Definition Of Bronchopulmonary Dysplasia Research Articles

Point prevalence, characteristics and treatment variations for preterm infants with bronchopulmonary dysplasia in China: a ‘snapshot’ study

ObjectiveThe incidence of bronchopulmonary dysplasia (BPD) is increasing, but data on its prevalence and management variations remain insufficient in China. The study aims to investigate its point prevalence and variations...

Association between bronchopulmonary dysplasia severity and its risk factors and long-term outcomes in three definitions: a historical cohort study

ObjectiveTo compare the association of the severity categories of the 2001-National Institutes of Health (NIH), the 2018-NIH and the 2019-Jensen bronchopulmonary dysplasia (BPD) definitions with neurodevelopmental and respiratory outcomes at...

Bronchopulmonary Dysplasia Definitions: How Well do They Predict School-Age Outcomes?

Bronchopulmonary Dysplasia Definitions: How Well do They Predict School-Age Outcomes?

Comparison Study of Respiratory Outcomes Based on Bronchopulmonary Dysplasia Definitions: Single Center Retrospective Study in South Korea

Comparison Study of Respiratory Outcomes Based on Bronchopulmonary Dysplasia Definitions: Single Center Retrospective Study in South Korea

Hsa_circ_0001359 in Serum Exosomes: A Promising Marker to Predict Bronchopulmonary Dysplasia in Premature Infants.

This prospective study is to explore the role of specific circRNAs in predicting the development of bronchopulmonary dysplasia (BPD). From July 1, 2021 to December 1, 2021, peripheral blood samples were collected from 62 premature infants with gestational age (GA) ≤32 weeks on the 7th, 14th, and 28th day after birth. Then, on the 28th day, the included infants were divided into the BPD group and the non-BPD group according to the definition of BPD. Serum exosomal circRNAs from peripheral blood were identified, sequenced, and compared between the BPD and non-BPD groups at different time points. Specific differentially expressed circRNAs were further verified from another 42 enrolled premature infants (GA ≤32 weeks). The classical lung biological markers in serum were also measured simultaneously. Hsa_circ_0001359 in serum exosomes showed continuous differential expression between the BPD group and the non-BPD group on the 7th, 14th, and 28th day. Compared with that, classical lung biological markers like IL-6, IL-33, KL-6, and ET-1 did not exhibit continuous differences. Moreover, the expression of hsa_circ_0001359 on day 7 had a higher predictive value in predicting BPD (area under curve:0.853, 95% CI:0.738-0.968; adjusted odds ratio:6.033, 95% CI:2.373-13.326). The calibration curve further showed the mean absolute error = 0.033, mean squared error = 0.00231, and quantile of absolute error = 0.058. Hsa_circ_0001359 in serum exosomes is a promising marker for predicting BPD in preterm infants with gestational age ≤32 weeks.

Noninvasive Monitoring Strategies for Bronchopulmonary Dysplasia or Post-Prematurity Respiratory Disease: Current Challenges and Future Prospects.

Definitions of bronchopulmonary dysplasia (BPD) or post-prematurity respiratory disease (PPRD) aim to stratify the risk of mortality and morbidity, with an emphasis on long-term respiratory outcomes. There is no univocal classification of BPD due to its complex multifactorial nature and the substantial heterogeneity of clinical presentation. Currently, there is no definitive treatment available for extremely premature very-low-birth-weight infants with BPD, and challenges in finding targeted preventive therapies persist. However, innovative stem cell-based postnatal therapies targeting BPD-free survival are emerging, which are likely to be offered in the first few days of life to high-risk premature infants. Hence, we need easy-to-use noninvasive tools for a standardized, precise, and reliable BPD assessment at a very early stage, to support clinical decision-making and to predict the response to treatment. In this non-systematic review, we present an overview of strategies for monitoring preterm infants with early and evolving BPD-PPRD, and we make some remarks on future prospects, with a focus on near-infrared spectroscopy (NIRS).

