Implementation of Rapid Genome Sequencing for Infants with Congenital Heart Disease

Background Rapid genome sequencing (rGS) has been shown to improve the care of critically ill infants. Congenital heart disease (CHD) is a leading cause of infant mortality, and is often caused by genetic disorders, yet the utility of rGS has not been prospectively studied in this population. Methods We conducted a prospective evaluation of the use of rGS to improve the care of infants with CHD in our cardiac neonatal intensive care unit (CNICU). Results In a cohort of 48 infants with CHD, rGS diagnosed 14 genetic disorders in 13 (27%) individuals and led to changes in clinical management in eight (62%) cases with diagnostic results. These included two cases in whom genetic diagnoses helped avert intensive, futile interventions prior to CNICU discharge, as well as three cases in whom eye disease was diagnosed and treated in early childhood. Genetic disorders were associated with small for gestational age birth weight. Conclusions Our study provides the first prospective evaluation of rGS for infants with CHD to our knowledge. We found that rGS diagnosed genetic disorders in 27% of cases and led to changes in management in 62% of cases with diagnostic results. Our model of care was enabled by multidisciplinary coordination between neonatologists, cardiologists, surgeons, geneticists, and genetic counselors. These findings highlight the important role for rGS in CHD and demonstrate the need for expanded study of how to implement this resource to a broader population of infants with CHD. ### Competing Interest Statement Wendy Chung is on the Board of Directors of Prime Medicine. ### Funding Statement TH is supported by a Thrasher Research Fund Early Career Award, 20-4614. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This single-center prospective cohort study was approved by the Columbia University Irving Medical Center Institutional Review Board which gave ethical approval for this work. Parents of infants gave written informed consent, and procedures were followed in accordance with institutional guidelines. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript.