Objective To investigate the relationship between peripheral blood inflammatory markers and the development of retinopathy of prematurity (ROP) in extremely low birth weight infants (ELBWI), and to preliminarily evaluate their predictive value for ROP. Methods A retrospective clinical study. A total of 191 ELBWI who were born at The Affiliated Hospital of Qingdao University and admitted to the neonatal intensive care unit between January 2018 and December 2023 were enrolled. According to the presence or absence of inflammation-related diseases (necrotizing enterocolitis, bronchopulmonary dysplasia, neonatal sepsis), infants were divided into an inflammation-related disease group (144 cases) and a non-inflammation-related disease group (47 cases). Clinical data and peripheral blood inflammatory markers at 7, 14, and 28 days after birth, including white blood cell count (WBC), C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) that were compared between the two groups, as well as between infants with and without ROP within the inflammation-related disease group. Logistic regression analysis was used to identify variables associated with the occurrence of ROP. A receiver operating characteristic (ROC) curve was constructed to assess the predictive performance of the combined model, and decision curve analysis (DCA) was applied to evaluate its potential clinical utility. Results Among the 191 infants included, 80 cases were diagnosed with ROP (41.9%, 80/191). The incidence of ROP was 68/144 (47.22%) in the inflammation-related disease group and 12/47 (25.53%) in the non-inflammation-related disease group, with a statistically significant difference between the two groups (χ²=6.849, P=0.010). In the inflammation-related disease group, compared with infants without ROP, those with ROP had lower birth weight (Z=?2.591) and gestational age (Z=?2.942), a lower proportion of cesarean delivery (χ²=5.846), longer durations of invasive and noninvasive mechanical ventilation (Z=?2.500, ?2.057), and a higher incidence of patent ductus arteriosus (χ²=4.598) (P＜0.05). Levels of inflammatory markers were significantly higher in the ROP group, including WBC and SII at 7 days (Z=?2.85, ?2.565), SII at 14 days (Z=?2.531), and WBC, NLR, and SII at 28 days after birth (Z=?2.385, ?3.051, ?2.719; P＜0.05). In contrast, CRP levels at 7, 14, and 28 days did not differ significantly between ROP and non-ROP infants (Z=?1.550, ?0.796, ?0.132; P＞0.05). Multivariate logistic regression analysis showed that decreased birth weight [95% confidence interval (CI) 0.990-0.998] and increased WBC at 7 days (95%CI 1.004-1.129) and SII at 28 days (95%CI 1.001-1.006) after birth were independent related factors for the occurrence of ROP (P＜0.05). ROC curve analysis indicated that the area under the curve for predicting ROP by combining birth weight, WBC at 7 days after birth, and SII at 28 days was 0.71, with a sensitivity of 91% and a specificity of 44%. DCA shows that when the risk threshold is 31% to 98%, this combined prediction model has a positive net clinical benefit. In the non-inflammation-related disease group, only birth weight was negatively correlated with the occurrence of ROP (95%CI 0.975-0.996, P=0.005). Conclusions In ELBWI patients with inflammation-related diseases, the levels of peripheral blood WBC and SII are associated with the occurrence of ROP. The combination of birth weight and inflammatory indicators at specific time points has certain predictive value for ROP.

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