Diagnosis Through Whole Genome Sequencing and Care Utilization in Children With Severe Illness

Importance: Whole genome sequencing (WGS) is increasingly used to diagnose children with severe illness, yet the long-term association of a genetic diagnosis with health care utilization and resource allocation remains poorly understood. Objective: To assess the association of a genetic diagnosis through WGS with long-term health care utilization metrics in children and young people (hereafter children) with severe illness. Design, Setting, and Participants: This multicenter retrospective cohort study of children aged 0 to 18 years who were severely ill who underwent WGS used data from The Next Generation of Children Project (from December 2016 to August 2020) with medical record linkage and analysis of primary care medical records conducted between January 2022 and June 2024. The primary care and hospital medical records were linked using the UK National Institute for Health and Care Research Rare Disease BioResource, Cambridge. Exposures: Receipt of a genetic diagnosis compared with those who remained undiagnosed following WGS. Main Outcomes and Measures: The main outcome was a comparison of 36 health care utilization parameters, including hospitalizations, primary care prescriptions, and diagnostic tests. Results: Among the 270 children analyzed (mean [SD] age 8.65 [6.58-9.46] years; 149 males [55.2%]), those receiving a genetic diagnosis (87 [32.2%]) exhibited significantly higher overall health care utilization compared with undiagnosed peers (183 [67.8%]). This included an increase in median (IQR) hospital admissions (37 [18-66] vs 22 [10-35]) and more primary and secondary care outpatient visits each year (14 [7-26] vs 8 [4-13]), particularly for neurodevelopmental (annual treatment costs: £1280 [£507-£2529] vs £130 [£21-£354]) and seizure-related (annual treatment costs: £1277 [£320-£2271] vs £60 [£15-£143]) conditions. Children with genetic diagnoses received a median (IQR) higher volume of neurological (48 [22-88] vs 0) and gastrointestinal (5 [1-18] vs 0 [0-2])prescriptions. Median (IQR) differences specifically in neurodevelopmental (neurological prescriptions: 42 [22-64] vs 0 [0-3]) and pediatric intensive care unit (total cost prescriptions: £1045 [£244-£1914] vs £38 [£14-£220]) settings were observed. While a genetic diagnosis was associated with sustained and intensive health care utilization during the study period, it was also associated with a shift toward targeted, condition-specific medical care. Conclusions and Relevance: In this cohort study, a WGS diagnosis was associated with the integration of specialist care and the alignment of health care resources to support specific needs of children with complex disorders. These findings suggest that while longitudinal health care utilization remains intensive following a genetic diagnosis, identifying these conditions is important for accurately mapping and managing the downstream clinical resource requirements of this population.