Severe Bronchopulmonary Dysplasia Research Articles

Autologous cord blood mononuclear cell infusion for the prevention of bronchopulmonary dysplasia in very preterm monozygotic twins: A study protocol for a randomized, placebo-controlled, double-blinded multicenter trial.

Preterm-associated complications remain the main cause of neonatal death. Survivors face the challenges of short- and long-term complications. Among all complications, bronchopulmonary dysplasia (BPD) remains the first important cause of neonatal mortality and morbidity. Current treatment does not address this main preterm complication. Cord blood is regarded as a convenient source of stem cells. The paracrine bioactive factors of stem cells contribute to tissue repair and immune modulation. Our clinical studies and those of others have shown that cord blood cell infusion is both safe and possibly effective in the prevention and treatment of BPD. The therapeutic use of cord blood has emerged as a promising therapy. However, the genetic heterogeneity between control and intervention groups may reduce the comparability especially among small sample trials. The purpose of this study protocol is to investigate the effects of autologous cord blood mononuclear cell (ACBMNC) infusion on the prevention of BPD in very preterm monozygotic twins of less than 32 gestation weeks. In this prospective, randomized, placebo-controlled, double-blinded multicenter clinical trial, 60 pairs of monozygotic twin preterm neonates of less than 32 weeks admitted to the Neonatal Intensive Care Unit are randomly assigned to receive intravenous ACBMNC infusion (targeted at 5 × 107 cells/kg) or placebo (normal saline) within 24 h after birth in a 1:1 ratio. The primary outcome will be survival without BPD at 36 weeks of postmenstrual age. The secondary outcomes will include the mortality rate, BPD severity, other common preterm complication rates, respiratory support duration, length and cost of hospitalization, and long-term respiratory and neurodevelopmental outcomes during a 2-year follow-up. Furthermore, we will perform single-cell RNA sequencing for cord blood cells and blood cells 3-10 days after intervention and detect whether reactive oxygen species and inflammatory cytokines are present. This will be the first randomized, placebo-controlled, double-blinded trial to evaluate the efficacy of ACBMNC infusion to prevent BPD in monozygotic twin premature infants and investigate the underlying protective mechanisms. The results of this trial will provide valuable clinical evidence for translational application of cord blood cell therapy in very preterm infants.Trial registration: ClinicalTrials.gov, NCT05087498, registered 10/09/2021, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BAD7&selectaction=Edit&uid=U0002PLA&ts=2&cx=qvyylv.

Approaches to Interdisciplinary Care for Infants with Severe Bronchopulmonary Dysplasia: A Survey of the Bronchopulmonary Dysplasia Collaborative.

Bronchopulmonary dysplasia (BPD) remains the most common late morbidity for extremely premature infants. Care of infants with BPD requires a longitudinal approach from the neonatal intensive care unit to ambulatory care though interdisciplinary programs. Current approaches for the development of optimal programs vary among centers. We conducted a survey of 18 academic centers that are members of the BPD Collaborative, a consortium of institutions with an established interdisciplinary BPD program. We aimed to characterize the approach, composition, and current practices of the interdisciplinary teams in inpatient and outpatient domains. Variations exist among centers, including composition of the interdisciplinary team, whether the team is the primary or consult service, timing of the first team assessment of the patient, frequency and nature of rounds during the hospitalization, and the timing of ambulatory visits postdischarge. Further studies to assess long-term outcomes are needed to optimize interdisciplinary care of infants with severe BPD. · Care of infants with BPD requires a longitudinal approach from the NICU to ambulatory care.. · Benefits of interdisciplinary care for children have been observed in other chronic conditions.. · Current approaches for the development of optimal interdisciplinary BPD programs vary among centers..

Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus

BackgroundCyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain.MethodsIn this multicenter, noninferiority trial, we randomly assigned infants with echocardiographically confirmed PDA (diameter, >1.5 mm, with left-to-right shunting) who were extremely preterm (<28 weeks’ gestational age) to receive either expectant management or early ibuprofen treatment. The composite primary outcome included necrotizing enterocolitis (Bell’s stage IIa or higher), moderate to severe bronchopulmonary dysplasia, or death at 36 weeks’ postmenstrual age. The noninferiority of expectant management as compared with early ibuprofen treatment was defined as an absolute risk difference with an upper boundary of the one-sided 95% confidence interval of less than 10 percentage points.ResultsA total of 273 infants underwent randomization. The median gestational age was 26 weeks, and the median birth weight was 845 g. A primary-outcome event occurred in 63 of 136 infants (46.3%) in the expectant-management group and in 87 of 137 (63.5%) in the early-ibuprofen group (absolute risk difference, −17.2 percentage points; upper boundary of the one-sided 95% confidence interval [CI], −7.4; P<0.001 for noninferiority). Necrotizing enterocolitis occurred in 24 of 136 infants (17.6%) in the expectant-management group and in 21 of 137 (15.3%) in the early-ibuprofen group (absolute risk difference, 2.3 percentage points; two-sided 95% CI, −6.5 to 11.1); bronchopulmonary dysplasia occurred in 39 of 117 infants (33.3%) and in 57 of 112 (50.9%), respectively (absolute risk difference, −17.6 percentage points; two-sided 95% CI, −30.2 to −5.0). Death occurred in 19 of 136 infants (14.0%) and in 25 of 137 (18.2%), respectively (absolute risk difference, −4.3 percentage points; two-sided 95% CI, −13.0 to 4.4). Rates of other adverse outcomes were similar in the two groups.ConclusionsExpectant management for PDA in extremely premature infants was noninferior to early ibuprofen treatment with respect to necrotizing enterocolitis, bronchopulmonary dysplasia, or death at 36 weeks’ postmenstrual age. (Funded by the Netherlands Organization for Health Research and Development and the Belgian Health Care Knowledge Center; BeNeDuctus ClinicalTrials.gov number, NCT02884219; EudraCT number, 2017-001376-28.)

Effects of less invasive surfactant administration versus intubation-surfactant-extubation on bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome: a single-center, retrospective study from China

BackgroundThis study evaluated the effects of less invasive surfactant administration (LISA) and intubation-surfactant-extubation (InSurE) on bronchopulmonary dysplasia (BPD) in preterm infants with respiratory distress syndrome (RDS).MethodsNeonates with respiratory distress syndrome requiring surfactant, with gestational age < 32 weeks and birth weight < 1500 g admitted to our neonatal intensive care unit from January 2018 to December 2019, were retrospectively analyzed. LISA and InSurE were used independently. The incidence of BPD at 36 weeks postmenstrual age, pre-discharge mortality, and need for mechanical ventilation (MV) within 72 h of birth were compared between LISA and InSurE group. Secondary outcomes including necrotizing enterocolitis requiring surgery, retinopathy of prematurity ≥ stage 3, patent ductus arteriosus requiring medical therapy or surgery, and length of hospitalization were analyzed.ResultsAmong the 148 included neonates, there were 46 and 102 infants in LISA group and InSurE group, respectively. There were no significant differences in BPD incidence, the severity of BPD at 36 weeks postmenstrual age, and the rate of MV within the first 72 h after birth between the two groups (P > 0.05, respectively). The incidences of necrotizing enterocolitis requiring surgery, retinopathy of prematurity ≥ stage 3, patent ductus arteriosus requiring medical therapy or surgery, and length of hospitalization did not differ significantly between the two groups (P > 0.05, respectively).ConclusionsFor surfactant administration among preterm infants with respiratory distress syndrome, LISA did not decrease bronchopulmonary dysplasia and severity of BPD at 36 weeks postmenstrual age. The benefits of LISA would require further evaluations.

Optimizing ventilator support in severe bronchopulmonary dysplasia in the absence of conclusive evidence.

Optimizing ventilator support in severe bronchopulmonary dysplasia in the absence of conclusive evidence.

Outcomes of infants with severe bronchopulmonary dysplasia who received tracheostomy and home ventilation.

