Diagnosis Of Bronchopulmonary Dysplasia Research Articles

Correlating Severity of Pulmonary Hypertension by Echocardiogram with Mortality in Premature Infants with Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth. Infants with BPD are at increased risk for pulmonary hypertension (PH). Cardiac catheterization is the gold standard for diagnosing PH, but cardiac catheterization is challenging to perform in small, sick, premature infants. The utility of echocardiography for diagnosing PH and predicting outcomes in extremely premature infants has not been clearly defined. Therefore, we sought to use predefined criteria to diagnose PH by echocardiogram and relate PH severity to mortality in extremely premature infants with BPD. Echocardiograms from 46 infants born ≤28 weeks' postmenstrual age with a diagnosis of BPD were assessed for PH by three pediatric cardiologists using predefined criteria, and survival times among categories of PH patients were compared. A total of 458 echocardiograms were reviewed, and 15 (33%) patients were found to have at least moderate PH. Patients with at least moderate PH had similar demographic characteristics to those with no/mild PH. Ninety percent of infants without moderate to severe PH survived to hospital discharge, compared with 67% of infants with at least moderate PH (p = 0.048). Patients with severe PH had decreased survival to hospital discharge (38%) compared with moderate (100%) and no/mild PH (90%) groups. Kaplan-Meier survival curves also differed among PH severity groups (Wilcoxon p < 0.001). Using predefined criteria for PH, premature infants with BPD can be stratified into PH severity categories. Patients diagnosed with severe PH by echocardiogram have significantly reduced survival. · A composite score definition of PH by echocardiogram showed high inter- and intrarater reliability.. · Infants with severe PH by echocardiogram had decreased survival rates.. · Early diagnosis of PH by echocardiogram dictates treatment which may improve outcomes..

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.

Implication of m6A Methylation Regulators in the Immune Microenvironment of Bronchopulmonary Dysplasia.

N6-methyladenosine (m6A) regulates gene expression and governs many important biological processes. However, the function of m6A in the development of bronchopulmonary dysplasia (BPD) remains poorly characterized. Thus, the purpose of this investigation was to evaluate the effects of m6A RNA methylation regulators on the development of BPD. BPD-related transcriptome data were downloaded from the GEO database. Differentially expressed m6A methylation regulators between BPD and control group were identified. Consensus clustering was conducted for the classification of BPD and association between clusters and BPD phenotypes were explored. Analysis of differentially expressed genes (DEGs) and immune-related DEGs was performed. The GSEA, GO and KEGG analyses were used to interpret the functional enrichments. The composition of immune cell subtypes in BPD subsets was predicted by CIBERSORT analysis. Compared with the control group, expression of most m6A regulators showed significant alteration, especially for IGF2BP1/2/3. BPD was classified into 2 subsets, and cluster 1 was correlated with severe BPD. Furthermore, the results of functional enrichment analyses showed a disturbed immune-related signaling pathway. Based on CIBERSORT analysis, we found that the proportion of immune cell subsets changed between cluster 1 and cluster 2. Our study revealed the implication of m6A methylation regulators in the development of BPD, which might provide a novel insight for the diagnosis and treatment 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.

Prescribing practices of inhaled corticosteroids for premature infants in the neonatal intensive care unit.

Despite limited safety and efficacy data, inhaled corticosteroids (ICS) are prescribed to premature infants in the neonatal intensive care unit (NICU). We examined contemporary use and risk factors for ICS use in the NICU. Infants <33 weeks gestational age and <1500 gm birth weight discharged from Pediatrix Medical Group NICUs between 2010 and 2020 were included. We evaluated the association between ICS prescription and clinical characteristics using univariable and multivariable logistic regression. Of 74,123 infants from 308 NICUs, 9253 (12.5%) were prescribed ICS: budesonide, fluticasone, or beclomethasone. Diagnosis of bronchopulmonary dysplasia (BPD), earlier gestational age, male sex, longer mechanical ventilation, oxygen support, and systemic steroids were independent risk factors for ICS prescription. Use of ICS is common in many NICUs and is associated with a diagnosis of BPD and healthcare utilization. Prospective trials are needed to establish the safety, efficacy, and optimal indication in this vulnerable population.

Identification of potential biomarkers in the peripheral blood of neonates with bronchopulmonary dysplasia using WGCNA and machine learning algorithms.

