Mild Bronchopulmonary Dysplasia Research Articles

Metabolomic Analysis Reveals the Association of Severe Bronchopulmonary Dysplasia with Gut Microbiota and Oxidative Response in Extremely Preterm Infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease mainly affecting premature infants needing ventilation or oxygen for respiratory distress. This study aimed to evaluate the molecular linkages for BPD in very and extremely preterm infants using a metabolomics-based approach. A case-control study of enrolling preterm infants born before 32 weeks gestational age (GA) was prospectively performed. These preterm infants were subsequently stratified into the following two groups for further analysis: no or mild BPD, and moderate or severe BPD based on the 2019 NICHD criteria. Urinary metabolomic profiling was performed using 1H-Nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA) at a corrected age of 6 months. Metabolites significantly differentially related to GA and BPD severity were performed between groups, and their roles in functional metabolic pathways were also assessed. A total of 89 preterm infants born before 32 weeks gestation and 50 infants born at term age (above 37 completed weeks' gestation) served as controls and were enrolled into the study. There were 21 and 24 urinary metabolites identified to be significantly associated with GA and BPD severity, respectively (p < 0.05). Among them, N-phenylacetylglycine, hippurate, acetylsalicylate, gluconate, and indoxyl sulfate were five metabolites that were significantly higher, with the highest importance in both infants with GA < 28 weeks and those with moderate to severe BPD, whereas betaine and N,N-dimethylglycine were significantly lower (p < 0.05). Furthermore, ribose and a gluconate related pentose phosphate pathway were strongly associated with these infants (p < 0.01). In conclusion, urinary metabolomic analysis highlights the crucial role of gut microbiota dysbiosis in the pathogenesis of BPD in preterm infants, accompanied by metabolites related to diminished antioxidative capacity, prompting an aggressive antioxidation response in extremely preterm infants with severe BPD.

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

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

Relationship between chorioamnionitis or funisitis and lung injury among preterm infants: meta-analysis involved 16 observational studies with 68,397 participants

BackgroundChorioamnionitis (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.MethodsWe 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.ResultsSixteen 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.ConclusionCurrently, 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.

Factors affecting length of stay according to bronchopulmonary dysplasia severity: a nationwide cohort study in Korea.

Longer hospitalizations for preterm infants with bronchopulmonary dysplasia (BPD) delay developmental outcomes, increase the risk for hospital-acquired complications, and exert a substantial socioeconomic burden. This study aimed to identify factors associated with an extended length of stay (LOS) at different levels of severity of BPD. A cohort study was conducted using the Korean Neonatal Network registry of very low birth weight infants with BPD between 2013 and 2017 through retrospective analysis. A total of 4263 infants were diagnosed with BPD. For mild BPD, infants requiring surgical treatment for patent ductus arteriosus needed a longer LOS [eadjusted β coefficients (adj β) 1.041; 95% confidence interval (CI): 0.01-0.08] and hydrocephalus (eadj β 1.094; 95% CI 0.01-0.17). In moderate BPD, infants administered steroids or with intraventricular hemorrhage required a longer LOS (eadj β 1.041; 95% CI 0.00-0.07 and eadj β 1.271; 95% CI 0.11-0.38, respectively). In severe BPD, infants with comorbidities required a longer LOS: pulmonary hypertension (eadj β 1.174; 95% CI 0.09-0.23), administrated steroid for BPD (eadj β 1.116; 95% CI 0.07-0.14), sepsis (eadj β 1.062; 95% CI 0.01-0.11), patent ductus arteriosus requiring surgical ligation (eadj β 1.041; 95% CI 0.00-0.08), and intraventricular hemorrhage (eadj β 1.016; 95% CI 0.05-0.26). Additionally, the higher the clinical risk index score, the longer the LOS needed for infants in all groups. The factors affecting LOS differed according to the severity of BPD. Individualized approaches to reducing LOS may be devised using knowledge of the various risk factors affecting LOS by BPD severity.

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.

Breast-feeding as protective factor against bronchopulmonary dysplasia in preterm infants.

