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.