Bronchopulmonary dysplasia (BPD) is often seen as a pulmonary complication of extreme preterm birth, resulting in persistent respiratory symptoms and diminished lung function. Unfortunately, current diagnostic and treatment options for this condition are insufficient. Hence, this study aimed to identify potential biomarkers in the peripheral blood of neonates affected by BPD. The Gene Expression Omnibus provided the expression dataset GSE32472 for BPD. Initially, using this database, we identified differentially expressed genes (DEGs) in GSE32472. Subsequently, we conducted gene set enrichment analysis on the DEGs and employed weighted gene co-expression network analysis (WGCNA) to screen the most relevant modules for BPD. We then mapped the DEGs to the WGCNA module genes, resulting in a gene intersection. We conducted detailed functional enrichment analyses on these overlapping genes. To identify hub genes, we used 3 machine learning algorithms, including SVM-RFE, LASSO, and Random Forest. We constructed a diagnostic nomogram model for predicting BPD based on the hub genes. Additionally, we carried out transcription factor analysis to predict the regulatory mechanisms and identify drugs associated with these biomarkers. We used differential analysis to obtain 470 DEGs and conducted WGCNA analysis to identify 1351 significant genes. The intersection of these 2 approaches yielded 273 common genes. Using machine learning algorithms, we identified CYYR1, GALNT14, and OLAH as potential biomarkers for BPD. Moreover, we predicted flunisolide, budesonide, and beclomethasone as potential anti-BPD drugs. The genes CYYR1, GALNT14, and OLAH have the potential to serve as diagnostic biomarkers for BPD. This may prove beneficial in clinical diagnosis and prevention of BPD.

Cardiopulmonary exercise testing in adolescence following extremely premature birth.

Although extremely premature birth disrupts lung development, adolescent survivors of extreme prematurity show good clinical and physiologic outcomes. Cardiopulmonary limitations may not be clinically evident at rest. Data regarding exercise limitation in adolescents following preterm birth in the postsurfactant era are limited. What are the long-term effects of bronchopulmonary dysplasia (BPD) and extreme prematurity (<29 weeks) on ventilatory response during exercise in adolescents in the postsurfactant era? We followed a longitudinally recruited cohort of children aged 13-19 years who were born at a gestational age of <29 weeks (study group - SG). We compared the cardiopulmonary exercise testing (CPET) results of those with and without BPD, to their own CPET results from elementary school age (mean 9.09 ± 1.05 years). Thirty-sevenchildren aged 15.73 ± 1.31 years, mean gestational age 26 weeks ( ± 1.19), completed the study. CPET parameters in adolescence were within the normal range for age, including mean V̇O2 peak of 91% predicted. The BPD and non-BPDsubgroups had similar results. In the longitudinal analysis of the SG, improvement was observed in adolescence, compared with elementary school age, in breathing reserve (36.37 ± 18.99 vs. 26.58 ± 17.92, p = 0.044), tidal volume as a fraction of vital capacity achieved at maximal load (0.51 ± 0.13 vs. 0.37 ± 0.08, p < 0.001), and respiratory exchange ratio at maximal load (1.18 ± 0.13 vs. 1.11 ± 0.10, p = 0.021). In the current cohort, adolescents born extremely premature have essentially normal ventilatory response during exercise, unrelated to BPD diagnosis. CPET results in this population improve over time.

Predictive and Diagnostic Values of Systemic Inflammatory Indices in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common respiratory complication in preterm infants, and there is a lag in the diagnosis of BPD. Inflammation is a vital pathogenic factor for BPD; we aim to evaluate the predictive and diagnostic values of systemic inflammatory indices in BPD. Between 1 January 2019 and 31 May 2023, the clinical data of 122 premature infants with a gestational age of <32 weeks in the Department of Neonatology, the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, were retrospectively collected and classified into non-BPD (n = 72) and BPD (n = 50) groups based on the National Institute of Child Health and Human Development 2018 criteria. To compare the general characteristics of each group, we identified the independent risk variables for BPD using multivariate logistic regression analysis, compared the systemic inflammatory indices at birth, 72 h, 1 week, 2 weeks, and 36 weeks postmenstrual age (PMA), and constructed the receiver operating characteristic curves of neutrophil-to-lymphocyte ratio (NLR) diagnosis of BPD at different time points. ① The independent risk factors for BPD in preterm infants were birth weight, small for gestational age, and days of oxygen therapy (all p < 0.05). ② At 72 h and 1 week after birth, the serum NLR of the BPD group was higher than for the non-BPD group (p < 0.05). Furthermore, the neutrophil count (N), NLR, monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index, systemic inflammation response index (SIRI), and pan-immune-inflammation value of infants with BPD were higher than the non-BPD group at 3 weeks after birth (p < 0.05). Moreover, at 36 weeks of PMA, the serum N, NLR, MLR, and SIRI of BPD infants were higher than those of non-BPD infants (p < 0.05). ③ The NLR of infants with and without BPD gradually increased after birth, reaching a peak at 72 h and 1 week, respectively. At 3 weeks postnatal, the NLR had the highest predictive power for BPD, with an area under the curve (AUC) of 0.717 (p < 0.001); the sensitivity was 56% and specificity was 86.1%. In addition, the NLR at 36 weeks of PMA exhibited some diagnostic value for BPD. The AUC was 0.693 (p < 0.001), the sensitivity was 54%, and specificity was 83.3%. At 3 weeks after birth and 36 weeks of PMA, some systemic inflammation indices (like N, NLR, SIRI) of preterm infants with BPD have specific predictive and diagnostic values; these indices may help the management of high-risk preterm infants with BPD.

