Monique Gardner, MD
Attending Physician, Pediatric Cardiac Critical Care
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania
Disclosure information not submitted.
Feng Chen, PhD
Senior Investigator, Lead Biochemical Studies
University of Pennsylvania, United States
Disclosure information not submitted.
Natalka Koterba
Research Specialist
University of Pennsylvania, United States
Disclosure information not submitted.
Isabel Reddy, n/a
Research Student
University of Pennsylvania, United States
Disclosure information not submitted.
Jill Thompson, MS
Research Assistant
Children's Hospital of Philadelphia, United States
Disclosure information not submitted.
Anh Mai, MS
Clinical Research Coordinator
Children's Hospital of Philadelphia, United States
Disclosure information not submitted.
Francis McGowan, MD
Attending physician
Children's Hospital of Philadelphia, United States
Disclosure information not submitted.
William Gaynor, MD
Attending surgeon, Professor of Pediatric Cardiothoracic Surgery
Children's Hospital of Philadelphia, United States
Disclosure information not submitted.
Simon Lacey, PhD
Professor
Center for Cellular Immunotherapies, Perelman School of Medicine, University of, United States
Disclosure information not submitted.
Nadir Yehya, MD, MSCE
Children's Hospital of Philadelphia
Cherry Hill, NJ
Disclosure information not submitted.
Title: Preoperative Biomarkers Associated with Poor Outcome after Neonatal Cardiac Surgery
Introduction: Neonates that undergo surgery for congenital heart disease (CHD) have higher mortality, longer intensive care unit (ICU) stays and multiple readmissions. While clinical factors identify patients at higher risk for these poor outcomes, the use of blood biomarkers to provide individualized prognostic measures is limited for this patient population. We aimed to determine whether pre-operatively measured inflammatory, coagulation, and organ injury biomarkers were associated with poor outcome after neonatal surgery with cardiopulmonary bypass (CPB).
Methods: Following parental consent, blood was collected from consecutive neonates (< 30 days of age) immediately before CPB. Twenty-eight plasma biomarkers were measured via individual or multiplexed ELISA and tested for association with poor outcome, defined as (1) mortality within 30 days of CPB, (2) ICU stay >30 days, or (3) ICU readmission within 30 days. Differences in biomarker concentrations between those with and without poor outcome were assessed using Wilcoxon rank-sum, with p< 0.05 reported as significant.
Results: Of 29 patients, 16 (55%) were male, 7 (24%) had transposition of the great arteries, 7 (24%) arch hypoplasia or coarctation, 7 (24%) coarctation of the aorta, and 6 (21%) single ventricle anatomy. Nine subjects (31%) had poor outcome with one non-survivor. Patient demographics and preoperative illness severity, including preoperative mechanical ventilation, vasoactive need and ECMO, and operative factors were similar between those with and without poor outcomes. Five biomarkers (median, pg/ml) were elevated preoperatively in those with poor outcome: ST2 (48,653 vs 34,318), NSE (17,002 vs. 12,456), TNF-α (12.9 vs. 9.6), IL-6 (23.0 vs. 6.5) and NGAL (31,608 vs. 25,936). Two coagulation biomarkers, ADAMTS13 (974,064 vs. 1,103,052) and D-dimer (467,066 vs. 3,538,269), were lower preoperatively in subjects with poor outcome.
Conclusions: This pilot study identified novel preoperative biomarkers that may be associated with poor postoperative outcome in neonates who undergo surgery with CPB to treat CHD. Notably, differences in cardiac, renal, neuronal, and coagulation markers were prominent. These results have the potential to identify preoperative risk factors and mechanistic pathways for prognostication and targeted therapeutic interventions.