Elevated HMGB1 Levels in Neonates With Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis.

BACKGROUND: To assess the clinical relevance of high-mobility group box 1 (HMGB1) in bronchopulmonary dysplasia (BPD), we conducted a systematic review and meta-analysis comparing HMGB1 levels in neonates with and without BPD. METHODS: Eight databases (PubMed, Cochrane Library, Web of Science, Embase, CNKI, VIP, Wanfang, and CBM) were searched up to March 1, 2025. Cohort studies reporting serum or bronchoalveolar lavage fluid (BALF) HMGB1 levels in neonates were included. Meta-analysis was performed using RevMan 5.4. RESULTS: Seven studies (n = 527 neonates; 308 BPD, 219 controls) were included. HMGB1 concentrations in BALF were significantly higher in neonates with BPD than in those without BPD (mean difference [MD], 5.04 ng/mL; 95% confidence interval [CI], 4.09-5.99; p < 0.00001). Serum HMGB1 concentrations were also higher in neonates with BPD (MD, 7.24 ng/mL; 95% CI, 4.53-9.96; p < 0.00001). Subgroup analyses across postnatal time points indicated that serum HMGB1 levels tended to be higher in infants with BPD than in controls; however, the progressive increase observed from Stage I to Stage III plateaued thereafter, with no further increase in Stage IV (> 20 days). CONCLUSION: Total HMGB1 concentrations in serum and BALF are elevated in neonates with BPD, which may reflect BPD-associated inflammatory lung injury. However, the clinical utility of HMGB1 is limited by its lack of disease specificity and the inability of current assays to distinguish among biologically distinct redox isoforms. Further prospective studies are needed to clarify its diagnostic and therapeutic relevance.