Clinical characteristics of bronchopulmonary dysplasia in very preterm infants.

With the development of perinatal and neonatal intensive care medicine, the survival rate of very premature infants increases year by year. However, the incidence of bronchopulmonary dysplasia (BPD) increases year by year, which seriously affects the survival prognosis of very premature infants. How to prevent and treat BPD effectively has become the focus of neonatologists. This study aims to provide ideas for the prevention and treatment of BPD in very preterm infants via analyzing the clinical characteristics of BPD. A total of 472 cases of very premature infants admitted to the Divison of Neonatology, Department of Pediatrics at the Second Xiangya Hospital of Central South University were retrospectively selected and assigned into a BPD group (n=147) and a non-BPD group (n=325) according to the diagnosis of BPD. Clinical data of each group were collected to find out the clinical characteristics of BPD in very preterm infants. Basic information, maternal pregnancy data, laboratory findings, nutritional support, respiratory support patterns and duration, and systemic complications were included. Compared with the non-BPD group, gestational age, birth weight, head circumference and body length in the BPD group were lower, the Apgar score in 1st min and 5th min and average body weight growth rate were lower (all P<0.05); the ratios of male, very low birth weight (VLBW), and extremely low birth weight (ELBW) in the BPD group were higher than those in the non-BPD group (all P<0.5); the incidence of maternal cervical insufficiency and the rate of using embryo transfer technology in the BPD group were higher than those in the non-BPD group, and the rate of using prenatal hormone in the BPD group was lower than that in the non-BPD group (all P<0.05). The positive rate of sputum culture in the BPD group was higher than that in the non-BPD group (P<0.05), and the white blood cell count, neutrophil ratio, and procalcitonin in the BPD group were higher than those in the non-BPD group (all P<0.05). The period of fasting, minimal feeding, total parenteral nutrition (TPN), and partial parenteral nutrition (PPN) in the BPD group were longer than those in the non-BPD group (all P<0.05). The duration of nasal catheter oxygen inhalation and mechanical ventilation in the BPD group was longer than that in the non-BPD group, and the rates of mechanical ventilation at Day 1, 3, 7, 14, 21 and 28 after birth were higher than those in the non-BPD group (all P<0.05). The incidence of respiratory distress syndrome, apnea of prematurity, respiratory failure, pneumonia, pulmonary hemorrhage, pleural effusion, persistent pulmonary hypertension, hemodynamic patent ductus arteriosus, cytomegalovirus infection, neonatal necrotic enterocolitis, cholestasis, anemia, abnormal blood system, hypothyroidism, retinopathy of prematurity, and internal environment disorders in the BPD group were significantly higher than those in non-BPD group (all P<0.05). There are significant differences between very premature infants with BPD and those without BPD in general information, maternal history, inflammatory indicators, nutritional support, respiratory support, comorbidities and complication rates. To ensure normal fetal development, reducing the inflammatory reaction of very premature infants, establishing enteral nutrition as early as possible, shortening the time of mechanical ventilation, and reducing the occurrence of complications are beneficial to decrease the incidence of BPD in very premature infants and improve the long-term prognosis of BPD.