59 Important Pulmonary Outcomes in Extremely Preterm Infants: Parental Perspectives

Abstract Background Lung Injury is frequent in extremely preterm infants. The definition of bronchopulmonary dysplasia (BPD) has changed since it was first described in 1967. Oxygen need at 36 weeks, the current definition, is not closely associated with long-term pulmonary outcomes. This outcome, used in neonatal research, has been chosen by clinicians and researchers, not by parents. Other outcomes related to chronic respiratory disease (such as hospital readmissions, work of breathing, and/or exercise limitation) are rarely measured or reported in outcome research. What pulmonary outcomes are of importance to parents is unknown. Objectives The primary objective of this part of the “parent voices project” was to create a list of respiratory outcomes that are important to parents, both during the NICU hospitalization and after discharge, to be considered in future respiratory outcome studies. Design/Methods Over one year (2020-2021), parents of infants born <29 weeks’ gestational age (GA) who came for follow-up visits when their children were between 18 months and 7 years old, in a large academic centre, were invited to participate. They were asked both closed and open-ended questions about the following topics: • The child’s health and what they would want to improve. • The impacts (negative and positive) of prematurity on the life of their family. • Their decisional regrets. • What they wish they had known both before birth and in the NICU, and their recommendations for clinicians. We examined all the parental answers with a view to discovering how many invoked pulmonary outcomes and which themes parents described when speaking about respiratory health. The goal was to make a list of all the respiratory outcomes that were important to families, both during the NICU hospitalization and longer term. Results were analyzed using mixed methods. Results Among parents (n=285, 98% participation rate), 44% spoke about important pulmonary outcomes. Parents invoked 25 themes when they described respiratory health, some pertaining to NICU hospitalization and others to long-term outcomes (see Table below). Some themes impacted the child (child-centred), such as exercise limitation. Many other pulmonary outcomes having an impact on parents or the whole family were described by parents (parent or family-centred themes). For example, a child who had difficulty breathing would struggle and could have disturbed sleep, but parents often described their own fear, lack of sleep (or disturbed sleep in other children). When children were hospitalized because of a respiratory illness, many of the outcomes described would be both child- and parent-centred: e.g., parental loss of work or income, and loss of equilibrium for the whole family. None of the 285 parents spoke about oxygen at 36 weeks or BPD. The prevalence of parents who describe pulmonary outcomes as impacting the child and/or family was statistically similar in parents of children with and without BPD, born before or after 25 weeks, with a BW of less or more than 750 g. Parents of male infants and those who were readmitted for respiratory issues were more likely to report important pulmonary outcomes. Conclusion Many parents of children born extremely preterm describe important pulmonary outcomes, independent of BPD. None of the parents mentioned oxygen at 36 weeks or BPD. More parents report such outcomes when their child has been readmitted for pulmonary reasons. These adverse outcomes often impact the whole family. Future research will indicate which outcomes need to be included in neonatal trials (or neonatal follow-up).

Pulmonary phenotypes of bronchopulmonary dysplasia in the preterm infant

Bronchopulmonary dysplasia (BPD) remains the most common complication of premature birth, imposing a significant and potentially life-long burden on patients and their families. Despite advances in our understanding of the mechanisms that contribute to patterns of lung injury and dysfunctional repair, current therapeutic strategies remain non-specific with limited success. Contemporary definitions of BPD continue to rely on clinician prescribed respiratory support requirements at specific time points. While these criteria may be helpful in broadly identifying infants at higher risk of adverse outcomes, they do not offer any precise information regarding the degree to which each compartment of the lung is affected. In this review we will outline the different pulmonary phenotypes of BPD and discuss important features in the pathogenesis, clinical presentation, and management of these frequently overlapping scenarios.

Comparison of two novel diagnostic criteria for bronchopulmonary dysplasia in predicting adverse outcomes of preterm infants: a retrospective cohort study

BackgroundThis study aimed to compare the predictive value of two diagnostic criteria for bronchopulmonary dysplasia (BPD) in preterm infants with gestational age (GA) < 32 weeks for death or severe respiratory morbidity at corrected age of 18–24 months.MethodsIn this retrospective cohort study, clinical data from July 2019 to September 2021 were classified by 2018 National Institute of Child Health and Human Development (NICHD) and 2019 Jensen definitions of BPD. Based on the follow-up results, the enrolled population was divided into adverse outcome group and normal outcome group. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to explore the risk factors of adverse outcomes and evaluate the predictive value of both diagnostic criteria.ResultsOf 451 infants, 141 (31.3%) had adverse outcomes, which increased with increasing severity of BPD. Logistic regression analysis showed only BPD was an independent risk factor for adverse outcomes in preterm infants. ROC analysis revealed that both diagnostic criteria showed similar predictive values (2018 NICHD definition AUC = 0.771 vs. 2019 Jensen definition AUC = 0.770), with specificities of 93.5% and 96.8%, respectively; however, combining them separately with GA or birth weight did not improve their predictive values.ConclusionsThe two novel definitions of BPD demonstrate similar predictive values in predicting death or severe respiratory morbidity at corrected age of 18–24 months, with higher specificity observed in both.