Breast-feeding is associated with fewer comorbidities in very-low-birth-weight (VLBW) preterm infants. Bronchopulmonary dysplasia (BPD) of VLBW infants is a multifactorial pathology in which nutritional aspects may be of special importance. The aim of this study is to determine, in a cohort of VLBW infants, whether breast milk nutrition is associated with a reduced prevalence and severity of BPD. A retrospective study was conducted to record the intake of mother's own milk (MOM), pasteurised donor human milk or preterm formula milk in the first 2 weeks of postnatal life of 566 VLBW newborns at our hospital during the period January 2008-December 2021. After applying the relevant exclusion criteria, data for 489 VLBW infants were analysed; 195 developed some degree of BPD. Moderate or severe BPD is associated with less weight gain. Moreover, the preferential ingestion of breast milk in the first and second postnatal weeks had effects associated with lower OR for BPD, which were statistically demonstrable for mild (OR 0·16; 95 % CI 0·03, 0·71) and severe (OR 0·08; 95 % CI 0·009, 0·91) BPD. Breast-feeding during the first weeks of postnatal life is associated with a reduced prevalence of BPD, which is frequently associated with less weight gain as a result of greater respiratory effort with greater energy expenditure.

Clinical assessment of the severity of bronchopulmonary dysplasia in children born prematurely

Bronchopulmonary dysplasia (BPD) – chronic lung disease, which evolves with broncho-obstructive syndrome, signs of respiratory failure, pulmonary fibrosis. Aim. Analytical case-control study included 41 children with BPD and 40 preterm children without BPD, who were clinically evaluated. Methods. Evaluation of clinical respiratory syndromes and degree of severity of bronchopulmonary dysplasia in premature infants. Results. The study demonstrated that the O2 saturation determined by pulse oximetry in premature children with BPD is reduced - 94.5±0.4%, compared to the O2 saturation of premature children without BPD (97.85±0.14%), which is significantly higher (F stat = 66.7, T stat = 8.17, p&lt;0.0001). Children with mild grade BPD present intercostal retractions in 22.2%: 95%CI 2.8-60, in moderate grade BPD – 52.6%: 95%CI 28.9-75.6 and in severe grade DBP all the children had chest retractions. Depending on the degrees of severity, children with mild BPD present intercostal retractions in 22.2%, in moderate BPD – 73.7% and in severe BPD all children had intercostal retractions. Costal retractions, which is an indicator of respiratory insufficiency, was found in all preterm infants with severe BPD, in 52.6%: 95%CI 28.9-75.6 preterm infants with moderate BPD. Premature children with mild BPD did not present costal retractions at the stage of diagnosis confirmation (χ2 = 15.3; p&lt;0.001). Conclusions. According to the study, bronchopulmonary dysplasia in children born prematurely is manifested by signs of respiratory insufficiency - accelerated breathing, intercostal and thoracic retractions, low values of O2 saturation. The severity of signs of respiratory impairment is dependent on the degree of bronchopulmonary dysplasia, having a clinical expression through different forms of thoracic retractions.

Effect of different courses and durations of invasive mechanical ventilation on respiratory outcomes in very low birth weight infants

This multicenter retrospective study was conducted to explore the effects of different courses and durations of invasive mechanical ventilation (MV) on the respiratory outcomes of very low birth weight infants (VLBWI) in China. The population for this study consisted of infants with birth weight less than 1500 g needing at least 1 course of invasive MV and admitted to the neonatal intensive care units affiliated with the Chinese Neonatal Network within 6 h of life from January 1st, 2019 to December 31st, 2020. Univariate and multivariate logistic regression analyses were performed to evaluate associations between invasive MV and respiratory outcomes. Adjusted odds ratios (ORs) were computed with the effects of potential confounders. (1) Among the 3183 VLBWs with a history of at least one course of invasive MV, 3155 (99.1%) met inclusion criteria and were assessed for the primary outcome. Most infants received one course (76.8%) and a shorter duration of invasive MV (62.16% with ventilation for 7 days or less). (2) In terms of the incidence of all bronchopulmonary dysplasia (BPD) (mild, moderate, and severe BPD), there were no significant differences between different invasive MV courses [For 2 courses, adjusted OR = 1.11 (0.88, 1.39); For 3 courses or more, adjusted OR = 1.07 (0.72, 1.60)]. But, with the duration of invasive MV prolonging, the OR of BPD increased [8–21 days, adjusted OR = 1.98 (1.59, 2.45); 22–35 days, adjusted OR = 4.37 (3.17, 6.03); ≥ 36 days, adjusted OR = 18.44 (10.98, 30.99)]. Concerning severe BPD, the OR increased not only with the course of invasive MV but also with the duration of invasive MV [For 2 courses, adjusted OR = 2.17 (1.07, 4.40); For 3 courses or more, adjusted OR = 2.59 (1.02, 6.61). 8–21 days, adjusted OR = 8.42 (3.22, 22.01); 22–35 days, adjusted OR = 27.82 (9.08, 85.22); ≥ 36 days, adjusted OR = 616.45 (195.79, > 999.999)]. (3) When the interaction effect between invasive MV duration and invasive MV course was considered, it was found that there were no interactive effects in BPD and severe BPD. Greater than or equal to three courses would increase the chance of severe BPD, death, and the requirement of home oxygen therapy. Compared with distinct courses of invasive MV, a longer duration of invasive MV (> 7 days) has a greater effect on the risk of BPD, severe BPD, death, and the requirement of home oxygen therapy.

