Abstract
BACKGROUND/OBJECTIVES: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. This systematic review and meta-analysis assess the association between eight serum biomarkers and the presence of ROP in premature neonates. These biomarkers are neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), red cell distribution width (RDW), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), platelet mass index (PMI), systemic immune-inflammation index (SII), and vitamin D. SUBJECTS/METHODS: A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Cochrane Library for studies published up to February 2025. Eligible studies included quantitative data on serum biomarker levels in premature neonates with and without ROP. A random-effects meta-analysis estimated standardised mean differences (SMDs) and 95% confidence intervals (CIs). Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Twenty-one studies comprising 3965 participants were included. Significant associations were found for NLR (SMD = 0.43, 95% CI: 0.16-0.71, P = 0.002), RDW (SMD = 0.41, 95% CI: 0.15-0.67, P = 0.002), and vitamin D (SMD = -1.18, 95% CI: -1.47--0.90, P < 0.00001). CRP, LMR, PLR, PMI, and SII did not show significant associations with ROP presence. CONCLUSIONS: NLR, RDW, and vitamin D levels are potential biomarkers associated with ROP presence in premature neonates, likely reflecting systemic inflammation and vascular pathology. Further large-scale prospective studies are warranted to establish standardised cutoff values for clinical implementation.