Does prenatal exposure to valproate increase risk of intellectual disability?

Prenatal exposure to a number of drugs, both prescription and over-the-counter, has been found to impact a child’s development. An investigation in JAMA Network Open looks into whether prenatal exposure to valproate and other antiepileptic drugs is linked to an increased risk of intellectual disability or delayed development in childhood milestones.¹

The investigators ran a population-based cohort study that looked at all singleton children who were the result of a live birth in Denmark between January 1997 and December 2011. Exposure to an antiepileptic drug was defined as a redeemed prescription for the mother within the exposure window, which was the period from 30 days before a child’s estimated conception date to the date of birth. Each child was followed from birth to either emigration, death, first diagnosis of either an intellectual disability or a delayed childhood milestone, or December 31, 2015, whichever came first.

The cohort included 913,301 children, which meant more than 10.2 million-person years of observation. In the cohort, 580 children had been exposed to valproate. When follow-up ended, 6958 children had been identified as having intellectual disability and 14,967 children had been identified as having an intellectual disability with delayed childhood milestones. When compared to children with no prenatal exposure to valproate, children with prenatal exposure to the drug were found to have an increased risk of intellectual disability (adjusted hazard ratio [aHR], 4.48; 95% CI, 2.97-6.76) as well as intellectual disability with delayed childhood milestones (aHR, 6.07; 95% CI, 4.67-7.89). Additionally, when compared to children with no prenatal exposure to any antiepileptic drug, the researchers found an increased risk of intellectual disability in children who had prenatal exposure to maternal monotherapy of carbamazepine (aHR, 3.84; 95% CI, 2.32-6.38), clonazepam (aHR, 2.41; 95% CI, 1.09-5.35), and oxcarbazepine (aHR, 3.70; 95% CI, 2.11-6.51) but not lamotrigine (aHR, 1.33; 95% CI, 0.71-2.48).

The researchers concluded that prenatal exposure to valproate led to an increased risk of intellectual disability as well as delayed childhood milestones. They also found statistically significant links for prenatal exposure to other antiepileptic drugs.

Reference

1. Daugaard C, Pedersen L, Sun Y, Dreier J, Christensen J. Association of prenatal exposure to valproate and other antiepileptic drugs with intellectual disability and delayed childhood milestones. JAMA Netw Open. 2020;3(11):e2025570. doi:10.1001/jamanetworkopen.2020.25570