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Prenatal valproate increased autism spectrum disorders risk in children

Children whose mothers used valproate during their pregnancy had a significantly increased risk for autism, according to new study results published in JAMA.

“In this population-based cohort study, children of women who used valproate during pregnancy had a higher risk of autism spectrum disorder and childhood autism compared with children of women who did not use valproate,” researchers wrote. "Their risks also were higher than those for children of women who were previous users of valproate but who stopped before their pregnancy.”

The study included 655,615 live births in Denmark from 1996 to 2006; of those, 5,437 had autism spectrum disorder, including 2,067 with childhood autism. Researchers analyzed national registers to identify which children were exposed to valproate during pregnancy.

Researchers found that 508 children were exposed to valproate during pregnancy and had an absolute risk of 4.42% (95% CI, 2.59-7.46) for autism spectrum disorders and an absolute risk of 2.5% (95% CI, 1.30-4.81) for childhood autism.

Researchers also found that when restricting the cohort to 6,584 children of women with epilepsy, the absolute risk of the 432 children exposed to valproate was 4.15% (95% CI, 2.2-7.81) for autism spectrum disorder and 2.95% (95% CI, 1.42-6.11) for childhood autism, whereas the 6,152 children not exposed to valproate had an absolute risk of 2.44% (95% CI, 1.88-3.16) for autism spectrum disorder and 1.02% (95% CI, 0.7-1.49) for childhood autism.

“Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism in the offspring, even after adjusting for parental psychiatric disease and epilepsy,” researchers wrote. “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.”

Disclosure: Christensen reports receiving honoraria for serving on the scientific advisory boards, lecture honoraria and travel funding from UCB Nordic and Eisai AD. See the study for a full list of disclosures.