[The diagnostic value of inflammation-related genes in bronchopulmonary dysplasia].

This study aims to explore the diagnostic value of inflammation-related genes in peripheral blood mononuclear cells in bronchopulmonary dysplasia (BPD). By using bioinformatics analysis, three datasets including GSE32472, GSE125873, and GSE220135, which contain whole-genome expression profile data of 251 neonates, were included. The GSE32472 dataset was used as a training dataset to detect differentially expressed genes between non-BPD and BPD neonates in peripheral blood mononuclear cells. The gene enrichment analysis (GSEA) was used to detect the pathway enrichment of up-regulated genes in BPD newborns. The main regulatory factors analysis (MRA) algorithm was used to filter the main regulatory genes in the inflammation-related pathway (GO:0006954). After obtaining the main regulatory genes, the expression of the main regulatory genes in the GSE32472, GSE125873, and GSE220135 datasets was detected. Through the logistic regression model, risk scoring was conducted for neonates, and the risk scores of non-BPD and BPD neonates were compared. Lastly, the classification performance of the model was evaluated using the area under the curve (AUC). The results showed that compared with non-BPD neonates, there were 486 up-regulated genes and 433 down-regulated genes in the peripheral blood mononuclear cells of BPD neonates. The inflammation-related pathway was highly enriched in the up-regulated genes. Ultimately, phospholipase C beta 1 (PLCB1), nidogen 1 (NID1), serum response factor binding protein 1 (SRFBP1), centrosomal protein 72 (CEP72), excision repair cross complementation group 6 like (ERCC6L), and peptidylprolyl isomerase like 1 (PPIL1) were identified as the main regulatory genes. The prediction model's calculation formula for risk score was PLCB1×0.26+NID1×0.97+SRFBP1×1.58+CEP72×(-0.36)+ERCC6L×2.14+PPIL1×0.67. The AUCs in the GSE32472 test dataset, GSE125873 dataset, and GSE220135 dataset were 0.88, 0.86, and 0.89, respectively. This prediction model could distinguish between non-BPD and BPD neonates. In conclusion, the prediction model based on inflammation-related pathway genes has a certain diagnostic value for BPD.

Using machine-learning models to predict extubation failure in neonates with bronchopulmonary dysplasia.

AIM: To develop a decision-support tool for predicting extubation failure (EF) in neonates with bronchopulmonary dysplasia (BPD) using a set of machine-learning algorithms. METHODS: A dataset of 284 BPD neonates on mechanical ventilation was used to develop predictive models via machine-learning algorithms, including extreme gradient boosting (XGBoost), random forest, support vector machine, naïve Bayes, logistic regression, and k-nearest neighbor. The top three models were assessed by the area under the receiver operating characteristic curve (AUC), and their performance was tested by decision curve analysis (DCA). Confusion matrix was used to show the high performance of the best model. The importance matrix plot and SHapley Additive exPlanations values were calculated to evaluate the feature importance and visualize the results. The nomogram and clinical impact curves were used to validate the final model. RESULTS: According to the AUC values and DCA results, the XGboost model performed best (AUC = 0.873, sensitivity = 0.896, specificity = 0.838). The nomogram and clinical impact curve verified that the XGBoost model possessed a significant predictive value. The following were predictive factors for EF: pO2, hemoglobin, mechanical ventilation (MV) rate, pH, Apgar score at 5 min, FiO2, C-reactive protein, Apgar score at 1 min, red blood cell count, PIP, gestational age, highest FiO2 at the first 24 h, heart rate, birth weight, pCO2. Further, pO2, hemoglobin, and MV rate were the three most important factors for predicting EF. CONCLUSIONS: The present study indicated that the XGBoost model was significant in predicting EF in BPD neonates with mechanical ventilation, which is helpful in determining the right extubation time among neonates with BPD to reduce the occurrence of complications.

