Risk Of Bronchopulmonary Dysplasia Research Articles

Patent ductus arteriosus management in very-low-birth-weight prematurity: a place for early surgery?

To evaluate neonatal outcomes based on treatment strategies and time points for haemodynamically significant patent ductus arteriosus (hsPDA) in very-low-birth-weight (VLBW) preterm infants, with a particular focus on surgical closure. This retrospective study included VLBW infants born between 2014 and 2021, received active treatment for hsPDA. Neonatal outcomes were compared between: (1) primary surgical closure vs primary ibuprofen, (2) early (<14th post-natal day) vs late primary surgical closure (≥14th post-natal day), and (3) primary vs secondary surgical closure after ibuprofen failure. Further analysis using 1:1 propensity score matching was performed. Logistic regression was conducted to analyze the risk factors for post-ligation cardiac syndrome (PLCS) and/or acute kidney injury (AKI). A total of 145 hsPDA infants underwent active treatment for closure. In-hospital death rate and severe bronchopulmonary dysplasia (BPD) were similar between the primary surgical closure group and primary ibuprofen group in 1:1 matched analysis. Severe BPD was significantly higher in late surgical closure group than in early primary surgical closure group with 1:1 propensity score matching (72.7% vs 40.9%, p=0.033). The secondary surgical closure group showed the mildest clinical condition, however, the probability of PLCS/AKI was highest (38.6%), compared to early (15.2%) or late primary surgical group (28.1%, p<0.001) especially in extremely premature infants (gestational age <28weeks). Surgical PDA closure is not inferior to pharmacological treatment. Timely decision and efforts should be made considering the harmful effect of prolonged PDA shunt exposure to minimize the risk of severe BPD and PLCS/AKI after surgical closure.

Personalized lung care: Bronchopulmonary dysplasia risk prediction tool tailored for neonates born in resource-limited settings.

Predicting bronchopulmonary dysplasia (BPD) to assess the risk-benefit of therapy is necessary considering the side effects of medications. We developed and validated an instrument for predicting BPD and compared it with an instrument currently used for neonates born in a Brazilian hospital. This was a retrospective cohort study of patients born between 2016 and 2020 with a gestational age (GA) between 23 and 30 weeks. Predictive equations were elaborated using methods of component variable selection collected on the 14th day of life; 70% of the sample was randomly selected for the construction of risk prediction equations and the remaining 30% for their validation, application, and comparison with the National Institute of Child Health and Human Development (NICHD) instrument. The sensitivity, specificity, and predictive values of the equations were calculated. The equation that used variables with p < 5% in Fisher's exact test presented the best results: specificity of 98% and positive predictive value of 93% and could be used for BPD prediction of all small-for-gestational-age (SGA) infants. The NICHD calculator applied to our population had a specificity of 93% and a positive predictive value of 75% and could not be applied to extremely SGA infants. Our tool can predict the risk of BPD on the 14th day of life, has higher specificity and positive predictive value to our population than the NICHD instrument, and can be suitable for SGA infants. The results must be confirmed by applying it to other populations to validate our tool.

A Bayesian Reanalysis of the Overall and Sex-Disaggregated Results of the Neonatal Oxygenation Prospective Meta-Analysis (NeOProM)

Data from the Neonatal Oxygenation Prospective Meta-analysis (NeOProM) indicate that targeting a higher (91–95%) versus lower (85–89%) pulse oximeter saturation (SpO2) range may reduce mortality and necrotizing enterocolitis (NEC) and increase retinopathy of prematurity (ROP). Aiming to re-evaluate the strength of this evidence, we conducted a Bayesian reanalysis of the NeOProM data. We used Bayes factors (BFs) to evaluate the likelihood of the data under the combination of models assuming the presence vs. absence of effect, heterogeneity, and moderation by sex. The Bayesian reanalysis showed moderate evidence in favor of no differences between SpO2 targets (BF10 = 0.30) in death or major disability, but moderate evidence (BF10 = 3.60) in favor of a lower mortality in the higher SpO2 group. Evidence in favor of differences was observed for bronchopulmonary dysplasia (BPD) (BF10 = 14.44, lower rate with lower SpO2), severe NEC (BF10 = 9.94), and treated ROP (BF10 = 3.36). The only outcome with moderate evidence in favor of sex differences was BPD. This reanalysis of the NeOProM trials confirmed that exposure to a lower versus higher SpO2 range is associated with a higher mortality and risk of NEC, but a lower risk of ROP and BPD. The Bayesian approach can help in assessing the strength of evidence supporting clinical decisions.

