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Application of the principles of pulmonary physiology and lung development to the care and management of respiratory disease in children is a distinguishing feature of pediatric pulmonology. In 2023, this was evident in numerous publications in Pediatric Pulmonology and other journals. This review will highlight some of the papers in this area., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Pulmonary hypertension (PH) is quite infrequent in pediatric age and its most common etiologies include idiopathic pulmonary arterial hypertension, PH related to congenital heart diseases, bronchopulmonary dysplasia (chronic lung disease), persistence of pulmonary hypertension of the newborn, and congenital diaphragmatic hernia. The developed for adult patients PH classification shows limitations when applied to pediatric subjects since the underlying causes are markedly different between the two ages. In 2011, the Pulmonary Vascular Research Institute Panama Task Force outlined the first specific pediatric pulmonary hypertensive vascular disease diagnostic classification, including 10 main categories and 109 subcategories, thus testifying PH complex pathophysiology during newborns/children growth and development. The unique, distinctive features of pediatric PH were recognized also during the fifth World Symposium on pulmonary hypertension in 2013 and then confirmed in the recent 2018 sixth World Symposium. For the sake of uniformity, an attempt to adapt the adult classification to pediatric patients was made. However, all these commendable classifications are very complex and maybe not of quick comprehension for clinicians. A clinical simpler and simplified method is now suggested, comprising only five groups: neonatal, cardiac, developmental, idiopathic, and syndromic PH. This approach is not aimed at replacing the already existing classifications but is mainly based on the kind of specialized physician ( neonatologist, pediatric cardiologist, pediatrician, pulmonologist, general practitioner ) who first faces and looks after the child with suspected PH. What is dramatically known is that pediatric PH is a severe disease which, when untreated or undertreated, may lead to increased morbidity and mortality.

Mesenchymal stem cells (MSCs) represent a potentially revolutionary therapy for a wide variety of pediatric diseases, but the optimal cell-based therapeutics for such diversity have not yet been specified. The published clinical trials for pediatric pulmonary, cardiac, orthopedic, endocrine, neurologic, and hematologic diseases provide evidence that MSCs are indeed efficacious, but the significant heterogeneity in therapeutic approaches between studies raises new questions. The purpose of this review is to stimulate new preclinical and clinical trials to investigate these factors. First, we discuss recent clinical trials for pediatric diseases studying MSCs obtained from bone marrow, umbilical cord and umbilical cord blood, placenta, amniotic fluid, and adipose tissue. We then identify factors, some unique to pediatrics, which must be examined to optimize therapeutic efficacy, including route of administration, dose, timing of administration, the role of ex vivo differentiation, cell culture techniques, donor factors, host factors, and the immunologic implications of allogeneic therapy. Finally, we discuss some of the practicalities of bringing cell-based therapy into the clinic, including regulatory and manufacturing considerations. The aim of this review is to inform future studies seeking to maximize therapeutic efficacy for each disease and for each patient. Stem Cells Translational Medicine 2017;6:539-565., (© 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Childhood interstitial lung disease represents a rare and heterogeneous group of diseases that can result in significant morbidity and mortality, some leading to death during infancy. CT is the imaging test of choice. Although many CT findings are nonspecific and a definitive diagnosis usually cannot be reached by CT alone, the interpreting radiologist is instrumental in defining disease extent and refining the diagnosis. Chest CTs are of key importance in guiding site selection for lung biopsy and for following disease progression and response to treatment. Thus, from the radiologist's perspective, ensuring maximal quality of CT imaging and interpretation is paramount., (Copyright © 2016 Elsevier Inc. All rights reserved.)

To better meet the needs of our readership for updated perspectives on the rapidly expanding knowledge in our field, we here summarize the past year's publications in our major topic areas, as well as selected publications in these areas from the core clinical journal literature outside our own pages. This is Part 2 of a series and covers articles on neonatal lung disease, pulmonary physiology, and respiratory infection., (© 2015 Wiley Periodicals, Inc.)

BACKGROUND AND OBJECTIVES: The challenge of identifying preterm infants with bronchopulmonary dysplasia (BPD) that need tracheostomy placement may delay goals of care (GOC) discussions. By identifying infants with a low probability of ventilation liberation, timely GOC discussions may reduce the time to tracheostomy. Our SMART aim was to reduce the postmenstrual age (PMA) of GOC discussions by 20% in infants with BPD and prolonged invasive ventilatory requirement by October 2020. METHODS: Our group conducted a quality improvement initiative at the University of Alabama at Birmingham. Infants were included if born at <32 weeks' gestation and exposed to invasive ventilation for ≥2 weeks beyond 36 weeks' PMA. Interventions included (1) consensus of BPD infants at risk for tracheostomy dependence, (2) monthly multidisciplinary tracheostomy meetings, and (3) development and utilization of tracheostomy educational content for families. Statistical process control charts were used for all analyses. RESULTS: A total of 79 infants were included in analyses, of which 44 infants either received a tracheostomy or died. From X-mR control chart analysis, there was special cause variation in the time to GOC discussions, which decreased from 62 to 51 weeks' PMA related to monthly multidisciplinary conferences. The average PMA at tracheostomy decreased from 80 weeks to 63 weeks with no change in the frequency of tracheostomy placement or discordant GOC discussions in which infants survived to hospital discharge without a tracheostomy. CONCLUSIONS: In infants with ventilator-dependent BPD, standardization of GOC discussions reduced the PMA of GOC discussions and tracheostomy. [ABSTRACT FROM AUTHOR]

Background: The existing literature lacks conclusive evidence regarding the relationship between bronchopulmonary dysplasia (BPD) and cerebral palsy (CP). This large epidemiological study aimed to explore the co-occurrence of BPD and CP among children. Methods: This retrospective cohort analysis utilized the National Inpatient Sample (NIS) dataset from 2016 to 2019, investigating pediatric patients with BPD and CP diagnoses. Descriptive and inferential statistics, including univariate and multivariate regression analyses, were conducted to explore the association between BPD and CP. Results: Overall, 3,951,039 patients were analyzed. Among them, 28,880 patients had CP (n = 796 with BPD and n = 28,084 without BPD). The rates of intraventricular hemorrhage grade 3 and 4, central nervous system anomalies, chromosomal disorders, retinopathy of prematurity (≥grade 3), periventricular leukomalacia, prematurity, and low birth weight were significantly higher in the CP-with-BPD arm contrasted to the CP-without-BPD arm. Univariate regression demonstrated a significant BPD–CP association (odds ratio [OR] = 7.78, 95% confidence interval [CI]: 7.24–8.37, p < 0.0001). Multivariate analysis, adjusting for various confounders, reinforced this association (OR = 5.70, 95% CI: 5.17–6.28, p < 0.0001). We observed a significant association between increasing prematurity in neonates with BPD and an elevated risk of CP. Conclusions: This nationwide study identified a strong correlation between the co-occurrence of BPD and CP, though it does not establish causality. Rigorous adjustments revealed that patients with BPD appear to have a six-fold increased likelihood of being diagnosed with CP later on, compared to those without BPD. While aligned with the existing literature, this study represents the largest sample size with recommendations for targeted preventive strategies to mitigate the burden of CP. [ABSTRACT FROM AUTHOR]