Factors associated with tracheostomy decannulation in infants with bronchopulmonary dysplasia

ObjectivePremature infants represent a unique subset of patients who may require tracheostomy. Bronchopulmonary dysplasia (BPD) is among one of the most common sequelae of prematurity contributing to the need for prolonged ventilation requiring tracheostomy after other airway options have been exhausted. Our objective is to understand socioeconomic barriers to decannulation and identify factors that accelerate safe decannulation, focusing on patients with BPD. MethodsAn existing internal database from a tertiary pediatric hospital of patients undergoing tracheostomy prior to one year old was reviewed. Data from January 1, 2005 through December 31, 2020 was used to compare patients who were successfully decannulated to those who were not. A further subset of infants with BPD were identified and analyzed. Of those decannulated, survival analysis was used to identify factors associated with decreased time to decannulation. ResultsWe identified 303 infants who underwent tracheostomy at less than one year old with 125 of those infants having a diagnosis of BPD. Of the 125 infants with BPD, 44 (35.2 %) were decannulated and 81 (64.8 %) were not. There was no significant difference in sex, race, ethnicity, insurance status, comorbidities, or presence of syndromes between those patients with BPD who were decannulated and those who were not. Those who were not decannulated had a significantly longer length of hospital stay, prolonged ventilator requirements after tracheostomy, and were more likely to be discharged home on the ventilator (p = 0.030; 0.020; 0.002, respectively). Of the 44 decannulated patients, mean and median time to decannulation were 37.9 and 27.8 months respectively (range 10.8–160.6 months). There was an inverse association with decannulation and both Black race (HR: 0.30) and neurological comorbidity (HR: 0.37) on multivariate analysis. Black race, presence of syndrome, and length of ventilator dependence were significantly associated with increased time to decannulation. Time to decannulation from time off the ventilator was not significantly influenced by sex, race, ethnicity, state of residence, or insurance status, but was significantly influenced by age (95 % CI: −6.9, −0.1; P = 0.044). While time from discharge to first follow up visit did not significantly impact time to decannulation, every additional follow up visit increased time to decannulation by 3.78 months when adjusting for confounding variables. ConclusionIn infants with BPD under one year requiring tracheostomy, socioeconomic factors were not found to influence likelihood of decannulation, however Black race, presence of underlying syndrome, and increased length of ventilator dependence were associated with prolonged timing. Children with more frequent follow up visits similarly had an increased time to decannulation, illustrating a vital point in the process. Ventilator weaning protocols and standardized decannulation protocols in patients with BPD, along with caregiver education, can safely expedite and facilitate decannulation.

Echocardiography Assessment of Left Ventricular Function in Extremely Preterm Infants, Born at Less Than 28 Weeks’ Gestation, With Bronchopulmonary Dysplasia and Systemic Hypertension

The survival of smaller and more immature premature infants has been associated with lifelong cardiorespiratory comorbidities. Infants with bronchopulmonary dysplasia (BPD) undergo routine screening echocardiography to evaluate for development of chronic pulmonary hypertension, a late manifestation of pulmonary vascular disease. Our aim was to evaluate left ventricular (LV) performance in infants with BPD and pulmonary vascular disease who developed systemic hypertension. We hypothesized that infants with hypertension were more likely to have impaired LV performance. We present a single-center cross-sectional study of premature infants born at less than 28 0/7weeks'gestational age with a clinical diagnosis of BPD. Infants were categorized by the systolic arterial pressure (SAP) at time of echocardiography as hypertensive (SAP ≥90mm Hg) or normotensive (SAP <90mm Hg). Sixty-four patients were included. Infants with hypertension showed altered LV diastolic function with prolonged tissue Doppler imaging-derived isovolumic relaxation time (54.2±5.1 vs 42.9±8.2, P<.001), lower E:A, and higher E:e'. Indices of left heart volume/pressure loading (left atrium:aorta and LV end-diastolic volume [6.1±2 vs 4.2±1.2, P<.001]) were also higher in the hypertensive group. Finally, infants in the hypertensive group had higher pulmonary vascular resistance index (4.42±1.1 vs 3.69±0.8, P=.004). We conclude that extremely preterm infants with BPD who develop systemic hypertension are at risk of abnormal LV diastolic dysfunction. Increased pulmonary vascular resistance index in the hypertensive group may relate to pulmonary venous hypertension secondary to LV dysfunction. This is an important consideration in this cohort when selecting the physiologically most appropriate treatment.

Lung function deficits and bronchodilator responsiveness at 12 years of age in children born very preterm compared with controls born at term.

