Rapid Genome Sequencing Compared with a Gene Panel in Critically Ill Infants with a Suspected Genetic Disorder: An Economic Evaluation

Date: October 31, 2025
Journal: The Journal of Pediatrics
Citation: Lavelle TA, Maron JL, Kingsmore SF, Lin CH, Zhu Y, Sweigart B, Reed D, Gelb BD, Vockley J, Davis JM. Rapid Genome Sequencing Compared with a Gene Panel in Critically Ill Infants with a Suspected Genetic Disorder: An Economic Evaluation. J Pediatr. 2025 Oct 31:114889. doi: 10.1016/j.jpeds.2025.114889. Epub ahead of print. PMID: 41177396.

Abstract

Objective: To compare 1-year healthcare costs and quality-adjusted life years (QALYs) for two diagnostic strategies in critically ill infants with suspected genetic disorders: 1) early rapid genome sequencing (within 7 days of admission) for all infants, and 2) early targeted neonatal gene sequencing (NewbornDx) for all infants, followed by later rGS (after 7 days) for undiagnosed infants.

Study design: The Genomic Medicine for Ill Neonates and Infants (GEMINI) study was a multicenter, prospective study that enrolled 400 hospitalized infants under one year of age with suspected genetic disorders. All participants underwent both rGS and NewbornDx. Using patient-level GEMINI data and 2023 Medicare rates, we developed a decision tree to compare total costs and QALYs over a 1-year period for these two hypothetical testing strategies.

Results: The diagnostic yield and upfront testing costs were higher for rGS (49%; $12,297) than NewbornDx (27%; $2,449; p<0.05). As neither early testing nor diagnosis significantly affected QALYs, we conducted a cost-minimization analysis, focusing solely on cost differences between strategies. Over one year, early rGS was estimated to save $158,592 per patient (95% CI: $63,701-$253,292) compared with early NewbornDx with later rGS if necessary.

Conclusions: Early rGS results in substantial healthcare cost savings, highlighting the need to expand reimbursement to improve access early in a hospitalization for critically ill infants.

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