Abstracts

Rationale: Typical left cerebral dominance for language and handedness can be altered by environmental factors during early neurodevelopment. In our prior NEAD investigation of neurodevelopmental effects of fetal antiseizure medication (ASM) exposure, we found children of women with epilepsy (WWE) taking ASMs had reduced right-handedness (86%) vs a normative sample of children (93%) from the Wechsler Intelligence Scale for Children (WISC-IV) and non-verbal minus verbal indices (mean difference= 1.93 (95% CI = 0.35 to 3.51) which is 0 for a normative sample. Here, we examine handedness and verbal vs non-verbal indices in our new Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) cohort at age 3 years.

Methods: The MONEAD study is a prospective, observational, multi-center investigation of pregnancy outcomes. Women with epilepsy (WWE) and healthy women (HW) were enrolled during pregnancy. Children were assessed at age 3 years old using the Differential Ability Scales-II (DAS-II) which yields both verbal and non-verbal cluster scores; in standard score format (X=100;sd=15). Handedness of children and mothers was assessed using the Edinburgh Handedness Inventory (EHI). Analyses were conducted comparing proportion of handedness and non-verbal minus verbal Index scores across children of WWE vs HW. Analyses of EHI in children were conducted on 4 items due to missing values on other items due to the children’s age; sensitivity analyses considered all items.

Results: Most pregnant WWE enrolled in the study were on monotherapy (76%), and 78% of monotherapies were lamotrigine or levetiracetam. Also, 41% of the polytherapies were on dual therapy with LTG+LEV. Right handedness did not differ between children of WWE (50%) vs those of HW (49%) (p= 0.805); see Figure 1. The mothers did not differ in right handedness (WWE = 88%; HW = 89%), which is similar to the general population (approx. 90%). The adjusted differences between non-verbal minus verbal indices did not differ between children of WWE (mean difference = 6.4 (95% CI 4.4, 8.3)) vs children of HW (mean difference = 6.1 (95% CI 2.3, 9.9)).

Conclusions: Our findings at 3yo in MONEAD show no differences in cerebral lateralization in children with fetal ASM exposure vs healthy controls as evidenced by handedness and non-verbal minus verbal abilities. In NEAD, we had no control group so we used WISC-IV norms. In MONEAD at age 3yo, both children of PWWE and HW demonstrate an asymmetry. Non-verbal/verbal asymmetries were seen at ages 3, 4.5 and 6yo in NEAD, although they were less at 6yo. The largest asymmetries were seen for valproate in NEAD, but lamotrigine showed asymmetries in NEAD at both 3yo (mean difference=9.7 (5.2,14.2)) and 6yo (2.8 (0.31, 5.33)). Although the direction of handedness is apparent early in life, it increases over ages 3 to 7yo. Thus, the differences in handedness results may be due to differences in assessment age. Planned future assessments in MONEAD will provide data in this regard.

Funding: Please list any funding that was received in support of this abstract.: NIH, NINDS and NICHD #U01-NS038455.