Association between viral infection and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis.

Bronchopulmonary dysplasia (BPD) is the most common serious complication of very preterm infants (VPI) or very low birth weight (VLBW) infants. Studies implicate viral infections in etiopathogenesis. The aim of this study was to summarize the relationship between viral infections and BPD through a systematic review and meta-analysis. We searched PubMed, Embase, the Web of Science Core Collection, and the Cochrane Database on December 19, 2023. We included observational studies that examined the association between viral infections and BPD in preterm infants. We extracted data on study methods, participant characteristics, exposure assessment, and outcome measures. We assessed study risk of bias using the Newcastle-Ottawa Scale (NOS). We included 17 and 15 studies in the qualitative review and meta-analysis, respectively. The meta-analysis showed a significant association between viral infection and BPD diagnosed at 36 weeks postmenstrual age (odds ratio (OR): 2.42, 95% confidence interval: 1.89-3.09, 13 studies, very low certainty of evidence). In a subgroup analysis of specific viruses, cytomegalovirus (CMV) proved to be significantly associated with BPD diagnosed at 36 weeks postmenstrual age (OR: 2.34, 95% confidence interval: 1.80-3.05, 11 studies). We did not find an association between viral infection and BPD diagnosed on the 28th day of life, probably due to the small sample size of the included prospective studies. Conclusion: Viral infections, especially CMV, are associated with an increased risk of BPD in preterm infants. Methodologically reliable prospective studies with large samples are needed to validate our conclusions, and high-quality randomized controlled studies are needed to explore the effect of prevention or treatment of viral infections on the incidence of BPD. What is Known: • Studies have attempted to identify viral infections and bronchopulmonary dysplasia in preterm infants; however, results have been inconsistent. What is New: • Systematic demonstration that viral infections, particularly cytomegalovirus, are positively associated with bronchopulmonary dysplasia diagnosed in preterm infants at the 36th week of postmenstrual age. • The importance of screening for viral infections in preterm infants, especially cytomegalovirus. More high-quality studies should be produced in the future to investigate the causal relationship between viral infections and bronchopulmonary dysplasia.

Respiratory outcomes and survival after unplanned extubation in the NICU: a prospective cohort study from the SEPREVEN trial.

To compare reintubation rates after planned extubation and unplanned extubation (UE) in patients in neonatal intensive care units (NICUs), to analyse risk factors for reintubation after UE and to compare outcomes in patients with and without UE. Prospective, observational study nested in a randomised controlled trial (SEPREVEN/Study on Epidemiology and PRevention of adverse EVEnts in Neonates). Outcomes were expected to be independent of the intervention tested. 12 NICUs in France with a 20-month follow-up, starting November 2015. n=2280 patients with a NICU stay >2 days, postmenstrual age ≤42 weeks on admission. Characteristics of UE (context, timing, sedative administration in the preceding 6 hours, weaning from ventilation at time of UE) and patients. Healthcare professional-reported UE rates, reintubation/timing after extubation, duration of mechanical ventilation, mortality and bronchopulmonary dysplasia (BPD). There were 162 episodes of UE (139 patients, median gestational age (IQR) 27.3 (25.6-31.7) weeks). Cumulative reintubation rates within 24 hours and 7 days of UE were, respectively, 50.0% and 57.5%, compared with 5.5% and 12.3% after a planned extubation. Independent risk factors for reintubation within 7 days included absence of weaning at the time of UE (HR, 95% CI) and sedatives in the preceding 6 hours (HR 1.93, 95% CI 1.04 to 3.60). Mortality at discharge did not differ between patients with planned extubation or UE. UE was associated with a higher risk of BPD. In the SEPREVEN trial, reintubation followed UE in 58% of the cases, compared with 12% after planned extubation. NCT02598609.

