Background
The use of valproic acid in the first trimester of pregnancy is associated with an increased
risk of spina bifida, but data on the risks of other congenital malformations
are limited.
Methods
We first combined data from eight published cohort studies (1565 pregnancies in
which the women were exposed to valproic acid, among which 118 major malformations
were observed) and identified 14 malformations that were significantly more
common among the offspring of women who had received valproic acid during the
first trimester. We 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 congenitalanomaly
registries. Registrations (i.e., pregnancy outcomes with malformations
included in EUROCAT) with any of these 14 malformations were compared with
two control groups, one consisting of infants with malformations not previously
linked to valproic acid use (control group 1), and one consisting of infants with
chromosomal abnormalities (control group 2). 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.
Background
The use of valproic acid in the first trimester of pregnancy is associated with an increased
risk of spina bifida, but data on the risks of other congenital malformations
are limited.
Methods
We first combined data from eight published cohort studies (1565 pregnancies in
which the women were exposed to valproic acid, among which 118 major malformations
were observed) and identified 14 malformations that were significantly more
common among the offspring of women who had received valproic acid during the
first trimester. We 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 congenitalanomaly
registries. Registrations (i.e., pregnancy outcomes with malformations
included in EUROCAT) with any of these 14 malformations were compared with
two control groups, one consisting of infants with malformations not previously
linked to valproic acid use (control group 1), and one consisting of infants with
chromosomal abnormalities (control group 2). 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.
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