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OBJECTIVES: The objective of this study is to determine the time to ventilator liberation and decannulation after tracheostomy placement in children with bronchopulmonary dysplasia (BPD) and pulmonary hypertension. METHODS: A prospective cohort study included all children (<18 years old) who underwent tracheostomy between 2015 and 2021 with or without a diagnosis of BPD. The primary outcomes were time to ventilator liberation, tracheostomy decannulation, or death with tracheostomy in place. RESULTS: A total of 303 children met inclusion with a median (interquartile range [IQR]) age at tracheostomy of 6.9 (IQR: 4.0-49.5) months. A diagnosis of BPD was made for 42% (N = 127) and this group was younger (5.1 vs. 24.5 months, p < .001) and more often had pulmonary hypertension (68% vs. 24%, p < .001). Children with BPD spent a median of 2.9 years (IQR: 1.6-4.0) on ventilation compared to 1.9 years (IQR: 0.9-3.7) for children without BPD (p = .009). The time to decannulation was greater among children with BPD (3.4 vs. 1.8 years, p < .001). However, unadjusted estimates of ventilator liberation (hazard ratio [HR]: 1.05, 95% confidence interval [95% CI]: 0.77-1.44) and decannulation (HR: 1.11, 95% CI: 0.74-1.66) over time were not prolonged by BPD. Pulmonary hypertension was associated with shorter time to death (adjusted HR [aHR] = 1.99, 95% CI: 1.17-3.38, p = .01), while BPD was associated with longer time to death (aHR: 0.38, 95% CI: 0.22-0.67, p = .001). CONCLUSION: BPD is associated with increased ventilation and duration of tracheostomy but over time many children with BPD will wean off the ventilator and be decannulated. Pulmonary hypertension and not BPD is associated with increased time to death after tracheostomy.

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Polyunsaturated fatty acids (PUFAs), especially arachidonic acid (ARA) and docosahexaenoic acid (DHA), are extremely important fatty acids for brain development in the fetus and early childhood. Premature infants face challenges obtaining these two fatty acids from their mothers. It has been reported that supplementation with triacylglycerols (TAGs) with an ARA:DHA (w/w) ratio of 2:1 may be optimal for preterm infants, as presented in commercial formulas such as Formulaid™. This study explored methods to produce TAGs with a 2:1 ratio (ARA:DHA), particularly at the more bioavailable sn-2 position of the glycerol backbone. Blending and enzymatic acidolysis of microalgae oil (rich in DHA) and ARA-rich oil yielded products with the desired ARA:DHA ratio, enhancing sn-2 composition compared to Formulaid™ (1.6 for blending and 2.3 for acidolysis versus 0.9 in Formulaid™). Optimal acidolysis conditions were 45 °C, a 1:3 substrate molar ratio, 10% Candida antarctica lipase, and 4 h. The process was reproducible, and scalable, and the lipase could be reused. In vitro digestion showed that 75.5% of the final product mixture was bio-accessible, comprising 19.1% monoacylglycerols, ~50% free fatty acids, 14.6% TAGs, and 10.1% diacylglycerols, indicating better bio-accessibility than precursor oils.

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BACKGROUND: Bronchopulmonary dysplasia (BPD) ranks among preterm infants' most common and severe respiratory diseases. Lung ultrasound scores (LUS) play a vital role in predicting early BPD and guiding treatment and intervention strategies for affected patients. OBJECTIVE: Performed a meta-analysis to assess the diagnostic LUS for newborns with BPD. METHODS: Online electronic databases such as MEDLINE, CINAHL, the Cochrane Library, and Web of Science were used to retrieve relevant research until May 2023. A total of 117 literatures were collected, and ten eligible articles were selected for meta-analysis. RESULTS: Meta-analysis was performed on 10 studies (1274 neonates). LUS at 7 days after birth (7 days of life, DOL 7) showed good diagnostic accuracy for any type of BPD, moderate and severe BPD. DOL 7 was more accurate in predicting all types of BPD (AUC = 0.87, sensitivity = 0.75, specificity = 0.83) than moderate and severe BPD (AUC = 0.80, sensitivity = 0.69, specificity = 0.79). There was no statistical significance between DOL 7 and DOL 14 in their accuracy for predicting all types of BPD (difference in AUC = 0.04, p= 0.068). There was no notable distinction between DOL 7 and DOL 14 in their accuracy for predicting moderate and severe BPD (difference in AUC =-0.04, p= 0.104). CONCLUSIONS: The diagnostic efficacy of LUS on DOL 7 in predicting the occurrence of all types of BDP and moderate-severe BPD is determined. This will facilitate rapid and accurate detection and timely treatment, thereby reducing the risk of neonatal mortality and sequelae.

