SeqFirst: Building equity access to a precise genetic diagnosis in critically ill newborns

Access to a precise genetic diagnosis (PrGD) in critically ill newborns is limited and inequitable because complex inclusion criteria used to prioritize testing eligibility omits many patients at high risk for a genetic condition. SeqFirst-neo is a program to test whether a genotype-driven workflow using simple, broad exclusion criteria to assess eligibility for rapid whole genome sequencing (rWGS) increases access to a PrGD in critically ill newborns. All 408 newborns admitted to a neonatal intensive care unit between January 2021 and February 2022 were assessed and of 240 eligible infants, 126 were offered rWGS (i.e., intervention group [IG]) and compared to 114 infants who received conventional care in parallel (i.e., conventional care group [CCG]). A PrGD was made in 62/126 (49.2%) IG neonates compared to 11/114 (9.7%) CCG infants. The odds of receiving a PrGD was [~]9 times greater in the IG vs. the CCG, and this difference was maintained at 12 months follow up. Access to a PrGD in the IG versus CCG differed significantly between infants identified as non-white (34/74, 45.9% vs. 6/29, 20.7%; p=0.024) and Black (8/10, 80.0% vs. 0/4; p=0.015). Neonatologists were significantly less successful at predicting a PrGD in non-white than non-Hispanic white patients. Use of a standard workflow in the IG with a PrGD revealed that a PrGD would have been missed in 26/62 (42%) of infants. Use of simple, broad exclusion criteria that increases access to genetic testing significantly increases access to a PrGD, improves access equity and results in fewer missed diagnoses.