A phase II, multicenter, nonblinded, randomized controlled trial for evaluating protective effects of ABPC/SBT plus, azithromycin versus erythromycin, in pregnant women with pPROM occurring at <28 weeks of gestation on the development of BPD in neonates: Study protocol.

This is a protocol for PPROM-AZM Study, phase II, nonblinded, randomized controlled trial. Bronchopulmonary dysplasia (BPD) at a postmenstrual age of 36 weeks (BPD36) is often observed in infants with preterm premature rupture of the membranes (pPROM). A regimen of ampicillin (ABPC) intravenous infusion for 2 days and subsequent amoxicillin (AMPC) oral administration for 5 days plus erythromycin (EM) intravenous infusion for 2 days followed by EM oral administration for 5 days is standard treatment for pPROM. However, the effect on the prevention of moderate/severe BPD36 using the standard treatment has not been confirmed. Recently, it is reported that ampicillin/sulbactam (ABPC/SBT) plus azithromycin (AZM) was effective for the prevention of moderate/severe BPD36 in pPROM patients with amniotic infection of Ureaplasma species. Therefore, our aim is to evaluate the occurrence rate of the composite outcome of "incidence rate of either moderate/severe BPD36 or intrauterine fetal death, and infantile death at or less than 36 weeks 0 days" comparing subjects to receive ABPC/SBT for 14 days plus AZM for 14 days (intervention group) and those to receive ABPC/SBT for 14 days plus EM for 14 days (control group), in a total of 100 subjects (women with pPROM occurring at 22-27 weeks of gestation) in Japan. The recruit of subjects was started on April 2022, and collection in on-going. We also investigate the association between the detection of Ureaplasma species and occurrence of BPD36. In addition, information on any adverse events for the mother and fetus and serious adverse events for infants are collected during the observation period. We allocate patients at a rate of 1:1 considering two stratification factors: onset of pPROM (22-23 or 24-27 weeks) and presence/absence of a hospital policy for early neonatal administration of caffeine. Trial registration: The trial number in the Japan Registry of Clinical Trials is jRCTs031210631.

High oxygen exposure's impact on newborn mice: Temporal changes observed via micro-computed tomography.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) impacts life expectancy and long-term quality of life. Currently, BPD mouse models exposed to high oxygen are frequently used, but to reevaluate their relevance to human BPD, we attempted an assessment using micro-computed tomography (µCT). METHODS: Newborn wildtype male mice underwent either 21% or 95% oxygen exposure for 4 days, followed until 8 wk. Weekly µCT scans and lung histological evaluations were performed independently. RESULTS: Neonatal hyperoxia for 4 days hindered lung development, causing alveolar expansion and simplification. Histologically, during the first postnatal week, the exposed group showed a longer mean linear intercept, enlarged alveolar area, and a decrease in alveolar number, diminishing by week 4. Weekly µCT scans supported these findings, revealing initially lower lung density in newborn mice, increasing with age. However, the high-oxygen group displayed higher lung density initially. This difference diminished over time, with no significant contrast to controls at 3 wk. Although no significant difference in total lung volume was observed at week 1, the high-oxygen group exhibited a decrease by week 2, persisting until 8 wk. CONCLUSION: This study highlights µCT-detected changes in mice exposed to high oxygen. BPD mouse models might follow a different recovery trajectory than humans, suggesting the need for further optimization.

Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Association of cord blood Ang-1 and sCD105 levels with bronchopulmonary dysplasia in preterm infants.

