EURAP & Development Study protocol of a Dutch prospective observational study into fetal Antiepileptic Drug exposure and long-term neurocognitive, behavioral and family outcomes

Background: Children exposed to antiepileptic drugs (AEDs) in utero are at higher risk for congenital malformations. Less is known about the long-term association with neurocognition and behavior. Research into family factors related to long-term developmental outcomes of children of women with epilepsy is also rare. We present a protocol to investigate the neurocognitive and behavioral development in children of mothers with epilepsy from a family perspective.
Methods: This is a prospective observational longitudinal study, of children exposed in utero to monotherapy carbamazepine, lamotrigine, valproate or levetiracetam whose mother were previously included in the European Registry of Antiepileptic Drugs and Pregnancy (EURAP-NL) database. Children are tested at age six or seven years (T1) and at eight or nine years (T2). Children, mothers and fathers are asked to undergo neuropsychological assessments and to complete questionnaires on behavioral functioning and distinct family factors.
Discussion: This study contributes to future counseling of women with epilepsy who have children or wishes to start a family. Strengths are the inclusion of levetiracetam, the longitudinal design, and alongside neurocognition, the inclusion of differential behavioral and family outcome measures. Anticipated limitations are discussed.