engleski

Valproic acid monotherapy in pregnancy and major congenital malformations

First trimester valproic acid (VPA) use is associated with an increased risk for spina bifida, but data are limited regarding risks for other malformations associated with VPA use. We first combined data from 8 published cohort studies (1565 exposed pregnancies and 118 major malformations) and identified 14 malformations that were significantly more common among women with first trimester VPA exposure. We then assessed associations between first trimester VPA use and these 14 malformations by performing a case control study using the EUROCAT database, derived from population-based congenital anomaly registers ; registrations with any of these 14 malformations (cases) were compared with 2 control groups: ((C1) other malformations not previously linked to VPA use, and (C2) chromosomal abnormalities). The dataset included 98, 075 malformed livebirths, stillbirths, or terminations, among 3.8 million births in 14 European countries 1995-2005. In total 180 registrations were VPA monotherapy exposed (122 cases, 45 in control group 1 and 13 in control group 2). As compared with no AED use, VPA monotherapy was associated with significant increased risks for 6 of the 14 malformations ; adjusted odds ratios ( 95% confidence intervals): spina bifida 12.7 [95%CI 7.7- 20.7], ASD 2.5 [1.4-4.4], cleft palate 5.2 [2.8-9.9], hypospadias 4.8 [2.9-8.1], polydactyly 2.2 [1.0-4.5] and craniosynostosis 6.8 [1.8-18.8]. Results were similar when VPA was compared with other AEDs. 1st trimester VPA use was associated with significantly increased risks for several congenital malformations, as compared with no maternal epilepsy or AED use or use of other AEDs.

valproic acid; pregnancy; congenital malformation

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