Maternal Valproic Acid Exposure and Autism in Offspring
Maternal Valproic Acid Exposure and Autism in Offspring
The absolute risk for any ASD was 1.53% (95% confidence interval [CI], 1.47-1.58) and 0.48% (95% CI, 0.46-0.51) for childhood autism. Among infants exposed to valproic acid during pregnancy, the absolute risk of developing an ASD was 4.4%, with an adjusted HR of 2.9. The absolute risk of being diagnosed with childhood autism was 2.5%, with an adjusted HR of 5.2. The increased HR for being diagnosed with any ASD after exposure to valproic acid was robust in almost all sensitivity analyses (eg, mothers with epilepsy, any trimester of valproic acid exposure, treatment with multiple antiepileptic drugs along with valproic acid). Furthermore, the HR was elevated regardless of whether the exposure was considered to be in the high or low dosing range.
Exposure to other antiepileptic drugs without valproic acid was not associated with increased risk for ASD or childhood autism. Even after excluding children with congenital malformations, the HRs for the diagnosis of autism and ASD were still elevated. The study's conclusion was that the offspring of women treated with valproic acid during pregnancy have an elevated risk for ASDs, and specifically childhood autism, compared with the offspring of women who did not take valproic acid.
Christensen and colleagues make a very important point -- that even among the offspring of women who took valproic acid, the absolute risk for any of the ASDs was < 5%. The finding of increased risk for ASD across all valproate use (different dose exposures, trimester of exposure, differences in whether it was used with other antiepileptic drugs or as a single agent) suggests a true biological effect of valproic acid on the developing fetus. Of note, in utero exposure to other antiepileptic drugs (such as carbamazepine, oxcarbazepine, lamotrigine, and clonazepam) did not appear to be associated with increased risk for autism in the offspring. The risk of having a child with autism must be weighed against potential benefits of treatment with valproic acid for any woman of reproductive age who requires treatment for epilepsy.
Abstract
Study Findings
The absolute risk for any ASD was 1.53% (95% confidence interval [CI], 1.47-1.58) and 0.48% (95% CI, 0.46-0.51) for childhood autism. Among infants exposed to valproic acid during pregnancy, the absolute risk of developing an ASD was 4.4%, with an adjusted HR of 2.9. The absolute risk of being diagnosed with childhood autism was 2.5%, with an adjusted HR of 5.2. The increased HR for being diagnosed with any ASD after exposure to valproic acid was robust in almost all sensitivity analyses (eg, mothers with epilepsy, any trimester of valproic acid exposure, treatment with multiple antiepileptic drugs along with valproic acid). Furthermore, the HR was elevated regardless of whether the exposure was considered to be in the high or low dosing range.
Exposure to other antiepileptic drugs without valproic acid was not associated with increased risk for ASD or childhood autism. Even after excluding children with congenital malformations, the HRs for the diagnosis of autism and ASD were still elevated. The study's conclusion was that the offspring of women treated with valproic acid during pregnancy have an elevated risk for ASDs, and specifically childhood autism, compared with the offspring of women who did not take valproic acid.
Viewpoint
Christensen and colleagues make a very important point -- that even among the offspring of women who took valproic acid, the absolute risk for any of the ASDs was < 5%. The finding of increased risk for ASD across all valproate use (different dose exposures, trimester of exposure, differences in whether it was used with other antiepileptic drugs or as a single agent) suggests a true biological effect of valproic acid on the developing fetus. Of note, in utero exposure to other antiepileptic drugs (such as carbamazepine, oxcarbazepine, lamotrigine, and clonazepam) did not appear to be associated with increased risk for autism in the offspring. The risk of having a child with autism must be weighed against potential benefits of treatment with valproic acid for any woman of reproductive age who requires treatment for epilepsy.
Abstract