Bronchopulmonary Dysplasia: Ongoing Challenges from Definitions to Clinical Care.

Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. Its etiology is multifactorial and is attributed to genetic susceptibility to prenatal and postnatal factors. As advancements in neonatology have led to the increased survival of premature infants, a parallel increase in the incidence of BPD has occurred. Over time, the definition and diagnostic criteria for BPD have evolved, as have management strategies. However, challenges continue to exist in the management of these infants, which is not surprising given the complexity of the disease. We summarize the key diagnostic criteria and provide insight into the challenges related to various aspects of BPD definitions, data comparisons, and clinical care implementation.

Association Between Enteral Supplementation With High-Dose Docosahexaenoic Acid and Risk of Bronchopulmonary Dysplasia in Preterm Infants

High-dose docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid, may affect the risk of bronchopulmonary dysplasia (BPD). However, high-level summative evidence supporting such clinical association in very preterm infants is lacking. To examine the association between enteral supplementation with high-dose DHA during the neonatal period and the risk of BPD in preterm infants born at less than 29 weeks' gestation. PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, medRxiv, and ClinicalTrials.gov were searched from inception to August 1, 2022, for eligible articles with no language restrictions. Randomized clinical trials (RCTs) were eligible for inclusion (1) if their interventions involved direct administration of a minimum DHA supplementation of 40 mg/kg/d or breast milk or formula feeding of at least 0.4% of total fatty acids, and (2) if they reported data on either BPD, death, BPD severity, or a combined outcome of BPD and death. Two investigators completed independent review of titles and abstracts, full text screening, data extraction, and quality assessment using the Cochrane Risk of Bias 2.0. Risk ratios (RRs) with 95% CIs were pooled using random-effect meta-analyses. Primary outcome was BPD using trial-specific definitions, which was further stratified for RCTs that used a more stringent BPD definition based on systematic pulse oximetry assessment at 36 weeks' postmenstrual age. Other outcomes were BPD, death, BPD severity, or combined BPD and death. Among the 2760 studies screened, 4 RCTs were included, which involved 2304 infants (1223 boys [53.1%]; mean [SD] gestational age, 26.5 [1.6] weeks). Enteral supplementation with high-dose DHA was associated with neither BPD (4 studies [n = 2186 infants]; RR, 1.07 [95% CI, 0.86-1.34]; P = .53; I2 = 72%) nor BPD or death (4 studies [n = 2299 infants]; RR, 1.04 [95% CI, 0.91-1.18]; P = .59; I2 = 61%). However, an inverse association with BPD was found in RCTs that used a more stringent BPD definition (2 studies [n = 1686 infants]; RR, 1.20 [95% CI, 1.01-1.42]; P = .04; I2 = 48%). Additionally, DHA was inversely associated with moderate-to-severe BPD (3 studies [n = 1892 infants]; RR, 1.16 [95% CI, 1.04-1.29]; P = .008; I2 = 0%). Results of this study showed that enteral supplementation with high-dose DHA in the neonatal period was not associated overall with BPD, but an inverse association was found in the included RCTs that used a more stringent BPD definition. These findings suggest that high-dose DHA supplementation should not be recommended to prevent BPD in very preterm infants.