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BACKGROUND: Hospital-level and international variations exist in the management strategies of bronchopulmonary dysplasia (BPD). However, studies evaluating hospital-level variations in the respiratory outcomes of pre-term infants associated with differing management strategies of BPD are lacking. OBJECTIVE: Herein, we aimed to assess inter-hospital variations in the respiratory outcomes of BPD in very pre-term and extremely pre-term infants. METHODS: In this cohort study, the administrative claims and discharge summary data were extracted from 276 hospitals in Japan between April 2014 and March 2016. This study assessed neonates of a gestational age of 22-31 weeks old, who had been hospitalised for ≥7 days. The primary outcome was a BPD defined using any respiratory support, such as supplemental oxygen, high-flow nasal cannula, CPAP, or mechanical ventilation at 36 weeks PMA. The median odds ratio (MOR) was calculated using a multilevel logistic regression model, including baseline characteristics, comorbidities, and treatment as covariates, to evaluate the inter-hospital variation of the outcome. RESULTS: Of the 8143 neonates from across 132 hospitals, 53.7% were male, with a mean gestational age (standard deviation) of 28.0 (2.5)-weeks-old and birthweight of 1086 (386) g. Among these patients, BPD occurred in 2737 (33.6%). The MOR was 2.49, representing the median value of odds ratios when comparing two neonates with identical covariates from hospitals with high and low propensity for the outcomes to occur. CONCLUSIONS: Outcome variations in the BPD were observed among hospitals in Japan, even after adjusting for individual factors, including gestational age, birthweight, comorbidities, and treatments. Thus, in Japan, developing strategies is essential to decrease the BPD rates, while minimising inter-hospital heterogeneity, to improve the healthcare quality for pre-term neonates.

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BACKGROUND: This meta-analysis aims to evaluate the potential link between common variations in the Surfactant Protein-B (SFTPB) gene and the risk of bronchopulmonary dysplasia (BPD) in preterm neonates. METHODS: All pertinent articles published prior to February 1, 2024, in PubMed, Web of Science, EMBASE, CNKI, and Scopus databases were reviewed. RESULTS: Nineteen case-control studies involving 1149 BPD cases and 1845 non-BPD controls, were analyzed. Combined data indicated a significant link between SFTPB -18 A > C and Intron 4 VNTR polymorphisms with increased BPD susceptibility, while the 1580 C > T polymorphism provides a protective impact on BPD initiation. CONCLUSIONS: Pooled data indicated a significant association between SFTPB -18 A > C and Intron 4 VNTR polymorphisms with increased BPD risk, whereas the 1580 C > T polymorphism confers protection. These findings suggest a genetic susceptibility to BPD, underscoring the complex interplay of different genetic elements in its development.

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Bronchopulmonary dysplasia (BPD) poses a significant challenge as the most common late morbidity of preterm infants. This study aimed to evaluate airway abnormalities in infants with BPD who underwent flexible bronchoscopy (FB) to gain insights into the prevalence of upper airway obstruction and associated complications. A retrospective case-control study was conducted on BPD patients who underwent FB at a tertiary center between 2013 and 2023. BPD patients were matched (1:3) with a reference group based on age, gender, and ethnicity, who also had undergone FB. Demographic data, comorbidities, indications for FB, findings, and complications during and after FB were collected. The study included 50 BPD patients (mean age 1.26 ± 0.9 years, 58% males), and 150 controls. As expected, BPD patients had a lower gestational age, lower birth weight, and longer hospitalizations and were treated with more medications. Abnormal bronchoscopy findings were significantly more common in the BPD group compared to the reference group, with an increased rate of turbinate hypertrophy (OR [95% CI]: 3.44 [1.27-9.37], P = 0.014), adenoid hypertrophy (OR: 2.7 [1.38-5.29], P = 0.004), lingual tonsils (OR: 5.44 [1.29-27.4], P = 0.0024), subglottic stenosis (OR: 6.95 [2.08-27.1], P = 0.002), and tracheomalacia (OR: 2.98 [1.06-8.19], P = 0.034). Complications including desaturation (OR: 3.89 [1.32-11.7], P = 0.013) and PICU admission (OR: 16.6 [2.58-322], P = 0.011) were more frequent in the BPD than in the reference group. CONCLUSION: The study revealed a high prevalence of structural anomalies leading to upper airway obstruction and complications in infants with BPD undergoing FB. These findings emphasize the importance of careful consideration and preparation for bronchoscopic procedures in this vulnerable population. WHAT IS KNOWN: • Bronchopulmonary dysplasia (BPD) represents the most prevalent late morbidity among preterm infants. • Preterm infants diagnosed with BPD frequently undergo diagnostic procedures, including flexible and rigid bronchoscopies, to identify structural pathologies within the respiratory tract. WHAT IS NEW: • A significantly higher prevalence of structural anomalies leading to upper airway obstruction was observed in the BPD group compared to controls. • The incidence of complications during flexible bronchoscopy was higher in the BPD group than in controls.

