was recorded for a total of 180 registrations, with 122 registrations in the case group, 45 in control group 1, and 13 in control group 2. As compared with no use of an antiepileptic drug during the first trimester (control group 1), use of valproic acid monotherapy was associated with significantly increased risks for 6 of the 14 malformations under consideration. The adjusted odds ratios were as follows: spina bifida 12.7, atrial septal defect 2.5, cleft palate 5.2, hypospadias 4.8, polydactyly 2.2, and craniosynostosis 6.8. Results for exposure to valproic acid were similar to results for exposure to other antiepileptic drugs."

The authors concluded: "The use of valproic acid monotherapy in the first trimester was associated with significantly increased risks of several congenital malformations, as compared with no use of antiepileptic drugs or with use of other antiepileptic drugs."

Valproate should be avoided in women who may become pregnant.

For the full abstract, click here.

N Engl J Med 362(23):2185-2193 10 June 2010 © 2010 to the Massachusetts Medical Society
Valproic Acid Monotherapy in Pregnancy and Major Congenital Malformations. Janneke Jentink, Maria A. Loane, Helen Dolk, et al. Correspondence to Dr. de Jong-van den Berg: [email protected]

Category: W. Pregnancy, Childbirth, Family Planning. Keywords: epilepsy, pregnancy, valproic acid, congenital malformations, case- control study, journal watch.
Synopsis edited by Dr Linda French, Toledo, Ohio. Posted on Global Family Doctor 22 June 2010

Pearls are an independent product of the Cochrane primary care group and are meant for educational use and not to guide clinical care.