Systemic Inflammatory Indices in Transient Tachypnea of the Newborn: A Retrospective Case–Control Study

<b>Background:</b> Transient tachypnea of the newborn (TTN) is traditionally viewed as a disorder of delayed lung fluid clearance, but emerging evidence suggests inflammatory involvement. <b>Aim:</b> This study investigated systemic inflammatory indices [(systemic immune-inflammation index (SII-i), systemic inflammation response index (SIR-i), neutrophil-to-lymphocyte ratio (NL-r), and platelet-to-lymphocyte ratio (PL-r)] and underlying mechanisms in TTN pathogenesis for the first time. <b>Methods:</b> This retrospective case-control study included 199 neonates (123 with TTN and 76 healthy controls) admitted between 2022 and 2025 to a tertiary care hospital. Complete blood count parameters were collected within the first two hours of life. Inflammatory indices were calculated and compared between groups. Subgroup analyses were conducted based on gestational age (late preterm vs. term) and mode of delivery (cesarean vs. vaginal). <b>Results:</b> Although not statistically significant, TTN infants showed a trend toward higher inflammatory indices with median NL-r (2.54 vs. 1.75, <i>p</i> = 0.197) and SII-i (729,307.83 vs. 373,593.50, <i>p</i> = 0.276). Term TTN infants had higher NL-r (3.08 vs. 2.04, <i>p</i> = 0.022) and SII-i (729,147.74 vs. 538,928.30, <i>p</i> = 0.133) than late preterm infants. SIR-i and NL-r values were higher in the full-term group than in the early-term and late-preterm groups (<i>p</i> = 0.014, <i>p</i> = 0.022, respectively). Cesarean births showed higher NL-r (3.20 vs. 2.33, <i>p</i> = 0.049) and SII-i (<i>p</i> = 0.040) than vaginal deliveries. Strong correlations existed between SII-I, NL-r (r = 0.886, <i>p</i> < 0.01), and SII-i, SIR-i (r = 0.817, <i>p</i> < 0.01). <b>Conclusions:</b> Elevated inflammatory indices in neonates with TTN, particularly in term infants and those delivered vaginally, suggest a supportive/potential role for systemic inflammation in TTN pathophysiology. These markers may serve as potential supplementary markers for risk stratification, though further prospective validation is required to confirm their clinical relevance. These findings suggest that the early assessment of systemic inflammatory indices may assist clinicians in identifying neonates at risk for TTN, thereby guiding initial respiratory support strategies.