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Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in infants and the most frequent adverse outcome of premature birth, despite major efforts to minimize injury. It is thought to result from aberrant repair response triggered by either prenatal or recurrent postnatal injury to the lungs during development. Intrauterine inflammation is an important risk factor for prenatal lung injury, which is also increasingly linked to BPD. However, the specific mechanisms remain unclear. This review summarizes clinical and animal research linking intrauterine inflammation to BPD. We assess how intrauterine inflammation affects lung alveolarization and vascular development. In addition, we discuss prenatal therapeutic strategies targeting intrauterine inflammation to prevent or treat BPD.

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Neonatal bronchopulmonary dysplasia (BPD) is associated with alveolar simplification and airway remodeling. Airway remodeling leads to deformation of airways characterized by peribronchial collagen deposition and hypertrophy of airway smooth muscle, which contribute to the narrowing of airways. Poorly developed lungs contribute to reduced lung function that deteriorates with the passage of time. We have earlier shown that sphingosine kinase 1 (SPHK 1)/ sphingosine-1-phosphate (S1P) /S1P receptor1 (S1PR1) signaling play a role in the pathogenesis of BPD. In this study, we investigated the role of fingolimod or FTY720, a known S1PR1 modulator approved for treatment of multiple sclerosis in the treatment of BPD. Fingolimod promotes degradation of S1PR1 by preventing its recycling thus serving as the equivalent of an inhibitor. Exposure of neonatal mice to hyperoxia enhanced the expression of S1PR1 in both airways and alveoli as compared to normoxia. This increased expression of S1PR1 in the airways persisted into adulthood accompanied by airway remodeling and airway hyperreactivity (AHR) post neonatal hyperoxia. Intranasal fingolimod at a much lower dose compared to intraperitoneal route of administration during neonatal hyperoxia improved alveolarization in neonates and reduced airway remodeling and AHR in adult mice associated with improved lung function. The intranasal route was not associated with leucopenia seen with intraperitoneal route of administration of the drug. An increase in S1PR1 expression in the airways was associated with an increase in the expression of enzyme lysyl oxidase (LOX) in the airways following hyperoxia which was suppressed by fingolimod. This association warrants further investigation.

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BACKGROUND: Premature infants requiring mechanical ventilation and supplemental oxygen for respiratory support are at increased risk for bronchopulmonary dysplasia (BPD), wherein inflammation have been proposed as a driver of hyperoxia-induced injuries, including persistent loss of endothelial progenitor cells (EPCs), impaired vascularization and eventual alveolar simplification in BPD lungs. However, the underlying mechanisms linking these phenomena remain poorly defined. METHODS: We used clodronate liposomes to deplete macrophages in a mouse model of neonatal hyperoxia-induced lung injury to evaluate if EPC loss in BPD lungs could be an effect of macrophage infiltration. We further generated in vitro culture systems initiated with cord blood (CB)-derived CD34+ EPCs and neonatal macrophages either polarized from CB-derived monocytes or isolated from tracheal aspirates of human preterm infants requiring mechanical ventilation and oxygen supplementation, to identify EV-transmitted molecular mechanism that is critical for inhibitory actions of hyperoxic macrophages on EPCs. RESULTS: Initial experiments using mouse model identified the crucial role of macrophage infiltration in eliciting significant reduction of c-Kit+ EPCs in BPD lungs. Further examination of this concept in human system, we found that hyperoxia-exposed neonatal macrophages hamper human CD34+ EPC maintenance and impair endothelial function in the differentiated progeny via the EV transmission of miR-23a-3p. Notably, treatment with antagomiR-23a-3p to silence miR-23a-3p in vivo enhances c-Kit+ EPC maintenance, and increases capillary density, and consequently mitigates simplified alveolarization in BPD lungs. CONCLUSION: Our findings highlight the importance of pulmonary intercellular communication in the pathophysiology of BPD, by identifying a linkage through vesicle transfer of miR-23a-3p from hyperoxic macrophages to EPCs, and thus demonstrating potential for novel therapeutic target in BPD.