Abstract Numerous studies have attempted to identify potential biomarkers for early detection of bronchopulmonary dysplasia (BPD) in preterm infants using metabolomics techniques. However, the presence of consistent evidence remains elusive. Our study aimed to conduct a systematic review and meta-analysis to identify differences in small-molecule metabolites between BPD and non-BPD preterm infants. Through meticulous screening of numerous samples, we identified promising candidates, providing valuable insights for future research. We searched PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Internet, Wan-fang database, Chinese Science and Technique Journal Database and Chinese Biomedical Literature Database from inception until January 16, 2024. Studies were comprehensively reviewed against inclusion criteria. We included case-control studies and adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Study quality was assessed with the Newcastle-Ottawa scale. We compared the changes in metabolite levels between the BPD and non-BPD preterm infants. A meta-analysis was conducted on targeted metabolomics research data based on the strategy of standardized mean differences (MD) and 95% confidence intervals (CI).Fifteen studies (1357 participants) were included. These clinical-based metabolomics studies clarified 110 differential metabolites between BPD and non-BPD preterm infants. The meta-analysis revealed higher glutamate concentration in the BPD group compared to the non-BPD group (MD = 1, 95% CI 0.59 to 1.41, p

Abstract Background Cytokines and growth factors (GF) have been implicated in the development of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD). We hypothesize that even small coordinated changes in inflammatory proteins or GFs may reveal changes in underlying regulating mechanisms that do not induce obvious changes in concentration of individual proteins. We therefore applied correlation network analysis of serum factors to determine early characteristics of these conditions. Methods Concentrations of 17 cytokines and five GFs were measured and analysed in blood samples from cord blood, on day one and during the following month in 72 extremely preterm infants. Spearman’s correlation networks distinguishing BPD and severe ROP patients from non-affected were created. Results Most cytokine concentrations correlated positively with each other and negatively with GFs. Very few individual cytokines differed between patients with and without ROP or BPD. However, networks of differently correlated serum factors were characteristic of the diseases and changed with time. In ROP networks, EPO, G-CSF and IL-8 (cord blood), BDNF and VEGF-A (first month) were prominent. In BPD networks, IL-1β, IGF-1 and IL-17 (day one) were noted. Conclusions Network analysis identifies protein signatures related to ROP or BPD in extremely preterm infants. The identified interactions between serum factors are not evident from the analysis of their individual levels, but may reveal underlying pathophysiological mechanisms in the development of these diseases.

Abstract Background Bronchopulmonary dysplasia (BPD) affects up to half of extremely preterm infants, and is associated with adverse long-term respiratory, neurodevelopmental, and educational sequelae and costly health service and family economic outcomes. The NICHD Neonatal Research Network Hydrocortisone for Bronchopulmonary Dysplasia (BPD) Trial evaluated the efficacy and safety of hydrocortisone treatment to prevent BPD in high-risk infants. The trial enrolled 800 very preterm infants with respiratory failure and followed the participants until 2 years corrected age to assess safety of the trial intervention. Longer-term impacts of hydrocortisone exposure and severity of BPD on functional outcomes of high-risk infants remain unknown. The HYdrocortisone for BPD Respiratory and Developmental (HYBRiD) Outcomes Study extends follow-up of all surviving children enrolled in the Hydrocortisone for BPD Trial until early school age. It aims to characterize the childhood functional motor, cognitive, academic, and pulmonary outcomes of this large, well-phenotyped trial cohort. Methods Parents of surviving trial participants complete telephone questionnaires when their children are 3 and 4 years corrected age. A single in-person study visit takes place at early school age (5 years, 0 months to 7 years, 11 months corrected age). Children undergo a multidimensional assessment of functional outcomes and parents complete a battery of questionnaires. In 5 of 19 participating centers, respiratory mechanics are evaluated with impulse oscillometry. Discussion The HYBRiD Outcomes Study will be the largest and most comprehensive evaluation to date of the functional early school age outcomes of children with a history of severe neonatal lung disease and of children exposed to HC during infancy. This will substantially improve understanding of the longer-term implications of severe neonatal lung disease; provide data to facilitate the development of future randomized intervention trials in this population; and inform public policy by enhancing knowledge about school age resource requirements in children with a history of prematurity and lung disease. Trial registration clinicaltrials.gov ID NCT01353313. Primary trial registration 5/11/11 modified to include followup through school age 12/13/17. This manuscript reflects version 3 of the trial manuscript, dated 10/12/2020.

Abstract 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). 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.

Abstract Background Metabolic acidosis occurs frequently during the first postnatal days in extremely preterm infants and is mainly attributed to renal immaturity. Recent studies suggested a link between metabolic acidosis and the development of BPD. The aim of this study was to systematically investigate the association between severe metabolic acidosis during the first two weeks of life and bronchopulmonary dysplasia (BPD) / mortality among preterm infants born before 28 weeks’ gestation. Methods Monocentric observational cohort study including 1748 blood gas samples of 138 extremely preterm infants born 2020–2022. Metabolic acidosis was defined as pH

Abstract Background Pulmonary vascular disease (PVD) and pulmonary hypertension (PH) is a significant disorder affecting prognosis of extremely preterm infants. However, there is still a lack of a consensus on the definition and optimal treatments of PH, and there is also a lack of research comparing these conditions with persistent pulmonary hypertension of newborn (PPHN), early PH, and late PH. To investigate PH in extremely preterm infants, this study compared the baseline characteristics, short-term outcomes, and treatment duration, categorized by the timing of requiring PH treatment. Methods This study retrospectively analyzed extremely preterm infants admitted to a single tertiary center. Between 2018 and 2022, infants with clinical or echocardiographic diagnosis of PH who required treatment were divided into three groups based on the timing of treatment initiation: initial 3 days (extremely early-period), from day 4 to day 27 (early-period), and after day 28 (late-period). The study compared the outcomes, including mortality rates, bronchopulmonary dysplasia (BPD) severity, PH treatment duration, and oxygen therapy duration, among the three groups. Results Among the 157 infants, 67 (42.7%) were treated for PH during their stay. Of these, 39 (57.3%) were treatment in extremely early, 21 (31.3%) in early, and seven (11.4%) in late periods. No significant differences were observed in maternal factors, neonatal factors, or morbidity between the three groups. However, infants who received extremely early-period treatment had a higher mortality rate, but shorter duration of noninvasive respiratory support, oxygen therapy, and PH medication use. On the other hand, the late-period treatment group received longer durations of respiratory support and treatment. Conclusions This study revealed differences in mortality rates, respiratory outcomes, and treatment duration between the three groups, suggesting varying pathophysiologies over time in extremely preterm infants.