Very preterm birth is associated with lung function impairment later in life, but several aspects have not been studied. We aimed to comprehensively assess lung function at school age in very preterm infants and term controls, with special emphasis on bronchopulmonary dysplasia (BPD), sex, and bronchodilator response. At 12 years of age, 136 children born very preterm (85 with and 51 without BPD) and 56 children born at term performed spirometry, body plethysmography, impulse oscillometry, measurement of diffusion capacity, and multiple breath washout, before and after bronchodilator inhalation. Airway symptoms and a diagnosis of asthma were more common in children born very preterm. These children had more airflow limitation, seen as lower forced expiratory volume in 1 s (FEV1 ) (p < .001), FEV1 /forced vital capacity (FVC) (p = .011), and mean forced expiratory flow between 25% and 75% of FVC (p < .001), and a higher total and peripheral airway resistance compared with term-born controls. There was no difference in total lung capacity but air trapping and lung clearance index were higher in children born very preterm. Diffusion capacity was lower in children born very preterm, especially in those with a diagnosis of BPD. In most other tests, the differences between preterm-born children with or without BPD were smaller than between children born preterm versus at term. Boys born preterm had more lung function deficits than preterm-born girls. In children born very preterm, airway obstruction was to a large extent reversible. At 12 years of age, children born very preterm had lower lung function than children born at term in most aspects and there was only little difference between children with or without BPD. Airway obstruction improved markedly after bronchodilator inhalation.

Elevated leukotriene B4 and 8-isoprostane in exhaled breath condensate from preterm-born infants

BackgroundInflammation 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 (< 32 weeks gestation) at 12–16 corrected months of age, and if increased levels were associated with BPD diagnosis and respiratory morbidity.MethodsEBC samples and respiratory questionnaires were collected from 15 term-born infants and 33 preterm-born infants, 12 with a neonatal BPD diagnosis. EBC samples were analysed for leukotriene B4 (inflammation) and 8-isoprostane (oxidative stress) concentrations using enzyme-linked immune-assays. Differences between groups were analysed by Kruskal-Wallis Test with post-hoc comparisons, independent samples t-test or Mann-Whitney U test depending on normality of the data.ResultsLeukotriene B4 and 8-isoprostane levels were elevated in exhaled breath condensate of preterm-born infants compared to those born at term (mean difference [95% CI]; 1.52 [0.45, 2.59], p = 0.02; 0.77 [0.52, 1.02], p < 0.001, respectively). Leukotriene B4 and 8-isoprostane levels were independent of BPD diagnosis and respiratory morbidity over the first year of life.ConclusionsInfants born very prematurely exhibit elevated markers of airway neutrophilic inflammation and oxidative stress beyond the first year of life, regardless of a neonatal diagnosis of chronic lung disease or respiratory morbidity during infancy. These findings may have implications for future lung health.Trial RegistrationN/A.

Inhaled corticosteroids to improve lung function in children (aged 6–12 years) who were born very preterm (PICSI): a randomised, double-blind, placebo-controlled trial

Despite the substantial burden of lung disease throughout childhood in children who were born very preterm, there are no evidence-based interventions to improve lung health beyond the neonatal period. We tested the hypothesis that inhaled corticosteroid improves lung function in this population. PICSI was a randomised, double-blind, placebo-controlled trial at Perth Children's Hospital (Perth, WA, Australia) to assess whether fluticasone propionate, an inhaled corticosteroid, improves lung function in children who had been born very preterm (<32 weeks of gestation). Eligible children were aged 6-12 years and did not have severe congenital abnormalities, cardiopulmonary defects, neurodevelopmental impairment, diabetes, or any glucocorticoid use within the preceding 3 months. Participants were randomly assigned (1:1) to receive 125 μg fluticasone propionate or placebo twice daily for 12 weeks. Participants were stratified for sex, age, bronchopulmonary dysplasia diagnosis, and recent respiratory symptoms using the biased-coin minimisation technique. The primary outcome was change in pre-bronchodilator forced expiratory volume in 1 s (FEV1) after 12 weeks of treatment. Data were analysed by intention-to-treat (ie, all participants who were randomly assigned and took at least the tolerance dose of the drug). All participants were included in the safety analyses. This trial is registered at the Australian and New Zealand Clinical Trials Registry, number 12618000781246. Between Oct 23, 2018, and Feb 4, 2022, 170 participants were randomly assigned and received at least the tolerance dose (83 received placebo and 87 received inhaled corticosteroid). 92 (54%) participants were male and 78 (46%) were female. 31 participants discontinued treatment before 12 weeks (14 in the placebo group and 17 in the inhaled corticosteroid group), mostly due to the impact of the COVID-19 pandemic. When analysed by intention-to-treat, the change in pre-bronchodilator FEV1 Z score over 12 weeks was -0·11 (95% CI -0·21 to 0·00) in the placebo group and 0·20 (0·11 to 0·30) in the inhaled corticosteroid group (imputed mean difference 0·30, 0·15-0·45). Three of 83 participants in the inhaled corticosteroid group had adverse events requiring treatment discontinuation (exacerbation of asthma-like symptoms). One of 87 participants in the placebo group had an adverse event requiring treatment discontinuation (inability to tolerate the treatment with dizziness, headaches, stomach pains, and worsening of a skin condition). As a group, children born very preterm have only modestly improved lung function when treated with inhaled corticosteroid for 12 weeks. Future studies should consider individual phenotypes of lung disease after preterm birth and other agents to improve management of prematurity-associated lung disease. Australian National Health and Medical Research Council, Telethon Kids Institute, and Curtin University.