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Prematurity is associated with lower exercise capacity, which relies on the integrity of the cardiovascular, pulmonary, and skeletal muscle systems. Our animal model mimicking prematurity-associated conditions showed altered muscle composition and atrophy in adulthood. This study aimed to compare muscle composition and strength in adults born preterm versus full-term controls. This observational cohort study recruited 55 adults born preterm, ≤ 29 weeks' of gestation and 53 full-term controls who underwent musculoskeletal ultrasound imaging to assess morphology of the rectus femoris at rest and during a maximal voluntary contraction. Maximal voluntary contraction of the hands and legs were measured by manual dynamometry. In adults born preterm, there was lower muscle strength (handgrip: - 4.8 kg, 95% CI - 9.1, - 0.6; knee extensor: - 44.6 N/m, 95% CI - 63.4, - 25.8) and smaller muscle area (- 130 mm2, 95% CI - 207, - 53), which was more pronounced with a history of bronchopulmonary dysplasia. Muscle stiffness was increased in the preterm versus term group (0.4 m/s, 95% CI 0.04, 0.7). Prematurity is associated with alterations in skeletal muscle composition, area, and function in adulthood. These findings highlight the necessity to implement preventive and/or curative approaches to improve muscle development and function following preterm birth to enhance overall health in this population.

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Bronchopulmonary dysplasia (BPD) is fundamentally characterized by the arrest of lung development and abnormal repair mechanisms, which result in impaired development of the alveoli and microvasculature. Hepatocyte growth factor (HGF), secreted by pulmonary mesenchymal and endothelial cells, plays a pivotal role in the promotion of epithelial and endothelial cell proliferation, branching morphogenesis, angiogenesis, and alveolarization. HGF exerts its beneficial effects on pulmonary vascular development and alveolar simplification primarily through two pivotal pathways: the stimulation of neovascularization, thereby enriching the pulmonary microvascular network, and the inhibition of the epithelial-mesenchymal transition (EMT), which is crucial for maintaining the integrity of the alveolar structure. We discuss HGF and its receptor c-Met, interact with various growth factors throughout the process of lung development and BPD, and form a signaling network with HGF as a hub, which plays the pivotal role in orchestrating and integrating epithelial, endothelial and mesenchymal.

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The objective of this study was to identify and characterize oxidative stress (OS)-related biomarkers in bronchopulmonary dysplasia (BPD) through a combination of bioinformatics analyses and wet experiments. The study utilized the Gene Expression Omnibus database to obtain the mRNA expression profile dataset GSE32472. Differential expression analysis and functional enrichment analysis were employed to investigate the role of OS-related genes in BPD. Gene Ontology Function Enrichment Analysis and Gene Set Enrichment Analysis were conducted to understand the mechanisms behind the signature. Protein-protein interaction analysis to identify hub genes in BPD, and predictions were made for microRNAs (miRNAs), transcription factors (TFs), and potential medications targeting these genes. CIBERSORT was utilized to investigate the correlation between hub genes and the infiltration of immune cells. Hub genes were ultimately determined and confirmed using expression analysis, correlation analysis, receiver operating characteristic (ROC) analysis, and quantitative real-time PCR (qRT-PCR). A novel OS-related gene signature (ARG1, CSF3R, IL1R1, IL1R2, MMP9, RETN, S100A12, and SOCS3) was constructed for the prediction of BPD. We identified 18 miRNAs, 14 TFs, and 30 potential medications targeting these genes. ROC analysis further validated that these genes could diagnose BPD with high specificity and sensitivity. The qRT-PCR revealed that IL1R1 and ARG1 were highly expressed in the lung tissue of the model group, while the expressions of RETN, SOCS3, IL1R2, and MMP9 were decreased. This study demonstrated that ARG1, CSF3R, IL1R1, IL1R2, MMP9, RETN, S100A12, and SOCS3 may serve as potential diagnostic biomarkers in BPD. Furthermore, a significant association between IL1R1 and the pathogenesis of BPD is observed.