Machine learning to predict late respiratory support in preterm infants: a retrospective cohort study

Bronchopulmonary dysplasia (BPD) has been a critical morbidity in preterm infants. To improve our definition and prediction of BPD is challenging yet indispensable. We aimed to apply machine learning (ML) to investigate effective models by using the recently-proposed and data-driven definition to predict late respiratory support modalities at 36 weeks’ post menstrual age (PMA). We collected data on very-low-birth-weight infants born between 2016 and 2019 from the Taiwan Neonatal Network database. Twenty-four attributes associated with their early life and seven ML algorithms were used in our analysis. The target outcomes were overall mortality, death before 36 weeks’ PMA, and severity of BPD under the new definition, which served as a proxy for respiratory support modalities. Of the 4103 infants initially considered, 3200 were deemed eligible. The logistic regression algorithm yielded the highest area under the receiver operating characteristic curve (AUROC). After attribute selection, the AUROC of the simplified models remain favorable (e.g., 0.801 when predicting no BPD, 0.850 when predicting grade 3 BPD or death before 36 weeks’ PMA, and 0.881 when predicting overall mortality). By using ML, we developed models to predict late respiratory support. Estimators were developed for clinical application after being simplified through attribute selection.

Association of newer definitions ofbronchopulmonary dysplasia with pulmonary hypertension and long-term outcomes.

The definition of bronchopulmonary dysplasia (BPD) has been evolved recently from definition by the National Institute of Child Health and Human Development in 2001 (NICHD 2001) to the definition reported in 2018 (NICHD 2018) and that proposed by Jensen et al. in 2019 (NICHD 2019). The definition was developed based on the evolution of non-invasive respiratory support and to achieve better prediction of later outcomes. Our objective was to evaluate the association between different definitions of BPD and occurrence of pulmonary hypertension (PHN) and long term outcomes. This retrospective study enrolled preterm infants born at < 32 weeks of gestation between 2014 and 2018. The association between re-hospitalization owing to a respiratory illness until a corrected age (CA) of 24 months, neurodevelopmental impairment (NDI) at a CA of 18-24 months, and PHN at a postmenstrual age (PMA) of 36 weeks was evaluated, with the severity of BPD defined based on these three definitions. Among 354 infants, the gestational age and birth weight were the lowest in severe BPD based on the NICHD 2019 definition. In total, 14.1% of the study population experienced NDI and 19.0% were re-hospitalized owing to a respiratory illness. At a PMA of 36 weeks, PHN was identified in 9.2% of infants with any BPD. Multiple logistic regression analysis showed that the adjusted odds ratio (OR) for re-hospitalization was the highest for Grade 3 BPD of the NICHD 2019 criteria (5.72, 95% confidence interval [CI]: 1.37-23.92), while the adjusted OR of Grade 3 BPD was 4.96 (95% CI: 1.73-14.23) in the NICHD 2018 definition. Moreover, no association of the severity of BPD was found in the NICHD 2001 definition. The adjusted ORs for NDI (12.09, 95% CI: 2.52-58.05) and PHN (40.37, 95% CI: 5.15-316.34) were also the highest for Grade 3 of the NICHD 2019 criteria. Based on recently suggested criteria by the NICHD in 2019, BPD severity is associated with long-term outcomes and PHN at a PMA of 36 weeks in preterm infants.

Comparison of new bronchopulmonary dysplasia definitions on long-term outcomes in preterm infants.

To compare the discriminative performances of the 2018 National Institutes of Health (NIH) and the 2019 Jensen definitions of bronchopulmonary dysplasia (BPD) with the 2001 NIH definition on adverse neurodevelopmental and respiratory outcomes at 2years and 5years corrected age. In this single-center retrospective cohort study, outcomes of infants born at <30weeks of gestational age were collected. The 3 definitions of BPD were compared by adding the different definitions to the National Institute of Child Health and Human Development's outcome prediction model for neurodevelopmental impairment (NDI) or death. Discriminative performance was compared for both outcomes at 2years and 5years corrected age by calculating the areas under the receiver operating characteristic curve and z-statistics. The presence of BPD and its severity were determined in 584 infants. There were considerable shifts in BPD grading among the different definitions. At both time points, all BPD definition models had comparable discriminating power for NDI and respiratory morbidity, with one exception. Compared with the 2001 NIH definition, the 2018 NIH definition had less predictive power for the neurologic outcome at 2years corrected age. Our comparison of the 3 BPD definitions shows similar discriminative performance on long term neurodevelopmental and respiratory outcomes at 2years and 5years corrected age.