Corticosteroids for the prevention and treatment of bronchopulmonary dysplasia: an overview of systematic reviews.

Corticosteroids for the prevention and treatment of bronchopulmonary dysplasia: an overview of systematic reviews.

Neurally adjusted ventilatory assist in preterm infants: A systematic review and meta-analysis.

To compare the effects of neurally adjusted ventilatory assist (NAVA) with other forms of synchronized artificial ventilation in preterm infants.A systematic review of randomized and quasi-randomized controlled trialswith individual group allocation, both parallel-group trials as well as crossover trials, that included preterm infants born at less than 37 weeks gestational age and compared NAVA with any other form of synchronized mechanical ventilation with or without volume guarantee. Primary outcomes were death or bronchopulmonary dysplasia (BPD) at 36 weeks, total duration of respiratory support and neurodevelopmental outcome at 2 years. Secondary outcomes consisted of important procedural and clinical outcomes.Seven studies with a total of 191 infants were included, five randomized crossover trials and two parallel group randomized trials. No significant difference in the primary outcome of death or BPD (RR: 1.08, 95% CI:0.33-3.55) was found. Peak inspiratory pressures were significantly lower with NAVA than with other forms of ventilation (MD -1.83 cmH2O [95% CI: -2.95 to -0.71]). No difference in any other clinical or ventilatory outcome was detected.Although associated with lower peak inspiratory pressures, the use of NAVAdoes not result in a reduced risk of death or BPD as compared to other forms of synchronized ventilation in preterm infants. However, the certainty of evidence is low due to imprecision of the effect estimate. Larger studies are needed to detect possible short- and long-term differences between ventilation modes.

The role of nutritional interventions in the prevention and treatment of chronic lung disease of prematurity.

Chronic lung disease of prematurity or bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Nutrition may affect incidence and severity of BPD. In this context, the Section on Nutrition, Gastroenterology and Metabolism, the Pulmonary Section of the European Society for Paediatric Research (ESPR) and SPR have joined forces to review the current knowledge on nutritional issues related to BPD. The aim of this narrative review is to discuss the clinical implications for nutritional practice. Nutrient deficiencies may influence pathogenesis of BPD. Adequate nutrition and growth can play a crucial role in the prevention of and recovery from BPD. Optimal nutrition strategy is an important principle, especially in the early postnatal period. As optimal energy intake in infants at risk of BPD or with evolving BPD is not yet defined, further research with well-designed studies on nutritional strategies for preterm infants with BPD is urgently needed. IMPACT: Based on current evidence it seems reasonable to recommend that BPD diagnosed infants should receive an energy supply ranging from 120 to 150 Kcal/kg/d. Exclusive MOM feed with adequate fortification should be encouraged as this is associated with a significant reduction in the risk of BPD. Suboptimal nutritional delivery is often seen in preterm infants with BPD compared to controls.

Risk Prediction of Severe Bronchopulmonary Dysplasia (BPD) Using the Respiratory Severity Score (RSS) in Extremely Preterm Infants: A Retrospective Study From Saudi Arabia.

