Advancing NICU Diagnosis: Genome Sequencing Delivers Clinical and Economic Benefits

Among the most important benefits of genomic sequencing technologies is their potential to speed the diagnosis of critically ill infants suspected to have a genetic disorder. Because many genetic diseases present with non-specific symptoms in early life, establishing a diagnosis is challenging and often relies on stepwise testing of specific genes.

Studies such as the Genomic Medicine in Ill Infants and Newborns (GEMINI) Study, co-led by Tufts CTSI Associate Director Jonathan Davis, MD, show that clinical genomics can have high diagnostic utility in the NICU. Although these findings are helping make whole genome sequencing (WGS) a first-line diagnostic tool in advanced centers, further evidence is needed to guide its broader adoption and optimal use.

 

Addressing this translational challenge remains a priority for Dr. Davis, the Vice Chair of Pediatrics at Tufts Medical Center, and his collaborators. A recent study he co-led with Tara Lavelle, PhD, Assistant Professor of Medicine at Tufts University School of Medicine, adds an economic evaluation to GEMINI’s clinical findings. GEMINI was the first study to address key uncertainties in neonatal genomic evaluation by comparing a WGS strategy, which identifies variants in all 20,000 genes, with a targeted neonatal gene-sequencing panel.

 

Supported by a CTSA Collaborative Innovation Award from NCATS—and Tufts CTSI biostatistical, clinical-study, and informatics services—GEMINI enrolled more than 400 newborns and infants with undiagnosed conditions at six CTSA-affiliated NICUs. The study found that WGS had a diagnostic yield nearly twice that of the targeted panel (49% vs 27%), though with a slightly longer median time to return of results (6.1 vs. 4.2 days).

 

The more recent analysis used patient-level data on diagnostic yield and healthcare utilization from the GEMINI Study to model one-year healthcare costs for each strategy. Although WGS had a higher upfront cost than the targeted panel ($12,297 vs. $2,449), it was found to reduce overall costs by $150,000 per patient, as the targeted approach often required additional testing when no diagnosis was initially identified and led to longer hospital stays.