Abstract 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.

Abstract 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

Bronchopulmonary dysplasia (BPD) remains a significant complication of prematurity, impacting approximately 18,000 infants annually in the United States. Advances in neonatal care have not reduced BPD, and its management is challenged by the rising survival of extremely premature infants and the variability in clinical practices. Leveraging statistical and machine learning techniques, predictive analytics can enhance BPD management by utilizing large clinical datasets to predict individual patient outcomes. This review explores the foundations and applications of predictive analytics in the context of BPD, examining commonly used data sources, modeling techniques, and metrics for model evaluation. We also highlight bioinformatics’ potential role in understanding BPD's molecular basis and discuss case studies demonstrating the use of machine learning models for risk prediction and prognosis in neonates. Challenges such as data bias, model complexity, and ethical considerations are outlined, along with strategies to address these issues. Future directions for advancing the integration of predictive analytics into clinical practice include improving model interpretability, expanding data sharing and interoperability, and aligning predictive models with precision medicine goals. By overcoming current challenges, predictive analytics holds promise for transforming neonatal care and providing personalized interventions for infants at risk of BPD.

ObjectivePrevious studies on the link between VEGF gene polymorphisms and bronchopulmonary dysplasia (BPD) have yielded inconsistent results. This meta-analysis sought to clarify the relationship between genetic variations in the VEGF gene and the risk of BPD.MethodsData were collected from multiple databases, including PubMed, Scopus, EMBASE, and CNKI, up to January 5, 2024.ResultsNineteen case-control studies were analyzed, featuring 1,051 BPD cases and 1,726 healthy neonates. The analysis included four studies on the −460T/C polymorphism (312 cases, 536 controls), four on the −2578C/A polymorphism (155 cases, 279 controls), six on the +405G/C polymorphism (329 cases, 385 controls), and five on the +936C/T polymorphism (225 cases, 526 controls). The meta-analysis suggests that the −460T/C polymorphism may protect against BPD (C vs. T: OR = 0.715, 95% CI 0.543–0.941, p = 0.017; CC vs. TT: OR = 0.478, 95% CI 0.233–0.983, p = 0.045; CC vs. CT + TT: OR = 0.435, 95% CI 0.248–0.764, p = 0.004). No significant associations were found between the −2578C/A, +405G/C, and +936C/T polymorphisms and BPD susceptibility.ConclusionsThis meta-analysis indicates that the C allele of the −460T/C polymorphism may offer protection against BPD. No significant associations were observed for the −2578C/A, +405G/C, and +936C/T polymorphisms.

BackgroundTo analyze the characteristics of blood metabolites within 24 h after birth in preterm infants with bronchopulmonary dysplasia (BPD) and to identify biomarkers for predicting the occurrence of BPD.MethodsDried blood spots (DBS) were collected at birth from preterm infants with gestational age (GA) of less than 32 weeks in the cohort. The infants were divided into the BPD group and non-BPD group based on whether they eventually developed BPD. Dried blood spot filter papers were prepared from venous blood collected within the first 24 h of life. Metabolites were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and analyzed using the R software package.ResultsDBS samples from 140 infants with the GA

AimTo provide a risk prediction for bronchopulmonary dysplasia (BPD) in premature infants under the new diagnostic criteria and establish a prediction model.MethodsIn this study, we retrospectively collected case data on preterm infants admitted to the NICU from August 2015 to August 2018. A lasso analysis was performed to identify the risk factors associated with the development of BPD. A nomogram predictive model was constructed in accordance with the new diagnostic criteria for BPD.ResultA total of 276 preterm infants were included in the study.The incidence of BPD under the 2018 diagnostic criteria was 11.2%. Mortality was significantly higher in the BPD group than the non-BPD group under the 2018 diagnostic criteria (P

BackgroundSerum lactate levels are used as biomarkers for perinatal asphyxia, while their value for outcome prediction in preterm infants is uncertain. It was the aim of this observational study to determine the association of the first postnatal serum-lactate levels on day 1 of life and short-term outcome in preterm infants less than 29 gestational weeks.MethodsWe analysed data in a population-based cohort of German Neonatal Network (GNN) preterm infants with available first postnatal lactate levels enrolled at 22–28 weeks of gestational age (GA) between 1st of April 2009 and 31st December 2020. We hypothesized that high lactate levels as measured in mmol/L increase the risk of intraventricular haemorrhage (IVH) and bronchopulmonary dysplasia (BPD) in infants with VLBW regardless of small-for-gestational-age (SGA) status. Hypotheses were evaluated in univariate analyses and multiple logistic regression models.ResultsFirst postnatal lactate levels were available in 2499 infants. The study population had a median GA of 26.7 [IQR 25.2–27.9] weeks and birth weight of 840 g [IQR 665–995]. Infants with short-term complications such as IVH and BPD had higher initial lactate levels than non-affected infants. The positive predictive value of a lactate cut-off of 4 mmol/L was 0.28 for IVH and 0.30 for BPD. After adjustment for known confounding variables, each 1 mmol/L increase of day 1 lactate levels was associated with a modestly increased risk of IVH (OR 1.18; 95% CI 1.03–1.37; p = 0.002) and BPD (OR 1.23; 95% CI 1.06–1.43; p = 0.005) but not with sepsis or mortality. Notably, SGA was associated with lower risk of any grade and severe IVH (OR 0.70; 95% CI 0.54–0.85; p = 0.001).ConclusionsIn our observational cohort study higher initial lactate levels were associated with adverse outcome regardless of SGA status. However, the predictive value of lactate cut-off levels such as 4 mmol/L is low.

