IMPORTANCE Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems.OBJECTIVE To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system. DESIGN, SETTING, AND PARTICIPANTS Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination, distributed leadership, and collective learning was used to facilitate adoption. EXPOSURES Ultra-rapid exome sequencing. MAIN OUTCOMES AND MEASURESThe primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge. RESULTSThe study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The mean time from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI, 3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing-based copy number analysis, use of international databases to identify novel gene-disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients (11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%).CONCLUSIONS AND RELEVANCE This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings.

As genomic sequencing has become available in pediatric clinical genetics settings, genetic counselors have been called upon to support individuals and families through the testing process. Technological and bioinformatic advancements, along with the availability of analytical expertise, have significantly reduced genomic sequencing turnaround times, enabling this powerful diagnostic tool to be used in neonatal intensive care units (NICUs) in place of or alongside traditional diagnostic strategies. It is important that pretest counseling for genomic sequencing prepares parents of critically unwell infants for the potential impacts of achieving a diagnosis, such as rare or ultra‐rare diagnoses with limited disease‐specific information, or the diagnosis of a life‐limiting condition. Genetic counseling experiences and challenges arising in rapid genomic sequencing settings are yet to be discussed in the literature in detail. This paper uses illustrative cases as the basis to describe and discuss the emerging role of genetic counselors in NICU multidisciplinary care teams and the challenges and considerations which arise when facilitating ultra‐rapid genomic diagnoses in acutely unwell neonates. Counseling issues discussed include providing pre‐ and posttest counseling in the medicalized NICU setting, facilitating informed decision‐making at a time of acute distress for families, and special considerations around the possibility of ultra‐rare diagnoses in neonates at the beginning of their diagnostic trajectory. As technology continues to drive practice, it is important genetic counselors remain abreast of these issues in order to appropriately support families through the genomic sequencing process and beyond.