86 - “SeqFirst-neo”: Improving access equity for a precise genomic diagnosis for critically ill neonates

Poster Number: 86
Publication Number: 86.438

Tara L. Wenger, University of Washington Division of Genetic Medicine, Seattle, WA, United States; Megan Sikes, Seattle Children's, Seattle, WA, United States; Abbey Scott, Seattle Children's, Seattle, WA, United States; Katrina M. Dipple, Seattle Children's, Seattle, WA, United States; Chayna J. Davis, University of Washington School of Medicine, Seattle, WA, United States; Kati J. Buckingham, University of Washington, Seattle, WA, United States; Jessica Chong, University of Washington School of Medicine, Seattle, WA, United States; Deborah Copenheaver, GeneDx, Inc, Potomac, MD, United States; Jane Juusola, GeneDx, Gaithersburg, MD, United States; Kyle Retterer, GeneDx, Gaithersburg, MD, United States; Kirsty McWalter, GeneDx, Inc, Gaithersburg, MD, United States; Paul S. Kruszka, GeneDx, Gaithersburg, MD, United States; Michael Bamshad, university of washington, seattle, WA, United States

Background:  Care for infants with rare diseases is often empirical, imprecise, and modestly effective - leaving substantial room for improvement and innovation. The “promise” of more precise, and by inference, better care, begins with an accurate genetic diagnosis. Yet, many if not most children with a rare disease are not offered, much less, receive genetic testing. Access to genetic testing typically depends on provider assessment of a need for genetics consultation, with subsequent testing taking place in a stepwise pattern. SeqFirst-neo is a project to develop and test approaches toward centering equity for a precise genetic diagnosis at initial point of care for infants hospitalized with a critical illness by simplifying clinical workflows and supporting provider readiness.

Objective: To improve access equity to genomic testing in the NICU by offering rapid whole genome sequencing (WGS) to all infants whose admissions were not fully explained by prematurity, trauma or infection.

Design/Methods: From January – December 2021, the EMR was reviewed daily by a clinical geneticist to ascertain eligible patients. A broad but simple algorithm was used to identify infants whose clinical findings were not fully explained by prematurity, trauma, or infection. Verbal results were communicated within seven days with final results within two weeks. Clinical genetics services were provided in parallel if requested by the neonatology team.

Results: 109 infants who met eligibility criteria were enrolled and of these, 56 (51%) had results that explained, fully or in part, their clinical findings (Table 1). Of these 56 a genetics consultation was requested in 40 (71%) whereas 16 (29%) were not suspected of having a genetic condition (i.e., no genetics consult). Of these 16, WGS results led to a change of management (e.g., specialty referral, surgery or other invasive procedure, change in medication) in 15 (93%), and 11 of these 16 identified as being non-white and/or Hispanic (Figure 1).Conclusion(s): The observed diagnostic rate of ~50% was as high if not higher than compared to studies prioritizing cases by clinical assessment of likelihood of genetic disorder based on presentation, family history, etc. Moreover, WGS resulted in a precise genetic diagnosis and a change of management in a large number of families, most of whom were non-white, in whom a genetic condition had not been suspected. Our results demonstrate clear opportunities exist to center equity for providing a precise genetic diagnosis that adds value for critically ill newborns.
Results of rapid whole genome sequencing
Figure 1: Racial/ethnic categories across groups