IntroductionDespite the advances in perinatal care, bronchopulmonary dysplasia (BPD) continues to be a highly prevalent chronic lung disease that affects newborns, especially affecting premature newborns. There is no specific cure for BPD, and treatments aimed at reducing the risk of developing BPD focus mainly on lung-protective ventilation strategies, surfactant therapy, and/or corticosteroid administration. Our objective was to evaluate whether systemic postnatal administration of a new glucocorticoid, ciclesonide, can attenuate the alteration of lung structure and pulmonary hypertension in a rat model of chorioamnionitis-induced BPD, with minimal adverse effects on the developing brain.MethodsEndotoxin (ETX) or saline was administered to pregnant rats by intra-amniotic (i.a.) injection on day 20 of pregnancy, and pups were delivered by cesarean section on day 22. Ciclesonide (0.5 mg/kg) was administered postnatally for five consecutive days to pups previously exposed to i.a. ETX. On postnatal day 14, we assessed lung function (compliance), lung structure (radial alveolar count, mean linear intercept, pulmonary vessel density), pulmonary hypertension, and brain histology (edema, inflammation, apoptosis, hemorrhage, and infarction).ResultOn postnatal day 14, the effects of i.a. ETX administration were evident in neonatal rats not receiving treatment; these animals showed impaired lung compliance, disrupted lung structure, and developing pulmonary hypertension compared to those receiving i.a. saline. Postnatal administration of ciclesonide for 5 days was associated with significantly better outcomes in terms of lung compliance, alveolarization, lung vascular growth, and pulmonary hypertension, without affecting the brain histological parameters evaluated.ConclusionPostnatal ciclesonide administration preserved lung function and structure and prevented pulmonary hypertension in a BPD model induced by antenatal i.a. ETX administration, without causing any adverse effects on brain development. These findings suggest that the new glucocorticoid, ciclesonide, may provide a novel strategy for the prevention of BPD; however, more long-term studies are required.

Background: Chronic diuretics are frequently used (off-label) in preterm infants to manage evolving or established bronchopulmonary dysplasia (BPD). Chronic diuretic use, however, is limited by tolerance with no long-term safety and efficacy data, leading to wide variation in its use in preterm infants. Objective: To determine the impact of the chronic diuretic clinical practice guideline (CPG) on the patterns of diuretic use, severity of BPD, and hospital length of stay (LOS) in preterm infants born less than 32 weeks gestation. Methods: Single-center retrospective pre-post CPG cohort study in a level IV neonatal intensive care unit. Chronic diuretic CPG was implemented in November 2021 and the data was collected one year before (Pre-CPG) and one year after (Post-CPG). Results: In total, 73 infants (39 Pre-CPG, and 34 Post-CPG) were identified. There were no significant differences in patient characteristics at birth or in the use and duration of respiratory support between the two groups. Compared to Pre-CPG, the frequency of thiazide diuretic use was not decreased in Post-CPG (30.8 vs. 20.6 %, p = 0. 42), but the duration of use was significantly reduced (35 vs. 6 days, p = 0.01). Both frequency (20.5 vs. 2.9 %) and duration (28.5 vs. 4 days) of spironolactone were reduced in the Post-CPG (p < 0.05). Furosemide exposure (69.2 vs. 41.2 %, p = 0.02) and total doses [3.0 (0.0–8.0) vs. 0.0 (0.0–2.3), p = 0.003] were also significantly reduced in the Post-CPG. The incidence of any BPD at 36 weeks and LOS were similar between groups, while the incidence of moderate/severe BPD and home oxygen use were decreased in the Post-CPG. Conclusions: Chronic diuretic CPG was associated with a reduction in diuretic exposure in preterm infants

Purpose Bronchopulmonary dysplasia (BPD) is a chronic lung disease that primarily affects premature infants receiving mechanical ventilation and oxygen therapy. Severe BPD leads to long-term respiratory complications, including lung tissue damage, vascular abnormalities, and airway diseases. This study aimed to investigate bronchoscopy findings and characteristics in patients with moderate-to-severe BPD, and to investigate BPD-associated airway diseases. Methods A retrospective study of preterm infants diagnosed with moderate-to-severe BPD who underwent bronchoscopic evaluation in the neonatal intensive care unit at Seoul National University Bundang Hospital between 2004 and December 2022 was conducted. Results Nineteen patients with a mean gestational age of 28.0±1.6 weeks and mean birth weight of 960.5±271.0 g were included in the study. Among these 19 patients, 18 were diagnosed with severe BPD. Tracheobronchomalacia, laryngomalacia, and subglottic stenosis were observed in 63.2%, 52.6%, and 36.8% of patients, respectively. Tracheostomy was performed in nine of the 19 patients (47.4%); five were discharged without requiring tracheostomy following surgical or medical interventions. Conclusion Tracheobronchomalacia, laryngomalacia, and subglottic stenosis were common in patients with moderate or severe BPD who underwent bronchoscopic evaluations, of which 50% required tracheostomy. Our study findings provide valuable insights into the pathophysiology of BPD-associated airway diseases and may inform future clinical management strategies for patients with BPD.

Background The relationship between early life factors and childhood pulmonary function and structure in preterm infants remains unclear. Purpose This study investigated the impact of bronchopulmonary dysplasia (BPD) and perinatal factors on childhood pulmonary function and structure. Methods This longitudinal cohort study included preterm participants aged ≥5 years born between 2005 and 2015. The children were grouped by BPD severity according to National Institutes of Health criteria. Pulmonary function tests (PFTs) were performed using spirometry. Chest computed tomography (CT) scans were obtained and scored for hyperaeration or parenchymal lesions. PFT results and chest CT scores were analyzed with perinatal factors. Results A total 150 children (66 females) aged 7.7 years (6.4–9.9 years) were categorized into non/mild BPD (n=68), moderate BPD (n=39), and severe BPD (n=43) groups. The median z score for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced midexpiratory flow (FEF25%–75%) were significantly lower in the severe versus non/mild BPD group (-1.24 vs. -0.18, -0.22 vs. 0.41, -1.80 vs. -1.12, and -1.88 vs. -1.00, respectively; all P

