Early predictive value of interleukin-6 and procalcitonin levels for bronchopulmonary dysplasia in preterm infants

Introduction

Background

Bronchopulmonary dysplasia (BPD) is a common chronic respiratory complication in preterm infants (1). Advances in therapy and neonatal care have significantly improved the survival rate of preterm infants; however, the incidence of BPD has also increased in recent years (2), with its pathogenesis remaining unclear (3,4). Multiple factors—including genetic susceptibility, inflammation, invasive ventilation, hyperoxia exposure, and chemical stimulation—can affect the immature lungs of preterm infants and contribute to the development of BPD. A large number of basic and clinical studies about BPD have improved the understanding of the BPD pathogenesis. Inflammation plays a key role in BPD and leads to persistent airway injury and pulmonary vascular diseases. Some corticosteroids, such as dexamethasone and hydrocortisone, have been proven beneficial for the prevention and management of BPD due to their anti-inflammatory characteristics (5). Despite this, no effective or specific treatments are currently available (6,7). Many surviving infants experience chronic respiratory dysfunction and neurodevelopmental disorders, which significantly affect their long-term quality of life and impose substantial burdens on families and society. Therefore, early identification of predictive indicators is helpful in facilitating our further understanding of the risk factors and mechanisms of BPD (8).

Interleukin-6 (IL-6) is an important member of the cytokine family, participating in cell-to-cell signaling and serving a crucial regulatory function in the immune system (9). Bioinformatics analysis indicates that IL-6 is among the top ten hub genes in BPD, and the levels of IL-6 are highly expressed in the peripheral blood of neonates with BPD (10). Previous studies have indicated the link between IL-6 and the occurrence of BPD, suggesting it as a potential biomarker for predicting BPD (11). IL-6 is an important proinflammatory cytokine involved in acute lung injury. It exacerbates ventilator-induced lung injury and plays a critical role in lung inflammation in preterm infants (12). During intrauterine infection, IL-6 is released into the amniotic fluid or umbilical cord blood and is associated with neonatal morbidity and long-term health complications, such as BPD and neonatal sepsis. IL-6 is activated early in the immune response to infections, with its levels rising rapidly in the first 24 h and declining shortly after (13).

Procalcitonin (PCT), the prohormone of calcitonin, is a 116-amino-acid peptide that is synthesized by thyroid parafollicular C cells and can be converted into calcitonin hormone, which is then released into the bloodstream to maintain calcium homeostasis. After a systemic inflammatory response, almost all the infected tissues in the body will initiate the synthesis process of PCT, resulting in a large amount of the peptide being released into the bloodstream (14). PCT is primarily produced by monocytes and hepatocytes and its levels increase significantly in response to infections in neonates. Serum PCT levels have been demonstrated to be significantly elevated in severe systemic infections such as sepsis, septic shock, and severe pneumonia (15). PCT levels begin to rise within 6 h of infection onset, peak at 18–24 h, and remain elevated for up to 48 h (16). Moreover, these levels have been found to be correlated with sepsis-associated lung injury (17), and a retrospective cohort study identified PCT level as a risk factor in patients with acute respiratory distress syndrome (18).

Rationale and knowledge gap

Owing to the complex etiology and pathogenesis of BPD, specific therapeutic approaches remain lacking. In this context, early identification and intervention are essential for improving BPD prognosis and reducing mortality in affected infants.

Objective

Therefore, this study aimed to develop an early diagnostic model for BPD by analyzing clinical data and serum IL-6 and PCT levels from our neonatal intensive care unit to provide a basis for early intervention in preterm infants. We present this article in accordance with the TRIPOD reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-548/rc).

Methods

Study design

This prospective observational study was conducted from January 1, 2022 to December 31, 2024, in the Neonatal Intensive Care Units of the Affiliated Hospital of Yang Zhou University Medical College, Huai’an Maternal and Child Health Care Center. The inclusion criterion was a gestational age (GA) of <32 weeks. The exclusion criteria were age at admission >24 h, parental withdrawal from treatment, or the presence of congenital abnormalities.

