A groundbreaking study published in the American Journal of Human Genetics has revealed significant gaps in current neonatal intensive care unit (NICU) genetic testing protocols, demonstrating that at least 60% of Level IV NICU infants should receive rapid genome sequencing (rGS) for optimal care.
The Seqfirst-neo study, conducted through a partnership between GeneDx, Seattle Children's, and the University of Washington, introduces a novel approach to genetic testing by using exclusion rather than inclusion criteria. This methodology represents a significant shift in identifying candidates for genomic testing in NICU settings.
Study Findings Reveal High Diagnostic Yield
The research evaluated 408 NICU infants, with 59% meeting eligibility criteria for rGS. Among the 126 infants who received testing in the interventional group, 49.2% received a precise genetic diagnosis (PrGD) - a rate significantly higher than the 9.7% achieved through conventional care protocols.
"There is a critical gap in our current approach to neonatal care," explains Dr. Mike Bamshad, Professor of Pediatrics at the University of Washington School of Medicine. "Too many critically ill infants and newborns, particularly from underrepresented populations, are not being offered genetic testing, leading to missed diagnoses and opportunities for precision care."
Addressing Healthcare Disparities
The study uncovered concerning disparities in current testing protocols:
- 42% of diagnosed infants would have been missed using conventional protocols
- 69% of missed diagnoses were in non-white patients
- 24% of diagnosed cases showed no initial suspicion of genetic conditions
The new exclusion-based approach demonstrated comparable diagnostic yields across racial groups, effectively reducing racial disparities in genetic diagnosis rates.
Clinical Impact and Implementation
Dr. Tara Wenger, Professor of Pediatrics at the University of Washington School of Medicine, highlighted the practical impact: "Since implementing exclusion-based identification, we are diagnosing more infants than ever before with genetic conditions in the Seattle Children's Hospital NICU."
The study showed that access to precise genetic diagnoses led to clinical management changes in nearly 97% of diagnosed infants, affecting:
- Medical consultations
- Additional testing protocols
- Medication adjustments
- Family health management
Nationwide Implications
With approximately 400,000 newborn NICU admissions annually across 800 U.S. facilities, the current testing gap suggests thousands of infants with genetic conditions may be going undiagnosed. The study's findings indicate that expanding access to rGS could dramatically improve early detection and enable more timely interventions.
Dr. Paul Kruszka, Chief Medical Officer at GeneDx, emphasizes the urgency: "With today's reliable and rapid genomic technology, we can now deliver answers in days. There is an urgent need to make rapid genome sequencing a standard part of NICU care to prevent missed diagnoses and ensure every infant gets the critical care they deserve."
Moving Forward
GeneDx has already begun implementing solutions to address these findings, including the introduction of ultraRapid Whole Genome Sequencing, which can deliver results in as little as 48 hours. The company has also integrated with Epic Aura to streamline the testing process within health systems.
The success of the Seqfirst-neo study has established a new benchmark for NICU care, demonstrating that broader implementation of genetic testing can lead to more equitable healthcare delivery and improved outcomes for critically ill infants.
