Multi-organ biomarkers for the identification of neonatal encephalopathy in the absence of traditional fetal acidemia: A three-year clinical cohort study

Background Traditional diagnostic criteria for hypoxic-ischemic encephalopathy (HIE) rely heavily on documented fetal acidemia, which may be missing or unavailable in resource-limited settings. This study evaluated the diagnostic utility of multi-organ biomarkers in identifying neonates with HIE who do not meet classic acidemic criteria (“non-classic HIE”). Methods This clinical population study analyzed 416 full-term and late-preterm neonates over 3 years at a tertiary neonatal intensive care unit (NICU). Participants were categorized into “classic HIE” (acidemia present) and “non-classic HIE” (no acidemia but presenting with clinical encephalopathy). Cardiac (Troponin-I), renal (urea/creatinine), hepatic (ALT/AST), and hematological (neutrophil-to-lymphocyte ratio [NLR]) biomarkers were evaluated to predict HIE severity and short-term outcomes. Results Of the cohort, 54.8% (n = 228) were classified into the non-classic HIE group. Within this group, 49.1% presented with mild, 43.4% with moderate, and 7.5% with severe clinical features, confirming systemic hypoxia despite “normal or near-normal” initial blood gases. Significant elevations in cardiac Troponin-I and AST were observed in the mild-to-severe classic HIE groups compared to the non-classic cohort ( p < 0.001). Troponin-I showed high performance (AUC = 0.711) in predicting moderate-to-severe HIE across both cohorts. The NLR was significantly higher in all infants with clinical evidence of moderate-to-severe hypoxic insult. Conclusions Multi-organ biomarkers, particularly Troponin-I and NLR, offer valuable adjunctive metrics reflecting the severity of systemic hypoxic insults. They assist in identifying asphyxiated neonates when early blood gases are inconsistently captured or fail to show fetal acidemia.