Fetal Exposure-Dependent Effects at Age 4.5 Years-Old in Children of Mothers with Epilepsy in the MONEAD Study
Abstract number :
2.191
Submission category :
4. Clinical Epilepsy / 4E. Women's Issues
Year :
2023
Submission ID :
536
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Kimford Meador, MD – Stanford University
Morris Cohen, EdD – Pediatric Neuropsychology International; David Loring, PhD – Emory University; Abigail Matthews, PhD – Emmes Company; Carrie Brown, MS – Emmes Company; Chelsea Robalino, MStat – Emmes Company; Laura Kalayjian, MD – University of Southern California; Elizabeth Gerard, MD – Northwestern University; Evan Gedzelman, MD – Emory University; Julie Hanna, MD – Minnesota Epilepsy Group; Jennifer Cavitt, MD – University of Cincinnati; Maria Sam, MD – Wake Forest University; Sean Hwang, MD – Northwell Heath; Alison Pack, MD – Columbia University; Jeffrey Tsai, MD – University of Washington; Page Pennell, MD – University of Pittsburgh
Rationale: Adverse neurodevelopmental effects can occur from fetal exposure to antiseizure medications (ASMs). All ASMs are potential teratogens and they act in an exposure-dependent manner. Here, we examine these effects of fetal ASMs for two measures at age 4.5 years old (yo) in children of women with epilepsy (WWE) in our ongoing Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.
Methods: The MONEAD study is a prospective, observational, multi-center investigation of pregnancy outcomes. WWE were enrolled during pregnancy. For this report, children were assessed at age 4.5yo using the General Adaptive Composite (GAC) score from the Adaptive Behavior Assessment System, Third Edition (ABAS-3) which is a nationally standardized rating scale of adaptive functioning, and the Global Executive Composite (GEC) score from the Behavior Rating Inventory of Executive Function Preschool (BRIEF-P) which is a measure of executive function. Both measures are completed by each child’s mother. Adjusted linear regression models were run to assess the associations between maximum third trimester ratio ASM concentrations and 4.5yo ABAS-3 GAC and BRIEF-P GEC scores by ASM overall and for individual ASMs with adequate sample sizes.
Results: There were 229 children of WWE on ASM with third trimester concentrations who were rated at age 4.5yo using the ABAS-3 and 230 rated using the BRIEF-P. Combining all ASMs, higher 3rd-trimester ASM concentrations were associated with lower ABAS-3 GAC scores in adjusted analyses (parameter estimate (95% CI)= -9.5 (-14.3, -4.6), p< 0.001). This effect was most evident for levetiracetam (-18.9 [-26.8, -10.9], p< 0.001) and to a much lesser degree for lamotrigine (-12.0 [-23.7, -0.3], p=0.044) (Figure 1). Higher 3rd-trimester ASM concentrations were also associated with worse (i.e., higher) BRIEF-P GEC scores across all ASMs (7.0 (2.9, 11.2), p=0.001, and separately for levetiracetam (12.9 (4.2, 21.6, p=0.004) (Figure 2). Note that the WWE cohort at enrollment was primarily on monotherapy (73%) with 79% of monotherapies on lamotrigine or levetiracetam, and 42% of polytherapies were on dual therapy with those two ASMs.
Clinical Epilepsy