Background Bronchopulmonary dysplasia (BPD) is a significant complication in extremely preterm infants. Therefore, early diagnosis of BPD is important for planning treatment strategies. In this study, we aimed to assess the predictive efficacy of the Respiratory Severity Score (RSS) in determining severe BPD or death outcomes in very preterm infants. Methodology This retrospective study included preterm infants born with a gestational age of ≤30 weeks. The inclusion criteria comprised individuals who were mechanically ventilated (<1 week) during the first four weeks of life. Any patients who died during the first seven days of life were excluded. RSS values were recorded on days 3, 14, 21, and 28 of life. Multivariate logistic regression was used to identify a correlation between RSS and patient outcomes. Results A total of 154 infants were included in the analysis, of whom 82 (53.24%) developed severe BPD and 38 (24.67%) died. RSS was higher in patients who either died or developed severe BPD compared to those who survived. The multivariate logistic regression analysis revealed that RSSs at postnatal day 14 (odds ratio (OR) = 3.970; 95% confidence interval (CI) = 1.114-14.147; p < 0.05), day 21 (OR = 6.201; 95% CI = 1.937-19.851; p < 0.05), and day 28 (OR = 8.925; 95% CI = 3.331-28.383; p < 0.05) was significantly associated with a higher risk of death or severe BPD. Conclusions The findings of the present study revealed that RSS can help predict the risk of severe BPD in very preterm infants.

Measurement of lung oxygenation by near-infrared spectroscopy in preterm infants with bronchopulmonary dysplasia.

It has recently been reported that it is possible to monitor lung oxygenation (rSO2 L) by near-infrared spectroscopy (NIRS) in preterm infants with respiratory distress syndrome (RDS). Thus, our aim was to assess the possibility of monitoring rSO2 L in infants with evolving and established bronchopulmonary dysplasia (BPD) and to evaluate if rSO2 L correlates with BPD severity and other oxygenation indices. We studied 40 preterm infants with gestational age ≤30 weeks at risk for BPD. Patients were continuously studied for 2 h by NIRS at 28 ± 7 days of life and 36 weeks ± 7 days of postmenstrual age. rSO2 L was similar at the first and second NIRS recordings (71.8 ± 7.2 vs. 71.4 ± 4.2%) in the overall population, but it was higher in infants with mild than in those with moderate-to-severe BPD at both the first (73.3 ± 3.1 vs. 71.2 ± 3.2%, p = .042) and second (72.3 ± 2.8 vs. 70.5 ± 2.8, p = .049) NIRS recording. A rSO2 L cutoff value of 71.6% in the first recording was associated with a risk for moderate-to-severe BPD with a sensitivity of 66% and a specificity of 60%. Linear regression analysis demonstrated a significant positive relationship between rSO2 L and SpO2 /FiO2 ratio (p = .013) and a/APO2 (p = .004). Monitoring of rSO2 L by NIRS in preterm infants with evolving and established BPD is feasible and safe. rSO2 L was found to be higher in infants with mild BPD, and predicts the risk for developing moderate-to-severe BPD and correlates with other indices of oxygenation.

A retrospective cohort study on the correlation between early energy management and bronchopulmonary dysplasia in premature infants

Objective: To investigate the correlation between early energy supplement and bronchopulmonary dysplasia (BPD) in very preterm and very low birth weight infants. Methods: A retrospective cohort study design was used. A total of 939 preterm infants who were admitted to the Department of Neonatology of the West China Second Hospital of Sichuan University within 24 h after birth from January 2019 to December 2021 were enrolled in the study. They were born with a gestational age of <32 weeks and (or) a birth weight of <1 500 g. Of them, 250 preterm infants who developed BPD were enrolled in the BPD group, and each of them was matched to a preterm infant who did not develop BPD (matched for gestational age and birth weight) in the order of priority after calculating propensity score. Their total energy, enteral energy, parenteral energy, total fluid intake and energy per unit of fluid per week were collected within the first 2 weeks of life. The independent sample t-test or Mann Whitney U test was used for continuous variables, and the χ2 test for between-group comparisons of categorical variables. Univariate and multivariate Logistic regression analyses were used to explore the association between total energy and total fluid and BPD incidence, respectively. The dose-response relationship between parenteral energy and BPD was investigated by a generalized additive model, and the threshold effect of parenteral energy on BPD used a two-piecewise linear regression model. Results: The gestational age was (28.4±1.9) weeks in the BPD group and (29.5±1.3) weeks in the control group; the birth weight was (1 107±258) g in the BPD group and (1 324±261) g in the control group; and there were 140 males (56.0%) and 131 males (52.4%) in each group, respectively. An increase in energy per unit of fluid in the second week of life was associated with a reduced risk of BPD (OR=0.32, 95%CI 0.12-0.84, P=0.021), and an increase in total energy in the second week of life was also associated with a reduced risk of BPD, with total energy of >418-502 kJ/(kg·d) was significantly lower than when total energy was ≤334 kJ/(kg·d) (OR=0.15, 95%CI 0.03-0.85, P=0.033). There was no association between the average total fluid intake and BPD incidence (both P>0.05) in the first and second week. The increase in the proportion of parenteral energy to total energy in the second week of life was associated with an increased incidence of BPD (OR=8.45, 95%CI 2.14-33.32, P=0.003); specifically, the risk of BPD significantly increased when the parenteral energy was ≥305 kJ/(kg·d) (OR=1.02, 95%CI 1.01-1.03, P=0.003). Conclusions: Maintaining a high total energy supply in the early postnatal period in preterm infants may reduce the risk of BPD, but continued reliance on high parenteral energy to meet total energy requirements increases the risk of BPD, so enteral feeds should be initiated as early as possible and maximized as tolerated.

