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Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism


Valproate is used for the treatment of epilepsy and other neuropsychological disorders and may be the only treatment option for women of childbearing potential. As a result, a study published in the Journal of the American Medical Association (2013;309:1730-1731), was performed to determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring.


The investigation was a population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). The risks associated with all autism spectrum disorders were analyzed as well as childhood autism. Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first.


The main outcomes measures were absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy.


Results showed that of 655,615 children born from 1996 through 2006, 5,437 were identified with autism spectrum disorder, including 2,067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14). The estimated absolute risk after 14 years of follow-up was 1.53% for autism spectrum disorder and 0.48% for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% for autism spectrum disorder (adjusted HR, 2.9) and an absolute risk of 2.50% for childhood autism (adjusted HR, 5.2). When restricting the cohort to the 6,584 children born to women with epilepsy, the absolute risk of autism spectrum disorder among 432 children exposed to valproate was 4.15% (adjusted HR, 1.7), and the absolute risk of childhood autism was 2.95% (adjusted HR, 2.9) vs, 2.44% for autism spectrum disorder and 1.02% for childhood autism among 6,152 children not exposed to valproate.


According to the authors, maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy, and that for women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.


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