BACKGROUND: To investigate the relationship between cord blood levels of Angiopoietin-1 (Ang-1) and S-endoglin (sCD105) and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Sixty-one preterm infants admitted to the neonatal intensive care unit of the study hospital between July 2021 and September 2022 were included. Cord blood was collected after the birth of premature infants. Ang-1 and sCD105 levels were quantified using the vascular endothelial growth factor enzyme-linked immunosorbent assay. Preterm infants were divided into BPD and non-BPD groups, and differences in Ang-1 and sCD105 levels between the two groups were compared. A binary logistic model was used to assess the association between low and high levels Ang-1 and BPD in preterm infants. RESULTS: In the study, there were 20 preterm infants with BPD (32.8%) and 41 preterm infants with non-BPD (67.2%). Ang-1 concentration levels were lower in the BPD group than in the non-BPD group (7105.43 (5617.01-8523.00) pg/ml vs. 10488.03 (7946.19-15962.77) pg/ml, P = 0.027). However, the sCD105 concentration levels were not significantly different between the BPD and non-BPD groups (P = 0.246). A median Ang-1 concentration of 8800.40 pg/ml was calculated. Logistic regression analysis showed that after adjusting for gestational age, birth weight, and maternal prenatal steroid hormone application, the odds ratio (OR) was 8.577 for the risk of BPD in preterm infants with Ang-1 concentrations of ≤ 8800.40 pg/ml compared to those with Ang-1 concentrations of > 8800.40 pg/ml (OR: 8.577, 95% confidence interval: 1.265-58.155, P = 0.028). CONCLUSION: Our study indicated that Ang-1 levels in the cord blood of preterm infants may be associated the risk of BPD. In the future, we will continue to conduct study with large samples.

[Role and mechanism of epithelial-mesenchymal transition in a rat model of bronchopulmonary dysplasia induced by hyperoxia exposure]. / 上皮-间å è´¨è½¬åŒ–åœ¨é«˜æ°§è¯±å¯¼å¤§é¼ æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯æ¨¡åž‹ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To investigate the role and mechanism of epithelial-mesenchymal transition (EMT) in a rat model of bronchopulmonary dysplasia (BPD). METHODS: The experiment consisted of two parts. (1) Forty-eight preterm rats were randomly divided into a normoxia group and a hyperoxia group, with 24 rats in each group. The hyperoxia group was exposed to 85% oxygen to establish a BPD model, while the normoxia group was kept in room air at normal pressure. Lung tissue samples were collected on days 1, 4, 7, and 14 of the experiment. (2) Rat type II alveolar epithelial cells (RLE-6TN) were randomly divided into a normoxia group (cultured in air) and a hyperoxia group (cultured in 95% oxygen), and cell samples were collected 12, 24, and 48 hours after hyperoxia exposure. Hematoxylin-eosin staining was used to observe alveolarization in preterm rat lungs, and immunofluorescence was used to detect the co-localization of surfactant protein C (SPC) and α-smooth muscle actin (α-SMA) in preterm rat lung tissue and RLE-6TN cells. Quantitative real-time polymerase chain reaction and protein immunoblotting were used to detect the expression levels of EMT-related mRNA and proteins in preterm rat lung tissue and RLE-6TN cells. RESULTS: (1) Compared with the normoxia group, the hyperoxia group showed blocked alveolarization and simplified alveolar structure after 7 days of hyperoxia exposure. Co-localization of SPC and α-SMA was observed in lung tissue, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 7 and 14 days of hyperoxia exposure compared to the normoxia group. In the hyperoxia group, the mRNA and protein levels of TGF-ß1, α-SMA, and N-cadherin were increased, while the mRNA and protein levels of SPC and E-cadherin were decreased at 7 and 14 days of hyperoxia exposure compared to the normoxia group (P<0.05). (2) SPC and α-SMA was observed in RLE-6TN cells, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 24 and 48 hours of hyperoxia exposure compared to the normoxia group. Compared to the normoxia group, the mRNA and protein levels of SPC and E-cadherin in the hyperoxia group were decreased, while the mRNA and protein levels of TGF-ß1, α-SMA, and E-cadherin in the hyperoxia group increased at 48 hours of hyperoxia exposure (P<0.05). CONCLUSIONS: EMT disrupts the tight connections between alveolar epithelial cells in a preterm rat model of BPD, leading to simplified alveolar structure and abnormal development, and is involved in the development of BPD. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 765-773.

Prophylactic sildenafil to prevent bronchopulmonary dysplasia: A systematic review and meta-analysis.