Comparison of definitions of bronchopulmonary dysplasia to reflect the long-term outcomes of extremely preterm infants

Survivors of neonatal bronchopulmonary dysplasia (BPD) have persistent respiratory, neurodevelopmental, and growth impairment over the first few years of life and later childhood, which represents an emerging burden for health systems. Therefore, there is an increasing need for a new definition and grading system of BPD that predicts long-term outcomes of high-risk infants who need timely and proper intervention to improve outcomes. We compared new definitions of BPD (National Institute of Child Health and Human Development [NICHD] 2018 and Neonatal Research Network [NRN] 2019) to the original NICHD 2001 definition at 3 years of age using a nationwide cohort of extreme preterm infants. New definitions and severity grading were clearly related to respiratory, neurodevelopmental, and growth impairments at 3 years of age and at 18–24 months corrected age (CA), whereas the original NICHD 2001 definition was not. Furthermore, the negative effect of BPD on growth was ameliorated at 3 years of age compared to 18–24 months CA. However, the negative effect of BPD in neonates on the respiratory system and neurodevelopment persisted at 3 years of age. These new definitions should be adopted to identify high-risk infants and improve long-term outcomes by exact diagnosis and BPD severity classification.

High doses of enteral docosahexaenoic acid omega-3 supplementation for prevention of bronchopulmonary dysplasia in very preterm infants: a protocol for a systematic review and meta-analysis

IntroductionDocosahexaenoic acid (DHA) supplementation in the neonatal period has been proposed to prevent bronchopulmonary dysplasia (BPD) in very preterm infants. We aim to determine the effects of an enteral supplementation...

Changes in respiratory management and the impact on bronchopulmonary dysplasia.

Noninvasive respiratory support has reduced the need for mechanical ventilation and surfactant administration in very premature neonates. We sought to determine how the increased use of noninvasive ventilation and less surfactant instillation has impacted the development of bronchopulmonary dysplasia (BPD) using four currently used BPD definitions. This is a retrospective, single-center cohort study of neonates born at less than 28 weeks gestation between 2010 and 2018. A respiratory practice change (less surfactant and more noninvasive ventilation) occurred in 2014 following participation in the Surfactant Positive Airway Pressure and Pulse Oximetry trial. Therefore, patients were divided into two epochs to compare postnatal respiratory and clinical course and BPD outcomes across four currently relevant definitions (Vermont Oxford Network, National Institute of Child Health and Human Development, Canadian, andNeonatal Research Network). Clinical and demographic variables were similar between epochs. Despite significant differences in maternal and infant characteristics and clinical course, the incidence of BPD was not significantly different between the twoepochs regardless of the BPD definition utilized. There was a wide range in the incidence of BPD depending on the definition used. Despite decreased use of surfactant administration and invasive mechanical ventilation between the two epochs, the incidence of BPD did not change and there was wide variation depending on the definition used. A better understanding of the risk factors associated with BPD and a consensus definition is urgently needed to: 1) more accurately compare various studies, 2) help facilitate the conduct of clinical trials, and 3) enhance the development of novel therapeutic interventions to improve outcome.

Definitions of Bronchopulmonary Dysplasia: Which One Should We Use?

To assess the clinical applicability of the current definitions of bronchopulmonary dysplasia (BPD) and their ability to predict subsequent respiratory outcomes. In this retrospective cohort study, data were collected from 104 preterm infants (mean gestational age, 25.8weeks) diagnosed with BPD between 2010 and 2018 at a single tertiary care center. The infants were classified according to the following definitions: 2001 National Institute of Child Health and Human Development (NICHD), 2017 Canadian Neonatal Network (CNN), 2018 NICHD, and 2019 Neonatal Research Network (NRN). Logistic regression and the area under the receiver operating characteristic curve (AUC) were used to assess the predictive ability of each definition on mortality or severe respiratory morbidity at 18-24months of age. All patients could be adequately classified by each definition, except for the 2001 NICHD definition, in which 11.4% were unclassifiable. The prevalence of BPD was 49% by the 2017 CNN definition and 70% by the 2018 NICHD and 2019 NRN definitions. The best regression model was the one that included the 2018 NICHD definition, which had an accuracy of 85.6% and a significantly higher AUC compared with the 2001 NICHD (0.891 vs 0.824; P=.015) and 2017 CNN (0.891 vs 0.811; P=.036) definitions, but not compared with the 2019 NRN definition (0.891 vs 0.833; P=.09). The current definitions of BPD showed a good predictive ability for mid-term respiratory outcomes, with the highest ability for the 2018 NICHD definition. Further studies are needed to establish the most appropriate definition of BPD.

