A population-based study of 655,615 children born in Denmark between 1996 and 2006 found that prenatal exposure to valproate was associated with an increased risk of autism spectrum disorders (ASD) and childhood autism. The study adjusted for potential confounders such as maternal age, parental psychiatric history, gestational age, birth weight, sex, and congenital malformations. Among 508 children exposed to valproate, the absolute risk of ASD was 4.42% (95% CI, 2.59%-7.46%) and for childhood autism was 2.50% (95% CI, 1.30%-4.81%). The adjusted hazard ratios (HRs) were 2.9 (95% CI, 1.7-4.9) for ASD and 5.2 (95% CI, 2.7-10.0) for childhood autism. When restricted to children of women with epilepsy, the absolute risk of ASD was 4.15% (95% CI, 2.20%-7.81%) and for childhood autism was 2.95% (95% CI, 1.42%-6.11%), with adjusted HRs of 1.7 (95% CI, 0.9-3.2) and 2.9 (95% CI, 1.4-6.0), respectively. The study also found that valproate exposure during pregnancy was associated with a higher risk of ASD and childhood autism compared to children of women who had previously used valproate but stopped at least 30 days before conception. The risk was higher for children exposed to valproate in the first trimester and for those exposed to valproate monotherapy. The study found no significant difference in risk based on the timing of exposure, but exposure in the first trimester was associated with higher risk. The study also found that valproate exposure was associated with a higher risk of ASD and childhood autism compared to children of women who used other antiepileptic drugs. The study concluded that maternal use of valproate during pregnancy was associated with a significantly increased risk of ASD and childhood autism in offspring, even after adjusting for maternal epilepsy. 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.A population-based study of 655,615 children born in Denmark between 1996 and 2006 found that prenatal exposure to valproate was associated with an increased risk of autism spectrum disorders (ASD) and childhood autism. The study adjusted for potential confounders such as maternal age, parental psychiatric history, gestational age, birth weight, sex, and congenital malformations. Among 508 children exposed to valproate, the absolute risk of ASD was 4.42% (95% CI, 2.59%-7.46%) and for childhood autism was 2.50% (95% CI, 1.30%-4.81%). The adjusted hazard ratios (HRs) were 2.9 (95% CI, 1.7-4.9) for ASD and 5.2 (95% CI, 2.7-10.0) for childhood autism. When restricted to children of women with epilepsy, the absolute risk of ASD was 4.15% (95% CI, 2.20%-7.81%) and for childhood autism was 2.95% (95% CI, 1.42%-6.11%), with adjusted HRs of 1.7 (95% CI, 0.9-3.2) and 2.9 (95% CI, 1.4-6.0), respectively. The study also found that valproate exposure during pregnancy was associated with a higher risk of ASD and childhood autism compared to children of women who had previously used valproate but stopped at least 30 days before conception. The risk was higher for children exposed to valproate in the first trimester and for those exposed to valproate monotherapy. The study found no significant difference in risk based on the timing of exposure, but exposure in the first trimester was associated with higher risk. The study also found that valproate exposure was associated with a higher risk of ASD and childhood autism compared to children of women who used other antiepileptic drugs. The study concluded that maternal use of valproate during pregnancy was associated with a significantly increased risk of ASD and childhood autism in offspring, even after adjusting for maternal epilepsy. 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.