Abstracts

Rationale: Previously, we reported that fetal exposure to valproate impairs IQ at age 3 years (Meador et al. NEJM 2009). Here, we extend our findings by examining the effects of fetal antiepileptic drug (AED) exposure on IQ at age 4.5 years. Methods: The NEAD Study is an ongoing prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on AED monotherapy from 1999 to 2004. The purpose of the investigation is to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, or valproate). The primary outcome is IQ at age 6 years. This planned interim analysis reports on IQ at age 4.5 in 209 children as measured by the Differential Ability Scale. Results: In a multivariate analysis with age 4.5 IQ as outcome, significant effects were found for AED group (p=.04; child IQ lower with valproate exposure), maternal IQ (p<.001; child IQ higher with higher maternal IQ), maternal education (p=.007; child IQ higher with higher maternal education), maternal age (p=.004; child IQ lower in youngest mothers), gestational age (p=.02; child IQ lower with lower gestational age), race (p=.008; child IQ higher in Caucasians), and alcohol use during pregnancy (p=.007; child IQ lower with alcohol exposure). IQ was negatively associated with valproate dose (r=-.33, p=.04), but associations for the other AEDs were not significant. Maternal IQ was associated with child IQ for children exposed to carbamazepine (r=.57, p<.001), lamotrigine (r=.35, p=.003), and phenytoin (r=.56, p<.001), but not valproate. Conclusions: The differential adverse cognitive effects of fetal valproate exposure persist at this later age. Further research is needed to determine if these effects persist at older ages, and to determine effects of other AEDs.