부산대학교 도서관

OBJECTIVES:: Analysis 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. DESIGN:: Ambidirectional multisite cohort study. SETTING:: Four tertiary children’s hospitals. PATIENTS:: Children 0–18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: A 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). CONCLUSIONS:: In 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.