BACKGROUND: Bronchopulmonary dysplasia (BPD) persists as one of the foremost factors contributing to mortality and morbidity in extremely preterm infants. The effectiveness of administering sildenafil early on to prevent BPD remains uncertain. The aim of this study was to investigate the efficacy and safety of prophylactically administered sildenafil during the early life stages of preterm infants to prevent mortality and BPD. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and Ichushi were searched. Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. Two reviewers independently screened the title, abstract, and full text, extracted data, assessed the risk of bias, and evaluated the certainty of evidence (CoE) following the Grading of Recommendations Assessment and Development and Evaluation approach. The random-effects model was used for a meta-analysis of RCTs. RESULTS: This review included three RCTs (162 infants). There were no significant differences between the prophylactic sildenafil and placebo groups in mortality (risk ratio [RR]: 1.32; 95% confidence interval [CI]: 0.16-10.75; very low CoE), BPD (RR: 1.20; 95% CI: 0.79-1.83; very low CoE), and all other outcome assessed (all with very low CoE). The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials. CONCLUSIONS: The prophylactic use of sildenafil in individuals at risk of BPD did not indicate any advantageous effects in terms of mortality, BPD, and other outcomes, or increased side effects.

Bioinformatics analyses and experimental validation of ferroptosis-related genes in bronchopulmonary dysplasia pathogenesis.

OBJECTIVE: We aimed to study the involvement of ferroptosis in the pathogenesis of bronchopulmonary dysplasia (BPD) by conducting bioinformatics analyses and identifying and validating the associated ferroptosis-related genes to explore new directions for treating BPD. METHODS: The dataset GSE32472 on BPD was downloaded from the public genome database. Using R language, differentially expressed genes (DEGs) between the BPD and normal group were screened. In the present study, we adopted weighted gene correlation network analysis (WGCNA) for identifying BPD-related gene modules and ferroptosis-related genes were extracted from FerrDb. Their results were intersected to obtain the hub genes. After that, to explore the hub gene-related signaling pathways, the hub genes were exposed to gene ontology enrichment analysis. With the purpose of verifying the mRNA expression of the hub genes, a single-gene gene set enrichment analysis and quantitative reverse transcription polymerase chain reaction were conducted. Immune cell infiltration in BPD was analyzed using the CIBERSORT inverse fold product algorithm. RESULTS: A total of 606 DEGs were screened. WGCNA provided the BPD-related gene module darkgreen4. The intersection of DEGs, intramodular genes, and ferroptosis-related genes revealed six ferroptosis-associated hub genes (ACSL1, GALNT14, WIPI1, MAPK14, PROK2, and CREB5). Receiver operating characteristic curve analysis demonstrated that the hub genes screened for BPD were of good diagnostic significance. According to the results of immune infiltration analysis, the proportions of CD8, CD4 naive, and memory resting T cells and M2 macrophage were elevated in the normal group, and the proportions of M0 macrophage, resting mast cell, and neutrophils were increased in the BPD group. CONCLUSIONS: A total of six ferroptosis-associated hub genes in BPD were identified in this study, and they may be potential new therapeutic targets for BPD.

Association of different doses of antenatal corticosteroids exposure with early major outcomes and early weight loss percentage in extremely preterm infants or extremely low birthweight infants: a multicentre cohort study.

