(63) Utilization and Outcomes of Genetic Testing in Neonates Admitted to the CTICU

Background: Due to improvements in genetic testing, particularly next-generation sequencing (NGS), genetic discoveries have increased over the past decade. Genetic disorders contribute significantly to morbidity and mortality in ICUs. A genetic diagnosis early in life has been shown to alter clinical management, reducing morbidity and mortality. While there is considerable research on genetic testing in NICUs, where rapid genome sequencing (rGS) is an emerging standard of care, less is known about genetic testing for neonates in other ICUs, like CTICUs, where most neonates with congenital heart defects (CHDs) are cared for.

Objectives: Characterize how testing and diagnoses have changed since the implementation of rapid genome sequencing and evaluate how lack of inpatient testing beyond CTICU protocol leads to delayed outpatient testing and diagnosis.

Design/Methods: Retrospective cohort study of neonates admitted to Nationwide Children's Hospital (NCH) CTICU from January 1 2015 to June 30 2024 followed through December 31 2024. Interrupted time series analysis was used to evaluate testing/diagnostic rates before/after rGS implementation in the NCH CTICU. A multi-state model was used to demonstrate clinical course from CTICU admission to genetic diagnosis, stratified by presence of extra cardiac anomalies (ECA).

Results: After rGS implementation in the NCH CTICU (3/3/2020), inpatient genetic testing increased. Genetic diagnosis rates increased by 9.3% (p = 0.001). Most of the increase was during index hospitalization (8.1% increase). If cytogenetic testing was non-diagnostic in the CTICU and no further testing was done before discharge, there was an average 249 day wait for further testing after discharge. Patients with and without ECA were equally likely to receive cytogenetic testing (p = 0.96), but patients with ECA were 2.1x more likely to receive NGS after admission and were 2.7x more likely to receive panel/sequencing testing after cytogenetics. Additionally, patients with ECA had 2.5x the rate (P < 0.001) of receiving a diagnosis from cytogenetic tests, and 1.4x the rate (P=0.26) of receiving a diagnosis from a panel/sequencing test.

Conclusions: Following rGS implementation, inpatient genetic testing and diagnostic yield increased in a single large CTICU. Patients with ECA were tested earlier and had higher diagnostic rates, particularly through NGS. Most patients receiving only cytogenetic tests remained undiagnosed in the first year. Early rGS use improves diagnostic outcomes and should be the first line genetic test for the CTICU.