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Background: Bronchopulmonary dysplasia (BPD) is a significant cause of morbidity and mortality in premature infants with several known risk factors. Recent literature described the harmful effect of inflammation on the developing lung. Recently, we showed that late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) causes acute lung injury (ALI) in preterm infants as measured by increases in pulmonary severity scores (PSS). The aim of this study was to investigate the association between LOS-induced ALI and BPD outcomes. We hypothesized that LOS would increase the likelihood of developing BPD, and the associated LOS-induced ALI will add to the ability to predict development of BPD. Objectives: 1) Determine if LOS and number of LOS events increase risk of developing BPD. 2) Determine if LOS-induced ALI is more likely to result in BPD. Methods: A retrospective single-center study of 523 infants < 31 weeks gestation and < 1500 grams admitted prior to day of life 7 from 2010-2020 who survived to at least 36 weeks gestation (Fig. 1). Culture positive and rule-out sepsis events were identified, and PSS scores were calculated starting from -72hr from event up to 1 week after the initiation of antibiotics. BPD was defined as per the NICHD (year 2000) consensus definition. Bivariate associations with BPD were assessed by Wilcoxon rank-sum test and Chi-squared test. BPD was predicted by conditional inference forest using demographic plus (1) LOS and (2) plus ALI summary statistics. Results: Among the 523 eligible infants, 198 had at least 1 sepsis event and 325 had no sepsis event. In the sepsis group, 69% developed BPD compared to only 49% of those without sepsis (Fig. 1). Development of BPD showed bivariate associations with sepsis and number of sepsis events (both p < 0.001, standardized mean difference or SMD 0.21 and 0.41, Table 1), the median area under the PSS curves (SMD 0.19, p-value < 0.008), as well as time points +48hr (SMD 0.2, p-value < 0.006), +72hr (SMD 0.2, p-value 0.007), and +168hr (SMD 0.32, p-value < 0.001). Adding sepsis, number of sepsis events, or PSS measures to demographic variables did not increase area under ROC curve in predicting BPD. Conclusions: Our preterm cohort revealed significant bivariate associations of sepsis, number of sepsis episodes, and PSS for BPD. However, they did not improve prediction accuracy of BPD to the demographic variables. Future work will examine the effect of sepsis-induced ALI on severe BPD and use additional parameters such as CRP to enrich our prediction models.




Presented at the Pediatric Academic Societies (PAS) 2023 Meeting; Washington, D.C.; April 27-May 1, 2023.

Sepsis-induced Acute Lung Injury and the Development of Bronchopulmonary Dysplasia in Premature Infants

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