"Bronchopulmonary Dysplasia Risk Prediction Models among Very Low Birth Weight Infants Receiving Caffeine Therapy"

"Bronchopulmonary Dysplasia Risk Prediction Models among Very Low Birth Weight Infants Receiving Caffeine Therapy"

Efficacy and safety of different inhaled corticosteroids for bronchopulmonary dysplasia prevention in preterm infants: A systematic review and meta-analysis

BackgroundThis systematic review and meta-analysis aimed to evaluate the efficacy and safety of inhaled corticosteroids (budesonide, beclomethasone, or fluticasone propionate) in preventing bronchopulmonary dysplasia (BPD) for premature infants. MethodElectronic databases, including PubMed, EMBASE, Web of science, Scopus, and Cochrane library, were searched from databases inception to January 2022 for eligible randomized controlled trials. Clinical outcomes such as BPD, mortality, BPD or death, adverse events, and neurodevelopmental outcomes were assessed. ResultsOverall, budesonide was significantly associated with a reduction in BPD at 36 weeks’ postmenstrual age (RR 0.48; 95 % CI [0.38, 0.62]) and patent ductus arteriosus (PDA) (RR 0.75; 95 % CI [0.63, 0.89]) compared with control treatments. Early longer duration inhalation of budesonide alone was associated with a lower risk of BPD at 36 weeks’ postmenstrual age and PDA compared with controls. Early shorter duration intratracheal instillation of budesonide with surfactant as vehicle was associated with a lower risk of BPD at 36 weeks’ postmenstrual age and all-cause mortality compared with surfactant. There was no statistically significant difference between budesonide and control groups regarding neurodevelopmental impairment. Beclomethasone and fluticasone propionate did not show any superior or inferior effect on clinical outcomes compared to control treatments. ConclusionThese findings suggest that budesonide, especially intratracheal instillation of budesonide using surfactant as a vehicle, is a safe and effective option in preventing BPD for preterm infants. More well-design large-scale trials with long-term follow-ups are necessary to verify the present findings.

Prediction of bronchopulmonary dysplasia in very preterm infants: competitive risk model nomogram.

