• Katherine M Rodriguez, Jordan Vaught, Lisa Salz, Jennifer Foley, Zaineb Boulil, Heather M Van Dongen-Trimmer, Drewann Whalen, Okonkwo Oluchukwu, Kuang Chuen Liu, Jennifer Burton, Prachi Syngal, Ofelia Vargas-Shiraishi, Stephen F Kingsmore, Erica Sanford Kobayashi, and Nicole G Coufal.
• Rady Children's Hospital, San Diego, CA.
• Pediatr Crit Care Me. 2024 Aug 1; 25 (8): 699709699-709.

ObjectivesAnalysis of the clinical utility of rapid whole-genome sequencing (rWGS) outside of the neonatal period is lacking. We describe the use of rWGS in PICU and cardiovascular ICU (CICU) patients across four institutions.DesignAmbidirectional multisite cohort study.SettingFour tertiary children's hospitals.PatientsChildren 0-18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023.InterventionsNone.Measurements And Main ResultsA total of 133 patients underwent clinical, phenotype-driven rWGS analysis, 36 prospectively. A molecular diagnosis was identified in 79 patients (59%). Median (interquartile range [IQR]) age was 6 months (IQR 1.2 mo-4.6 yr). Median time for return of preliminary results was 3 days (IQR 2-4). In 79 patients with a molecular diagnosis, there was a change in ICU management in 19 patients (24%); and some change in clinical management in 63 patients (80%). Nondiagnosis changed management in 5 of 54 patients (9%). The clinical specialty ordering rWGS did not affect diagnostic rate. Factors associated with greater odds ratio (OR [95% CI]; OR [95% CI]) of diagnosis included dysmorphic features (OR 10.9 [95% CI, 1.8-105]) and congenital heart disease (OR 4.2 [95% CI, 1.3-16.8]). Variables associated with greater odds of changes in management included obtaining a genetic diagnosis (OR 16.6 [95% CI, 5.5-62]) and a shorter time to genetic result (OR 0.8 [95% CI, 0.76-0.9]). Surveys of pediatric intensivists indicated that rWGS-enhanced clinical prognostication ( p < 0.0001) and contributed to a decision to consult palliative care ( p < 0.02).ConclusionsIn this 2016-2023 multiple-PICU/CICU cohort, we have shown that timely genetic diagnosis is feasible across institutions. Application of rWGS had a 59% (95% CI, 51-67%) rate of diagnostic yield and was associated with changes in critical care management and long-term patient management.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

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