OBJECTIVES: To determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI) or extremely low birthweight infants (ELBWI). METHODS: A multicentre, retrospective cohort study of EPI or ELBWI born between 2017 and 2018 was conducted. Infants were classified into no ANS, partial ANS and complete ANS exposure group; three subgroups were generated by gestational age and birth weight. Multiple logistic regression and multiple linear regression were performed. RESULTS: There were 725 infants included from 32 centres. Among no ANS, partial ANS and complete ANS exposure, there were significant differences in the proportions of bronchopulmonary dysplasia (BPD) (24.5%, 25.4% and 16.1%), necrotising enterocolitis (NEC) (6.7%, 2.0% and 2.0%) and death (29.6%, 18.5% and 13.5%), and insignificant differences in the proportions of intraventricular haemorrhage (IVH) (12.5%, 13.2% and 12.2%), and extrauterine growth restriction (EUGR) (50.0%, 56.6% and 59.5%). In the logistic regression, compared with no ANS exposure, complete ANS reduced the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91), NEC (OR 0.21, 95% CI 0.08 to 0.57) and death (OR 0.36, 95% CI 0.23 to 0.56), and partial ANS reduced the risk of NEC (OR 0.23, 95% CI 0.07 to 0.72) and death (OR 0.54, 95% CI 0.34 to 0.87). Compared with partial ANS exposure, complete ANS decreased the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91). There were insignificant associations between ANS exposure and IVH, EUGR. In the multiple linear regression, partial and complete ANS exposure increased EWLP only in the ≥28 weeks (w) and <1000 g subgroup (p<0.05). CONCLUSIONS: Different doses of ANS (dexamethasone) exposure were protectively associated with BPD, NEC, death in hospital, but not EUGR at discharge among EPI or ELBWI. Beneficial dose-dependent associations between ANS (dexamethasone) exposure and BPD existed. ANS exposure increased EWLP only in the ≥28 w and<1000 g subgroup. ANS administration, especially complete ANS, is encouraged before preterm birth. TRIAL REGISTRATION NUMBER: NCT06082414.

Early Antibiotic Exposure and Bronchopulmonary Dysplasia in Very Preterm Infants at Low Risk of Early-Onset Sepsis.

Importance: The overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities. Nevertheless, the association of early antibiotic exposure with bronchopulmonary dysplasia (BPD) remains equivocal. Objective: To evaluate the association of varying durations and types of early antibiotic exposure with the incidence of BPD in VPIs at low risk of EOS. Design, Setting, and Participants: This national multicenter cohort study utilized data from the Chinese Neonatal Network (CHNN) which prospectively collected data from January 1, 2019, to December 31, 2021. VPIs less than 32 weeks' gestational age or with birth weight less than 1500 g at low risk of EOS, defined as those born via cesarean delivery, without labor or rupture of membranes, and no clinical evidence of chorioamnionitis, were included. Data analysis was conducted from October 2022 to December 2023. Exposure: Early antibiotic exposure was defined as the total number of calendar days antibiotics were administered within the first week of life, which were further categorized as no exposure, 1 to 4 days of exposure, and 5 to 7 days of exposure. Main Outcomes and Measures: The primary outcome was the composite of moderate to severe BPD or mortality at 36 weeks' post menstrual age (PMA). Logistic regression was employed to assess factors associated with BPD or mortality using 2 different models. Results: Of the 27 176 VPIs included in the CHNN during the study period (14 874 male [54.7%] and 12 302 female [45.3%]), 6510 (23.9%; 3373 male [51.8%] and 3137 female [48.2.%]) were categorized as low risk for EOS. Among them, 1324 (20.3%) had no antibiotic exposure, 1134 (17.4%) received 1 to 4 days of antibiotics treatment, and 4052 (62.2%) received 5 to 7 days of antibiotics treatment. Of the 5186 VPIs who received antibiotics, 4098 (79.0%) received broad-spectrum antibiotics, 888 (17.1%) received narrow-spectrum antibiotics, and 200 (3.9%) received antifungals or other antibiotics. Prolonged exposure (5-7 days) was associated with increased likelihood of moderate to severe BPD or death (adjusted odds ratio [aOR], 1.23; 95% CI, 1.01-1.50). The use of broad-spectrum antibiotics (1-7 days) was also associated with a higher risk of moderate to severe BPD or death (aOR, 1.27; 95% CI, 1.04-1.55). Conclusions and Relevance: In this cohort study of VPIs at low risk for EOS, exposure to prolonged or broad-spectrum antibiotics was associated with increased risk of developing moderate to severe BPD or mortality. These findings suggest that VPIs exposed to prolonged or broad-spectrum antibiotics early in life should be monitored for adverse outcomes.

Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension: Basing Care on Physiology.

Bronchopulmonary dysplasia (BPD) is the heterogeneous chronic lung developmental disease of prematurity, which is often accompanied by multisystem comorbidities. Pulmonary vascular disease and pulmonary hypertension (PH) contribute significantly to the pathogenesis and pathophysiology of BPD and dramatically influence the outcomes of preterm infants with BPD. When caring for those patients, clinicians should consider the multitude of phenotypic presentations that fall under the "BPD-PH umbrella," reflecting the need for matching therapies to specific physiologies to improve short- and long-term outcomes. Individualized management based on the patient's prenatal and postnatal risk factors, clinical course, and cardiopulmonary phenotype needs to be identified and prioritized to provide optimal care for infants with BPD-PH.

Early Bubble CPAP Protocol Implementation and Rates of Death or Severe BPD.

BACKGROUND: A multidisciplinary comprehensive protocol to use bubble continuous positive airway pressure (bCPAP) as the primary respiratory support in the delivery room (DR) and the NICU was introduced. With this study, we aimed to assess the association of this change with respiratory outcomes over time. METHODS: Infants with gestational age <32 weeks and birth weight <1250 g admitted between January 2012 and June 2020 were included and categorized into 4 periods, including pre-implementation (P0: 2012-2014), and post-implementation (P1: 2014-2016, P2: 2016-2018, P3: 2018-2020). The primary outcome was the rates of death and severe bronchopulmonary dysplasia (BPD), and the secondary outcomes included the rates of DR and NICU intubation ≤7 days of age, need of surfactant, and pneumothorax. Multivariate logistic regression models accounting for relevant risk factors were used to calculate adjusted odds ratios (ORs). RESULTS: The study included 440 infants (P0 = 90, P1 = 91, P2 = 128, P3 = 131). Over time, more infants were free of BPD (P < .001), and the rates of death and severe BPD decreased significantly: P1 = OR 1.21 (95% confidence interval [CI] 0.56-2.67), P2 = OR 0.45 (95% CI 0.20-0.99), and P3 = OR 0.37 (95% CI 0.15-0.84). DR intubation decreased from 66% (P0) to 24% (P3) in the entire cohort (P < .001) and from 96% (P0) to 40% (P3) in infants <26 weeks of age (P < .001). The need for NICU intubation was similar (P = .98), with a decreased need for surfactant (P = .001) occurring at higher FiO2 (P0 = 0.35 vs P3 = 0.55, P < .001). Pneumothorax rates were unchanged. CONCLUSIONS: In very preterm infants, the implementation of a comprehensive bCPAP protocol led to a significant and consistent improvement in respiratory practices and the rates of death and severe BPD.

Improving early diagnosis of bronchopulmonary dysplasia.

INTRODUCTION: Bronchopulmonary disease (BPD) is associated with long-term neurodevelopmental and cardiorespiratory complications, often requiring significant use of resources. To reduce this healthcare burden, it is essential that those at high risk of BPD are identified early so that strategies are introduced to prevent disease progression. Our aim was to discuss potential methods for improving early diagnosis in the first week after birth. AREAS COVERED: A narrative review was undertaken. The search strategy involved searching PubMed, Embase and Cochrane databases from 1967 to 2024. The results of potential biomarkers and imaging modes are discussed. Furthermore, the value of scoring systems is explored. EXPERT OPINION: BPD occurs as a result of disruption to pulmonary vascular and alveolar development, thus abnormal levels of factors regulating those processes are promising avenues to explore with regard to early detection of high-risk infants. Data from twin studies suggests genetic factors can be attributed to 82% of the observed difference in moderate to severe BPD, but large genome-wide studies have yielded conflicting results. Comparative studies are required to determine which biomarker or imaging mode may most accurately diagnose early BPD development. Models which include the most predictive factors should be evaluated going forward.