To describe the survival rate, timing of liberation from the ventilator, and factors favorable for decannulation among infants with severe bronchopulmonary dysplasia (sBPD) who received tracheostomy. Demographics and clinical outcomes were obtained through retrospective chart review of 98 infants with sBPD who were born between 2004 and 2017, received tracheostomy at <1 year of age, and were followed in the Infant Tracheostomy and Home Ventilator clinic up to 4 years of age. The number of infants with sBPD who received tracheostomy increased significantly over the study period. The median age at tracheostomy was 4 months (IQR 3, 5) or 43 weeks corrected gestational age; the median age at NICU discharge was 7 months (IQR 6, 9). At 48 months of age, all subjects had been liberated from the ventilator, at a median age of 24 months (IQR 18, 29); 52% had been decannulated with a median age at decannulation of 32 months (IQR 26, 39). Only 1 (1%) infant died. Multivariate logistic regression showed infants who were White, liberated from the ventilator by 24 months of age and have public insurance had significantly greater odds of being decannulated by 48 months of age. Tracheobronchomalacia was associated with decreased odds of decannulation. Infants with sBPD who received tracheostomy had an excellent survival rate. Liberation from home ventilation and decannulation are likely to occur by 4 years of age.

Risk factors and machine learning prediction models for bronchopulmonary dysplasia severity in the Chinese population

BackgroundBronchopulmonary dysplasia (BPD) is a common chronic lung disease in extremely preterm neonates. The outcome and clinical burden vary dramatically according to severity. Although some prediction tools for BPD exist, they seldom pay attention to disease severity and are based on populations in developed countries. This study aimed to develop machine learning prediction models for BPD severity based on selected clinical factors in a Chinese population.MethodsIn this retrospective, single-center study, we included patients with a gestational age < 32 weeks who were diagnosed with BPD in our neonatal intensive care unit from 2016 to 2020. We collected their clinical information during the maternal, birth and early postnatal periods. Risk factors were selected through univariable and ordinal logistic regression analyses. Prediction models based on logistic regression (LR), gradient boosting decision tree, XGBoost (XGB) and random forest (RF) models were implemented and assessed by the area under the receiver operating characteristic curve (AUC).ResultsWe ultimately included 471 patients (279 mild, 147 moderate, and 45 severe cases). On ordinal logistic regression, gestational diabetes mellitus, initial fraction of inspiration O2 value, invasive ventilation, acidosis, hypochloremia, C-reactive protein level, patent ductus arteriosus and Gram-negative respiratory culture were independent risk factors for BPD severity. All the XGB, LR and RF models (AUC = 0.85, 0.86 and 0.84, respectively) all had good performance.ConclusionsWe found risk factors for BPD severity in our population and developed machine learning models based on them. The models have good performance and can be used to aid in predicting BPD severity in the Chinese population.

Mechanical ventilation characteristics and their prediction performance for the risk of moderate and severe bronchopulmonary dysplasia in infants with gestational age &lt;30 weeks and birth weight &lt;1,500 g

Moderate and severe bronchopulmonary dysplasia (BPD) is a common pulmonary complication in premature infants, which seriously affects their survival rate and quality of life. This study aimed to describe the mechanical ventilation characteristics and evaluate their prediction performance for the risk of moderate and severe BPD in infants with gestational age <30 weeks and birth weight <1,500 g on postnatal Day 14. In this retrospective cohort study, 412 infants with gestational age <30 weeks and birth weight <1,500 g were included in the analysis, including 104 infants with moderate and severe BPD and 308 infants without moderate and severe BPD (as controls). LASSO regression was used to optimize variable selection, and Logistic regression was applied to build a predictive model. Nomograms were developed visually using the selected variables. To validate the model, receiver operating characteristic (ROC) curve, calibration plot, and clinical impact curve were used. From the original 28 variables studied, six predictors, namely birth weight, 5 min apgar score, neonatal respiratory distress syndrome (≥Class II), neonatal pneumonia, duration of invasive mechanical ventilation (IMV) and maximum of FiO2 (fraction of inspiration O2) were identified by LASSO regression analysis. The model constructed using these six predictors and a proven risk factor (gestational age) displayed good prediction performance for moderate and severe BPD, with an area under the ROC of 0.917 (sensitivity = 0.897, specificity = 0.797) in the training set and 0.931 (sensitivity = 0.885, specificity = 0.844) in the validation set, and was well calibrated (P Hosmer-Lemeshow test = 0.727 and 0.809 for the training and validation set, respectively). The model included gestational age, birth weight, 5 min apgar score, neonatal respiratory distress syndrome (≥Class II), neonatal pneumonia, duration of IMV and maximum of FiO2 had good prediction performance for predicting moderate and severe BPD in infants with gestational age <30 weeks and birth weight <1,500 g on postnatal Day 14.

Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial

Bronchopulmonary dysplasia (BPD) is a disease of chronic respiratory insufficiency stemming from premature birth and iatrogenic lung injury leading to alveolar simplification, impaired alveolar-capillary development, interstitial fibrosis, and often pulmonary hypertension. BPD is the most common pulmonary sequela of prematurity and is often fatal; however, there remains no FDA-approved therapies to treat or prevent BPD. Sildenafil is increasingly used off-label in premature infants despite scant safety and efficacy data. Sildenafil reduces lung injury and preserves normal vasculature in preclinical models, and improves outcomes in children with pulmonary hypertension, and thus is a promising candidate for BPD. Following phase I studies, we developed the phase II SIL02 trial to describe the safety, pharmacokinetics and preliminary effectiveness of intravenous and enteral sildenafil in premature infants at risk for BPD. SIL02 is a randomized, double-blind, placebo-controlled, 3-cohort, sequential dose-escalating trial of enteral or intravenous (IV) sildenafil dosed every 8 h for up to 34 days. The target IV doses were 0.125, 0.5 and 1 mg/kg/dose in cohorts 1, 2 and 3, respectively; while the enteral doses will be double the IV doses. Eligible infants must be < 29 weeks' gestation at birth and requiring respiratory support at 7–28 days' postnatal age. Adverse events and preliminary effectiveness will be compared by treatment group. Using the final population PK model, empirical Bayesian estimates will be generated for each patient. Preliminary effectiveness will be measured by the incidence of moderate to severe BPD or death at 36 weeks and change in the BPD risk estimation.

AMPK-driven Macrophage Responses Are Autophagy Dependent in Experimental Bronchopulmonary Dysplasia.

The pathogenesis of bronchopulmonary dysplasia (BPD) remains incompletely understood. Recent studies suggest insufficient AMP-activated protein kinase (AMPK) activation as a potential cause of impaired autophagy in rodent and nonhuman primate models of BPD. Impaired autophagy is associated with enhanced inflammatory signaling in alveolar macrophages (AMs) and increased severity of murine BPD induced by neonatal hyperoxia exposure. The goal of this study was to determine the role of autophagy and AMPK activation in macrophage responses in murine BPD. C57BL/6J mice were exposed to neonatal hyperoxia starting on postnatal day (P)1 and treated with the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) between P3 and P6. Mice were euthanized on P7, and markers of AMPK activation and autophagy were assessed by immunoblotting. Alveolarization was assessed using radial alveolar counts, mean linear intercept measurements, and quantification of alveolar septal myofibroblasts. Relative mRNA expression of M1-like and M2-like genes was assessed in AMs isolated from BAL fluid from wild-type, LysMCre--Becn1fl/fl, and LysMCre+-Becn1fl/fl mice after neonatal hyperoxia exposure. AICAR treatment resulted in AMPK activation and induction of autophagic activity in whole-lung and BAL cell lysates and attenuated hyperoxia-induced alveolar simplification in neonatal lungs. AICAR-treated control but not Beclin1-deficient AMs demonstrated significantly decreased expression of M1-like markers and significantly increased expression of M2-like markers. In conclusion, pharmacologic activation of AMPK by AICAR resulted in induction of autophagy and played a protective role, at least in part, through attenuation of proinflammatory signaling in AMs via autophagy-dependent mechanisms in a murine model of BPD.

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.

Microbial-induced Redox Imbalance in the Neonatal Lung Is Ameliorated by Live Biotherapeutics.