Background: Preterm delivery is a risk factor for increased respiratory morbidity in early childhood. This study aimed to quantify respiratory morbidity in preterm survivors, comparing incidence rates among different gestational ages, birth weighst, and current age groups. Additionally, we sought to evaluate variations in respiratory outcomes between groups with and without bronchopulmonary dysplasia (BPD). Methods: Our study included 89 prematurely born children who were receiving palivizumab prophylaxis for respiratory syncytial virus infection. We categorized the patients based on four criteria: 1) current age of less and more than 1 year, 2) gestational age (GA) of less and more than 30 weeks, 3) birth weight (BW) of less than 1000 g, between 1000 g and 1500 g, and more than 1500 g, 4) with and without BPD. We compared these groups in terms of respiratory morbidity and respiratory therapy. Results: The average age was 11.9 months, the average GA was 28.9 weeks and the average BW was 1202.4 g. According to the 28-day definition of BPD 75.3% patients had BPD. Around one-third (35.9%) of patients experienced wheezing episodes, 7.8% had pneumonia, 10.1% were hospitalized due to respiratory exacerbation and just 1.1% had RSV infection. There were no statistically significant differences between the different age, GA, BW, or BPD/non-BPD groups in the number of hospitalizations or pneumonia. On the other hand, children older than 12 months and children with BPD had significantly more wheezing episodes. Fifty-nine (66.3%) patients had been receiving inhaled corticosteroids (ICS), all of whom had BPD. Conclusion: Prematurely-born children receiving palivizumab had significant respiratory morbidity, but majority did not have RSV infection. Further clinical studies are necessary to improve our understanding of the role of ICS in patients with established BPD.

Abstract Background Long-term survival after premature birth is significantly determined by development of morbidities, primarily affecting the cardio-respiratory or central nervous system. Existing studies are limited to pairwise morbidity associations, thereby lacking a holistic understanding of morbidity co-occurrence and respective risk profiles. Methods Our study, for the first time, aimed at delineating and characterizing morbidity profiles at near-term age and investigated the most prevalent morbidities in preterm infants: bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), mild cardiac defects, perinatal brain pathology and retinopathy of prematurity (ROP). For analysis, we employed two independent, prospective cohorts, comprising a total of 530 very preterm infants: AIRR (“Attention to Infants at Respiratory Risks”) and NEuroSIS (“Neonatal European Study of Inhaled Steroids”). Using a data-driven strategy, we successfully characterized morbidity profiles of preterm infants in a stepwise approach and (1) quantified pairwise morbidity correlations, (2) assessed the discriminatory power of BPD (complemented by imaging-based structural and functional lung phenotyping) in relation to these morbidities, (3) investigated collective co-occurrence patterns, and (4) identified infant subgroups who share similar morbidity profiles using machine learning techniques. Results First, we showed that, in line with pathophysiologic understanding, BPD and ROP have the highest pairwise correlation, followed by BPD and PH as well as BPD and mild cardiac defects. Second, we revealed that BPD exhibits only limited capacity in discriminating morbidity occurrence, despite its prevalence and clinical indication as a driver of comorbidities. Further, we demonstrated that structural and functional lung phenotyping did not exhibit higher association with morbidity severity than BPD. Lastly, we identified patient clusters that share similar morbidity patterns using machine learning in AIRR (n=6 clusters) and NEuroSIS (n=8 clusters). Conclusions By capturing correlations as well as more complex morbidity relations, we provided a comprehensive characterization of morbidity profiles at discharge, linked to shared disease pathophysiology. Future studies could benefit from identifying risk profiles to thereby develop personalized monitoring strategies. Trial registration AIRR: DRKS.de, DRKS00004600, 28/01/2013. NEuroSIS: ClinicalTrials.gov, NCT01035190, 18/12/2009.

Abstract Background Bronchopulmonary dysplasia (BPD) is a major complication affecting the survival rate and long-term outcomes of preterm infants. A large, prospective, multicenter cohort study was conducted to evaluate early nutritional support during the first week of life for preterm infants with a gestational age 4 were enrolled. Antenatal and postnatal information focusing on nutritional parameters was collected through medical systems. Statistical analyses were also performed to identify BPD risk factors. Results The primary outcomes were BPD and severity at 36 weeks postmenstrual age. A total of 1410 preterm infants were enrolled in this study. After applying the exclusion criteria, the remaining 1286 infants were included in this analysis; 614 (47.7%) infants were in the BPD group, and 672 (52.3%) were in the non-BPD group. In multivariate logistic regression model, the following six factors were identified of BPD: birth weight (OR 0.99, 95% CI 0.99–0.99; p = 0.039), day of full enteral nutrition (OR 1.03, 95% CI 1.02–1.04; p 3.5 g/kg/d during the first week (OR 1.65, 95% CI 1.25–2.17; p

Abstract Background Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. Methods We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. Results Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06–1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57–0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93–3.72) nor FV (OR = 1.23, 95%CI: 0.48–3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15–22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35–0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68–6.03; FV: OR = 6.36, 95%CI: 2.45–16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38–3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68–11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13–90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99–5.31) did not. Conclusion Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this “protective effect” only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

BackgroundBronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease in preterm infants. Studies have shown that Ureaplasma urealyticum (UU) infection is linked to its pathogenesis. However, it remains controversial whether UU colonization in preterm infants increases the risk of developing BPD.ObjectiveThis study aimed to conduct a systematic review and meta-analysis to summarize the correlation between UU and BPD.MethodsWe searched PubMed, Embase, the Cochrane Library, Web of Science, Wanfang Database, Chinese National Knowledge Infrastructure Database, Chinese Science and Technique Journal Database, and the China Biology Medicine disc from their inception to March 15, 2024. We included cohort and case-control studies investigating the association between UU infections and BPD in preterm infants, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle-Ottawa Scale was used for quality assessment. The outcome was defined as the continued need for oxygen or respiratory support at 28 days after birth (BPD28) or at 36 weeks postmenstrual age (BPD36). Considering the potential publication bias in observational studies, we used a random-effects meta-analysis model, assessed heterogeneity (I2), performed subgroup analyses, evaluated publication bias, and graded the quality of evidence.ResultsThe meta-analysis included 36 cohort studies encompassing 5,991 participants. Among these, 20 reported on BPD28, 13 on BPD36, and 3 on both. The results indicated a significant association between UU colonization and BPD28 (odds ratio (OR): 2.26, 95% confidence interval (CI): 1.78–2.85, P

Bronchopulmonary dysplasia (BPD) is a common morbidity affecting preterm infants and is associated with substantial long-term disabilities. The pathogenesis of BPD is multifactorial, and the clinical phenotype is variable. Extensive research has improved the current understanding of the factors contributing to BPD pathogenesis. However, effectively preventing and managing BPD remains a challenge. This review aims to provide an overview of the current evidence regarding the prevention of BPD in preterm infants, offering practical insights for clinicians.

