Authors :
Presenting Author: Yi Li, MD, PhD – Stanford University
David Loring, PhD – Emory University
Morris Cohen, EdD – Pediatric Neuropsychology International
Abigail Matthews, PhD – The Emmes Company
Angela Birnbaum, PhD – University of Minnesota
Page Pennell, MD – University of Pittsburgh
Kimford Meador, MD – Stanford University
Rationale:
Our previous study showed that fetal exposure to antiseizure medications (ASMs), especially valproate, was associated with reduced right-handedness and poorer verbal vs. non-verbal performance in children at age 6 years old (yo). This investigation enrolled a second cohort - The MONEAD (Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs) cohort, and here we examine the impact of fetal exposure to newer generation ASMs on handedness, dexterity and verbal/non-verbal abilities in children of women with epilepsy (WWE) at age 6 yo, compared to healthy controls.
Methods:
MONEAD is a prospective, multicenter, observational cohort across 20 US epilepsy centers, following pregnant women with and without epilepsy and their children until 6 yo. Handedness was assessed using the Edinburgh Handedness Inventory, manual dexterity was measured with the Grooved Pegboard (GPB) Test, and verbal/non-verbal abilities were evaluated using the Differential Ability Scales-2nd Edition to examine the relationships between fetal ASM exposure and these neurodevelopmental markers of cerebral lateralization while controlling for potential confounding factors.
Results:
A total of 1123 pregnant women were screened, and 456 were enrolled from 2012 through 2016. Among the children born to these participants, 345 children were born to WWE, while 106 children were born to healthy women (HW). Dextrality increased over ages 2-6 yo, and at age 6 was 74.8% in the ASM-exposed group and 79.3% in children of HW (Figure 1), which did not significantly differ from each other (Table 1). However, higher third-trimester ASM concentrations correlated with increased non-dextrals for levetiracetam (p=0.03) and reduced dominant hand GPB dexterity for both levetiracetam (p=0.046) and the overall WWE group (p=0.04). There were no significant differences found in overall verbal minus non-verbal performance. Regression analysis indicated that the mother's age at pregnancy and whether the pregnancy was unplanned were associated with the outcomes of the verbal minus non-verbal performance. Of note, the polytherapy subgroup consistently exhibited lower verbal and non-verbal scores at both 3 yo (p < 0.001 for verbal score; p = 0.01 for non-verbal score) and 6 yo (p = 0.01 for verbal score; p = 0.05 for non-verbal score), when compared to HW group.
Conclusions:
This study adds to the literature on possible prenatal factors which might affect brain lateralization. There was no overall difference in handedness lateralization between children of HW and WWE. The study revealed dose-dependent effects of fetal ASM exposure on manual dexterity in children born to WWE. Furthermore, polytherapy was associated with poorer verbal and non-verbal outcomes at 3 yo and 6 yo. Additionally, factors such as unplanned pregnancy significantly influenced developmental outcomes, emphasizing the importance of proactive screening and interventions for children exposed to ASMs. Future research is essential to further explore the long-term cognitive implications of ASM exposure.Funding:
NIH, NINDS and NICHD #U01-NS038455