Bronchopulmonary dysplasia (BPD) is a common lung disease of premature infants. Hyperoxia exposure and microbial dysbiosis are contributors to BPD development. However, the mechanisms linking pulmonary microbial dysbiosis to worsening lung injury are unknown. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that regulates oxidative stress responses and modulates hyperoxia-induced lung injury. We hypothesized that airway dysbiosis would attenuate Nrf2-dependent antioxidant function, resulting in a more severe phenotype of BPD. Here, we show that preterm infants with a Gammaproteobacteria-predominant dysbiosis have increased endotoxin in tracheal aspirates, and mice monocolonized with the representative Gammaproteobacteria Escherichia coli show increased tissue damage compared with germ-free (GF) control mice. Furthermore, we show Nrf2-deficient mice have worse lung structure and function after exposure to hyperoxia when the airway microbiome is augmented with E. coli. To confirm the disease-initiating potential of airway dysbiosis, we developed a novel humanized mouse model by colonizing GF mice with tracheal aspirates from human infants with or without severe BPD, producing gnotobiotic mice with BPD-associated and non-BPD-associated lung microbiomes. After hyperoxia exposure, BPD-associated mice demonstrated a more severe BPD phenotype and increased expression of Nrf2-regulated genes, compared with GF and non-BPD-associated mice. Furthermore, augmenting Nrf2-mediated antioxidant activity by supporting colonization with Lactobacillus species improved dysbiotic-augmented lung injury. Our results demonstrate that a lack of protective pulmonary microbiome signature attenuates an Nrf2-mediated antioxidant response, which is augmented by a respiratory probiotic blend. We anticipate antioxidant pathways will be major targets of future microbiome-based therapeutics for respiratory disease.

Maternal preeclampsia as a risk factor for developing bronchopulmonary dysplasia in neonates.

To determine the effect of preeclampsia on the development of bronchopulmonary dysplasia (BPD) in preterm infants. Retrospective cohort study of infants' ≤32 weeks' gestation admitted to a level-IV single center neonatal intensive care unit from 2014 to 2016. Infants with major congenital anomalies, death or transfer before 28 days were excluded. Infants were stratified by maternal preeclampsia status. Demographic, clinical, and laboratory data were reviewed. Logistic regression was used to examine predictors for BPD. The primary outcome was BPD incidence. 432 infants met inclusion criteria; 22% developed BPD, of which, 16% had severe BPD. Thirty-eight percent of infants were born to preeclamptic mothers, with 23% of those infants developing BPD. Infants born to preeclamptic mothers were delivered by cesarean section (88% vs. 60%; p<0.0001) more often and had lower birthweight (Median=1265g, IQR 910-1555 vs. Median=1388g, IQR 959-1752; p=0.008) compared to infants born to non-preeclamptic mothers. Higher incidence of intrauterine growth restriction was noted in pre-eclampsia group,24% vs 8%, p=0.0001). Gestational age, length of stay and days on ventilator were all associated with the development of BPD. In multivariable logistic regression, preeclampsia was not a risk factor for development of BPD (OR 1.12 [0.68, 1.83]). Preeclampsia was not a significant risk factor for development of BPD nor the severity of BPD in infants' ≤32 weeks' gestation. IUGR infants with or without preeclampsia mothers were at higher risk for BPD.

Tracheostomy in a Preterm Infant with Severe Bronchopulmonary Dysplasia.

Tracheostomy in a Preterm Infant with Severe Bronchopulmonary Dysplasia.

Pre-viable preterm premature rupture of membranes under 20 weeks of pregnancy: A retrospective cohort analysis for potential outcome predictors

ObjectiveWhile preterm premature rupture of membranes complicates an estimated 3 % of pregnancies, rupture near the limit of fetal viability is rarer (estimated 0.04 %). This study aimed to analyze maternal and neonatal outcomes in patients with premature preterm rupture of membranes (PPROM) before 20 0/7 weeks of pregnancy with the goal of identifying potential outcome predictors.Study Design.This retrospective cohort study examined 60 patients with preterm premature rupture of membranes before 20 0/7 weeks of pregnancy from 01/01/2008 through 12/31/2018 in a university hospital setting. Two patients were excluded from analysis due to fetal kidney dysplasia. Multiples (5 twins, 2 triplets) were excluded. The remaining 51 cases were analyzed. ResultsThirty-three patients (Range 12 5/7 weeks to 19 2/7 weeks) medically terminated pregnancy (64.7 %). Ten patients spontaneously aborted (19.6 %). Fifteen patients were diagnosed with intraamniotic infection (29.4 %). Neonatal mortality was 28.6 %% (one case of pulmonary hypoplasia). The baby take home rate was 9.8 % (27.8 % after excluding medical terminations) after a mean prolongation of 92.9 days. Neonatal morbidity included respiratory distress syndrome (57.1 %), infection (100 %, including all cases (direct postpartum and during admission), one case of sepsis), pulmonary hypoplasia (42.9 %), pulmonary hypertension (28.6 %), bronchopulmonary dysplasia (14.3 %), and sepsis combined pneumonia (14.3 %). 57.1 % of the infants could be discharged without severe morbidity and 80 % of the survivors had normal development at two and four years. ConclusionAnhydramnios combined with low gestational age at PPROM appear to negatively influence neonatal outcome after pre-viable preterm premature rupture of membranes. The incidence of neonatal complications decreased with increasing gestational age. Survival without long term severe morbidity is possible. Maximal therapy is an interdisciplinary decision and the patients should be counseled accordingly. Delivery in centers where potential postnatal complications including pulmonary hypoplasia, severe bronchopulmonary dysplasia and respiratory distress syndrome can be aggressively treated is recommended.