Elevated pulmonary capillary wedge pressure, higher blood pressure, and lower cardiac index in infants with bronchopulmonary dysplasia.

BACKGROUND: Left ventricular diastolic dysfunction indicated by elevated pulmonary capillary wedge pressure (ePCWP) may worsen cardiorespiratory status in bronchopulmonary dysplasia (BPD), but the scope of ePCWP by cardiac catheterization is not well described. METHODS: This single-center retrospective cohort study included infants with BPD without congenital heart disease, significant intracardiac shunts, or pulmonary vein stenosis who underwent cardiac catheterization from 2010 to 2021. ePCWP was defined as >10 mmHg. Quantitative measures of ventricular systolic and diastolic function were performed on existing echocardiograms. Patients with and without ePCWP were compared using the Chi-squared or Wilcoxon rank-sum tests. Associations between catheterization hemodynamics and echocardiographic parameters were assessed by simple linear regression. RESULTS: Seventy-one infants (93% Grade 2 or 3 BPD) met inclusion criteria, and 30 (42%) had ePCWP. Patients with ePCWP were older at catheterization (6.7 vs. 4.5 months, p < 0.001), more commonly underwent tracheostomy (66.7% vs. 29.3%, p = 0.003), and had higher mean systemic blood pressure [64.5 (56.0, 75.0) vs. 47.0 (43.0, 55.0) mm Hg, p < 0.001], higher systemic vascular resistance [11.9 (10.4, 15.6) vs. 8.7 (6.7, 11.2) WU*m2, p < 0.001), and lower cardiac index [3.9 (3.8, 4.9) vs. 4.7 (4.0, 6.3) L/min/m2, p = 0.03] at catheterization. Mean pulmonary artery pressure, pulmonary vascular resistance, and mortality were similar between the groups. Echocardiographic indices of left ventricular diastolic dysfunction did not correlate with PCWP. CONCLUSIONS: ePCWP was common in infants with severe BPD who underwent cardiac catheterization in this cohort. The association between ePCWP and higher systemic blood pressure supports further study of afterload reduction in this population.

[Risk factors for bronchopulmonary dysplasia in twin preterm infants: a multicenter study]. / åŒèƒŽæ—©äº§å„¿æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯å±é™©å› ç´ åˆ†æžï¼šä¸€é¡¹å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.

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In infants with severe bronchopulmonary dysplasia (sBPD), severe pulmonary lobar emphysema may occur as a complication, contributing to significant impairment in ventilation. Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation. However, prior to the lobectomy, it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively. In addition, preoperative planning and perioperative management are also quite challenging in these patients. This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema. Since infants with sBPD already have poor lung development and significant lung injury, lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution. Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema. However, given the technical difficulty, successful application of this technique requires close collaboration of an experienced interdisciplinary team.

Right ventricular function indices and platelet parameters for early prediction value of bronchopulmonary dysplasia: a retrospective study.

BACKGROUND: To examine the value of early echocardiographic indices for the right ventricular function combined with platelet(PLT) parameters for predicting bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: This retrospective study included infants with gestational age (GA) below 32 weeks, who were admitted to the neonatal intensive care unit(NICU). The detection rate of tricuspid regurgitation jet velocity (TRVJ), ventricular septal flattening, pulmonary artery widening, right ventricular dilation, and right atrial enlargement on the 7th day of life (DOL 7) were compared between BPD and non-BPD infants. Echocardiographic indices of the right ventricular function including tricuspid annular plane systolic excursion (TAPSE) and right ventricular index of myocardial performance (RIMP) were measured on 1 day of life (DOL 1)、on DOL 7 and on 14 day of life (DOL 14) respectively. The PLT parameters including the PLT count, mean platelet volume (MPV), platelet hematocrit (PCT) level, and platelet distribution width (PDW) were measured on the DOL 1,DOL 7, and DOL 14. Multivariate logistic regression was used to analyze the relationship between these parameters and BPD. Receiver operating characteristic curve analysis was performed to assess the predictive value of the right ventricular function indices and PLT parameters for BPD. RESULTS: A total of 220 preterm infants were included in this study, and of these, 85 infants developed BPD among them. The RIMP of the BPD group on DOL 14 was higher than that of the non-BPD group (P < 0.05). The TAPSE of the BPD group on DOL 14 was lower than that of the non-BPD group (P < 0.05). The PLT count of the BPD group on DOL 1 was lower than that of the non-BPD group (P < 0.05), and the MPV of the BPD group on DOL 1 was higher than that of the non-BPD group (P < 0.05). Using multivariate logistic regression, GA、invasive mechanical ventilation duration ≥ 7 days、 PLT、 MPV、 TAPSE and RIMP were found to be independent risk factors for BPD. The area under the receiver operating characteristic curve was 0.846 (95CI: 0.794∼0.899), which improved when using right ventricular function indices combined with platelet parameters. CONCLUSION: TAPSE and RIMP combined with PLT count and MPV can help identify preterm infants at an increased risk of developing BPD.

