Developing a Plasma Biomarker Risk Profile for 30-Day Morbidity and Mortality for Neonates Requiring Cardiopulmonary Bypass for Congenital Heart Disease

CHILDREN’S HOSPITAL OF PHILADELPHIA

Primary Investigator: Monique M. Gardner, MD* & Co-PI: Nadir Yehya, MD MSCE
*Assistant Professor, Division of Cardiac Critical Care Medicine, Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Children’s Hospital of Philadelphia

Of the 1 in 100 infants in the United States born with heart disease, a quarter will require cardiac intervention in the first weeks of life. While surgical and perioperative care has advanced over the past decades [1], significant morbidity and mortality remains for neonates undergoing cardiopulmonary bypass (CPB) for surgical palliation of congenital heart disease (CHD) [2].  In addition to a 30-day postoperative mortality rate of 2-9% for the most complicated operations, prolonged cardiac intensive care unit (CICU)-stay or readmissions to the CICU are also important outcomes and markers of chronic critical illness. To date, identification of high-risk infants has been limited to demographic and cardiac disease-based determinants [3]. These clinical factors provide partial insight into the categories of patients with CHD that are at-risk but fail to address specific biologic factors contributing to poor outcomes. Additionally, clinical risk factors provide limited insight into specific mechanisms leading to poor outcomes. Blood-based biomarkers can serve as individualized, patient-based, organ-specific markers for these outcomes. Sensitive and specific early identification of at-risk patients can facilitate triaging of resources, expedite and direct more aggressive care, and delineate mechanisms leading to worse outcomes, all with the goal of improving outcomes in this vulnerable population.

Overall Hypotheses: We hypothesize that a profile of plasma biomarkers representing several different organ systems, tissue beds, and inflammation can identify high-risk neonates undergoing CPB for the ICU-30 composite outcome. We further hypothesize that we can determine patterns of change between pre- and post- operative markers that may offer improved prediction of our outcome