To develop predictive clinical models of bronchopulmonary dysplasia (BPD) through competing risk analysis. Retrospective observational cohort study, including preterm newborns ≤32 weeks gestational age, conducted between January 1, 2013 and September 30, 2022 in a third-level Neonatal Intensive Care Unit in Spain. A prediction study was carried out using competing risk models, where the event of interest was BPD and the competing event was death. A multivariate competing risk model was developed separately for each postnatal day (days 1, 3, 7 and 14). Nomograms to predict BPD risk were developed from the coefficients of the final models and internally validated. A total of 306 patients were included in the study, of which 73 (23.9%) developed BPD and 29 (9.5%) died. On day 1, the model with the greatest predictive capacity was that including birth weight, days since rupture of membranes, and surfactant requirement (area under the receiver operating characteristic (ROC) curve (AUC), 0.896; 95% CI, 0.792-0.999). On day 3, the final predictive model was based on the variables birth weight, surfactant requirement, and Fraction of Inspired Oxygen (FiO2) (AUC, 0.891; 95% CI, 0.792-0.989). Competing risk analysis allowed accurate prediction of BPD, avoiding the potential bias resulting from the exclusion of deceased newborns or the use of combined outcomes. The resulting models are based on clinical variables measured at bedside during the first 3 days of life, can be easily implemented in clinical practice, and can enable earlier identification of patients at high risk of BPD.

Combined gestational age and serum fucose for early prediction of risk for bronchopulmonary dysplasia in premature infants

ObjectiveAs the predominant complication in preterm infants, Bronchopulmonary Dysplasia (BPD) necessitates accurate identification of infants at risk and expedited therapeutic interventions for an improved prognosis. This study evaluates the potential of Monosaccharide Composite (MC) enriched with environmental information from circulating glycans as a diagnostic biomarker for early-onset BPD, and, concurrently, appraises BPD risk in premature neonates.Materials and methodsThe study incorporated 234 neonates of ≤32 weeks gestational age. Clinical data and serum samples, collected one week post-birth, were meticulously assessed. The quantification of serum-free monosaccharides and their degraded counterparts was accomplished via High-performance Liquid Chromatography (HPLC). Logistic regression analysis facilitated the construction of models for early BPD diagnosis. The diagnostic potential of various monosaccharides for BPD was determined using Receiver Operating Characteristic (ROC) curves, integrating clinical data for enhanced diagnostic precision, and evaluated by the Area Under the Curve (AUC).ResultsAmong the 234 neonates deemed eligible, BPD development was noted in 68 (29.06%), with 70.59% mild (48/68) and 29.41% moderate-severe (20/68) cases. Multivariate analysis delineated several significant risk factors for BPD, including gestational age, birth weight, duration of both invasive mechanical and non-invasive ventilation, Patent Ductus Arteriosus (PDA), pregnancy-induced hypertension, and concentrations of two free monosaccharides (Glc-F and Man-F) and five degraded monosaccharides (Fuc-D, GalN-D, Glc-D, and Man-D). Notably, the concentrations of Glc-D and Fuc-D in the moderate-to-severe BPD group were significantly diminished relative to the mild BPD group. A potent predictive capability for BPD development was exhibited by the conjunction of gestational age and Fuc-D, with an AUC of 0.96.ConclusionA predictive model harnessing the power of gestational age and Fuc-D demonstrates promising efficacy in foretelling BPD development with high sensitivity (95.0%) and specificity (94.81%), potentially enabling timely intervention and improved neonatal outcomes.

Establishment and efficiency test of a clinical prediction model of bronchopulmonary dysplasia associated pulmonary hypertension in very premature infants

Objective: To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants. Methods: This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1st, 2015 to December 31st, 2021 of the Seventh Medical Center of the People's Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children's Hospital from January 1 st, 2020 to December 31st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks' corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model's discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results: A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95%CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions: A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

EBNEO commentary: Umbrella review evaluating interventions to decrease risk of bronchopulmonary dysplasia in preterm neonates.

EBNEO commentary: Umbrella review evaluating interventions to decrease risk of bronchopulmonary dysplasia in preterm neonates.

TGF-β controls alveolar type 1 epithelial cell plasticity and alveolar matrisome gene transcription in mice.

