27: PRE-CARDIOPULMONARY BYPASS BIOMARKERS PREDICT POOR OUTCOMES IN NEONATAL CONGENITAL HEART DISEASE

Abstract

Introduction: Neonates requiring cardiopulmonary bypass (CPB) for congenital heart disease have higher rates of postoperative mortality and morbidity than older children. However, identified risk factors for poor outcome to date have been limited to non-modifiable demographic or surgical factors. We aimed to identify novel biomarkers measured preoperatively that correlate with poor outcomes. Methods: Plasma samples were collected immediately prior to CPB in 65 consented subjects. Twenty-eight soluble analytes were measured via individual or multiplexed ELISA and tested for association with the validated “ICU-30” composite 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 subjects with and without ICU-30 were assessed using a Wilcoxon rank sum test. Associations of standardized biomarkers and ICU-30 was tested with logistic regression, adjusting for surgical complexity. Results: Samples for 63 patients were included for analysis (2 subjects did not undergo CPB after blood collection); 18 subjects (28%) had the ICU-30 outcome. Patients with ICU-30 were more likely to have a chromosomal abnormality, with no difference in gestational age or birth weight. There was no difference between age at CPB surgery and CPB time during operation. Seven biomarkers differed between those with and without ICU-30: angiopoietin 2, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, growth differentiation factor-15, C-C motif ligand 2 (CCL2), and neutrophil gelatinase-associated lipocalin (NGAL) were higher in patients with ICU-30, and ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin motifs 13) was lower in those with ICU-30. When controlling for STAT category, TNF-alpha (aOR 5.4, 95% CI 1.6-19.0), IL-6 (aOR 3.0, 95% CI 1.3-6.8), CCL2 (aOR 2.6, 95% CI 1.3-5.2), and NGAL (aOR 2.6, 95% CI 1.3-5.1) were associated with ICU-30. Conclusions: Four novel preoperative plasma biomarkers implicating innate immunity and renal function were associated with worse outcomes in neonates requiring CPB independent of STAT operation. Biomarkers have the potential to identify preoperative risk factors and mechanistic pathways for prognostication and targeted therapeutic interventions.