Relationship between bronchopulmonary dysplasia phenotypes with high-resolution computed tomography score in early preterm infants.

ObjectiveTo assess the relationship between high-resolution computed tomography (HRCT) abnormalities and clinical phenotypes of bronchopulmonary dysplasia (BPD).MethodsA retrospective, single-center study was carried out at the Children’s Hospital of Fudan University between 2013 and 2020. Preterm infants born at ≤ 32 weeks’ gestation who were diagnosed with BPD and had HRCT between 40 and 50 weeks postmenstrual age (PMA)were included in the study. HRCT images from six pulmonary lobes were scored based on seven types of pulmonary lesions from two categories: hyperaeration lesions and parenchymal lesions. The hyperaeration score (HS) included scores of decreased attenuation, mosaic attenuation, and bulla/bleb, while the parenchymal score (PS) included those of linear lesion, consolidation, bronchial wall thickening, and bronchiectasis. All seven scores were summed up to create the total score (TS). One-way ANOVA testing or Kruskal-Wallis testing was adopted for the comparison of HRCT scores with BPD severity and clinical phenotypes. The correlation between HRCT scores and clinical phenotypes was evaluated by Spearman’s correlation analysis.ResultsA total of 81 cases were included in the study. Cases with more severe BPD had a higher TS (p = 0.01), HS (p = 0.02), PS (p = 0.02), mosaic attenuation score (p = 0.03), bulla/Bleb score (p = 0.03), and linear density score (p = 0.01). TS (r = 0.28), PS (r = 0.35), linear density (r = 0.34), and consolidation (r = 0.24) were correlated with pulmonary hypertension (PH). However, no HRCT score was significantly different between the patients with or without tracheobronchomalacia (TBM). BPD patients with a combination of lung parenchymal disease, PH, and TBM had the highest TS and HS.ConclusionHRCT scores correlated with BPD severity and PH in our study. HS might be a useful tool in the assessment of BPD severity while linear densities and consolidation might be helpful in predicting PH.

Role of left atrial hypertension in pulmonary hypertension associated with bronchopulmonary dysplasia.

Left atrial hypertension (LAH) may contribute to pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD). Primary causes of LAH in infants with BPD include left ventricular diastolic dysfunction or hemodynamically significant left to right shunt. The incidence of LAH, which is definitively diagnosed by cardiac catheterization, and its contribution to PH is unknown in patients with BPD-PH. We report the prevalence of LAH in an institutional cohort with BPD-PH with careful examination of hemodynamic contributors and impact on patient outcomes. This single-center, retrospective cohort study examined children <2 years of age with BPD-PH who underwent cardiac catheterization at Lucile Packard Children's Hospital Stanford. Patients with unrepaired simple shunt congenital heart disease (CHD) and pulmonary vein stenosis (only 1 or 2 vessel disease) were included. Patients with complex CHD were excluded. From April 2010 to December 2021, 34 patients with BPD-PH underwent cardiac catheterization. We define LAH as pulmonary capillary wedge pressure (PCWP) or left atrial pressure (LAP) of at least 10 mmHg. In this cohort, median PCWP was 8 mmHg, with LAH present in 32% (n = 11) of the total cohort. A majority (88%, n = 30) of the cohort had severe BPD. Most patients had some form of underlying CHD and/or pulmonary vein stenosis: 62% (n = 21) with an atrial septal defect or patent foramen ovale, 62% (n = 21) with patent ductus arteriosus, 12% (n = 4) with ventricular septal defect, and 12% (n = 4) with pulmonary vein stenosis. Using an unadjusted logistic regression model, baseline requirement for positive pressure ventilation at time of cardiac catheterization was associated with increased risk for LAH (odds ratio 8.44, 95% CI 1.46–48.85, p = 0.02). Small for gestational age birthweight, sildenafil use, and CHD were not associated with increased risk for LAH. LAH was associated with increased risk for the composite outcome of tracheostomy and/or death, with a hazard ratio of 6.32 (95% CI 1.72, 22.96; p = 0.005). While the etiology of BPD-PH is multifactorial, LAH is associated with PH in some cases and may play a role in clinical management and patient outcomes.

