Dr. Mike Bamshad: 'Our findings showcase that by shifting today’s standard of care to an exclusion-based model for genomic testing, we can significantly expand access, improve health outcomes, and ensure that more families receive the answers they need at the most critical times.'
The American Journal of Human Genetics today published peer-reviewed research from the Seqfirst-neo study conducted in partnership with GeneDX, Seattle Children’s, and the University of Washington. Seqfirst-neo is a pioneering study focused on the application of rapid genome sequencing (rGS) in NICU settings to improve to genetic diagnoses overall and, specifically, in underserved communities to reduce missed diagnoses and improve clinical outcomes for patients.
Seqfirst-neo is the first study to use exclusion, rather than inclusion, criteria for which infants should receive genomic testing in the NICU, setting a new standard of care by enabling neonatologists to more easily identify patients to receive testing, and expanding access to patients who previously would not have been offered testing.
Infants were eligible to receive rGS unless their clinical findings were fully explained by birth or physical trauma, complications of prematurity, infection, or a pre-existing precise genetic diagnosis (PrGD).
Findings from the paper, "SeqFirst: Building equity access to a precise genetic diagnosis in critically ill newborns," show that applying simple exclusion criteria significantly increased the number of infants in the NICU receiving a diagnosis, shortened the time to diagnosis, and drove more equitable access for diverse populations. The findings further prove that expanding access to genetic testing dramatically increases the rate of a PrGD, enhances healthcare equity. and reduces missed diagnoses.
“There is a critical gap in our current approach to neonatal care – 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,” said Mike Bamshad, M.D., Professor of Pediatrics at the UW School of Medicine and Clinical Genetics Division Chief at Seattle Children’s. “Our findings showcase that by shifting today’s standard of care to an exclusion-based model for genomic testing, we can significantly expand access, improve health outcomes, and ensure that more families receive the answers they need at the most critical times.”
Bamshad is also a member of the Brotman Baty Institute.
“Seqfirst-neo’s findings have had a major impact on the way we deliver genetics services in the inpatient setting,” said Tara Wenger, M.D., Ph.D., Professor of Pediatrics at the UW School of Medicine and Associate Medical Director, Inpatient Service at Seattle Children’s. “Since implementing exclusion-based identification, we are diagnosing more infants than ever before with genetic conditions in the Seattle Children’s Hospital NICU. By offering genetic testing at the first unexplained issue in critically ill newborns, we have an opportunity to make diagnoses before they are old enough to experience many of the complications of their genetic disorders. This allows neonatologists and other health care providers the opportunity to introduce the most precise treatments as early as possible.”
Seqfirst-neo’s findings suggest that at least 60 percent of Level IV NICU infants should be receiving rGS. With approximately 400,000 newborn admissions across 800 NICUs annually in the U.S., tens of thousands of infants with genetic conditions are likely being undiagnosed due to lack of access to testing.
Additional findings from the study:
- The study evaluated 408 infants in the NICU, of whom 59 percent met eligibility criteria for rGS. Of those eligible, 126 infants were enrolled in the interventional group (IG) and received rGS, while others followed current diagnostic workflow protocols.
- Nearly half (49.2%) of infants in the IG received a PrGD – an unexpectedly high yield despite broad testing criteria, compared to conventional care (9.7 percent). The odds of receiving a PrGD were nine times higher in the IG compared to conventional care.
- 42 percent of diagnosed infants would have been missed using conventional NICU protocols (69 percent of whom were non-white), highlighting the limitations of current diagnostic approaches and the correlated inequity of care.
- 24 percent of diagnosed infants were not suspected of having a genetic condition based on electronic medical records and would not have been offered testing under standard care protocols.
- By using simple, broad exclusion criteria, the diagnostic yield and access to testing were comparable across racial groups, with significantly more non-white and Black infants receiving a PrGD than through conventional care, effectively mitigating racial disparities.
- Access to a PrGD led to a change in clinical management for nearly 97 percent of diagnosed infants, influencing medical consultations, additional testing, medication adjustments, and family health implications.
“With today’s reliable and rapid genomic technology, we can now deliver answers in days,” said Paul Kruszka, M.D., Chief Medical Officer at GeneDx. “More importantly, we finally have clear, simple criteria to guide neonatologists in determining which infants should receive genomic screening in the NICU. 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. By expanding access, we can dramatically improve early detection of genetic conditions, enabling timely interventions and driving more equitable care for all infants.”
