381 - Implementation of first-tier rapid genome sequencing in the PICU and CICU

Publication Number: 381.5420

Abbey A. Scott, Seattle Children's, Seattle, WA, United States; Alexandra C. Keefe, Seattle Children's, Seattle, WA, United States; Lukas Kruidenier, Seattle Children's, Seattle, WA, United States; Darci L. Sternen, Seattle Children's Hospital and PLUGS, Seattle, WA, United States; Sarah Clowes Candadai, Seattle Children's Hospital/PLUGS, Seattle, WA, United States; Shannon M. Stasi, Seattle Children’s Hospital, Seattle, WA, United States; Julia Parish-Morris, Perelman School of Medicine at the University of Pennsylvania, FORT WASHINGTON, PA, United States; Megan Sikes, Seattle Children's, Lake Forest Park, WA, United States; Margaret AAEA. Adam, University of Washington School of Medicine, Seattle, WA, United States; Anita E. Beck, University of Washington School of Medicine, Seattle, WA, United States; Jennifer C. Hayek, University of Washington School of Medicine, Seattle, WA, United States; Ian A. Glass, Univ of Washington, Seattle, WA, United States; James T. Bennett, Seattle Children's, Seattle, WA, United States; Ghayda Mirzaa, University of Washington School of Medicine, Seattle, WA, United States; Paul Kruszka, GeneDx, Alexandria, VA, United States; Kirsty McWalter, GeneDx, Gaithersburg, MD, United States; Deborah Copenheaver, GeneDx, Potomac, MD, United States; Bethany Friedman, GeneDx, Gaithersburg, MD, United States; Michael Bamshad, university of washington, seattle, WA, United States; Katrina Dipple, Seattle Children's, Seattle, WA, United States; Tara L. Wenger, Seattle Children's Hospital, Lake Tapps, WA, United States

Background: Data from over 3,500 critically ill children have demonstrated that first-tier clinical rapid genomic testing leads to improved access to a precise genetic diagnosis (PrGD), reduces medical costs, and impacts medical management for children with a suspected genetic condition. Limited data exist on hospital-wide clinical implementation of policies to transition from conventional genetic testing based on clinical suspicion to first-tier rapid exome and/or whole genome sequencing (rES/rWGS) for inpatients. Our hospital implemented a policy change in May 2022 approving first-tier rES/rWGS, allowing evaluation of implementation and impact on rates and time to PrGD.

Objective: The objective of this study was to examine the impact of the policy change allowing first-tier rES/rWGS on testing patterns and rate of PrGD in the Cardiac Intensive Care Unit (CICU) and Pediatric Intensive Care Unit (PICU) at a large quaternary children’s hospital.

Design/Methods: A retrospective chart review was performed from January 1, 2021 to September 15, 2024 for patients admitted to the CICU and PICU who received a genetics consult prior to (January 1, 2021-May 4, 2022; n=64) and following (May 5, 2022-September 15, 2024; n=211) the policy change.

Results: The overall diagnostic yield of ES/WGS (standard and rapid) was 37% (35/94) in the CICU and 32% (24/76) in the PICU. Prior to the policy change, 83% (35/42) of CICU patients and 86% (19/22) of PICU patients had genetic testing completed, but few received rES/rWGS (6% in the CICU; 16% in the PICU). A PrGD was reached in 22.8% (8/35) of CICU patients and 42% (8/19) of PICU patients, with average times to diagnosis of 23 days (CICU) and 33 days (PICU). After the policy change, there was an increase in requested genetics consults for each unit and an increase in the percentage of patients receiving rES/rWGS. In the CICU, 70% (99/141) of patients received genetic testing and 80% (79/99) received rES/rWGS. In the PICU, 93% (65/70) of patients received genetic testing, with 95% (62/65) receiving rES/rWGS. The rate of PrGD was 34% (34/99) in the CICU and 28% (18/65) in the PICU, with averages times to diagnosis of 12 days (CICU) and 16 days (PICU).

Conclusion(s): Following the policy change, there were a greater number of genetics consults in the CICU and PICU and higher percentages of patients receiving rES/rWGS as first-tier testing. This resulted in an increase in PrGD after the policy change (5 vs. 14 PrGD/year in the CICU; 6 vs. 8 PrGD/year in the PICU) and a decrease in the time to diagnosis (23 vs. 12 days in the CICU; 33 vs. 16 days in the PICU).