ObjectiveThis study aims to investigate the effects of hyperoxia exposure on TGF-β1-induced endothelial-mesenchymal transition (EndoMT) and regulatory T cell (Treg)—mediated immunomodulation in human pulmonary microvascular endothelial cells (HPMECs), which could provide a theoretical basis for further studies of the pathogenesis of bronchopulmonary dysplasia (BPD).MethodsA BPD cell model was established by exposing HPMECs to hyperoxia. Flow cytometry was used to isolate CD4 + CD3 + CD25 + CD127- Tregs from the peripheral blood samples of preterm infants. HPMECs were divided into four groups based on whether they were exposed to hyperoxia and/or co-cultured with Tregs. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to test the expression levels of TGF-β1, α-SMA, Foxp3, IL-10, and reactive oxygen species (ROS).ResultsThe results showed that the expression levels of TGF-β1 and α-SMA in HPMECs increased at 24 h, 48 h, and 72 h of hyperoxia exposure. In the co-culture group of HPMECs and Tregs, Foxp3 and IL-10 expressions decreased at 48 h and 72 h of hyperoxia exposure. ROS expression increased in the hyperoxia group of HPMECs at 24 h, 48 h, and 72 h of hyperoxia exposure, which were higher than those in the hyperoxia group of HPMECs and Tregs.ConclusionThese findings suggest that hyperoxia exposure promotes EndoMT in HMPECs and inhibits the immunosuppressive effect of Tregs. Despite this, Tregs still seem could protect HPMECs from oxidative stress injury.

Abstract The aim of this study is to research the expression of the transient receptor potential canonical channel 3 (TRPC3) in a neonatal hyperoxic lung injury model of bronchopulmonary dysplasia (BPD), and to further investigate the role of the TRPC3/nuclear factor‐κB (NF‐κB) signaling pathway in hyperoxia‐induced BPD by a TRPC3 agonist (GSK1702934A). The hyperoxic lung injury model of BPD was established in Sprague–Dawley neonatal rats. Hematoxylin and eosin (HE) staining and radial alveolar count (RAC) values showed that the hyperoxic lung injury model of BPD was successfully established in the neonatal rats, and pulmonary edema was found in the neonatal rats with BPD. The results of reference transcriptome sequencing, Quantitative real‐time PCR (qPCR), and western blot showed lower pulmonary expression of TRPC3 in the BPD group than in the control group. Immunofluorescence showed predominant expression of TRPC3 in airways and pulmonary vessels, and the fluorescence intensity of the BPD group was lower than that of the control group. Lung dry‐to‐wet weight ratio, HE staining, and RAC value showed that the lung histomorphology significantly improved in the BPD + TRPC3 agonist group compared with the BPD group on day 14 but did not revert to the level of the control group. According to qPCR results, compared with the control group, the expression of NF‐κB1 decreased and the expression of NF‐κBiz increased in the BPD group, whereas the expression of NF‐κBiz decreased in the BPD + TRPC3 agonist group. Therefore, we draw the conclusion that TRPC3 may activate NF‐κB by inhibiting NF‐κBiz to promote cell proliferation and lung growth and development.

Background: Chronic diuretics such as thiazides and spironolactone are frequently used off-label in preterm infants with evolving or established bronchopulmonary dysplasia (BPD). Infants who are high risk for BPD are already predisposed to poor postnatal growth and the effect of chronic diuretics on postnatal growth is not well studied. Objective: Exploratory study to determine the association between chronic diuretic exposure and short-term postnatal growth in preterm infants born at less than ≤ 29 weeks gestational age (GA). Methods: Single-center retrospective cohort study in a level IV neonatal intensive care unit over a 2-year period (2021–22). Eligible infants exposed to chronic diuretics > 5 days for BPD (diuretic group) were compared to infants who were not (non-diuretic group). Results: In total, 53 infants (19 diuretic, and 35 non-diuretic group) were identified. The GA (25.3 vs 27.0 weeks) and birth weight (780 vs. 995 gs) were significantly lower in diuretic vs. non-diuretic group (p = 0.01). Diuretic group had higher intubation rate at birth, more days on non-invasive ventilation, higher incidence of moderate/severe BPD, and longer hospital stay (all p < 0.05). The GA adjusted z-scores for weight, length, and head circumference at birth, at 36-week corrected GA, and at discharge were similar in both groups. Also, the z-score change from birth at 36-week corrected GA, and at discharge were similar in both groups. There was no significant short-term change in weight z-score in the 2 weeks following chronic diuretic exposure. Conclusions: Chronic diuretic exposure has no significant association with short-term postnatal growth in preterm infants.

Abstract Objective As 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 methods The 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). Results Among 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. Conclusion A 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.

Objective: This study investigates the effectiveness of extubation from conventional mechanical ventilation using an endotracheal tube (MVET) compared to synchronized non-invasive positive-pressure ventilation (sNIPPV) using neurally adjusted ventilatory assist (NAVA) and conventional non-invasive positive-pressure ventilation (NIPPV) in extremely low-birth-weight (ELBW) infants. Methods: An institutional review board (IRB) approved this study (#12175) to conduct a single-center randomized control trial including 60 ELBW infants assigned in a one-to-one computer-generated scheme to either sNIPPV using NAVA or NIPPV. The primary outcome involved the need for reintubation, and the secondary outcome involved the assessment of moderate/severe BPD, defined as an oxygen requirement at 36 weeks, as in #NCT03613987 (clinicaltrials.gov). Results: There were 60 ELBW infants enrolled and randomized. The overall gestational age was 26 (1.5) weeks, and the birth weight was 773 (157) g [mean (SD)]. There were no statistically significant differences between the NAVA and NIPPV patient characteristics. There was a 41% extubation failure rate in the NIPPV group and 35% in the NAVA group (p = NS). The NAVA group had less moderate and severe BPD (p = 0.03), a shorter oxygen therapy duration (p = 0.002), a decreased length of stay (p = 0.03), and less need for home oxygen (0, 43%; p = 0.0004). Conclusions: This study found similar extubation failure rates among ELBW infants as in prior studies. However, the NAVA group had lower rates of moderate/severe BPD and need for oxygen at discharge, as well as shorter oxygen therapy duration and length of stay. The use of NAVA may be a reasonable alternative mode of non-invasive ventilation in the ELBW population.