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INTRODUCTION: Bronchopulmonary dysplasia (BPD) stands as the primary chronic respiratory complication in premature infants, posing a substantial public health concern due to its rising prevalence, potential mortality, and socioeconomic burden. AIM: The aim of this study was to determine the prevalence of BPD in very preterm infants and identify its associated risk factors. METHODS: We conducted a retrospective, descriptive, and analytical study including all premature infants born between 26 and 31 weeks of gestation age (GA) who survived beyond the 28th day of life, over a five-year period (2017-2021). Patients were divided into two groups based on the presence or absence of BPD, which was defined by the need for oxygen supplementation for at least 28 days. RESULTS: we included 231 newborns. The prevalence of BPD was 37.7% among survivors on the 28th day of life and 36.7% among those reaching 36 weeks postmenstrual age. BPD was mild, moderate and severe in 25.2%, 4.9% and 6.6% of cases, respectively. Multivariate analysis identified maternal hypertensive disorders (RR=6.15, 95%CI=[2.27-16.67], p<0.001), chorioamnionitis (RR=4.23, 95%CI=[1.25 -14.27], p=0.02), intrauterine growth restriction (IUGR) (RR =20.4, 95%CI=[3.39 -122.66], p=0.001), GA less than 30 weeks (RR=26.97, 95%CI=[10.23 -71.14], p<0.001), and mechanical ventilation (MV) (RR=5.33, 95%CI=[1.95-14.54], p=0.001) as independent factors associated with BPD occurrence. The mortality rate was 10.3% among patients with BPD versus 0.7% in patients without BPD (p = 0.001). CONCLUSION: Our study revealed a high prevalence of BPD in very preterm infants and identified several independent risk factors such as maternal hypertensive disorders, IUGR, chorioamnionitis, MV, and GA less than 30 weeks.

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BACKGROUND: To evaluate the impact of implementation of 2019 European respiratory distress syndrome (RDS) guidelines on the incidence of bronchopulmonary dysplasia (BPD). METHOD: We retrospectively collected the clinical data of very preterm infants (VPIs) born before 32 gestational weeks from January 1st 2018 to December 31st 2021. VPIs were divided into group A and group B according to their birth date which was before or at/after January 1st 2020, when the 2019 European RDS guidelines were introduced. BPD is considered as primary outcome. We statistically analyzed all the data, and we compared the general characteristics, ventilation support, medication, nutrition and the outcomes between the two groups. RESULTS: A total of 593 VPIs were enrolled, including 380 cases in group A and 213 cases in group B. There were no statistic differences regarding to gender ratio, gestational age, birth weight and delivery mode between the two groups. Compared with group A, group B showed higher rate of antenatal corticosteroid therapy (75.1% vs. 65.5%). The improvement of ventilation management in these latter patients included lower rate of invasive ventilation (40.4% vs. 50.0%), higher rate of volume guarantee (69.8% vs. 15.3%), higher positive end expiratory pressure (PEEP) [6 (5, 6) vs. 5 (5, 5) cmH2O] and higher rate of synchronized nasal intermittent positive pressure ventilation (sNIPPV) (36.2% vs. 5.6%). Compared with group A, group B received higher initial dose of pulmonary surfactant [200 (160, 200) vs. 170 (130, 200) mg/Kg], shorter antibiotic exposure time [13 (7, 23) vs. 17 (9, 33) days], more breast milk (86.4% vs. 70.3%) and earlier medication for hemodynamically significant patent ductus arteriosus (hsPDA) treatment [3 (3, 4) vs. 8 (4, 11) days] (p < 0.05). As the primary outcome, the incidence of BPD was significantly decreased (16.9% vs. 24.2%) (p < 0.05), along with lower extrauterine growth retardation (EUGR) rate (39.0% vs. 59.7%), while there were no statistic differences regarding to other secondary outcomes, including mortality, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of preterm (ROP) and necrotizing enterocolitis (NEC). However, in the subgroups of infants less than 28 gestational weeks or infants less than 1,000 g, the incidence of BPD was not significantly decreased (p > 0.05). CONCLUSIONS: After implementation of 2019 European RDS guidelines, the overall incidence of BPD was significantly decreased in VPIs. Continuous quality improvement is still needed in order to decrease the incidence of BPD in smaller infants who are less than 28 gestational weeks or less than 1,000 g.

