Therapeutic Hypothermia Modulates S100B and Oxidative Stress in Neonatal Hypoxic–Ischemic Encephalopathy: Implications of SDF4 as a Novel Biomarker

AIM: This study investigated the dynamic profile of stromal cell-derived factor 4 (SDF4), a hypoxia-inducible chemokine and S100B, an established astroglial injury marker, in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Its potential as a biomarker was assessed by examining its relationship with baseline severity, clinical trajectories and metabolic recovery. METHODS: In this prospective cohort study, 33 term neonates with moderate-to-severe HIE treated with TH and 20 healthy controls were enrolled. Serum levels of SDF4, S100B, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) and thiol-disulphide homeostasis were measured before TH (baseline) and on Day 5 (after rewarming). Effect sizes (Cohen's d) were calculated for significant results. RESULTS: Before TH, HIE infants had significantly higher SDF4, S100B, OSI and disulphide levels and lower native thiol and TAS than controls (all p < 0.01). Following TH, all six biomarkers changed significantly in the anticipated direction across the total cohort (all p ≤ 0.020). In stage-specific sub-analysis, post-TH reductions in SDF4 and S100B were statistically significant only in Stage 2 HIE (p = 0.013 and p = 0.030, respectively), whereas oxidative stress parameters (OSI, native thiol, TAS) improved significantly in both severity groups. CONCLUSION: SDF4 appears to be a novel biomarker reflecting both HIE severity and the dynamic response to TH. The selective lack of SDF4 and S100B clearance in Stage 3 HIE highlights a more sustained pattern of neuroinflammatory injury, supporting SDF4's potential role in monitoring metabolic recovery and guiding individualised neuroprotective strategies.