Findings from a new study indicate that compared with children who were not exposed to the drug, children with in utero exposure to sodium valproate have lower scores on national tests at age 7 years. Results were published on March 27, 2018 in the Journal of Neurology, Neurosurgery and Psychiatry. First author Arron Lacey, MSc, of Swansea University (Swansea, UK), and colleagues report that weighing the need for effective seizure control during pregnancy against the potential risk of antiepileptic drugs (AEDs) is essential: “. . . in utero exposure to certain AEDs can cause developmental problems in children. Women with epilepsy should be informed of this risk and alternative treatment regimens should be discussed before their pregnancy with a physician who specializes in epilepsy.”
Background. Recent studies have suggested that in utero exposure to sodium valproate may negatively affect the cognitive development and IQ of offspring. Yet few of these studies have used data from real-world settings. The study was undertaken to determine how in utero exposure to sodium valproate and other AEDs may affect cognition in offspring in the real world.
Methods. A database of about 77% of primary care records for the Welsh population was used and linked to the Key Stage 1 (KS 1) exam scores. The KS 1 is a national standardized exam in math, language, and science taken by children in Wales starting at age 7. The study included 440 children born to women with epilepsy between 1996 and 2001.
Researchers compared KS 1 scores for children born to women who had epilepsy to children whose mothers did not have epilepsy. Mothers were separated into the following groups: carbamazepine, lamotrigine, or sodium valproate monotherapy; polytherapy with multiple AEDs; or epilepsy not treated with AEDs. Fifty-four percent of women received sodium valproate as part of their polytherapy regimen.
Study Findings. Results showed no significant differences between children with in utero exposure to carbamazepine, lamotrigine, or epilepsy not treated with AEDs, compared with children born to mothers without epilepsy. However, up to 13% fewer children with in utero exposure to sodium valproate met national minimum standard scores for the KS 1, compared with children of mothers without epilepsy. Children with in utero exposure to multiple AEDs fared worse. Up to 22% fewer children in this group met national minimum standard scores for KS 1, compared with children of mothers without epilepsy.
Limitations. The authors noted that the study could not take into account maternal IQ, weight or alcohol consumption during pregnancy, as well as folic acid supplementation or AED dosage. Additionally, the lamotrigine group was small, which could explain why it had nonsignificant results. Finally, women prescribed sodium valproate as part of polytherapy may have had more severe epilepsy, which could also have affected the cognitive development of their children.
Take Home Point. The need for effective seizure control during pregnancy should be carefully weighed against the potential risk of AEDs to offspring.