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Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants, with its incidence rising due to improved survival rates of these infants. BPD results from a combination of prenatal and postnatal factors, such as mechanical ventilation, oxygen toxicity, and infections, all of which significantly impact the prognosis and growth of affected infants. Current treatment options for BPD are largely supportive and do not address the underlying pathology. Exosomes are cell-derived bilayer-enclosed membrane structures enclosing proteins, lipids, RNAs, growth factors, cytokines and metabolites. They have become recognized as crucial regulators of intercellular communication in various physiological and pathological processes. Previous studies have revealed the therapeutic potential of human umbilical cord mesenchymal stem cells-derived exosomes (HUCMSCs-Exos) in promoting tissue repair and regeneration. Therefore, HUCMSCs-Exos maybe a promising and effective therapeutic modality for BPD. In this review, we firstly provide a comprehensive overview of BPD, including its etiology and the mechanisms of lung injury. Then we detail the isolation, characterization, and contents of HUCMSCs-Exos, and discuss their potential mechanisms of HUCMSCs-Exos in BPD treatment. Additionally, we summarize current clinical trials and discuss the challenges in translating these findings from bench to bedside. This review aims to lay the groundwork for future clinical applications of HUCMSCs-Exos in treating BPD.

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BACKGROUND: Antenatal corticosteroids (ACS) are administered to prevent neonatal complications and death in women at risk of imminent preterm birth. Internationally, the optimal interval from ACS to delivery (ACS-to-delivery interval) is within seven days; however, evidence in Asian populations specifically is limited. This study aimed to investigate the association between ACS-to-delivery interval and the incidence of neonatal complications in Japan. METHODS: This retrospective observational study enrolled singleton neonates born preterm at < 32 weeks of gestational age between 2012 and 2020 at two tertiary centers. A total of 625 neonates were divided into the following four groups according to the timing of ACS (measured in days): no ACS (n = 145), partial ACS (n = 85), ACS 1-7 (n = 307), and ACS ≥ 8 (n = 88). The following outcomes were compared between the groups: treated respiratory distress syndrome (RDS), severe intraventricular hemorrhage (IVH), treated patent ductus arteriosus (PDA), necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (ROP), periventricular leukomalacia, and death discharge. RESULTS: The ACS 1-7 group had significantly decreased adjusted odds ratios (ORs) for treated RDS (0.37 [95% confidence interval: 0.23, 0.57]), severe IVH (0.21 [0.07, 0.63]), treated PDA (0.47 [0.29, 0.75]), and treated ROP (0.50 [0.25, 0.99]) compared with the no ACS group. The ACS ≥ 8 group also showed significantly reduced adjusted ORs for RDS (0.37 [0.20, 0.66]) and treated PDA (0.48 [0.25, 0.91]) compared with the no ACS group. However, the adjusted ORs for BPD significantly increased in both the ACS 1-7 (1.86 [1.06, 3.28]) and ACS ≥ 8 groups (2.94 [1.43, 6.05]) compared to the no ACS group. CONCLUSIONS: An ACS-to-delivery interval of 1-7 days achieved the lowest incidence of several complications in preterm neonates born at < 32 weeks of gestational age. Some of the favorable effects of ACS seem to continue even beyond ≥ 8 days from administration. In contrast, ACS might be associated with an increased incidence of BPD, which was most likely to be prominent in neonates delivered ≥ 8 days after receiving ACS. Based on these findings, the duration of the effect of ACS on neonatal complications should be studied further.