MRI pulmonary artery flow detects lung vascular pathology in preterms with lung disease.

Pulmonary vascular disease (PVD) affects the majority of preterm neonates with bronchopulmonary dysplasia (BPD) and significantly determines long-term mortality through undetected progression into pulmonary hypertension. Our objectives were to associate characteristics of pulmonary artery (PA) flow and cardiac function with BPD-associated PVD near term using advanced magnetic resonance imaging (MRI) for improved risk stratification. Preterms <32 weeks postmenstrual age (PMA) with/without BPD were clinically monitored including standard echocardiography and prospectively enrolled for 3 T MRI in spontaneous sleep near term (AIRR (Attention to Infants at Respiratory Risks) study). Semi-manual PA flow quantification (phase-contrast MRI; no BPD n=28, mild BPD n=35 and moderate/severe BPD n=25) was complemented by cardiac function assessment (cine MRI). We identified abnormalities in PA flow and cardiac function, i.e. increased net forward volume right/left ratio, decreased mean relative area change and pathological right end-diastolic volume, to sensitively detect BPD-associated PVD while correcting for PMA (leave-one-out area under the curve 0.88, sensitivity 0.80 and specificity 0.81). We linked these changes to increased right ventricular (RV) afterload (RV-arterial coupling (p=0.02), PA mid-systolic notching (t2; p=0.015) and cardiac index (p=1.67×10-8)) and correlated echocardiographic findings. Identified in moderate/severe BPD, we successfully applied the PA flow model in heterogeneous mild BPD cases, demonstrating strong correlation of PVD probability with indicators of BPD severity, i.e. duration of mechanical ventilation (rs=0.63, p=2.20×10-4) and oxygen supplementation (rs=0.60, p=6.00×10-4). Abnormalities in MRI PA flow and cardiac function exhibit significant, synergistic potential to detect BPD-associated PVD, advancing the possibilities of risk-adapted monitoring.

Bronchopulmonary Dysplasia: A Five-Year Retrospective Cohort Study on Differences in Clinical Characteristics and Morbidities According to Severity Grading.

Bronchopulmonary dysplasia (BPD) is the most common complication associated with extreme prematurity. Although several criteria defining severity were developed over time, there are a few studies describing the differences in BPD phenotype and neonatal morbidities and complications between severity groups. We aimed to describe these differences in BPD patients of a neonatal intensive care unit (NICU). We conducted an observational retrospective cohort study through a medical record review over a five-year period. Participants were newborns admitted to an NICU who were diagnosed with BPD. We performed a descriptive statistical analysis of gestational complications and the use of antenatal corticosteroid therapy, birth-related data, and complications throughout the NICU stay, as well as the respiratory support used. We also compared different severity groups across these variables. The patients were divided into severe and non-severe BPD using the severity criteria of the 2001 NICHD/NHLBI/ORD consensus workshop. A total of 101 newborns with BPD participated in the study and 73 had data on BPD severity. The median gestational age was 27 weeks, ranging from 23 to 32 weeks. Of these 73 newborns, 36 had mild BPD (49.3%), 10 had moderate BPD (13.7%), and 27 had severe BPD (37.0%). When comparing severe and non-severe BPD, we found that extreme prematurity, extremely low birth weight, and small size for gestational age were more frequent in the severe BPD group (p-value=0.012, p-value<0.001, and p-value=0.012, respectively). Infants with severe BPD had a longer duration of invasive ventilation than those with mild or moderate BPD (p-value<0.001). Late sepsis, necrotizing enterocolitis, severe brain injury, and retinopathy of prematurity were more frequent in severe BPD (p-value=0.017, p-value=0.045, p-value=0.033, p-value=0.003, respectively). Previously published evidence describing causal links between BPD development and comorbidities exists but data on their impact on BPD severity are scarce. In our study, severe BPD seemed to be associated with a higher frequency of comorbidities and complications. Further studies are needed to ascertain the impact of each morbidity on the severity of BPD and if measures to prevent them could lead to potentially milder BPD disease.