Ethics approval and informed consent

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. It was approved by the ethics committee of Affiliated Hospital of Yang Zhou University Medical College, Huai’an Maternal and Child Health Care Center (approval No. 2019045). Informed consent was obtained from all the parents of the included infants.

Definitions

In 2018, the National Institute of Child Health and Human Development (NICHD) revised the diagnostic and grading criteria for BPD. The diagnosis applies to preterm infants with a GA <32 weeks who show imaging evidence of persistent parenchymal lung disease and require continuous respiratory support for at least 3 days to maintain 90–95% oxygen saturation at 36 weeks postmenstrual age. According to the degree of oxygen dependence of the patients, the severity of BPD is classified into grades I, II, III and IIIa (19). In this study, BPD was further divided into three subgroups: the mild BPD group (grade I), the moderate BPD group (grade II) and the severe BPD group (grade III).

Collection of clinical data

The following data were collected from hospital records: (I) infant characteristics, including sex, GA, birth weight (BW), mode of delivery, in vitro fertilization (IVF), twin or multiple birth, small for GA (SGA), and Apgar scores (1 minute ≤3 or 5 minutes ≤7). Laboratory findings within 24 h of admission included white blood cell count, neutrophil count, platelet count, hemoglobin level, and C-reactive protein level (CRP); (II) maternal conditions, including age, gestational hypertension, pre-eclampsia, gestational diabetes mellitus, placenta previa, placental abruption, preterm premature rupture of membrane (PROM) ≥18 h, and antenatal use of medications (antibiotics, magnesium sulfate, and steroids); (III) in-hospital treatments for preterm infants, including days of oxygen inhalation, invasive ventilation, blood transfusion, enteral and parenteral nutrition, and the use of steroids, caffeine, ibuprofen, and intravenous immunoglobulin; (IV) comorbidities, including neonatal respiratory distress syndrome (NRDS), sepsis, central nervous system (CNS) infection, necrotizing enterocolitis (NEC), extra uterine growth restriction (EUGR), hemodynamically significant patent ductus arteriosus (hs-PDA), periventricular or intraventricular hemorrhage (PVH-IVH), periventricular leukomalacia (PVL), severe retinopathy of prematurity (sROP), ventilator-associated pneumonia (VAP), pulmonary hypertension (PH), parenteral nutrition-associated cholestasis (PNAC), and death. A total of 57 infants with matching general characteristics, such as sex, GA, and BW, were randomly selected as the non-BPD group at a 1:1 ratio with the BPD group (Figure 1).

Figure 1 Flow chart of the study. BPD, bronchopulmonary dysplasia; GA, gestational age.

Serum IL-6 and PCT detection

Peripheral venous blood (1 mL) was collected on days 1, 3, and 7 after birth and centrifuged at 2,000 ×g for 10 min (New Era Beili DT5-3, Beijing, China). The separated serum was analyzed using a chemiluminescence method with IL-6 and PCT assay kits (Siemens Healthcare Diagnostics Inc., New York, USA).

Statistical analysis

Data analysis was performed using GraphPad Software (version Prism 9.0, GraphPad Inc., San Diego, CA, USA). Categorical data were presented as cases (%) and analyzed using the Chi-squared test or Fisher’s exact test. Normally distributed continuous data were expressed as mean ± standard deviation, whereas non-normally distributed data were presented as median (P25, P75). t-tests were used for two-group comparisons, and analysis of variance was applied for multiple-group comparisons when normality assumptions were met. For non-normally distributed data, the Mann-Whitney U test was used for two-group comparisons, whereas the Kruskal-Wallis H test was used for multiple-group comparisons. Continuous variables were analyzed using Pearson’s correlation analysis. Variables with P<0.05 in the univariate analysis were included in the multivariate regression analysis to identify risk factors for BPD. Receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of risk factors, and a logistic regression model was constructed for early BPD prediction. The level of statistical significance was set at P<0.05.

