Effects of fetal antiepileptic drug exposure
Meador KJ et al. – Adverse cognitive effects of fetal valproate exposure persist to 4.5 years and are related to performances at earlier ages. Verbal abilities may be impaired by commonly used antiepileptic drug (AED).Methods
- The NEAD Study is an ongoing prospective observational multicenter study, which enrolled pregnant women with epilepsy on AED monotherapy (1999-2004) to determine if differential long-term neurodevelopmental effects exist across 4 commonly used AEDs (carbamazepine, lamotrigine, phenytoin, or valproate).
- The primary outcome is IQ at 6 years of age.
- Planned analyses were conducted using Bayley Scales of Infant Development (BSID at age 2) and Differential Ability Scale (IQ at ages 3 and 4.5).
- Multivariate intent-to-treat (n=310) and completer (n=209) analyses of age 4.5 IQ revealed significant effects for AED group.
- IQ for children exposed to valproate was lower than each other AED.
- Adjusted means (95% confidence intervals) were carbamazepine 106 (102-109), lamotrigine 106 (102-109), phenytoin 105 (102-109), valproate 96 (91-100).
- IQ was negatively associated with valproate dose, but not other AEDs.
- Maternal IQ correlated with child IQ for children exposed to the other AEDs, but not valproate.
- Age 4.5 IQ correlated with age 2 BSID and age 3 IQ.
- Frequency of marked intellectual impairment diminished with age except for valproate (10% with IQ <70 at 4.5 years).
- Verbal abilities were impaired for all 4 AED groups compared to nonverbal skills.