Application of lung ultrasound in monitoring bronchopulmonary dysplasia and pulmonary arterial pressure in preterm infants.

The aim of this study was to evaluate the application value of lung ultrasound in monitoring bronchopulmonary dysplasia (BPD) and pulmonary artery pressure in premature infants. A total of 98 preterm infants diagnosed with BPD in the Fourth Hospital in Shijiazhuang were recruited, and their disease severity was classified as mild (n=32), moderate (n=33), or severe BPD (n=33) based on gestational age and oxygen concentration. Lung ultrasonography of the children was performed. The correlation between lung ventilation scores and disease severity was statistically analyzed, and the discrete optimization results were documented. The pulmonary hypertension indexes of the three groups of children were compared. Aberrant alterations of the pleural line were observed in all included children, and the B-line rose as the disease progressed. The duration of invasive ventilation, medication, and hospital stay increased with disease exacerbation (p<0.05). The three groups significantly differed in terms of ultrasound pulmonary ventilation scores and clinical severity (p<0.05). Only mild BDP was identified by lung ultrasound on the first day of birth (T1), and severe BDP was detectable during the first and second week (T2-T3) as well as the third and fourth week (T4-T5). Severe BPD was associated with significantly higher levels of pulmonary hypertension indices vs. mild and moderate BPD (p<0.05). Pulmonary ultrasonography demonstrates great potential to predict pulmonary hypertension in children and assesses the disease severity. Pulmonary ultrasound allows for dynamical real-time observation of the pulmonary lesions in children with pulmonary hypertension, thereby revealing the severity of pulmonary hypertension in premature children.

Two-stage learning-based prediction of bronchopulmonary dysplasia in very low birth weight infants: a nationwide cohort study.

The aim of this study is to develop an enhanced machine learning-based prediction models for bronchopulmonary dysplasia (BPD) and its severity through a two-stage approach integrated with the duration of respiratory support (RSd) using prenatal and early postnatal variables from a nationwide very low birth weight (VLBW) infant cohort. We included 16,384 VLBW infants admitted to the neonatal intensive care unit (NICU) of the Korean Neonatal Network (KNN), a nationwide VLBW infant registry (2013-2020). Overall, 45 prenatal and early perinatal clinical variables were selected. A multilayer perceptron (MLP)-based network analysis, which was recently introduced to predict diseases in preterm infants, was used for modeling and a stepwise approach. Additionally, we applied a complementary MLP network and established new BPD prediction models (PMbpd). The performances of the models were compared using the area under the receiver operating characteristic curve (AUROC) values. The Shapley method was used to determine the contribution of each variable. We included 11,177 VLBW infants (3,724 without BPD (BPD 0), 3,383 with mild BPD (BPD 1), 1,375 with moderate BPD (BPD 2), and 2,695 with severe BPD (BPD 3) cases). Compared to conventional machine learning (ML) models, our PMbpd and two-stage PMbpd with RSd (TS-PMbpd) model outperformed both binary (0 vs. 1,2,3; 0,1 vs. 2,3; 0,1,2 vs. 3) and each severity (0 vs. 1 vs. 2 vs. 3) prediction (AUROC = 0.895 and 0.897, 0.824 and 0.825, 0.828 and 0.823, 0.783, and 0.786, respectively). GA, birth weight, and patent ductus arteriosus (PDA) treatment were significant variables for the occurrence of BPD. Birth weight, low blood pressure, and intraventricular hemorrhage were significant for BPD ≥2, birth weight, low blood pressure, and PDA ligation for BPD ≥3. GA, birth weight, and pulmonary hypertension were the principal variables that predicted BPD severity in VLBW infants. We developed a new two-stage ML model reflecting crucial BPD indicators (RSd) and found significant clinical variables for the early prediction of BPD and its severity with high predictive accuracy. Our model can be used as an adjunctive predictive model in the practical NICU field.