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BACKGROUND: Bronchopulmonary dysplasia (BPD) is a severe chronic lung disease primarily affecting premature infants, often resulting from prolonged mechanical ventilation and oxygen therapy. Oxidative stress plays a critical role in the pathogenesis of BPD, contributing to lung injury, inflammation, and impaired lung development. Despite extensive research, there is a need to systematically map out the research trends and hotspots in this field to inform future studies and therapeutic strategies. METHODS: This study utilized bibliometric and visualized analysis to explore global research trends and hotspots on oxidative stress and BPD from 2004 to 2024. A comprehensive literature search was conducted in the Web of Science Core Collection, focusing on publications related to oxidative stress and BPD. Tools such as VOSviewer, Citespace, and the R package Bibliometrix were employed to analyze Coauthorship, co-citation, and keyword co-occurrence networks, as well as to identify emerging research fronts and influential studies. RESULTS: The analysis identified 597 relevant publications, showing a steady increase in research output over the 20-year period, with a significant surge in the last decade. The United States led in research contributions, followed by China and Germany, with notable collaborations among these countries. Coauthorship analysis highlighted key research institutions, such as Harvard University and the University of California, as central nodes in the research network. Thematic clustering revealed five major research areas: antioxidant mechanisms, inflammation, molecular pathways, lung development, and therapeutic interventions. The keyword co-occurrence analysis showed a shift in research focus over time. Early studies concentrated on basic pathophysiological mechanisms, while recent research has increasingly focused on advanced molecular techniques, such as gene expression and targeted therapies. Notably, the study identified emerging research hotspots, including the role of extracellular vesicles and cellular senescence in BPD, as well as the potential therapeutic applications of antioxidants like superoxide dismutase mimetics. CONCLUSION: This bibliometric study provides a comprehensive overview of the research landscape on oxidative stress and BPD, identifying key trends, influential authors, and emerging research topics. The findings underscore the importance of continued research in this field, particularly in translating basic scientific insights into clinical applications to improve outcomes for infants affected by BPD. The study also highlights potential areas for future investigation, including the development of novel therapeutic strategies targeting oxidative stress in BPD.

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Bronchopulmonary dysplasia (BPD) remains the most common respiratory disorder of prematurity for infants born before 32 weeks of gestational age (GA). Early and prolonged exposure to chronic hypoxia and inflammation induces pulmonary hypertension (PH) with the characteristic features of a reduced number and increased muscularisation of the pulmonary arteries resulting in an increase in the pulmonary vascular resistance (PVR) and a fall in their compliance. BPD and BPD-associated pulmonary hypertension (BPD-PH) together with systemic hypertension (sHTN) are chronic cardiopulmonary disorders which result in an increased mortality and long-term problems for these infants. Previous studies have predominantly focused on the pulmonary circulation (right ventricle and its function) and developing management strategies accordingly for BPD-PH. However, recent work has drawn attention to the importance of the left-sided cardiac function and its impact on BPD in a subset of infants arising from a unique pathophysiology termed postcapillary PH. BPD infants may have a mechanistic link arising from chronic inflammation, cytokines, oxidative stress, catecholamines, and renin-angiotensin system activation along with systemic arterial stiffness, all of which contribute to the development of BPD-sHTN. The focus for the treatment of BPD-PH has been improvement of the right heart function through pulmonary vasodilators. BPD-sHTN and a subset of postcapillary PH may benefit from afterload reducing agents such as angiotensin converting enzyme inhibitors. Preterm infants with BPD-PH are at risk of later cardiac and respiratory morbidities as young adults. This paper reviews the current knowledge of the pathophysiology, diagnosis, and treatment of BPD-PH and BPD-sHTN. Current knowledge gaps and emerging new therapies will also be discussed.

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The lung macrophages play a crucial role in health and disease. Sexual dimorphism significantly impacts the phenotype and function of tissue-resident macrophages. The primary mechanisms responsible for sexually dimorphic outcomes in bronchopulmonary dysplasia (BPD) remain unidentified. We tested the hypothesis that biological sex plays a crucial role in the transcriptional state of alveolar macrophages, using neonatal murine hyperoxia-induced lung injury as a relevant model for human BPD. The effects of neonatal hyperoxia exposure (95 % FiO2, PND1-5: saccular stage) on the lung myeloid cells acutely after injury and during normoxic recovery were measured. Alveolar macrophages (AM) from room air- and hyperoxia exposed from male and female neonatal murine lungs were subjected to bulk-RNA Sequencing. AMs are significantly depleted in the hyperoxia-exposed lung acutely after injury, with subsequent recovery in both sexes. The transcriptome of the alveolar macrophages is impacted by neonatal hyperoxia exposure and by sex as a biological variable. Pathways related to DNA damage and interferon-signaling were positively enriched in female AMs. Metabolic pathways related to glucose and carbohydrate metabolism were positively enriched in the male AMs, while oxidative phosphorylation was negatively enriched. These pathways were shared with monocytes and airway macrophages from intubated male and female human premature neonates.

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