Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016-2023.
Pediatr Crit Care Med
; 25(8): 699-709, 2024 Aug 01.
Article
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| MEDLINE
| ID: mdl-38668387
ABSTRACT
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 MAINRESULTS:
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Unidades de Cuidado Intensivo Pediátrico
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Secuenciación Completa del Genoma
Límite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
Pediatr Crit Care Med
Asunto de la revista:
PEDIATRIA
/
TERAPIA INTENSIVA
Año:
2024
Tipo del documento:
Article