Packed Red Blood Cell Transfusion as a Predictor of Moderate-Severe Bronchopulmonary Dysplasia: A Comparative Cohort Study of Very Preterm Infants.

Bronchopulmonary dysplasia (BPD) is a leading cause of morbidity and mortality in neonatal intensive care units. Our aim was to evaluate association between packed red blood cell transfusion and the development of BPD in very preterm infants. This retrospective study of very preterm infants (mean gestational age 27.1 ± 2.4 weeks, birthweight 970 ± 271 g) was conducted at Biruni University (Turkey) between July 2016 and December 2020. BPD developed in 107 of the 246 enrolled neonates, including 47 (43.9%), 27 (25.3%), and 33 (30.8%) diagnosed with mild, moderate, and severe BPD, respectively. A total of 728 transfusions were administered. The increased number (4 transfusions [2-7] vs. 1 [1-3], p = 0.001) and volume of transfusions (75 mL/kg volume [40-130] vs. 20 [15-43], p = 0.001) were significantly higher in infants with BPD compared to those without BPD. The transfusion volume cut-off for the prediction of BPD by ROC curve analysis was 42 mL/kg (sensitivity 73.6%; specificity 75%; area under the receiver-operating characteristic curve 0.82). In multivariate analysis, multiple transfusions and larger transfusion volume were independent risk factors for moderate-severe BPD. The increased number and volume of transfusions were associated with BPD in very preterm infants. A packed red blood cell transfusion volume ≥ 42 mL/kg was a statistically significant predictor of the development of BPD at a postmenstrual age of 36 weeks.

Predictive values of clinical data,molecular biomarkers, and echocardiographic measurements in preterm infants with bronchopulmonary dysplasia.

We aimed to use molecular biomarkers and clinical data and echocardiograms that were collected during admission to predict bronchopulmonary dysplasia (BPD) in preterm infants with gestational age ≤32 weeks. Eighty-two patients (40 with BPD, BPD group and 42 healthy as controls, non-BPD group) admitted to the Department of Neonatology of the Children's Hospital of Soochow University between October 1, 2018, and February 29, 2020, were enrolled in this study at the tertiary hospital. Basic clinical data on the perinatal period, echocardiographic measurements, and molecular biomarkers (N-terminal-pro-B-brain natriuretic peptide, NT-proBNP) were collected. We used multiple logistic regression analysis to establish an early predictive model for detecting BPD development in preterm infants of gestational age ≤32 weeks. We also used a receiver operating characteristic curve to assess the sensitivity and specificity of the model. No significant differences were found between the BPD and non-BPD groups in terms of sex, birth weight, gestational age, incidence of asphyxia, maternal age, gravidity, parity, mode of delivery, premature rupture of membranes >18 h, use of prenatal hormones, placental abruption, gestational diabetes mellitus, amniotic fluid contamination, prenatal infections, and maternal diseases. The use of caffeine, albumin, gamma globulin; ventilation; days of FiO2 ≥ 40%; oxygen inhalation time; red blood cell suspension infusion volume (ml/kg); and proportion of infants who received total enteral nutrition (120 kcal/kg.d) ≥24 d after birth were higher in the BPD group than in the non-BPD group. The levels of hemoglobin, hematocrit, and albumin in the BPD group were significantly lower than those in the non-BPD group. The total calorie intake was significantly lower in the BPD group on the 3rd, 7th, and 14th day after birth than in the non-BPD group (P < 0.05). The incidence rates of patent ductus arteriosus (PDA), pulmonary hypertension, and tricuspid regurgitation were significantly higher in the BPD group than in the non-BPD group (P < 0.05). The serum level of NT-proBNP 24 h after birth was significantly higher in the BPD group than in the non-BPD group (P < 0.05). Serum NT-proBNP levels were significantly higher in infants with severe BPD than in those with mild or moderate BPD (P < 0.05). As there were various risk factors for BPD, a combining clinical data, molecular biomarkers, and echocardiogram measurements can be valuable in predicting the BPD. The tricuspid regurgitation flow rate (m/s), NT-proBNP (pg/ml), ventilator-associated pneumonia, days of FiO2 ≥ 40% (d), red blood cell suspension infusion volume (ml/kg), and proportion of infants who received total enteral nutrition (120 kcal/kg.d) ≥24 d after birth were the most practical factors considered for designing an appropriate model for predicting the risk of BPD.

Ventilatory response and stability of oxygen saturation during a hypoxic challenge in very preterm infants.

