“Rapid Whole Genome Sequencing Decreases Morbidity and Healthcare Cost of Hospitalized Infants”, Lauge Farnaes, Amber Hildreth, Nathaly M. Sweeney, Michelle M. Clark, Shimul Chowdhury, Shareef Nahas, Julie A. Cakici, Wendy Benson, Robert H. Kaplan, Richard Kronick, Matthew N. Bainbridge, Jennifer Friedman, Jeffrey J. Gold, Yan Ding, Narayanan Veeraraghavan, David Dimmock, Stephen F. Kingsmore, on behalf of the RCIGM Investigators2018-01-26 (; similar)⁠:

Background: 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.

Method: Retrospective cohort study of acutely ill inpatient infants in a regional children’s hospital from July 2016–March 2017. 42 families received rWGS for etiologic diagnosis of genetic disorders. Probands received standard genetic testing as clinically indicated. Primary end-points were rate of diagnosis, clinical utility, and healthcare usage. The latter was modelled in six infants by comparing actual usage with matched historical controls and/or counterfactual usage had rWGS been performed at different time points.

Results: The diagnostic sensitivity was 43% (18⁄42 infants) for rWGS and 10% (4⁄42 infants) for standard of care (p = 0.0005). The rate of clinical utility for rWGS (31%, 13⁄42 infants) was statistically-significantly greater than for standard of care (2%, one of 42; p = 0.0015). 11 (26%) infants with diagnostic rWGS avoided morbidity, one had 43% reduction in likelihood of mortality, and one started palliative care. In 6 of the 11 infants, the changes in management reduced inpatient cost by $800,000 to $2,000,000.

Discussion: 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.