Genetic Testing and Challenges in a level IV Midwestern NICU: Who, What, When, and Then?

Objective: To examine genetic testing strategies and their impact on redirection of care and on reducing prognostic uncertainty in the NICU Study design: Retrospective cohort study from 2020-2021 Results: 133 out of 774 (17%) NICU infants received genetic testing, most commonly whole exome sequencing. A genetic diagnosis was achieved in 33% of cases. 70% of infants who received genetic testing were not critically ill. Decisions about redirection of care were associated with presence of critical illness and not by presence of genetic diagnosis. Many rare diagnoses were made through genetic testing in the NICU, but except for certain chromosomal anomalies, these diagnoses had wide variability in reported phenotypic presentations. Conclusions Genetic testing achieves a unifying diagnosis for many NICU patients, yet many of these diagnoses have variable clinical presentations. Redirection of care in the NICU is reliant on clinical illness severity more often than achievement of a genetic diagnosis. Clinicians must provide meaningful interpretation of genetic test results to families and be prepared to confront uncertainty even after pathogenic variants are found.