Exploring the Prognostic Value of Cardiac Biomarkers in Perinatal Asphyxia—A Hybrid Study Design

Purpose To compare cardiac biomarker levels in asphyxiated and healthy term neonates, assess their association with asphyxia severity and evaluate their ability to predict clinical cardiac dysfunction and in-hospital mortality. Methods This single-centre hybrid-design study was conducted at a tertiary care hospital in Haryana, India (November 2022-January 2024). It included 30 term neonates with perinatal asphyxia (PNA) and 30 gestational age-matched healthy controls. Maternal and neonatal clinical data, including Apgar scores and cord blood findings, were recorded. Blood samples for highly sensitive C-reactive protein (hs-CRP), creatine kinase-MB (CK-MB), cardiac troponin-I (cTnI) and N-terminal pro B-type natriuretic peptide (NT-proBNP) were collected between 12 and 24 h of age. Data were analysed using non-parametric tests, correlation analysis and receiver operating characteristic (ROC) curves. Results All four biomarkers (at 12-24 h of age) were significantly elevated in cases compared to controls, correlating well with clinical and laboratory variables of severity of PNA, hypoxic-ischaemic encephalopathy (HIE) and in-hospital mortality. Serum cTnI and NT-proBNP showed excellent predictive value for clinical cardiac dysfunction (area under the curve (AUC) 0.907 and 0.905; P < .001), with optimal cut-offs of 0.02 ng/mL and 7,085 pg/mL, yielding 100% sensitivity, 72.2% specificity, 70.6% positive predictive value (PPV) and 100% negative predictive value (NPV). For in-hospital mortality, CK-MB, cTnI and NT-proBNP showed very good to excellent predictive value (AUC 0.913, 0.875, 0.900; P = .009, .017, .010), at cut-offs of 157 IU/L, 0.02 ng/mL and 14,760 pg/mL, respectively. All had 100% sensitivity and NPV, while PPV ranged from 23.5% to 49.9% and specificity from 50.0% to 84.6%. Conclusions Serum cTnI, NT-proBNP and CK-MB measured at 12-24 h of life demonstrate significant potential in predicting in-hospital mortality and clinical cardiac dysfunction among neonates with PNA with an excellent NPV. However, wide confidence intervals due to the small number of outcome events limit precision, underscoring the need for larger multicentre studies to validate these findings and refine cut-offs to enhance clinical applicability.