Serum Zinc Dynamics as a Diagnostic and Immunomodulatory Biomarker in Neonatal Sepsis

Abstract Objective This study aimed to investigate serum zinc levels in neonates with sepsis and evaluate its correlation with immune parameters, while assessing zinc's diagnostic efficacy in identifying neonatal sepsis. Methods We conducted a retrospective cohort study involving two groups: 52 sepsis-diagnosed neonates admitted to our neonatal intensive care unit (NICU) between January 2022 and June 2023, and 50 healthy controls matched for gestational age and birth weight. Serum zinc levels, cytokines, and C-reactive protein (CRP) were assessed in both cohorts. Results No statistically significant differences were observed in baseline characteristics between the sepsis group (n = 52) and healthy controls (n = 50). Neonates with sepsis exhibited significantly lower serum zinc levels compared to controls (52.6 ± 17.4 µg/dL vs 83.2 ± 21.4 µg/dL, P < 0.05), alongside markedly elevated pro-inflammatory cytokine profiles (interleukin-6 [IL-6], interleukin-8 [IL-8], interleukin-10 [IL-10], and interleukin-12 [IL-12]). Spearman correlation analysis revealed significant associations: serum zinc levels showed strong negative correlations with IL-6 (r=-0.510, P < 0.05) and IL-8 (r=-0.625, P < 0.05), while a positive correlation was observed with IL-12 (r = 0.627, P < 0.05). ROC curve analysis demonstrated serum zinc’s moderate diagnostic utility for neonatal sepsis (AUC = 0.812, P < 0.0001), with sensitivity and specificity of 78% and 76.9%, respectively. These findings highlight zinc’s potential role in sepsis pathophysiology and diagnostic utility, despite its inferior performance compared to CRP (AUC = 0.865, P < 0.0001). Conclusion Our findings demonstrate an inverse correlation between serum zinc levels and inflammatory response intensity in neonatal sepsis. Zinc deficiency may serve as both a diagnostic biomarker and therapeutic target, given its significant negative association with pro-inflammatory cytokine profiles (IL-6, IL-8, and IL-12) while maintaining moderate predictive accuracy for disease detection.