Results

Demographics of preterm infants

Between January 1, 2022 and December 31, 2024, a total of 253 preterm infants with GA <32 weeks were enrolled in the study. Of these, 9 were excluded due to parental withdrawal from treatment, 2 for genetic metabolic diseases, 10 for age at admission >24 h, and 5 due to death within 14 days of admission. After exclusions, 227 infants were enrolled. Among them, 57 infants developed BPD, including 32 classified as mild, 22 as moderate, and 3 as severe BPD. A matched control group of 57 infants—based on sex, GA, and BW—was randomly selected at a 1:1 ratio as the non-BPD group (Figure 1). No significant differences were observed in infant or maternal characteristics between the BPD and non-BPD group (P>0.05) (Table 1).

Risk factors for BPD in preterm infants

The rates of steroid use (P<0.001), ibuprofen use (P<0.001), intravenous immunoglobulin use (P=0.004), and red blood cell transfusion (P<0.001) were significantly higher in the BPD group than in the non-BPD group. Moreover, the BPD group had a significantly longer time to achieve total enteral nutrition (>30 days) (P<0.001), more days of total parenteral nutrition (TPN) (P=0.001), greater use of peripherally inserted central catheters (PICC) (P<0.001), longer durations of oxygen therapy (P<0.001) and invasive ventilation (P<0.001), a higher rate of invasive ventilation >7 days (P<0.001), and longer hospital stays (P<0.001). The incidences of late-onset sepsis (LOS) (P<0.001), EUGR (P=0.01), PDA (P=0.04), hs-PDA (P<0.001), sROP (P=0.01), VAP (P=0.04), and PH (P=0.04) were significantly higher in the BPD group than in the non-BPD group (P<0.05) (Table 2).

Serum IL-6 and PCT levels

The serum IL-6 levels in the preterm infants were significantly higher in the BPD group than in the non-BPD group on both the 1st (P=0.01) and 3rd (P=0.02) days of life. The serum PCT levels in the preterm infants were significantly higher in the BPD group than in the non-BPD group on both the 1st (P=0.02) and 3rd (P=0.03) days of life (Figure 2). Additionally, the serum IL-6 levels on days 1 (P<0.001) and 3 (P<0.001) were significantly higher in the severe BPD groups than in the mild BPD group. The serum IL-6 levels on days 1 (P=0.04) and 3 (P=0.045) were significantly higher in the moderate BPD groups than in the mild BPD group. The serum PCT levels on days 1 (P<0.001) and 3 (P<0.001) were significantly higher in the severe BPD groups than in the mild BPD group. The serum PCT levels on days 1 (P=0.04) and 3 (P=0.045) were significantly higher in the moderate BPD groups than in the mild BPD group (Figure 3). The area under the ROC curve (AUC) for the IL-6 level on day 1 in predicting BPD was 0.8129 [95% confidence interval (CI): 0.7309–0.8948], with a cut-off value of 11.85 pg/mL, yielding 96.49% sensitivity and 74.91% specificity. The AUC for the IL-6 level on day 3 was 0.6320 (95% CI: 0.5291–0.7350), with a cut-off value of 3.74 pg/mL, yielding 87.72% sensitivity and 40.35% specificity (Figure 4A). Moreover, the AUC for the PCT level on day 1 was 0.8215 (95% CI: 0.7438–0.8991), with a cut-off value of 3.86 ng/mL, yielding 94.74% sensitivity and 71.4% specificity. The AUC for the PCT level on day 3 was 0.6905 (95% CI: 0.5926–0.7884), with a cut-off value of 1.34 ng/mL, yielding 68.42% sensitivity and 64.91% (Figure 4B). The AUC for the IL-6 and PCT levels on day 1 was larger than on day 3.

Figure 2 Trends of serum IL-6 (A) and PCT (B) in the BPD group and the non-BPD group. BPD, bronchopulmonary dysplasia; IL-6, interleukin-6; PCT, procalcitonin.

Figure 3 Trends of serum IL-6 (A) and PCT (B) in different degrees of BPD. BPD, bronchopulmonary dysplasia; IL-6, interleukin-6; PCT, procalcitonin.

Figure 4 ROC curve for the serum IL-6 (A) and PCT (B) level. IL-6, interleukin-6; PCT, procalcitonin; ROC, receiver operating characteristic.

