AbstractIncreased inflammation in premature infants in the prenatal period reduces respiratory distress syndrome (RDS). Several systemic inflammatory indices have been used to evaluate inflammatory responses in different pathologies. Our study aimed to determine the systemic inflammatory indices as predictors of lung maturation in preterm infants born before 32 weeks of gestation. In this study, preterm infants born before 32 weeks of gestation were enrolled and categorized based on the diagnosis of RDS. At birth, infants were assessed for various systemic inflammatory indices, including the systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), systemic inflammation response index (SIRI), and the monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). The study included 365 infants, of whom 211 had RDS. The median gestational ages (GA) were 27 (range: 25–29) and 30 (range: 29–31) weeks, and the median birth weights were 850 (range: 660–1,360) and 1,375 (1,090–1,600) g in the RDS and control groups, respectively. Infants in the RDS group had significantly lower MLR, NLR, PIV, SII, and SIRI values (p = 0.001) compared to the control group. The cutoff values for predicting RDS in the whole group were 239 for SII, 0.44 for SIRI, and 78 for PIV. For the group of preterm infants born at ≤28 weeks of gestation, values of 171, 0.5, and 87 for SII, SIRI and PIV, respectively, provided the best ability to predict RDS. For the whole cohort, SII level ≥239 was associated with a reduced risk of RDS, as revealed by multivariate analyses (p = 0.001). To account for GA, we performed regression analyses for infants born at ≤28 weeks. SII ≥171 (odds ratio [OR]: 0.12; 95% confidence interval [CI]: 0.05–0.3), PIV ≥87 (OR: 0.08; 95% CI: 0.03–0.21), and SIRI ≥0.5 (OR: 0.08; 95% CI: 0.03–0.2) were associated with a reduced risk of RDS. Inflammation in the perinatal period may reduce the frequency of RDS in premature infants.