Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization

Title

Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization

Creator

Farnaes L; Hildreth A; Sweeney NM; Clark MM; Chowdhury S; Nahas S; Cakici JA; Benson W; Kaplan RH; Kronick R; Bainbridge MN; Friedman J; Gold JJ; Ding Y; Veeraraghavan N; Dimmock D; Kingsmore SF

Publisher

NLJ Genomic Medicine

Date

2018

Subject

infant; childhood mortality; retrospective study; priority journal; cohort analysis; human; article; female; male; controlled study; clinical article; palliative therapy; cost control; hospitalization cost; infant disease/di [Diagnosis]; infant disease/dm [Disease Management]; rapid whole genome sequencing; whole genome sequencing; acutely ill patient; diagnostic test accuracy study; diagnostic value; genetic screening; mortality risk; risk reduction; sensitivity and specificity

Description

Genetic disorders are a leading cause of morbidity and mortality in infants. Rapid whole-genome sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants. We report a retrospective cohort study of acutely ill inpatient infants in a regional children's hospital from July 2016-March 2017. Forty-two families received rWGS for etiologic diagnosis of genetic disorders. Probands also received standard genetic testing as clinically indicated. Primary end-points were rate of diagnosis, clinical utility, and healthcare utilization. The latter was modelled in six infants by comparing actual utilization with matched historical controls and/or counterfactual utilization had rWGS been performed at different time points. The diagnostic sensitivity of rWGS was 43% (eighteen of 42 infants) and 10% (four of 42 infants) for standard genetic tests (P =.0005). The rate of clinical utility of rWGS (31%, thirteen of 42 infants) was significantly greater than for standard genetic tests (2%, one of 42; P =.0015). Eleven (26%) infants with diagnostic rWGS avoided morbidity, one had a 43% reduction in likelihood of mortality, and one started palliative care. In six of the eleven infants, the changes in management reduced inpatient cost by $800,000-$2,000,000. These findings replicate a prior study of the clinical utility of rWGS in acutely ill inpatient infants, and demonstrate improved outcomes and net healthcare savings. rWGS merits consideration as a first tier test in this setting.

Citation List Month

February 2019 List

Collection

Citation

Farnaes L; Hildreth A; Sweeney NM; Clark MM; Chowdhury S; Nahas S; Cakici JA; Benson W; Kaplan RH; Kronick R; Bainbridge MN; Friedman J; Gold JJ; Ding Y; Veeraraghavan N; Dimmock D; Kingsmore SF, “Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization,” Pediatric Palliative Care Library, accessed September 26, 2021, https://pedpalascnetlibrary.omeka.net/items/show/16020.

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