Relevant analysis of the IL-6 and PCT levels

Pearson correlation analysis revealed a positive correlation between the serum IL-6 and PCT levels on the 1st and 3rd days of life in the BPD group. The correlation coefficients (R-values) were 0.7523 (P<0.001) and 0.7171 (P<0.001) on the 1st and 3rd days, respectively (Table 3).

Risk factors for BPD

Binary logistic regression analysis identified invasive ventilation >7 days [odds ratio (OR) =29, 95% CI: 4.192–318.100, P=0.002], LOS (OR =6.166, 95% CI: 1.376–33.170, P=0.02), IL-6 level on day 1 (OR =1.959, 95% CI: 1.094–3.997, P=0.04) and PCT level on day 1 (OR =1.934, 95% CI: 1.012–3.991, P=0.04) as significant risk factors for BPD (Table 4). ROC curves were generated using four variables, including invasive ventilation >7 days, LOS, IL-6 level on day 1 and PCT level on day 1. Each variable demonstrated statistically significant predictive value for BPD compared with the non-BPD group (P<0.001) (Figure 5).

Figure 5 ROC curve for predicting BPD. BPD, bronchopulmonary dysplasia; d, day; IL-6, interleukin-6; LOS, late-onset sepsis; PCT, procalcitonin; ROC, receiver operating characteristic.

BPD prediction model

A BPD prediction model was constructed using four indicators, including invasive ventilation >7 days (X1), LOS (X2), IL-6 level on day 1 (X3), and PCT level on day 1 (X4). The P value of the logistic regression prediction model is less than 0.001. The Hosmer-Lemeshow test was calculated using the classification cross table, with P>0.05, indicating that the goodness of fit of this prediction model is relatively good. The regression equation for the model is as follows:

P=1/[1+e−(−0.7273+2.094×X1+0.9664×X2−0.02025×X3−0.07878×X4)][1]

A multi-index combined logistic regression for BPD

A multi-index combined logistic regression was used to construct a prediction model for BPD. Four indicators, including invasive ventilation >7 days, LOS, IL-6 level on day 1 and PCT level on day 1, were combined with logistic regression to build a prediction model for BPD in preterm infants (total AUC: 0.9563, 95% CI: 0.9201–0.9925) (P<0.001), with a sensitivity of 92.98% and specificity of 87.72%. The AUC for the combined logistic regression model incorporating the four predictors exceeded the predictive performance of each indicator alone (Figure 6).

Figure 6 ROC curve of four-indicator combined logistic regression for predicting BPD. BPD, bronchopulmonary dysplasia; ROC, receiver operating characteristic.

Discussion

BPD is a severe pulmonary disease that significantly threatens the survival of preterm infants. Its occurrence is associated with various factors, such as lung immaturity, inflammation-induced lung tissue damage, and abnormal post-injury repair (20). Given its complex etiology and pathogenesis, specific treatments remain lacking, underscoring the importance of early diagnosis. In this study, the overall incidence of BPD among preterm infants (<32 weeks’ GA) was 25.11% (57/227). Among the BPD cases, 56.14% were classified as mild, 38.60% as moderate, and 5.26% as severe, according to the NICHD 2018 severity classification. These results are consistent with those of Abushahin et al. (21). Risk factors for the development of BPD in preterm infants were analyzed by matching those with GA <32 weeks and considering maternal conditions. Our findings indicated that oxygen inhalation, invasive ventilation for >7 days, and LOS were significant risk factors for BPD.

BPD primarily affects extremely preterm infants, whose lungs are still in the tubular and capsular stages of development (22). Prolonged exposure to a hyperoxic environment induces reactive oxygen species formation, triggering oxidative stress responses (23,24). This process leads to excessive alveolar cell apoptosis, impairs lung tissue growth and maturation, and results in abnormal tissue repair (25,26). Oxidative stress also disrupts mesenchymal-epithelial signaling, promotes the differentiation of alveolar lipofibroblasts into myofibroblasts, interferes with the growth and differentiation of lung epithelial cells, and ultimately disrupts alveolarization (27).

