Minor/Major Congenital Malformations and Neurodevelopmental Outcomes in Children Prenatally Exposed to Levetiracetam, Lamotrigine, and Carbamazepine Monotherapy.

Abstract

Objectives: The relationship of older antiseizure drugs with congenital malformations has been known for many years. Studies are mostly limited to major malformations and few studies have investigated minor malformations. In recent years, the long-term cognitive and behavioral effects of these drugs have also come to the fore. The aim of our study was to evaluate the incidence of major and minor congenital malformations and neurodevelopmental outcomes in children prenatally exposed to levetiracetam (LEV), lamotrigine (LTG), and carbamazepine (CBZ) monotherapy.

Methods: This was a prospective observational study conducted in two university hospital epilepsy centers. It included 32 pregnant women who were continuously treated with LEV, LTG, or CBZ from conception throughout pregnancy. Children were followed up from birth until 18 months. Neurodevelopmental outcomes were evaluated with the Ages and Stages Questionnaire and Denver Developmental Screening Test.

Results: Eighteen of the patients were on LEV, 10 were on LTG, and 4 were on CBZ. Diaphragmatic hernia was detected in a child. At least one minor anomaly was observed in 58.1% of the patients. More than 80% of children were normal in the Ages and Stages Questionnaire.

Conclusions: The risk of major congenital malformations is lower with newer antiseizure drugs. We found a high incidence of minor ones. However, because the population prevalence of minor malformations is also variable, more studies are needed to confirm the results. Neurodevelopmental outcomes were favorable with LTG and LEV and slightly unfavorable with CBZ. Longer-term follow-up with large groups of children is required to reach more reliable results.