Health Care Utilization During the COVID-19 Pandemic Among Individuals Born Preterm

Limited data exist on pediatric health care utilization during the COVID-19 pandemic among children and young adults born preterm. To investigate differences in health care use related to COVID-19 concerns during the pandemic among children and young adults born preterm vs those born at term. In this cohort study, questionnaires regarding COVID-19 and health care utilization were completed by 1691 mother-offspring pairs from 42 pediatric cohorts in the National Institutes of Health Environmental Influences on Child Health Outcomes Program. Children and young adults (ages 1-18 years) in these analyses were born between 2003 and 2021. Data were recorded by the August 31, 2021, data-lock date and were analyzed between October 2021 and October 2022. Premature birth (<37 weeks' gestation). The main outcome was health care utilization related to COVID-19 concerns (hospitalization, in-person clinic or emergency department visit, phone or telehealth evaluations). Individuals born preterm vs term (≥37 weeks' gestation) and differences among preterm subgroups of individuals (<28 weeks', 28-36 weeks' vs ≥37 weeks' gestation) were assessed. Generalized estimating equations assessed population odds for health care used and related symptoms, controlling for maternal age, education, and psychiatric disorder; offspring history of bronchopulmonary dysplasia (BPD) or asthma; and timing and age at COVID-19 questionnaire completion. Data from 1691 children and young adults were analyzed; among 270 individuals born preterm, the mean (SD) age at survey completion was 8.8 (4.4) years, 151 (55.9%) were male, and 193 (71.5%) had a history of BPD or asthma diagnosis. Among 1421 comparison individuals with term birth, the mean (SD) age at survey completion was 8.4 (2.4) years, 749 (52.7%) were male, and 233 (16.4%) had a history of BPD or asthma. Preterm subgroups included 159 individuals (58.5%) born at less than 28 weeks' gestation. In adjusted analyses, individuals born preterm had a significantly higher odds of health care utilization related to COVID-19 concerns (adjusted odds ratio [aOR], 1.70; 95% CI, 1.21-2.38) compared with term-born individuals; similar differences were also seen for the subgroup of individuals born at less than 28 weeks' gestation (aOR, 2.15; 95% CI, 1.40-3.29). Maternal history of a psychiatric disorder was a significant covariate associated with health care utilization for all individuals (aOR, 1.44; 95% CI, 1.17-1.78). These findings suggest that during the COVID-19 pandemic, children and young adults born preterm were more likely to have used health care related to COVID-19 concerns compared with their term-born peers, independent of a history of BPD or asthma. Further exploration of factors associated with COVID-19-related health care use may facilitate refinement of care models.

Pulmonary important outcomes after extremely preterm birth: Parental perspectives.

To describe pulmonary important outcomes (PIO) reported by parents of children born extremely preterm. Over 1-year, all parents of children aged 18 months-7-years born <29 weeks' GA were asked regarding their perspectives. The proportion of parents who described PIO and the themes they invoked were examined. Results were analysed using mixed methods. Among parental responses (n= 285, 98% participation rate), 44% spoke about PIO, invoking 24 themes pertaining to NICU hospitalisation and/or long-term respiratory health. Some themes had an impact primarily on the child (e.g. exercise limitation), while the majority had an impact on the whole family (e.g. hospital readmissions). None mentioned oxygen at 36 weeks nor bronchopulmonary dysplasia (BPD). The proportion of responses invoking PIO were statistically similar between parents of children with and without BPD, born before or after 25 weeks or with birthweight < or ≥750 g. PIO were more likely to be mentioned in males and among those readmitted for respiratory problems. Parents describe many PIO, most related to the functional impact of lung disease on their child (and family), rather than the diagnosis of BPD itself. Most of these PIO are not primary outcomes in large neonatal trials nor collected in neonatal databases.

