Krantz ID, Medne L, Weatherly JM, et al. - Whole-genome sequencing (WGS) introduction led to a significant increase in focused clinical management, relative to usual care, among acutely ill infants in an intensive care unit. Findings lend support to WGS implementation for acutely ill infants with a suspected genetic condition.

• This randomized time-delayed clinical trial included a diverse population of 354 infants who were randomized to receive WGS either 15 days (early) or 60 days (delayed) post-enrollment.

• Change of management (COM) and a molecular diagnosis, at 60 days, were received by twice as many infants in the early group vs the delayed group [COM: 34 of 161 vs 17 of 165; odds ratio, 2.3; molecular diagnosis: 55 of 176 vs 27 of 178].

• A doubling of COM (to 45 of 161) and diagnostic efficacy (to 56 of 178) was evident in the delayed group, at 90 days.

• There were no differences in length of stay or survival.

• Access to first-line WGS may allow diagnostic equity, which could attenuate health care disparities.