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Published on: August 25, 2014
Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning at age 6years
Morris J Cohen1, Kimford J Meador, Nancy Browning
1Neurology, Georgia Regents University, Augusta, GA, USA.
Insights
Fetal exposure to valproate antiepileptic drugs (AEDs) in pregnant women with epilepsy may lead to lower adaptive functioning and increased ADHD risk in children at age six. Lamotrigine and phenytoin showed fewer adverse neurodevelopmental effects.
Area of Science:
- Neurodevelopmental toxicology
- Pediatric neurology
- Pharmacology
Background:
- Epilepsy affects pregnant women, necessitating antiepileptic drug (AED) treatment.
- Concerns exist regarding potential neurodevelopmental effects of AEDs on fetuses.
- The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study investigated these risks.
Purpose of the Study:
- To assess long-term neurodevelopmental effects of four common AEDs (carbamazepine, lamotrigine, phenytoin, valproate) on children exposed in utero.
- To compare adaptive and emotional/behavioral functioning at age six across different AED exposure groups.
Main Methods:
- Prospective observational multicenter study (USA and UK, 1999-2004).
- Enrolled pregnant women with epilepsy on AED monotherapy.
- Assessed 195 children at age six using parent/teacher rating scales (ABAS-II, BASC).
Main Results:
- Overall adaptive and emotional/behavioral functioning scores were in the low average to average range.
- Children exposed to valproate showed significantly lower General Adaptive Composite scores compared to lamotrigine and phenytoin groups.
- Valproate and phenytoin exposure showed a dose-related decline in adaptive functioning.
- Valproate exposure was associated with increased atypical behaviors, inattention, and higher risk for ADHD diagnosis.
Conclusions:
- Fetal valproate exposure is linked to poorer adaptive functioning and increased ADHD risk in children.
- Lamotrigine and phenytoin appear to have a comparatively better neurodevelopmental profile in this cohort.
- Women with epilepsy requiring AEDs should be informed about valproate's potential risks; further research is warranted.
Abstract:
The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study is a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on adaptive and emotional/behavioral functioning at 6years of age in 195 children (including three sets of twins) whose parent (in most cases, the mother) completed at least one of the rating scales. Adjusted mean scores for the four AED groups were in the low average to average range for parent ratings of adaptive functioning on the Adaptive Behavior Assessment System-Second Edition (ABAS-II) and for parent and teacher ratings of emotional/behavioral functioning on the Behavior Assessment System for Children (BASC). However, children whose mothers took valproate during pregnancy had significantly lower General Adaptive Composite scores than the lamotrigine and phenytoin groups. Further, a significant dose-related performance decline in parental ratings of adaptive functioning was seen for both valproate and phenytoin. Children whose mothers took valproate were also rated by their parents as exhibiting significantly more atypical behaviors and inattention than those in the lamotrigine and phenytoin groups. Based upon BASC parent and teacher ratings of attention span and hyperactivity, children of mothers who took valproate during their pregnancy were at a significantly greater risk for a diagnosis of ADHD. The increased likelihood of difficulty with adaptive functioning and ADHD with fetal valproate exposure should be communicated to women with epilepsy who require antiepileptic medication. Finally, additional research is needed to confirm these findings in larger prospective study samples, examine potential risks associated with other AEDs, better define the risks to the neonate that are associated with AEDs for treatment of seizures, and understand the underlying mechanisms of adverse AED effects on the immature brain.