Invasive mechanical ventilation is associated with ventilator-induced lung injury, oxygen toxicity, and inflammation, all of which contribute to the pathogenesis of BPD. Our study demonstrated that mechanical ventilation for >7 days was a risk factor for BPD in preterm infants, aligning with previous results (28). Nascimento et al. reported that the duration of invasive mechanical ventilation performed during the first 48 h of life was a significant clinical predictor of BPD in preterm infants (29). Consistent with this finding, our study revealed that rates of oxygen inhalation and invasive ventilation >7 days were higher in the BPD group than in the non-BPD group. These findings may inform future strategies to prevent lung injury and mitigate BPD severity in extremely preterm infants. Moreover, there is a consensus that avoiding invasive ventilation is an evidence-based strategy for reducing the risk of BPD. Notably, our study revealed that half of the infants who survived until hospital discharge received mechanical ventilation, and more than two-thirds underwent invasive respiratory support.

Additionally, sepsis was considered in this study owing to its role in inducing inflammation, causing lung injury, and disrupting lung growth in vulnerable immature lungs (30). LOS was identified as a significant risk factor for BPD (OR =3.788, 95% CI: 4.167–58.14). However, early-onset sepsis (EOS) showed no significant association with BPD. These results are consistent with those of studies that have correlated LOS with the risk of BPD (31). Still, some reports have demonstrated EOS, rather than LOS, as a predictor of BPD (32). These discrepancies may stem from varying definitions of EOS and LOS across these studies. The requirement for mechanical ventilation during LOS has been independently associated with the risk of developing BPD in preterm infants. A study reported that preterm infants diagnosed with LOS were at a higher risk of developing BPD (33). Therefore, implementing protective ventilation strategies can help reduce the need for invasive mechanical ventilation and shorten the duration of oxygen inhalation to mitigate lung oxidative stress and reduce the incidence of BPD.

Antenatal corticosteroids are routinely administered to pregnant females at risk of preterm delivery owing to their well-established benefits in promoting lung maturation and reducing respiratory distress syndrome in preterm infants (34). Antenatal steroids reduce the incidence of BPD, particularly in infants at the lowest GAs, and lower the rates of serious complications, including mortality and long-term neurodevelopmental impairment (35). In our study, over 80% of pregnant females received antenatal corticosteroids. Corticosteroids are also commonly used in preterm infants to prevent BPD owing to their anti-inflammatory effects (36). However, clinicians should carefully weigh the benefits against potential adverse effects, particularly with dexamethasone, which is associated with increased risks of neurodevelopmental impairment, intestinal perforation, and impaired growth (37). Given these adverse effects, early use of dexamethasone for BPD prevention is not recommended (38). In the present study, systemic postnatal dexamethasone was administered starting on day 14 after birth. Notably, the rate of steroid use was significantly higher in the BPD group than in the non-BPD group.

Moreover, IL-6 and PCT can reflect the inflammatory response more promptly and sensitively than C-reactive protein (CRP). Serum IL-6 and PCT levels were found to be significant predictive indicators for BPD. IL-6, a proinflammatory cytokine, plays a critical role in various diseases. It is released by diverse cell types—including T helper 2 cells, macrophages, fibroblasts, and endothelial cells—and functions as a mediator in the regulation of inflammation (39). Our results suggest that IL-6 is a promising biomarker for identifying BPD in preterm infants. With a threshold of IL-6 >11.85 pg/mL on the 1st day of life, the AUC for predicting BPD was 0.8129, yielding a sensitivity of 96.49% and a specificity of 74.91%. This result is consistent with a previous study (40). These findings strongly indicate that IL-6 is a sensitive biomarker for predicting BPD. Notably, the serum IL-6 levels were significantly higher in the BPD group than in the non-BPD group on both days 1 and 3. The predictive significance of serum IL-6 was higher on day 1 (AUC: 0.8129) than on day 3 (AUC: 0.6320). PCT, a member of the calcitonin superfamily of peptides, comprises 116 amino acids and has a molecular weight of approximately 14.5 kDa (41). Our findings demonstrated that PCT is a promising biomarker for identifying BPD in preterm infants. Using a threshold of PCT >3.86 ng/mL on the 1st day of life, the AUC for predicting BPD was 0.8215, yielding a sensitivity of 94.74% and a specificity of 71.4%. These results strongly indicate that PCT is a sensitive biomarker for predicting BPD. Notably, the serum PCT levels were significantly higher in the BPD group than in the non-BPD group on both days 1 and 3. The predictive significance of serum PCT level was higher on day 1 (AUC: 0.8215) than on day 3 (AUC: 0.6905). This result is similar to that of a previous study (42). These findings likely reflect the increased degree of oxidative stress and inflammatory response in the early stages of BPD. Additionally, a positive correlation was observed between IL-6 and PCT levels on both the 1st and 3rd days of life in the BPD group. Elevated IL-6 and PCT levels may provide mechanistic insights into BPD pathogenesis. The increase in IL-6 and PCT indicates that the body is in a pro-inflammatory response stage. Administering appropriate anti-inflammatory treatment in the early postnatal period may reduce the occurrence of severe BPD in the later stage. These findings may provide some new evidence for the prevention and treatment of BPD.

