617 - Seq4NICUs: Universal Rapid Genome Sequencing for NICU Infants

Publication Number: 4604.617

Courtney Verscaj, Boston Children's Hospital, Boston, MA, United States; Sophie Blumberg, Boston Children's Hospital, Newton, MA, United States; Anna-Thérèse Mehra, Boston Children's Hospital, Boston, MA, United States; Retna Arun, Boston Children's Hospital, Shrewsbury, MA, United States; Gwendolyn Strickland, Boston Children's Hospital, Boston, MA, United States; Monica Wojcik, Boston Children's Hospital, Boston, MA, United States

Background: Rapid genomic sequencing (GS) has emerged as a powerful tool for diagnosis in the neonatal intensive care unit (NICU), although access to GS remains limited and dependent upon clinician selection for testing, even at level IV NICUs that offer the highest level of intensive care. As many infants in level IV NICUs have suspected or confirmed underlying genetic disorders, universal access to rapid GS in this setting may be superior to current selective approaches.

Objective: To determine the diagnostic and clinical utility of universal rapid GS in a level IV NICU compared to the standard of care selective approach.

Design/Methods: Prospective cohort study of infants admitted to a level IV NICU for at least 48 hours who were molecularly undiagnosed. Following enrollment of a pre-implementation cohort (Phase I) for evaluation of outcomes under usual care, all subsequent families without prior GS were offered clinical rapid GS either a) via the genetics consult service or b) via the Seq4NICUs study team for families where the genetics team either was not consulted or was consulted but did not offer rapid GS (Phase II).

Results: In Phase I (2.5 months), 38 infants were enrolled and 16/38 had rapid GS (42%) via usual care. In Phase II (3 months), 47 infants were enrolled and all had rapid GS: 39/47 (83%) through the study and 8/47 (17%) via usual care. Of all families approached for rapid GS in Phase II, 47% declined.

Clinically actionable diagnoses were identified in 25% of infants who received GS in Phase I (4/16) and in 15% (7/47) of infants who received GS in Phase II. In Phase II, 15% (6/39) of infants tested via the Seq4NICUs study team and 13% (1/8) of those tested clinically had diagnostic findings. Non-diagnostic variants were found in 31% (5/16) in Phase I and 15% (7/47) in Phase II (only in infants tested via the Seq4NICUs study). In Phase II, 60% (28/47) of infants had GS results return prior to discharge to inform care at our hospital, although this rate differed between those tested via the clinical genetics team (7/8, 88%) and the Seq4NICUs team (21/39, 54%). (Figure 1).

Conclusion(s): Admission to a level IV NICU presents an opportunity to identify an impactful genetic diagnosis. Universal access to rapid GS in a level IV NICU was able to increase the number of diagnoses identified compared to usual care, although several results returned after infants were discharged or transferred to another hospital. Future studies are needed to determine the clinical utility of these diagnoses beyond the level IV NICU admission.

Table 1. Clinical Characteristics


Figure 1. Genome Sequencing Sent Date and Results Date Compared to Discharge
For infants sequenced in the NICU who have been discharged, we display the date of sample collection for genome sequencing (GS, circle 1) and GS results return (circle 2) to discharge date (dashed line). Negative values indicate dates prior to discharge, positive values indicate dates after discharge. Purple circles indicate GS results that revealed a molecular diagnosis for the tested infant. Red dots indicate GS sent in Phase I (all clinical), green dots indicate GS sent in Phase II by the clinical genetics team, and blue dots indicate GS sent in Phase II by the Seq4NICUs team.