High-Resolution Computed Tomography Scores in Cases of Bronchopulmonary Dysplasia.

Background Bronchopulmonary dysplasia (BPD) carries a risk of long-term pulmonary sequelae. High-resolution computed tomography (HRCT) is a method of detecting such structural changes. This study is aimed at characterizing structural abnormalities associated with BPD and at evaluating the clinical findings in the newborn period associated with HRCT scores. Methods 28 patients born with a mean gestation age of 30 ± 2.9 weeks and diagnosed as BPD in their neonatal period were reevaluated when they were between the postnatal ages of 6 and 12 months. HRCT was performed in 20 patients with a history of moderate and severe BPD. Scans were interpreted by one radiologist using a scoring system. Results Patients were 9.8 ± 2.3 months at the time of reevaluation. The average HRCT score of patients was, respectively, 7.20 ± 4.05 with moderate and 7.40 ± 2.84 with severe BPD. The difference between them was not significant (p = 0.620). When moderate and severe groups were collected as a whole on the basis of physical findings and drug treatment, 6 had normal physical examination findings, no oxygen and no drug requirement; 14 had at least one finding at the time of reevaluation. No significant difference was detected in terms of HRCT score between the two groups (6.50 ± 3.83 versus 7.64 ± 3.30). Conclusions More studies are needed in terms of the role of HRCT in the assessment of BPD prognosis. A contemporary definition of BPD that correlates with respiratory morbidity in childhood is needed. Also, a new lung ultrasound technique for predicting the respiratory outcome in patients with BPD can be used instead of HRCT.

The Consensus Definition of Bronchopulmonary Dysplasia Is an Adequate Predictor of Lung Function at Preschool Age.

BackgroundRecent attempts to refine the definition bronchopulmonary dysplasia (BPD) have based its predictive capacity on respiratory outcome in the first 2 years of life, eliminating the pre-existing requirement of 28 days of oxygen therapy prior to 36 weeks postmenstrual age (PMA). The objective of this study was to assess the utility of the 2001 consensus definition in predicting impaired lung function at preschool age.MethodsThis cohort study included children aged 4–6 years old who were born at gestational age (GA) <32 weeks or bodyweight <1500 g. Univariate and multivariate analyses were performed to assess differences in antenatal and neonatal variables between BPD and non-BPD children. All participants underwent incentive spirometry. Lung function parameters were contrasted with the Global Lung Function Initiative (GLI-2012) reference equations and, together with antenatal and neonatal variables, compared among the different subgroups (no BPD, mild BPD, and moderate-to-severe BPD). A multivariate model was generated to identify independent risk factors for impaired lung function.ResultsGA, hemodynamically significant patent ductus arteriosus, and late sepsis were independent risk factors for the development of BPD. A total of 119 children underwent incentive spirometry. All lung function parameters were significantly altered relative to reference values. Greater impairment of lung function was observed in the mild BPD vs. the no BPD group (forced expiratory volume in the first 0.75 seconds [FEV0.75]: −1.18 ± 0.80 vs. −0.55 ± 1.13; p = 0.010), but no difference in forced vital capacity (FVC) was observed (−0.32 ± 0.90 vs. −0.18 ± 1; p = 0.534). The moderate-to-severe BPD group exhibited the most severe FEV0.75 reduction (FEV0.75: −2.63 ± 1.18 vs. −0.72 ± 1.08; p = 0.000) and was the only condition with FVC impairment (FVC: −1.82 ± 1.12 vs. −0.22 ± 0.87; p = 0.000). The multivariate analysis identified a diagnosis of moderate-to-severe BPD as an independent risk factor for lung function impairment.ConclusionThe 2001 consensus definition of BPD has adequate predictive capacity for lung function measured by spirometry at 4–6 years of age. Moderate-to-severe BPD was the best predictor of respiratory impairment. Children with mild BPD showed greater alteration of FEV0.75 than those without BPD.