Various factors, including immature lung development, invasive ventilation, and infection, contribute to BPD. Changes in serum IL-6 and PCT levels are also closely associated with its development. Therefore, this study developed a regression model that combines clinical risk factors and biological markers to enable the early prediction of BPD in preterm infants. However, there are some limitations in this study, including its single-center design, small sample size, only three severe (grade 3) BPD and short study duration. Larger, multicenter studies are needed to validate the early diagnostic value of IL-6 and PCT levels. Additionally, the predictive accuracy of the BPD model requires further improvement.

Conclusions

In conclusion, invasive ventilation >7 days and LOS were identified as risk factors for BPD. Incorporating these clinical risk factors with serum IL-6 and PCT levels on day 1 of life allowed the construction of a regression model that facilitated enhanced and early prediction of BPD in preterm infants.

Acknowledgments

We would like to thank Editage (www.editage.cn) for English language editing.

Footnote

Reporting Checklist: The authors have completed the TRIPOD reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-548/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-548/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-548/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-548/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. It was approved by the ethics committee of Affiliated Hospital of Yang Zhou University Medical College, Huai’an Maternal and Child Health Care Center (approval No. 2019045). Informed consent was obtained from all the parents of the included infants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Schmidt AR, Ramamoorthy C. Bronchopulmonary dysplasia. Paediatr Anaesth 2022;32:174-80. [Crossref] [PubMed]
2. Jeon GW, Oh M, Chang YS. Increased bronchopulmonary dysplasia along with decreased mortality in extremely preterm infants. Sci Rep 2025;15:8720. [Crossref] [PubMed]
3. Xiao S, Ding Y, Du C, et al. Analysis and Validation of Autophagy-Related Gene Biomarkers and Immune Cell Infiltration Characteristic in Bronchopulmonary Dysplasia by Integrating Bioinformatics and Machine Learning. J Inflamm Res 2025;18:549-63. [Crossref] [PubMed]
4. Deng X, Xie A, Ye D, et al. Melatonin Activates KEAP1/NRF2/PTGS2 Pathway to Attenuate Hyperoxia-Driven Ferroptosis in Bronchopulmonary Dysplasia. J Inflamm Res 2025;18:7571-83. [Crossref] [PubMed]
5. Htun ZT, Schulz EV, Desai RK, et al. Postnatal steroid management in preterm infants with evolving bronchopulmonary dysplasia. J Perinatol 2021;41:1783-96. [Crossref] [PubMed]
6. Dini G, Ceccarelli S, Celi F. Strategies for the prevention of bronchopulmonary dysplasia. Front Pediatr 2024;12:1439265. [Crossref] [PubMed]
7. Oluwole-Ojo T, Harris C, Greenough A. Advances in the pharmacological management of bronchopulmonary dysplasia: an update of the literature. Expert Opin Pharmacother 2024;25:1349-58. [Crossref] [PubMed]
8. McOmber BG, Moreira AG, Kirkman K, et al. Predictive analytics in bronchopulmonary dysplasia: past, present, and future. Front Pediatr 2024;12:1483940. [Crossref] [PubMed]