Background: The impact of and countermeasures for Ureaplasma spp. in neonates remain controversial. The aim of this study was to evaluate the associated perinatal factors that can predict the likelihood of respiratory tract Ureaplasma spp. colonization and analyze the subsequent clinical course of affected infants, thereby providing the rationale for their diagnosis, treatment, and future study. Methods: This was a retrospective observational study of infants born at a gestational age (GA) of less than 32 weeks. Results: The prevalence of respiratory tract Ureaplasma spp. colonization was 25.8% (75/291), and it increased with a decrease in GA and birth weight (BW). Maternal vaginal Ureaplasma spp. colonization increased the risk of neonatal Ureaplasma spp. colonization, with an OR of 7.8 (95% CI: 3.1, 20.0). Infants with Ureaplasma spp. colonization had a higher white blood cell (WBC) count, normal C-reactive protein (CRP) level, and higher failure rate of weaning from mechanical ventilation (30.7% vs. 17.1%, p = 0.014); they also suffered more from interstitial pneumonia (20.0% vs. 5.6%, p < 0.001) and bronchopulmonary dysplasia (36.0% vs. 13.4%, p < 0.001). Infants receiving anti-Ureaplasma spp. treatment had a lower GA, lower BW, and more severe respiratory syndromes. However, the difference in respiratory manifestation became insignificant after adjusting for GA. Conclusions: GA and maternal vaginal Ureaplasma spp. colonization could be used to predict neonatal respiratory tract Ureaplasma spp. colonization. An elevated WBC count combined with normal CRP is a good marker of Ureaplasma spp. colonization/infection. It is conventional practice to start anti-Ureaplasma spp. treatment when infants present with a deteriorated respiratory condition. This practice warrants further investigation considering GA as a predominant intermediate variable.

Background: The existing literature lacks conclusive evidence regarding the relationship between bronchopulmonary dysplasia (BPD) and cerebral palsy (CP). This large epidemiological study aimed to explore the co-occurrence of BPD and CP among children. Methods: This retrospective cohort analysis utilized the National Inpatient Sample (NIS) dataset from 2016 to 2019, investigating pediatric patients with BPD and CP diagnoses. Descriptive and inferential statistics, including univariate and multivariate regression analyses, were conducted to explore the association between BPD and CP. Results: Overall, 3,951,039 patients were analyzed. Among them, 28,880 patients had CP (n = 796 with BPD and n = 28,084 without BPD). The rates of intraventricular hemorrhage grade 3 and 4, central nervous system anomalies, chromosomal disorders, retinopathy of prematurity (≥grade 3), periventricular leukomalacia, prematurity, and low birth weight were significantly higher in the CP-with-BPD arm contrasted to the CP-without-BPD arm. Univariate regression demonstrated a significant BPD–CP association (odds ratio [OR] = 7.78, 95% confidence interval [CI]: 7.24–8.37, p < 0.0001). Multivariate analysis, adjusting for various confounders, reinforced this association (OR = 5.70, 95% CI: 5.17–6.28, p < 0.0001). We observed a significant association between increasing prematurity in neonates with BPD and an elevated risk of CP. Conclusions: This nationwide study identified a strong correlation between the co-occurrence of BPD and CP, though it does not establish causality. Rigorous adjustments revealed that patients with BPD appear to have a six-fold increased likelihood of being diagnosed with CP later on, compared to those without BPD. While aligned with the existing literature, this study represents the largest sample size with recommendations for targeted preventive strategies to mitigate the burden of CP.

Respiratory complications are the most frequent incidents in pediatric anesthesia after cardiac events. The pediatric respiratory physiology and airway anatomy are responsible for the particular respiratory vulnerability in this stage of life. This article explains the aspects of pulmonary embryogenesis relevant for anesthesia and their impact on the respiration of preterm infants and neonates. The respiratory distress syndrome and bronchopulmonary dysplasia are highlighted as well as the predisposition to apnea of preterm infants and neonates. Due to the anatomical characteristics, the low size ratios and the significantly shorter apnea tolerance, airway management in children frequently represents a challenge. This article gives useful assistance and provides an overview of formulas for calculating the appropriate tube size and depth of insertion. Finally, the pathophysiology and adequate treatment of laryngospasm are explained. [ABSTRACT FROM AUTHOR]

ObjectivesTo evaluate serial tissue Doppler cardiac imaging (TDI) in the evolution of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) among extremely preterm infants.DesignProspective observational study.SettingSingle-center, tertiary-level neonatal intensive care unit.PatientsInfant born

Background: Despite numerous clinical strategies performed over the years, Bronchopulmonary dysplasia (BPD) still remains a common disease with considerable long-term adverse effects in very premature infants. This study investigated the effect of budesonide-instilled surfactant on the incidence of BPD in preterm infants.Methods: In this clinical trial, a total of 190 neonates with a gestational age of less than 30 weeks, who were identified as candidates for surfactant therapy, were randomly assigned to two groups. The control group (S) received surfactant at a dosage of 200 mg/kg for the initial dose and 100 mg/kg for subsequent doses. In cases where it was deemed necessary (n=95), the intervention group (BS) received surfactant along with budesonide, instilled once at a dose of 0.25 mg/kg (n=95). The primary outcome was the occurrence of BPD, and the combined incidence of BPD and death Secondary outcomes encompassed other complications related to prematurity and adverse effects associated with corticosteroid use.Results: Demographic characteristics of the neonates were comparable between the two groups. Although a slight reduction was seen in the incidence of BPD in the group receiving budesonide, BPD rates remained statistically unchanged after the intervention (48.4% in the BS group vs 50.5% in the S group, P value = 0.772). The combined outcome of BPD and death was insignificantly different between the two groups (61.1% in the BS group vs. 63.2% in the S group, P value = 0.765). The addition of budesonide resulted in an increased incidence of sepsis and pneumothorax in the control group. However, secondary outcomes such as IVH (Inra ventricular Hemorrhage(, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus, and hyperglycemia were unaffected. Duration of total parenteral nutrition and hospitalization time were longer in the BS group than in the S group.Conclusion: The addition of budesonide to surfactant in very premature neonates at gestational age

Background: Very preterm infants are at risk for neurodevelopmental impairment because of postnatal morbidities. This study aims to (1) compare the outcomes of very-low-birth-weight (VLBW) infants in Singapore during two time periods over a decade; 2) compare performances among Singaporean neonatal intensive care units (NICUs); and 3) compare a Singapore national cohort with one from the Australian and New Zealand Neonatal Network (ANZNN). Methods: Singapore national data on VLBW infants born during two periods, 2007–2008 (SG2007, n = 286) and 2015–2017 (SG2017, n = 905) were extracted from patient medical records. The care practices and clinical outcomes among three Singapore NICUs were compared using SG2017 data. Third, using data from the ANZNN2017 annual report, infants with gestational age (GA) ≤29 weeks in SG2017 were compared with their Oceania counterparts. Results: SG2017 had 9.9% higher usage of antenatal steroids (p

