581 - Expanding the Role of Genetic Testing in Neonatal Seizures: Insights from a Contemporary Cohort

Publication Number: 3562.581

Anna C. Cole, Indiana University School of Medicine, Indianapolis, IN, United States; Beatrice Stefanescu, Indiana University School of Medicine, Indianapolis, IN, United States; Kristen Suhrie, Indiana University School of Medicine and Riley Children's Health, Indianapolis, IN, United States; Hannah Bolte, Indiana University School of Medicine, Bloomington, IN, United States

Background: Emerging research has shown that genetic disease may underlie a substantial proportion of neonatal seizures. Prior studies in neonatal epilepsies demonstrate that whole exome sequencing (WES) and whole genome sequencing (WGS) improve diagnostic yield, reduce hospital stay, and are cost-effective; however, these studies largely excluded infants with other neurologic co-morbid conditions. Recent data in infants with hypoxic-ischemic encephalopathy (HIE) suggests that genetic evaluation may also be valuable in this group, raising the question of whether broader genetic testing in all neonates with seizures could further inform diagnosis and management.

Objective: The primary objective of this study was to provide a contemporary overview of the use and diagnostic yield of genetic testing in a cohort of infants with confirmed electrographic seizures and their associated NICU outcomes.

Design/Methods: A retrospective observational cohort study was conducted in neonates with confirmed electrographic seizures admitted to a level IV neonatal intensive care unit (NICU) in Indianapolis, IN between January 2021 and December 2023. Patient genetic testing/diagnostic yield, co-morbid conditions, and outcomes were analyzed.

Results: In total, 222 infants met inclusion criteria; 125 (56%) underwent genetic testing, 49 (39%) received a diagnostic result, representing 22% of the total cohort. Diagnostic yield varied by neurologic co-morbidities (Table 1), ranging from 10-100%. Mortality was highest in patients with a genetic diagnosis following testing; 38% vs 17% (p=0.006). Infants who received a genetic diagnosis were 4.2 times more likely to be discharged on anticonvulsive medications. No difference in length of stay was noted. WGS was the most common test used (Figure 1). The median turnaround time for genetic testing was 8 days. Of the 49 genetic diagnoses confirmed in the cohort, 29 (59%) were diagnosed with WES/WGS.

Conclusion(s): Genetic diagnoses were confirmed in 22% of infants overall when only 56% underwent any genetic testing. Yields were notable in all patient groups. These findings suggest that broader genetic testing in neonates with seizures may provide significant clinical utility, improve prognostic accuracy, and support more targeted therapeutic interventions.

Table 1.
Genetic testing rates and diagnostic outcomes in neonates with seizures, stratified by neurologic co-morbid conditions.

Figure 1.
Frequency of genetic test type utilized (n, %) out of total 172 tests sent on the 127 patients with genetic testing performed.