9. Gao L, Yang P, Luo C, et al. Machine learning predictive models for grading bronchopulmonary dysplasia: umbilical cord blood IL-6 as a biomarker. Front Pediatr 2023;11:1301376. [Crossref] [PubMed]
10. Yan W, Jiang M, Zheng J. Identification of key pathways and differentially expressed genes in bronchopulmonary dysplasia using bioinformatics analysis. Biotechnol Lett 2020;42:2569-80. [Crossref] [PubMed]
11. Hagman C, Björklund LJ, Bjermer L, et al. Perinatal inflammation relates to early respiratory morbidity and lung function at 12 years of age in children born very preterm. Acta Paediatr 2021;110:2084-92. [Crossref] [PubMed]
12. Witkowski SM, de Castro EM, Nagashima S, et al. Analysis of interleukins 6, 8, 10 and 17 in the lungs of premature neonates with bronchopulmonary dysplasia. Cytokine 2020;131:155118. [Crossref] [PubMed]
13. Orfanos I, Krusell ET, Elfving K. Utility of interleukin-6 to identify serious bacterial infections in febrile infants aged ≤60 days. Acta Paediatr 2025;114:173-9. [Crossref] [PubMed]
14. Nardone V, Giannicola R, Bianco G, et al. Inflammatory Markers and Procalcitonin Predict the Outcome of Metastatic Non-Small-Cell-Lung-Cancer Patients Receiving PD-1/PD-L1 Immune-Checkpoint Blockade. Front Oncol 2021;11:684110. [Crossref] [PubMed]
15. Lee S, Song J, Park DW, et al. Diagnostic and prognostic value of presepsin and procalcitonin in non-infectious organ failure, sepsis, and septic shock: a prospective observational study according to the Sepsis-3 definitions. BMC Infect Dis 2022;22:8. [Crossref] [PubMed]
16. Eichberger J, Resch E, Resch B. Diagnosis of Neonatal Sepsis: The Role of Inflammatory Markers. Front Pediatr 2022;10:840288. [Crossref] [PubMed]
17. Lu S, Li R, Deng Y, et al. GDF15 ameliorates sepsis-induced lung injury via AMPK-mediated inhibition of glycolysis in alveolar macrophage. Respir Res 2024;25:201. [Crossref] [PubMed]
18. Yan Y, Geng B, Liang J, et al. A prediction model for nonresponsive outcomes in critically ill patients with acute respiratory distress syndrome undergoing prone position ventilation: A retrospective cohort study. Intensive Crit Care Nurs 2025;86:103804. [Crossref] [PubMed]
19. Higgins RD, Jobe AH, Koso-Thomas M, et al. Bronchopulmonary Dysplasia: Executive Summary of a Workshop. J Pediatr 2018;197:300-8. [Crossref] [PubMed]
20. Enzer KG, Baker CD, Wisniewski BL. Bronchopulmonary Dysplasia. Clin Chest Med 2024;45:639-50. [Crossref] [PubMed]
21. Abushahin A, Hamad SG, Sabouni A, et al. Incidence and Predictors of Bronchopulmonary Dysplasia Development and Severity Among Preterm Infants Born at 32 Weeks of Gestation or Less. Cureus 2024;16:e59425. [Crossref] [PubMed]
22. Durlak W, Thébaud B. BPD: Latest Strategies of Prevention and Treatment. Neonatology 2024;121:596-607. [Crossref] [PubMed]
23. Teng M, Wu TJ, Jing X, et al. Temporal Dynamics of Oxidative Stress and Inflammation in Bronchopulmonary Dysplasia. Int J Mol Sci 2024;25:10145. [Crossref] [PubMed]
24. Wu TJ, Jing X, Teng M, et al. Role of Myeloperoxidase, Oxidative Stress, and Inflammation in Bronchopulmonary Dysplasia. Antioxidants (Basel) 2024;13:889. [Crossref] [PubMed]
25. Cannavò L, Perrone S, Viola V, et al. Oxidative Stress and Respiratory Diseases in Preterm Newborns. Int J Mol Sci 2021;22:12504. [Crossref] [PubMed]
