Anticonvulsants during pregnancy have been linked to an increased risk of RAS in children
A cohort study by US scientists has found that the incidence of autism spectrum disorders is higher among children whose mothers took anticonvulsant drugs during pregnancy. Doctors examined the effect of topiramate, valproic acid and lamotrigine. However, after adjustment, the association found weakened significantly for topiramate and lamotrigine, while the increased risk persisted for valproate. The results of the study are published in The New England Journal of Medicine.
Most women with epilepsy are treated with anticonvulsant medications throughout pregnancy. However, it is well known that valproate and, to a lesser extent, other traditional anticonvulsants (e.g., phenobarbital and carbamazepine) are highly teratogenic. Among anticonvulsants approved in the past 25 years, most (e.g., lamotrigine) do not appear to significantly affect the risk of malformations, with the exception of topiramate, whose use is associated with an increased risk of cleft palate.
However, the effect of anticonvulsant use during pregnancy on the risk of autism spectrum disorder (ASD) remains unclear. For example, valproate in studies decreased neurocognitive function in children aged 4-18 years and increased the risk of ASD. In contrast, studies, with few exceptions, generally did not associate lamotrigine use during pregnancy with adverse neurodevelopmental outcomes. This inconsistency of studies warrants further evaluation of the risk of RAS development in children with prenatal exposure to anticonvulsant medications.
Researchers led by Sonia Hernández-Díaz of Harvard University conducted such an assessment. To do so, they examined data from 4292539 eligible pregnancies, among them 28952 women with epilepsy. Of these, 1030 received at least one administration of topiramate in the second half of pregnancy, 800 of valproate, and 4205 of lamotrigine; 8815 received no anticonvulsant medication for 90 days before and during pregnancy. The median follow-up was two years. More than 400,000 children in the entire population were followed up for at least eight years.
The cumulative incidence of autism spectrum disorders at age eight among children whose mothers did not take anticonvulsants during pregnancy was 1.89 percent. In the maternal epilepsy group, the overall cumulative incidence of autism spectrum disorders at age eight years was 4.21 percent for no exposure to anticonvulsants, 6.15 percent for exposure to topiramate, 10.51 percent for valproate, and 4.08 percent for lamotrigine.
The weighted mean risk ratios compared with no anticonvulsant exposure were 0.96 for topiramate, 2.67 for valproate exposure, and 1.00 for lamotrigine exposure. Compared with lamotrigine monotherapy, the risk ratios adjusted with maternal condition and drug dose were 1.22 for topiramate and 1.79 for valproate.
According to the researchers, these results further support the risks to the fetus when the mother takes anticonvulsant medications. However, the simultaneous study of three drugs at once allowed the identification of the safest drug, lamotrigine, which may be considered a first-line treatment for pregnant women with epilepsy.