Retrospective Application of Genome-Based Newborn Screening Platforms Identifies Diagnoses in Critically Ill Children

Purpose To evaluate the proportion of children in intensive care units (ICU) that were diagnosed with genetic diseases that could have been identified by population newborn screening by genome sequencing (gNBS) at birth. Methods A multi-site retrospective observational cohort study of patients admitted to the neonatal, pediatric, or cardiac ICU at two tertiary children's hospitals between July 2017 and March 2025 and received rapid diagnostic genomic sequencing (RDGS) during ICU admission. RDGS results were translated to gNBS results for 778 genes included in three gNBS research platforms. Results Of 1,044 infants and children who received RDGS, 29% had reportable likely pathogenic/pathogenic results Eleven percent of those who received RDGS would have screened positive by gNBS, representing 39% of patients with a reported diagnostic finding. Eighty-seven percent of patients with likely pathogenic or pathogenic results, who would have screened positive by gNBS, had a documented change in their subsequent clinical management as a result of RDGS. Conclusions These findings suggest that population gNBS could have substantial impact on children who would subsequently be admitted to the NICU, PICU, or CVICU. Where admission or RDGS was delayed, population gNBS has potential to accelerate diagnosis and therapeutic intervention and possibly to prevent serious illness or ICU admission.