379 - Genetic testing for neonatal seizures: A necessary diagnostic tool?

Publication Number: 379.4806

Kevin Heringman, Ucsd Health Care System - - San Diego, CA, San Diego, CA, United States; Jeffrey Gold, Rady Children's Hospital San Diego, San Diego, CA, United States

Background: Neonatal seizures are a devastating cause of mortality and morbidity, with an incidence of 1-5/1000 live births. 33% of infants with neonatal seizures die, and 40-60% of survivors have disability. Optimal treatment of seizures requires accurate and timely diagnosis of their cause. Neonates at our institution often receive genetic testing to look for genetic causes of seizures through the Rady Children’s Institute of Genomic Medicine.

Objective: We investigated the utilization and yield of genetic testing in a consecutive series of neonates with seizures form 2016-2022.

Design/Methods: We performed a retrospective chart review from 2016 to 2022 of all newborns admitted to the NICU at Rady Children’s Hospital with seizures. Patterns of ordering and yield of genetic testing were identified. Statistical analysis was performed with Chi-square tests. Statistical significance was determined with a p value set at < 0.05.

Results: We identified 248 neonates with seizure. 4 were excluded due to incomplete information in their charts. 101 patients (41%) had genetic testing performed in the NICU and 43 (43%) had abnormal results. 90 newborns were diagnosed with hypoxic-ischemic encephalopathy (HIE); 18 (20%) had genetic testing, and 2 (11%) were abnormal. 154 patients had a diagnosis other than HIE; 83 (54%) had genetic testing done, and 41 (49%) of these results were abnormal. Patients with lower APGAR scores (0-4) at the 1 and 5 minute were significantly less likely to have genetic testing ordered than the neonates with higher scores (5-9), chi square p< 0.05; Median APGAR at 1 and 5 minutes was significantly higher in infants who got genetic testing (3 vs 7 and 6 vs 8 P < 0.01). Infants who had an abnormal head ultrasound were less likely to get genetic testing (p < 0.05). 70 of the 90 infants with HIE survived to discharge; 3 who did not receive genetic testing in the NICU subsequently had genetic testing as outpatients. 2 out of the 3 had abnormal results.

Conclusion(s): Genetic testing has a high yield in neonates with seizures, with abnormal results 41% of the time. At our institution, physicians appear to decline genetic testing in neonates with low APGAR scores, likely because HIE is considered a contraindication for genetic testing. Our findings indicate this likely leads to missed genetic diagnoses, as we found abnormal genetic results in 11% of neonates diagnosed with HIE who obtained genetic testing in the NICU, and 2 of 3 patients diagnosed with HIE who had genetic testing after NICU discharge. Broader testing in the neonatal intensive care is likely to find more infants with genetic causes of seizures.