A study found a higher percentage of behavioral problems reported in children of mothers with epilepsy prenatally exposed to antiepileptic drug (AED) monotherapy. The highest percentage of behavioral problem reports were found in valproate-exposed children compared with children exposed to carbamazepine, lamotrigine, and levetiracetam, according to study findings published in Epilepsia.
The European Registry of Antiepileptic Drugs and Pregnancy (EURAP) database was used to identify children of mothers with epilepsy in The Netherlands. Only children (ages 6 to 7 years 11 months) whose mothers undergoing carbamazepine (n=37), lamotrigine (n=88), levetiracetam (n=30), or valproate (n=26) monotherapy prior to conception and during pregnancy were included in the study. The nature and severity of childhood behavioral problems was assessed between January 2015 and March 2018 using the Child Behavior Checklist and the Social Emotional Questionnaire. Direct comparisons were made between lamotrigine and levetiracetam, as well as valproate vs carbamazepine, lamotrigine, and levetiracetam.
The highest percentage of children with behavioral problems was found in children exposed to valproate (32%) vs carbamazepine (14%), lamotrigine (16%), and levetiracetam (14%). Exposure to valproate was associated with significantly greater social problems compared with exposure to lamotrigine (−2.8, 95% CI, −5.2 to −0.4; P =.022) or levetiracetam (−3.2, CI, −6.1 to −0.3; P = 0.028) in a multilevel regression analysis. In addition, valproate exposure was associated with significantly more attention problems vs exposure to levetiracetam (−3.7, 95% CI, −6.7 to −0.8; P =.013). Attention deficits were greater in the lamotrigine-exposed group (−9.2, 95% CI, −17.3-1.1; P =.026). Conversely, exposure to lamotrigine was associated with less anxious behavior vs exposure to levetiracetam (9.0, 95% CI, 0.3‐17.6; P =.042).
Study limitations include the reliance on parental reports for identifying child behaviors, as well as the inclusion of only children from The Netherlands.
According to investigators, additional research may be necessary in prenatal AED exposure “to understand the (ir)reversibility of the exposure.” By doing so, researchers may identify “opportunities for interventions that help parents cope with, or ideally decrease child behavioral problems.”
The authors report financial interests with Janssen‐Cilag, GlaxoSmithKline, Pfizer, and The Netherlands Epilepsy Foundation.
Huber‐Mollema Y, Oort FJ, Lindhout D, Rodenburg R. Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy. Epilepsia. 2019;60(6):1069-1082.