(85) Contemporary Genetic Testing Patterns in Neonatal Seizures

Background: Emerging research has shown that genetic disease may be the underlying etiology for many neonatal seizures. Prior studies focused specifically on neonatal epilepsies have shown the superiority of exome (ES) and genome (GS) sequencing to confirm a diagnosis as well as evidence of cost-effectiveness and shorter hospital length of stay. However, these studies excluded infants with seizures attributed to other underlying etiologies. Recent research in the HIE population suggests that genetic evaluation in this group may be important and necessary. These findings raise the question of whether broader genetic testing in all infants with seizures may improve the diagnostic yield and inform long-term management.

Objectives: To provide a contemporary account of the patterns of genetic testing and associated diagnostic yield in a cohort of NICU patients with confirmed electrographic seizures.

Design/Methods: A retrospective observational cohort study was conducted in NICU patients with confirmed electrographic seizures admitted to a level IV NICU in Indianapolis, IN between January 2021 and December 2023. Patient demographics, seizure history, genetic testing, and outcomes were collected. Infants were categorized based on primary neurological abnormality(s): HIE, intracranial hemorrhage, congenital hydrocephalus, brain malformation, stroke, brain infection, metabolic, other, and none.

Results: There were 222 infants included in this study. Demographic data are outlined in Table 1. The majority of patients (127, 57%) had genetic testing with 172 tests performed. A total of 73 infants (57% of tested infants, 33% of entire cohort) had some reported finding on genetic testing and 40 of these infants (31% of those tested, 18% of entire cohort) had a diagnostic result. Patterns of genetic testing and diagnostic yield for underlying neurologic diagnosis are described in Table 2.

Conclusions: An underlying genetic diagnosis was confirmed in 18% of the cohort when only 57% of patients underwent some form of genetic testing. HIE was the most common underlying neurologic diagnosis in this NICU cohort, but only 13% underwent some form of genetic testing. However, out of those who underwent testing 27% received a diagnosis. The remaining underlying diagnoses had high diagnostic yields ranging from 42-100%. These findings suggest that genetic testing in all neonates with seizures may have greater clinical utility than previously recognized. Genetic testing in this population may provide better prognostic assessments and support more targeted therapeutic interventions.