Verbal Abilities at Age 6-years-old of Children of Women with vs. Without Epilepsy in the MONEAD Study
Kimford Meador1, Morris Cohen2, David Loring3, Carrie Brown4, Chelsea Robalino4, Andrea Carmack4, Abigail Matthews5, Page Pennell6
1Department of Neurology & Neurological Sciences, Stanford University School of Medicine, 2Pediatric Neuropsychology International, 3Emory Univ, Dept of Neurology, 4Emmes, 5The Emmes Company, LLC, 6University of Pittsburgh School of Medicine
Objective:
To compare age 6-years-old neurodevelopmental outcomes of children of women with epilepsy (WWE) vs. healthy women (HW).
Background:
Antiseizure medications (ASMs) are all potential teratogens which might impair neurodevelopmental outcomes.
Design/Methods:
The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multi-center investigation. WWE and HW were enrolled during pregnancy. The a priori primary neurodevelopmental outcome for children is age 6 Verbal Index score calculated by averaging Differential Ability Scales-II Word Definitions and Verbal Similarities subtests, Expressive One-Word Picture Vocabulary Test-4, Peabody Picture Vocabulary Test-4, and NeuroPSYchological Assessment-2 Phonological Processing, Comprehension of Instructions, and Sentence Repetition subtests. We compared the outcomes in children of WWE vs. HW using linear regression adjusting for potential confounders chosen via a stepwise selection algorithm. Missing age 6 outcomes were imputed from available age 3 data using multiple imputation.
Results:
Analyses included 298 children of WWE and 89 of HW. No difference on the primary outcome was present for children of WWE vs. HW (parameter estimate (95% CI)= -0.5 (-3.1,2.1), p=0.71)). Significant factors in the final model included mother's IQ (0.3 (0.2,0.4), p<.001), mother's education level (reference: college degree (advanced), no college degree (-5.9 (-9.4,-2.3), p=0.001), college degree (not advanced) (-3.0 (-5.6,-0.3) p=0.027)), mother's age at enrollment (0.3 (0.1,0.5), p=0.008), child's small for gestational age status: yes vs. no (-8.5 (-13.5,-3.5), p<.001), and child's sex: male vs. female (-2.9 (-5.0,-0.7), p=0.009). In children of WWE, 78% had mothers on lamotrigine or levetiracetam alone or in combination with another ASM(s) in 3rd-trimester.
Conclusions:
Verbal abilities of children of WWE vs. HW did not differ at age 6-years-old. These findings are largely limited to lamotrigine and levetiracetam exposures in the children of WWE group. Additional research is needed to address the large number of ASMs with inadequate information on risks of fetal exposure.