Elsevier

The Journal of Pediatrics

Volume 163, Issue 3, September 2013, Pages 922-926
The Journal of Pediatrics

Current Best Evidence
Prenatal valproate exposure is associated with autism spectrum disorder and childhood autism

https://doi.org/10.1016/j.jpeds.2013.06.050Get rights and content

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Question

Controlling for known risk factors, what is the association of prenatal valproate exposure with development of autism spectrum disorder or childhood autism, compared with unexposed children?

Design

Prospective, population-based birth cohort study.

Setting

Denmark.

Participants

All children born 1996-2006.

Intervention

Prenatal valproate.

Outcomes

Autism spectrum disorder and childhood autism.

Main Results

Of 655 615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI,

Conclusions

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. 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.

Commentary

Christensen et al present strong evidence that fetal valproate exposure is associated with increased risks of autism and autism spectrum disorder. Study strengths include the large population-based cohort, extended longitudinal follow-up, very few subjects lost to follow-up, and analyses adjusting for many potentially confounding factors. Limitations include inadequate information on folate, alcohol or illicit drugs use, no adjustments for other prescribed drugs, and lack of measures for

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References (3)

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