Introduction: Neonatal sequential organ failure assessment (nSOFA) score predicts mortality in preterm newborns. The aim of the study was to assess whether nSOFA score could predict respiratory outcomes in preterm infants with late-onset sepsis (LOS). Methods: This retrospective, observational, single-center study enrolled infants with gestational age <32 weeks born between January 2016 and June 2023 who experienced an episode of LOS during NICU stay. The primary outcome was death or bronchopulmonary dysplasia (BPD); secondary outcomes were BPD, death or mechanical ventilation (MV) on day 5 after the onset of LOS, and MV on day 5 after the onset of LOS. The nSOFA score was assessed at the onset of LOS and after 6 ± 1, 12 ± 3, and 24 ± 3 h. Results: Neonatal SOFA score was significantly higher in patients who developed each outcome versus those who did not at all timings. Maximal nSOFA score during the first 24 h after onset of LOS was an independent predictive factor for death or BPD (p = 0.007), BPD (p = 0.009), and death or MV on day 5 (p = 0.009), areas under the curve (AUC) were 0.740 (95% CI: 0.656–0.828), 0.700 (95% CI: 0.602–0.800), and 0.800 (95% CI: 0.710–0.889), respectively. Maximal nSOFA score also predicted moderate to severe BPD (p = 0.019) and death or moderate to severe BPD (p < 0.001). Maximal nSOFA ≥4 was associated with odds ratio (OR) of 7.37 (95% CI: 2.42–22.44) for death or BPD, 4.86 (95% CI: 1.54–15.28) for BPD, and 7.99 (95% CI: 3.47–18.36) for death or MV on day 5. AUC of the predicting model was 0.895 (95% CI: 0.801–0.928) for BPD, 0.897 (95% CI: 0.830–0.939) for death or BPD, 0.904 (95% CI: 0.851–0.956) for MV on day 5, 0.923 (95% CI: 0.892–0.973) for death or MV on day 5. Conclusion: Maximal nSOFA score during the first 24 h after the onset of LOS predicts respiratory outcomes and allows identification of patients who may crucially benefit from lung-protective measures.

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