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Elevated HMGB1 Levels in Neonates With Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis
Hejia Li1, Jiao Li1, Shanshan Li1
1Department of Pediatrics, First Hospital of Hebei Medical University, Shijiazhuang 050000, China, hebmu.edu.cn.
Insights
High-mobility group box 1 (HMGB1) levels are elevated in neonates with bronchopulmonary dysplasia (BPD), indicating lung injury. However, HMGB1
Area of Science:
- Neonatal research
- Pulmonology
- Biomarker discovery
Background:
- Bronchopulmonary dysplasia (BPD) is a chronic lung disease in neonates.
- High-mobility group box 1 (HMGB1) is implicated in inflammatory processes.
- The role of HMGB1 in BPD pathogenesis requires further elucidation.
Purpose of the Study:
- To systematically review and meta-analyze studies on HMGB1 levels in neonates with and without BPD.
- To assess the clinical relevance of HMGB1 as a biomarker for BPD.
Main Methods:
- Systematic review and meta-analysis of cohort studies.
- Inclusion of studies reporting serum or bronchoalveolar lavage fluid (BALF) HMGB1 levels.
- Data synthesis using RevMan 5.4.
Main Results:
- Seven studies (n=527) were included.
- Elevated HMGB1 concentrations in BALF (MD, 5.04 ng/mL) and serum (MD, 7.24 ng/mL) in neonates with BPD.
- Serum HMGB1 levels increased with BPD severity up to Stage III, plateauing thereafter.
Conclusions:
- Elevated HMGB1 in serum and BALF suggests BPD-associated lung injury.
- Clinical utility is limited by lack of specificity and assay limitations.
- Further research is needed for diagnostic and therapeutic relevance.
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.