MORPHOLOGICAL EVOLUTION AND DIAGNOSIS OF BRONCHOPULMONARY DYSPLASIA IN VERY PRETERM INFANTS

Bronchopulmonary dysplasia (BPD) remains one of the most common and severe diseases in very preterm infants, which can cause death. Since the first description of BPD in 1967, not only understanding of the disease’s nature, its definition, classification, epidemiology, features of the clinical course, diagnosis, prevention, treatment, and prognosis but the specific autopsy histopathological features have changed. The primarily reason for these is considered a change in the population of sick and dead infants as a result of improving clinical practice, increasing the survival rates of the most immature neonates, and reducing the incidence of severe BPD forms and the associated mortality.The BPD form that has been described initially is now called "old" BPD and is characterized by significant lung injury. In the smallest neonates, who were treated with exogenous surfactant, the histopathological signs of the disease changed, determining the need to modify the theoretical concept of BPD. The leading feature of the new BPD form was the disorder of lung development and formation, not their injury. Morphologically, this was manifested by a reduced number and simplified structure of acini, changes in the capillary structure with less obvious fibrosis of the lungs. Such morphometric methods as the radial alveolar count and the count of mean number of alveoli intercepts can be used for the histopathological diagnosis of a simplified lung structure. The use of these techniques helps to objectively assess lung growth retardation. Although the number of cases of "new" BPD currently prevails, some autopsies are still characterized by histopathological changes typical for the "old" form of the disease. A combination of classic and new features is also possible. When establishing a pathological diagnosis of BPD, it is essential to consider all specific histopathological changes that may indicate the presence and severity of the disease, as well as its role in thanatogenesis. This is important not only for the correct postmortem diagnosis of BPD, but also for the studying of various disease phenotypes.The article describes the main histopathological characteristic of various BPD forms, as well as methods of evaluating the simplified lung structure.

The association between βeta 2-microglobulin and bronchopulmonary dysplasia

Abstract Objectives Previous studies showed that increased urinary Beta 2-microglobulin (β2-M) level is associated with fetal inflammatory response and successfully predict bronchopulmonary dysplasia (BPD). We aimed to investigate the clinical utility of serum β2-M levels to predict BPD in preterm infants. Method Infants born between May and November 2018 and whose gestational age (GA) was &lt;32 weeks were included into the study. During routine blood work in the first couple of hours of life an extra 0.5 mL blood was drawn to study β2-M levels later on. β2-M levels were compared between infants who developed BPD or not. Results Data analysis of 111 infants was performed. Out of 111 infants, 37 died before BPD diagnosis and out of the rest 74 infants, 38 (34.2%) were diagnosed with BPD. Mean GA was 28 ± 1.8 and 29.9 ± 1.4 weeks (p &lt; 0.01) and mean birth weights (BW) were 1,086 ± 316 and 1,395 ± 348 g (p &lt; 0.01) in BPD group and without BPD respectively. Demographic characteristics of the two groups were similar. While the white blood cell count, CRP and IL-6 levels were similar in both groups, β2-M levels were significantly higher in BPD group (4.84 ± 1.0 and 3.79 ± 0.95 mg/L, p = 0.01). Furthermore a weak correlation between β2-M level and BPD was observed (r = 0.23, p = 0.04). Conclusion Serum β2-M levels which obtained in the early postnatal life could predict developing BPD. Monitoring β2-M levels in infants who have high clinical risk factors for BPD development may provide additional benefit in predicting BPD.

