The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants

TLDR

Genetic disorders are a leading cause of morbidity and mortality in NICU/PICU infants, yet genomic sequencing results are often delayed and fail to guide inpatient management. The study tested whether rapid whole‑genome sequencing increases the proportion of NICU/PICU infants receiving a genetic diagnosis within 28 days. Families of infants under 4 months with unexplained illness in a regional NICU/PICU were randomized to trio rapid whole‑genome sequencing plus standard genetic testing between October 2014 and June 2016, with follow‑up until November 2016.

Abstract

Genetic disorders are a leading cause of morbidity and mortality in infants in neonatal and pediatric intensive care units (NICU/PICU). While genomic sequencing is useful for genetic disease diagnosis, results are usually reported too late to guide inpatient management. We performed an investigator-initiated, partially blinded, pragmatic, randomized, controlled trial to test the hypothesis that rapid whole-genome sequencing (rWGS) increased the proportion of NICU/PICU infants receiving a genetic diagnosis within 28 days. The participants were families with infants aged <4 months in a regional NICU and PICU, with illnesses of unknown etiology. The intervention was trio rWGS. Enrollment from October 2014 to June 2016, and follow-up until November 2016. Of all, 26 female infants, 37 male infants, and 2 infants of undetermined sex were randomized to receive rWGS plus standard genetic tests (