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

Area of Science:

• Genetics and Genomics
• Neonatal Intensive Care
• Clinical Diagnostics

Background:

• Access to precise genetic diagnosis (PrGD) for critically ill newborns is limited and inequitable due to complex eligibility criteria.
• Existing criteria often exclude high-risk infants, leading to missed diagnoses and delayed treatment.

Purpose of the Study:

• To evaluate the SeqFirst-neo program, a genotype-driven workflow using broad exclusion criteria for rapid genome sequencing (rGS) in critically ill newborns.
• To determine if this simplified approach increases access to PrGD and improves equity in neonatal intensive care units (NICUs).

Main Methods:

• A total of 408 newborns in a NICU were assessed; 240 were eligible.
• 126 infants received rGS (intervention group [IG]), compared to 114 receiving conventional care (conventional care group [CCG]).
• Eligibility was determined using simple, broad exclusion criteria for the IG.

Main Results:

• A PrGD was achieved in 49.2% of IG neonates versus 9.7% of CCG infants, a ~9-fold increase.
• Improved access equity was observed, with significantly higher PrGD rates in non-White and Black infants in the IG.
• A PrGD would have been missed in 42% of diagnosed infants without the standardized workflow.

Conclusions:

• Simple, broad exclusion criteria for rGS significantly increase access to PrGD in critically ill newborns.
• The SeqFirst-neo workflow improves diagnostic equity across racial and ethnic groups.
• This approach reduces missed diagnoses and enhances the effectiveness of genetic testing in neonatal care.