Premature birth disrupts normal lung development and places infants at risk for bronchopulmonary dysplasia (BPD), a disease disrupting lung health throughout the life of an individual and that is increasing in incidence. The TGF-β superfamily has been implicated in BPD pathogenesis, however, what cell lineage it impacts remains unclear. We show that TGFbr2 is critical for alveolar epithelial (AT1) cell fate maintenance and function. Loss of TGFbr2 in AT1 cells during late lung development leads to AT1-AT2 cell reprogramming and altered pulmonary architecture, which persists into adulthood. Restriction of fetal lung stretch and associated AT1 cell spreading through a model of oligohydramnios enhances AT1-AT2 reprogramming. Transcriptomic and proteomic analyses reveal the necessity of TGFbr2 expression in AT1 cells for extracellular matrix production. Moreover, TGF-β signaling regulates integrin transcription to alter AT1 cell morphology, which further impacts ECM expression through changes in mechanotransduction. These data reveal the cell intrinsic necessity of TGF-β signaling in maintaining AT1 cell fate and reveal this cell lineage as a major orchestrator of the alveolar matrisome.

Estimating the effect of diuretics and inhaled corticosteroids for evolving bronchopulmonary dysplasia in preterm infants.

Off-label treatment of extremely preterm infants with diuretics and inhaled corticosteroids (ICS) for evolving bronchopulmonary dysplasia (BPD) is common. Their effectiveness in reducing mortality or BPD severity, and optimal treatment timing, are unclear. To determine whether diuretic treatment or ICS administration for infants with early evolving (between 10-27 days postnatal) and progressively evolving (28th-day-36th-week postnatal) BPD are independently associated with reduced mortality and moderate or severe BPD at 36-weeks postmenstrual age (PMA). We examined neonates born before 28 weeks' gestation and admitted to neonatal intensive care units on postnatal Day 0 between 2006 and 2016 using data collected during routine care recorded within the Paediatric Health Information System (PHIS). An early evolving BPD cohort consisted of infants treated with oxygen, positive pressure or mechanical ventilation at 10 days postnatal. The progressively evolving BPD cohort consisted of infants treated with these modalities at 28 days. In new users, we evaluated the effect of diuretic and ICS treatment on mortality or BPD severity at 36 weeks PMA, adjusting for time-dependent confounding by respiratory status using marginal structural models. Early evolving BPD was present in 10,135 patients; progressively evolving BPD in 11,728. New diuretic exposure during early evolving BPD (adjusted risk ratio [aRR] 0.77, 95% confidence interval [CI] 0.65, 0.93) was associated with decreased mortality or moderate/severe BPD risk. New diuretics (aRR 0.86, 95% CI 0.75, 0.99) during progressively evolving BPD between 28-days-36-weeks PMA were less strongly associated with mortality or moderate/severe BPD reduction. There was no strong association for ICS in patients with early evolving (aRR: 1.40; 95% CI: 0.79, 2.51) or progressively evolving BPD (aRR 1.16, 95% CI 0.95, 1.49). Diuretics, but not ICS, for evolving BPD were associated with mortality and BPD risk reduction.

Montelukast Sodium to Prevent and Treat Bronchopulmonary Dysplasia in Very Preterm Infants: A Quasi-Randomized Controlled Trial.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and lacks effective methods for prevention and treatment. The aim of this study is to explore the efficacy and safety of montelukast in preventing or treating BPD in preterm infants. The preterm infants with BPD risk factors were divided randomly into a montelukast group and a control group. In the montelukast group, preterm infants were given 1 mg/kg of montelukast sodium daily. There was no placebo in the control group. There was no significant difference in the incidence of moderate or severe BPD between the two groups (31.8% vs. 35%). The duration of respiratory support in the montelukast group was shorter than that in the control group (36.4 ± 12.8 d vs. 43.1 ± 15.9 d, p = 0.037). The pulmonary severity score (PSS) at 21 days of life in the montelukast group was significantly lower than that in the control group (0.56 ± 0.13 vs. 0.62 ± 0.14, p = 0.048). There were no significant differences in the duration of mechanical ventilation, length of stay, hospitalization expenses, or incidence of adverse events. Although montelukast cannot alleviate the severity of BPD, it may shorten the duration of respiratory support and decrease the PSS in very preterm infants. There were no significant adverse drug events associated with montelukast treatment.