BackgroundAn increased risk for bronchopulmonary dysplasia (BPD) exists when moderate-to-large patent ductus arteriosus shunts (hsPDA) persist beyond 14 days.GoalTo examine the interaction between prolonged exposures to tracheal ventilation (≥10 days) and hsPDA on the incidence of BPD in infants 14 days, 41 died before 36 weeks. Among survivors, 93/266 had BPD. The association between BPD and hsPDA depended on the length of intubation. In multivariable analyses, prolonged hsPDA shunts were associated with increased BPD (odds ratio (OR) (95% confidence interval (CI)) = 3.00 (1.58-5.71)) when infants required intubation for ≥10 days. In contrast, there was no significant association between hsPDA exposure and BPD when infants were intubated

BackgroundFamily Integrated Care (FICare) benefits preterm infants compared with Family-Centered Care (FCC), but research is lacking in United States (US) Neonatal Intensive Care Units (NICUs). The outcomes for infants of implementing FICare in the US are unknown given differences in parental leave benefits and health care delivery between the US and other countries where FICare is used. We compared preterm weight and discharge outcomes between FCC and mobile-enhanced FICare (mFICare) in the US.MethodsIn this quasi-experimental study, we enrolled preterm infant (≤ 33 weeks)/parent dyads from 3 NICUs into sequential cohorts: FCC or mFICare. Our primary outcome was 21-day change in weight z-scores. Our secondary outcomes were nosocomial infection, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and human milk feeding (HMF) at discharge. We used intention-to-treat analyses to examine the effect of the FCC and mFICare models overall and per protocol analyses to examine the effects of the mFICare intervention components.Findings253 infant/parent dyads participated (141 FCC; 112 mFICare). There were no parent-related adverse events in either group. In intention-to-treat analyses, we found no group differences in weight, ROP, BPD or HMF. The FCC cohort had 2.6-times (95% CI: 1.0, 6.7) higher odds of nosocomial infection than the mFICare cohort. In per-protocol analyses, we found that infants whose parents did not receive parent mentoring or participate in rounds lost more weight relative to age-based norms (group-difference=-0.128, CI: -0.227, -0.030; group-difference=-0.084, CI: -0.154, -0.015, respectively). Infants whose parents did not participate in rounds or group education had 2.9-times (CI: 1.0, 9.1) and 3.8-times (CI: 1.2, 14.3) higher odds of nosocomial infection, respectively.ConclusionWe found indications that mFICare may have direct benefits on infant outcomes such as weight gain and nosocomial infection. Future studies using implementation science designs are needed to optimize intervention delivery and determine acute and long-term infant and family outcomes.Clinical trial registrationNCT03418870 01/02/2018.

Abstract Background As the survival rates of very low birth weight (VLBW) infants have increased, their neurodevelopmental outcomes are of concern. This study aims to determine the demographic and perinatal characteristics of premature infant according to head growth, identify clinical factors affecting growth catch-up, and explore differences in developmental outcomes according to catch-up states. Methods This nationwide prospective cohort study of Korean Neonatal Network data analyzed premature infants with very low birth weight (

Abstract Background Inflammation and oxidative stress play a key role in the development of bronchopulmonary dysplasia (BPD), possibly contributing to persistent respiratory morbidity after preterm birth. We aimed to assess if inflammatory markers were elevated in exhaled breath condensate (EBC) of infants born very prematurely (

Background: The patent ductus arteriosus (PDA) treatment in very preterm infants is controversial. This study focused on preterm infants born at 28–32 weeks of gestation and analyzed the association between various PDA treatments and clinical outcomes. Methods: We conducted a retrospective cohort study of infants born at 28–32 weeks of gestation between 2016 and 2019 at 22 hospitals in the Taiwan Premature Infant Follow-up Network. We categorized the infants into four groups according to treatment strategies: medication, primary surgery, medication plus surgery, or conservative treatment. Results: A total of 1244 infants presented with PDA, and 761 (61.1%) were treated. Medication was the predominant treatment (50.0%), followed by conservative treatment (38.9%), medication plus surgery (7.6%), and primary surgery (3.5%). The risk of mortality was not reduced in the active treatment group compared to the conservative treatment group. There was a higher prevalence of severe intraventricular hemorrhage, necrotizing enterocolitis (NEC), and any degree of bronchopulmonary dysplasia (BPD) in both the primary surgery and medication plus surgery groups than in the conservative treatment group. After adjustment, both the primary surgery and medication plus surgery groups still had higher odds ratios for the occurrence of NEC and any degree of BPD. Conclusions: Compared with active PDA treatment, conservative treatment for PDA did not increase the risk of mortality and morbidity in very preterm infants born at 28–32 weeks of gestation. The risks and benefits of surgery (PDA ligation) in these infants must be considered cautiously.

Abstract Background With the advances in neonatal intensive care, the survival rate of extremely preterm infants is increasing. However, bronchopulmonary dysplasia (BPD) remains a major cause of morbidity among infants in this group. This study examined the changes in respiratory support modalities, specifically heated humidified high-flow nasal cannula (HHHFNC), and their association with BPD incidence among preterm infants born at

Abstract Background Bronchopulmonary dysplasia (BPD) is the most common chronic pulmonary disease in premature infants. Blood proteins may be early predictors of the development of this disease. Methods In this study, protein expression profiles (blood samples during their first week of life) and clinical data of the GSE121097 was downloaded from the Gene Expression Omnibus. Weighted gene co-expression network analysis (WGCNA) and differential protein analysis were carried out for variable dimensionality reduction and feature selection. Least absolute shrinkage and selection operator (LASSO) were conducted for BPD prediction model development. The performance of the model was evaluated by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Results The results showed that black module, magenta module and turquoise module, which included 270 proteins, were significantly correlated with the occurrence of BPD. 59 proteins overlapped between differential analysis results and above three modules. These proteins were significantly enriched in 253 GO terms and 11 KEGG signaling pathways. Then, 59 proteins were reduced to 8 proteins by LASSO analysis in the training cohort. The proteins model showed good BPD predictive performance, with an AUC of 1.00 (95% CI 0.99-1.00) and 0.96 (95% CI 0.90-1.00) in training cohort and test cohort, respectively. Conclusion Our study established a reliable blood-protein based model for early prediction of BPD in premature infants. This may help elucidate pathways to target in lessening the burden or severity of BPD.