Preterm infants have immature control of breathing and impaired pulmonary gas exchange. We hypothesized that infants with bronchopulmonary dysplasia (BPD) have a blunted ventilatory response and peripheral oxygen saturation (SpO2 ) instability during a hypoxic challenge. We evaluated the response to hypoxia in 57 very preterm infants (38 no BPD, 10 mild BPD, 9 moderate-to-severe BPD) at 36 weeks' postmenstrual age. The fraction of inspired oxygen (FI O2 ) was reduced stepwise at 5-min intervals to achieve peripheral SpO2 between 86% and 95%. The lowest permissible FI O2 and SpO2 were 0.14% and 86%. We recorded SpO2 , FI O2 , and the respiratory signal (respiratory inductive plethysmography). We calculated respiratory rate (RR), tidal volume (VT ), minute ventilation (VE ), and respiratory drive (ratio between VT and inspiratory time, VT /TI ). SpO2 variability was expressed as the interquartile range (IQR). FI O2 was reduced from a median (Q1, Q3) of 0.21 (0.21, 0.21) to 0.17 (0.17, 0.18). We observed a marked individual variability in the ventilatory response to the hypoxic challenge, regardless of BPD severity. At the lowest permissible FI O2 , 37(65%) infants reduced their VE , and 20 (35%) increased minute ventilation; 20infants (35%) developed periodic breathing associated with increased SpO2 IQR and lower SpO2 minima, and 16 (28%) exhibited an oscillatory pattern in VE and SpO2 without end-expiratory pauses, regardless of BPD severity. In very preterm infants, a mild hypoxic challenge reduced ventilation, increased SpO2 variability and periodic breathing regardless of BPD severity.

Discharge Practices for Infants with Bronchopulmonary Dysplasia: A Survey of National Experts.

To establish consensus practices among a panel of national experts for the discharge of premature infants with bronchopulmonary dysplasia (BPD) from the hospital to home. We conducted a Delphi study that included US neonatologists and pediatric pulmonologists from the Bronchopulmonary Dysplasia Collaborative to establish consensus practices-defined as recommendations with at least 80% agreement-for infants with BPD being discharged from the hospital. Specifically, we evaluated recommendations for diagnostic tests to be completed around discharge, follow-up respiratory care, and family education. Thirty-one expert participants completed 3 rounds of surveys, with a 99% response rate (92 of 93). Consensus was established that infants with moderate-severe BPD (ie, those who remain on respiratory support at 36weeks) and those discharged on oxygen should be targeted for in-person pulmonary follow-up within 1month of hospital discharge. Specialized neonatal follow-up is an alternative for infants with mild BPD. Infants with moderate or severe BPD should have an echocardiogram performed after 36weeks to screen for pulmonary hypertension. Infants with BPD warrant additional evaluations if they have growth restriction or poor growth, pulmonary hypertension, or tachypnea and if they are discharged to home on oxygen, diuretics, or nonoral feeds. This Delphi survey establishes expert consensus around best practices for follow-up respiratory management and routine evaluation for infants with BPD surrounding neonatal discharge. Areas of disagreement for which consensus was not established are discussed.

Role of Systemic Inflammatory Indices in the Prediction of Moderate to Severe Bronchopulmonary Dysplasia in Preterm Infants

IntroductionThe role of systemic inflammatory indices in the diagnosis of bronchopulmonary dysplasia (BPD) is unknown. The aim of the study was to determine the possible clinical utility of systemic inflammatory indices in the prediction of moderate to severe BPD. MethodsPremature infants<32 weeks of gestational age were included in the study. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI) were calculated at birth and at the time of diagnosis of BPD (at 36th weeks of postmenstrual age). The patients were divided into two groups as no or mild BPD and moderate or severe BPD. ResultsA total of 1146 infants were included in the study, 957 in Group 1 and 189 in Group 2. The SIRI value was significantly higher in moderate or severe BPD both at birth and at the 36th week of postmenstrual age (p<0.001 and p<0.001, respectively). The AUC value of SIRI was 0.809 and the cut-off value was>0.98 in the predictivity of BPD at birth. The AUC value of SIRI was 0.842 and the cut-off value was>1.33 for the diagnosis of BPD at 36th week of postmenstrual age. After multiple logistic regression analysis, SIRI was shown to be a significant parameter for the diagnosis of BPD (OR 2.847, 95% CI 1.557–4.875). ConclusionsSIRI may be a useful biomarker for predicting moderate to severe BPD and a marker of clinical importance in the follow-up of infants with BPD.