26. Sridharan K, Al Jufairi M, Hejab AAM, et al. Evaluation of Genetic Polymorphisms of the Antioxidant Enzymes and Biomarkers of Oxidative Stress in Preterm Neonates With Respiratory Distress Syndrome Receiving External Surfactant. Biomark Insights 2022;17:11772719221137608. [Crossref] [PubMed]
27. Thomas JM, Sudhadevi T, Basa P, et al. The Role of Sphingolipid Signaling in Oxidative Lung Injury and Pathogenesis of Bronchopulmonary Dysplasia. Int J Mol Sci 2022;23:1254. [Crossref] [PubMed]
28. Rutkowska M, Hożejowski R, Helwich E, et al. Severe bronchopulmonary dysplasia - incidence and predictive factors in a prospective, multicenter study in very preterm infants with respiratory distress syndrome. J Matern Fetal Neonatal Med 2019;32:1958-64. [Crossref] [PubMed]
29. Nascimento CP, Maia LP, Alves PT, et al. Invasive mechanical ventilation and biomarkers as predictors of bronchopulmonary dysplasia in preterm infants. J Pediatr (Rio J) 2021;97:280-6. [Crossref] [PubMed]
30. Gilfillan M, Bhandari V. Moving bronchopulmonary dysplasia research from the bedside to the bench. Am J Physiol Lung Cell Mol Physiol 2022;322:L804-21. [Crossref] [PubMed]
31. Cokyaman T, Kavuncuoglu S. Bronchopulmonary dysplasia frequency and risk factors in very low birth weight infants: A 3-year retrospective study. North Clin Istanb 2020;7:124-30. [Crossref] [PubMed]
32. Maytasari GM, Haksari EL, Prawirohartono EP. Predictors of Bronchopulmonary Dysplasia in Infants With Birth Weight Less Than 1500 g. Glob Pediatr Health 2023;10:2333794X231152199.
33. Ebrahimi ME, Romijn M, Vliegenthart RJS, et al. The association between clinical and biochemical characteristics of late-onset sepsis and bronchopulmonary dysplasia in preterm infants. Eur J Pediatr 2021;180:2147-54. [Crossref] [PubMed]
34. Gilfillan MA, Kiladejo A, Bhandari V. Current and Emerging Therapies for Prevention and Treatment of Bronchopulmonary Dysplasia in Preterm Infants. Paediatr Drugs 2025;27:539-62. [Crossref] [PubMed]
35. Travers CP, Carlo WA, McDonald SA, et al. Mortality and pulmonary outcomes of extremely preterm infants exposed to antenatal corticosteroids. Am J Obstet Gynecol 2018;218:130.e1-130.e13. [Crossref] [PubMed]
36. Doyle LW, Mainzer R, Cheong JLY. Systemic Postnatal Corticosteroids, Bronchopulmonary Dysplasia, and Survival Free of Cerebral Palsy. JAMA Pediatr 2025;179:65-72. [Crossref] [PubMed]
37. Perrone S, Orlando S, Petrolini C, et al. Current Concepts of Corticosteroids Use for the Prevention of Bronchopulmonary Dysplasia. Curr Pediatr Rev 2023;19:276-84. [Crossref] [PubMed]
38. Doyle LW, Cheong JL, Hay S, et al. Early (< 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 2021;10:CD001146. [Crossref] [PubMed]
39. Hou T, Huang D, Zeng R, et al. Accuracy of serum interleukin (IL)-6 in sepsis diagnosis: a systematic review and meta-analysis. Int J Clin Exp Med 2015;8:15238-45.
40. Collaco JM, McGrath-Morrow SA, Griffiths M, et al. Perinatal Inflammatory Biomarkers and Respiratory Disease in Preterm Infants. J Pediatr 2022;246:34-39.e3. [Crossref] [PubMed]
41. He RR, Yue GL, Dong ML, et al. Sepsis Biomarkers: Advancements and Clinical Applications-A Narrative Review. Int J Mol Sci 2024;25:9010. [Crossref] [PubMed]
42. Yang Y, He X, Zhang X, et al. Clinical characteristics of bronchopulmonary dysplasia in very preterm infants. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2023;48:1592-601. [Crossref] [PubMed]