Prevalence, Severity Patterns and Risk Factors of Bronchopulmonary Dysplasia in Preterm Infants Younger than 32 Weeks of Gestation in a Tertiary Centre in Oman.

Objectives: This study aimed to determine the rate and severity patterns of bronchopulmonary dysplasia (BPD) and identify antenatal and postnatal factors associated with BPD in preterm infants <32 weeks of gestational age (GA). Methods: This retrospective observational study included preterm neonates <32 weeks of gestation admitted into the neonatal intensive care unit between January 2010 and December 2017 at Sultan Qaboos University Hospital, Muscat, Oman. A data set of antenatal and perinatal factors were collected. BPD was defined as the need for oxygen and/or respiratory support at 36 weeks post-menstrual age (PMA). Infants with and without BPD were compared in their antenatal and perinatal factors. Results: A total of 589 preterm infants <32 weeks were admitted. Among them, 505 (85.7%) survived to 36 weeks' PMA and 90 (17.8%) had BPD. The combined BPD and mortality rate was 28.4%. Grades 1, 2 and 3 BPD constituted 77.8%, 7.8% and 14.4%, respectively. BPD was associated with lower GA, lower birth weight, need for intubation at resuscitation, lower Apgar scores, longer duration of ventilation, surfactant therapy and higher rates of neonatal morbidities. On binary logistic regression analysis, predictors of BPD were longer duration of ventilation, intraventricular haemorrhage (IVH) and necrotising enterocolitis (NEC). Conclusion: In an Omani centre, 17.8% of preterm infants (<32 weeks GA) developed BPD. Various perinatal and neonatal factors were associated with BPD. However, longer duration of ventilation, IVH grades 1 and 2 and NEC stages II and III were significant predictors. Future multicentre research is necessary to provide the overall prevalence of BPD in Oman to help optimise the resources for BPD prevention and management in preterm infants.

Leveraging Integrated RNA Sequencing to Decipher Adrenomedullin's Protective Mechanisms in Experimental Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (Adm), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the molecular and cellular mechanisms through which Adm influences BPD pathogenesis using a lipopolysaccharide (LPS)-induced model of experimental BPD in mice. Bulk RNA sequencing of Adm-sufficient (wild-type or Adm+/+) and Adm-haplodeficient (Adm+/-) mice lungs, integrated with single-cell RNA sequencing data, revealed distinct gene expression patterns and cell type alterations associated with Adm deficiency and LPS exposure. Notably, computational integration with cell atlas data revealed that Adm-haplodeficient mouse lungs exhibited gene expression signatures characteristic of increased inflammation, natural killer (NK) cell frequency, and decreased endothelial cell and type II pneumocyte frequency. Furthermore, in silico human BPD patient data analysis supported our cell type frequency finding, highlighting elevated NK cells in BPD infants. These results underscore the protective role of Adm in experimental BPD and emphasize that it is a potential therapeutic target for BPD infants with an inflammatory phenotype.