Depakote During Pregnancy May Increase the Risk of Autism

Here's news Abbott will love. Use of the anticonvulsant sodium valproate during pregnancy may increase the risk of autism spectrum disorder (ASD), according to a preliminary report in this week's Neurology. Abbott markets the proprietary form of divalproex sodium or Depakote, a 1-to-1 molar combination of sodium valproate and valproic acid. The use of Abbott's drug during pregnancy has been previously linked to an increased risk of neural tube defects in children, and prescribing information for the anticonvulsant contains a black-box warning to this effect.*

In an ongoing, prospective study of the effect of anticonvulsants during pregnancy, UK investigators detected a relatively high incidence, 1.6%, of ASD in a cohort of 632 live births, 47% of which were to women with epilepsy. Those children diagnosed with ASD were significantly more likely to have been exposed to anticonvulsants in utero (7/168), and to sodium valproate in particular. None of the children diagnosed with ASD had a family history of the disorder.

Anticonvulsant Exposure In Utero	No. With ASD (%)
Sodium valproate (n = 64)	4 (6.3)
Sodium valproate with lamotrigine (n = 51)	1 (2)
Phenytoin (n = 9)	1 (11)
Lamotrigine (n = 44)	1 (2)
None (n = 336)	3 (0.9)

The authors acknowledge the preliminary nature of their findings, and that little can be concluded from the rate of ASD in very small treatment subgroups—for instance, phenytoin-treated women. In addition, the relatively young ages of some children in the study may have limited the detection of ASD: a small percentage, 4.3%, were younger than 3 years of age.

* The risk of neural tube defects is decreased with the preconception use of folic-acid supplements.