Longer duration of initial invasive mechanical ventilation is still a crucial risk factor for moderate-to-severe bronchopulmonary dysplasia in very preterm infants: a multicentrer prospective study

ObjectivesWe aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia (BPD) and focus on discussing its relationship with the duration of initial invasive mechanical ventilation (IMV) in very preterm neonates less than 32 weeks of gestational age (GA).MethodsWe performed a prospective cohort study involving infants born at 23–31 weeks of GA who were admitted to 47 different neonatal intensive care unit (NICU) hospitals in China from January 2018 to December 2021. Patient data were obtained from the Sina-northern Neonatal Network (SNN) Database.ResultsWe identified 6538 very preterm infants, of whom 49.5% (3236/6538) received initial IMV support, and 12.6% (823/6538) were diagnosed with moderate-to-severe BPD symptoms. The median duration of initial IMV in the moderate-to-severe BPD group was 26 (17–41) days, while in the no or mild BPD group, it was 6 (3–10) days. The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs. Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV [adjusted odds ratio (AOR): 1.97; 95% confidence interval (CI): 1.10–2.67], late-onset neonatal sepsis (LONS), and patent ductus arteriosus (PDA).ConclusionIn this multicenter cohort study, the duration of initial IMV was still relatively long in very premature infants, and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD.

Influencing factors for the development and severity of bronchopulmonary dysplasia in preterm infants with a gestational age of

To study the influencing factors for the development and severity of bronchopulmonary dysplasia (BPD) in preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g. A retrospective analysis was performed on the medical data of preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g who were admitted to Women and Children's Hospital Affiliated to Xiamen University from January 1, 2017 to December 31, 2021. According to oxygen dependence on day 28 after birth, they were divided into two groups: BPD (n=218) and non-BPD (n=142). According to disease severity based on oxygen concentration required at the corrected age of 36 weeks or at discharge, the infants with BPD were divided into two groups: mild BPD (n=154) and moderate/severe BPD (n=64). Indices such as perinatal data and nutritional status were compared between groups. The multivariate logistic regression analysis was used to determine the influencing factors for BPD and its severity. The incidence rate and severity of BPD increased with the reduction in gestational age and birth weight (P<0.05). The multivariate logistic regression analysis showed that a long duration of invasive mechanical ventilation (OR=1.320, P<0.05), hemodynamically significant patent ductus arteriosus (OR=2.032, P<0.05), and a prolonged time to reach oral calorie goal of 110 kcal/(kg·d) (OR=1.041, P<0.05) were risk factors for BPD, while an older gestational age was a protective factor against BPD (OR=0.535, P<0.05). Early-onset sepsis (OR=2.524, P<0.05) and a prolonged time to reach oral calorie goal of 110 kcal/(kg·d) (OR=1.029, P<0.05) were risk factors for moderate/severe BPD, while a high mean weight growth velocity was a protective factor against moderate/severe BPD (OR=0.906, P<0.05). The incidence rate and severity of BPD in preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g can be reduced by shortening the duration of invasive mechanical ventilation, giving early treatment of early-onset sepsis and hemodynamically significant patent ductus arteriosus, adopting active enteral nutritional strategies, and increasing mean weight growth velocity.

Resting energy expenditure in preterm newborns with bronchopulmonary dysplasia.

Greater energy expenditure is reported in newborns with bronchopulmonary dysplasia (BPD). This study assessed resting energy expenditure (REE) in newborns with BPD. BPD was classified as mild and moderate/severe. REE was assessed using indirect calorimetry between the time points of the discontinuation of oxygen (O2) (T1) and at term-equivalent age (T2) in preterm newborns with BPD. The moderate group (10 newborns) presented with higher REE (kcal/kg/day) after discontinuation of mechanical ventilation and a decrease of 18% between the two time points; 72.7 and 59.6kcal/kg/day at T1 and T2 respectively (p value 0.08). No differences were observed in REE in the mild BPD group between timepoints; 50.9-56.4kcal/kg/day at T1 and T2 respectively (p value 0.73). Newborns with BPD presented different metabolic behaviors depending on the classification criteria: those classified as having moderate BPD showed a decrease in REE toward term-equivalent age.