Managing the Uncertainty of "Precision" While Navigating Goals of Care: A Framework for Collaborative Interpretation...

Each year, many neonates are born with genetic diagnoses that carry a range of prognoses. As the types and availability of genetic testing have expanded, neonatal intensive care units (NICUs) have served as "launching points" for their clinical application. Broad genetic testing has both improved diagnostic precision and expanded uncertainty. Genetic information may be explicitly uncertain, as in the case of a variant of unknown significance (VUS). But it is also frequently uncertain whether/how the information relates to a patient's phenotype or what it may mean for a child's future. Even without ambiguity in the diagnosis or prognosis, the significance within a clinical and familial context may be less certain. Applying the information to clinical care is complex and may engender confusion among clinicians and families as readily as it offers guidance. Since genetic testing results can impact management and, at times, end-of-life decisions, misunderstanding and misapplication of genetic results pose a significant risk. We describe a hypothetical case of an infant with congenital hypotonia and respiratory failure. The family, after discussions with the care team about medically appropriate care paths, is navigating goals of care and considering tracheostomy placement for chronic mechanical ventilation. They consent to rapid genome sequencing in hopes of better understanding the etiology and severity of the neuromuscular condition. We explore three possible scenarios following different genomic results. With each, we discuss how the results may impact decision-making about the best plan of care. We propose a framework for navigating discussions about genetic testing results with families of critically ill children. We illustrate the importance of a multidisciplinary approach with collaboration between neonatology, genetics, and palliative care. By employing the strengths of each subspecialty, providers can manage the inherent uncertainty in genetic testing results, help determine the meaning of the results to the family in the context of their child's medical care, and enhance the care and support of critically ill neonates and their families.