Changes and significance of type 2 innate lymphoid cells and their related factors in bronchopulmonary dysplasia

To investigate the changes and significance of type 2 innate lymphoid cells (ILC2), interleukin-33 (IL-33), interleukin-25 (IL-25), thymic stromal lymphopoietin (TSLP), interleukin-5 (IL-5), and interleukin-13 (IL-13) in peripheral blood of preterm infants with bronchopulmonary dysplasia (BPD). A total of 76 preterm infants with a gestational age of <32 weeks and a length of hospital stay of ≥14 days who were admitted to the Department of Pediatrics of the Affiliated Hospital of Jiangsu University from September 2020 to December 2021 were enrolled. According to the diagnostic criteria for BPD, they were divided into a BPD group with 30 infants and a non-BPD group with 46 infants. The two groups were compared in terms of the percentage of ILC2 and the levels of IL-33, IL-25, TSLP, IL-5, and IL-13 in peripheral blood on days 1, 7, and 14 after birth. The BPD group had significantly lower birth weight and gestational age than the non-BPD group (P<0.05). On days 7 and 14 after birth, the BPD group had significantly higher levels of ILC2, IL-33, TSLP, and IL-5 than the non-BPD group (P<0.05), and these indices had an area under the curve of >0.7 in predicting the devolpment of BPD (P<0.05). Multivariate logistic regression analysis showed that after adjusting for gestational age and birth weight, peripheral blood IL-33, TSLP and IL-5 on days 7 and 14 after birth were closely related to the devolpment of BPD (P<0.05). Early innate immune activation and upregulated expression of related factors may be observed in preterm infants with BPD. ILC2, IL-33, TSLP, and IL-5 may be used as biological indicators for early diagnosis of BPD.

Long-Term Complications of Neonatal Necrotic Enterocolitis: Twisting of Stenosed Small Intestine

Neonatal necrotic enterocolitis (NEC) is a nonspecific inflammatory disease of unknown etiology with multifactorial pathogenesis, which development is explained as a result of hypoperfusion of the immature intestinal mucosa of a newborn who has undergone perinatal hypoxia and, as a result, a change in blood flow in the mesenteral vascular system. This disease more often affects the intestinal wall of premature babies. In typical cases, mucosal necrosis develops in the terminal iliac and right parts of the colon, and when the process progresses, it can spread to the entire thickness of the intestinal wall, causing its perforation, so peritonitis is a frequent complication of NEC. But in addition, distant complications of NEC are distinguished, which include the development of intestinal obstruction in view of a decrease in the contractility of the intestinal wall section due to its fibrosis and, as a result, narrowing of the lumen.We report the clinical case of surgical treatment of the twisting of stenosed portion of the ileum in a child who underwent NEC in the early neonatal period. A mother sought assistance with a child of 3 months at the Reginal Children’s Hospital (born at 28 weeks of gestation). After birth, there was a violation of the absorption of enteral nutrition (periodic posseting, bloating), blood in the stool was determined. On the 14th day of life a pediatric surgeon examined the baby: necrotizing enterocolitis II A. After stabilizing the condition (2 months), the child was transferred from the perinatal center to a pediatric hospital with a diagnosis of bronchopulmonary dysplasia, a new form, a severe course, and a period of exacerbation. At the age of 2.5 months, he was discharged in a satisfactory condition to the outpatient stage. On the 15th day from the moment of discharge (3 months of life), the mother noted the expressed anxiety of the baby, bloating, stool retention. On the 16th day from the moment of discharge during feeding, the child began to suck sluggishly, did not absorb the age norm. He was examined by a pediatrician, the consultation of a pediatric surgeon was recommended. Due to the severity of the condition, the baby was hospitalized.In the initial examination, no data for intestinal obstruction were detected. The patient received parenteral nutrition, antibacterial therapy. Ultrasound and radiography of abdominal organs were performed daily. On the third day of observation, deterioration is noted (abdomen bloated mainly in the upper parts, soft upon with palpation, the baby was anxious, peristalsis was reduced), with ultrasound: between the loops of the enlarged intestine, an echogenic band of up to 18 mm (adhesion?) was determined, there was the liquid component between the loops. A laparotomy was performed, during the revision there was a displacement of the large intestine into the left parts of the abdominal cavity. Ten cm from the ileocecal angle, a section of the ileum with a length of up to 15 cm was found, which was like a “double trunk” wrapped at the base around its axis around a cord-like adhesive stretching to the posterior abdominal wall. Visually, the loop was dark bard in color, its walls were swollen, infiltrated, and their cartilaginous density was determined upon palpation in the contact area of the walls of the intestine. The resection of this loop was performed, end-to-end anastomosis was formed according to the method of J. Louw. After the operation, the baby received treatment in the intensive care unit, enteral feeding on day 5, on day 9, after expanding the volume of feeding, he was transferred to the department of pediatric surgery. Discharged in satisfactory condition on the 12th day after surgery.