Non-standard therapeutic methods for severe bronchopulmonary dysplasia in a premature newborn – case report

Bronchopulmonary dysplasia is a lung disease that is the most common complication of prematurity and the most common chronic lung disease in neonates treated with mechanical ventilation and/or oxygen therapy. Children with bronchopulmonary dysplasia are at risk of cardiovascular complications, such as pulmonary arterial hypertension and left ventricular hypertrophy. The presented case concerns a premature infant born at 24 weeks gestation with severe bronchopulmonary dysplasia complicated by pulmonary arterial hypertension, interstitial emphysema and emphysema. The patient was subject to non-standard therapeutic procedures including L-citrulline, which may have a beneficial effect on the treatment of complications of severe bronchopulmonary dysplasia. Despite proper treatment, it is not always possible to avoid severe complications of bronchopulmonary dysplasia. Currently, available therapies are not always fully effective and it is necessary to continue searching and implementing new treatments to lower the risk of infant death and minimise long-term complications.

Clinical Correlates of Moderate-to-Severe Bronchopulmonary Dysplasia in Preterm Infants following Surgical Necrotizing Enterocolitis.

The aim of the study is to determine clinical correlates of moderate to severe bronchopulmonary dysplasia (BPD) in preterm infants following surgical necrotizing enterocolitis (NEC). This is a retrospective, single-center cohort study comparing patients with moderate to severe BPD to patients with non/mild BPD among surgical NEC infants. BPD was defined by NIH 2001 consensus definition. Of 92 consecutive neonates with surgical NEC, 77% (71/92) had moderate/severe BPD and 22% (21/92) had non/mild BPD. The patent ductus arteriosus (PDA) was significantly higher in those developing moderate/severe BPD (67.6% [48/71]) than non/mild BPD (28.6% [6/21]; p = 0.001). Postoperatively, infants with moderate/severe BPD had more severe acute kidney injury (AKI; 67.6 [48/71] vs. 28.6% [6/21]; p = 0.001), were intubated longer (40.5 [interquartile (IQR): 12, 59] vs. 6 days [IQR: 2, 13]; p <0.001), received more parenteral nutrition (109 [IQR: 77, 147] vs. 55 days [IQR: 19, 70]; p <0.001), developed higher surgical morbidity (46.5 [33/71] vs. 14.3% [3/21]; p = 0.008), had more intestinal failure (62.5 vs. 13.3%; p <0.001), required a longer hospital stay (161 [IQR: 112, 186] vs. 64 days [IQR: 20, 91]; p <0.001), and were more likely to need home oxygen. In a multivariable analysis, lower birth weight (OR = 0.3, [95% confidence interval (CI): 0.1-0.5]; p = 0.001), PDA (OR = 10.3, [95% CI: 1.6-65.4]; p = 0.014), and longer parenteral nutritional days (OR = 8.8; [95% CI: 2.0-43.0]; p = 0.005) were significantly and independently associated with higher odds of moderate/severe versus non-/mild BPD. Development of moderate/severe BPD occurred in the majority of preterm infants with surgical NEC in this consecutive series. Preterm infants with moderate/severe BPD were more likely to have a PDA before NEC. Development of moderate/severe BPD was associated with significantly greater burden and duration of postoperative morbidity following surgical NEC. Identifying surgical NEC infants at increased risk of moderate/severe BPD and developing lung protection strategies may improve surgical NEC outcomes. · Three-fourths of preterm infants experienced severe lung injury following surgical NEC.. · The infants with severe moderate/severe BPD were most likely associated with greater duration of postoperative morbidity.. · There is need to understand and develop lung protective strategies in infants with surgical NEC..

Analysis of “true extrauterine growth retardation” and related factors in very preterm infants—A multicenter prospective study in China

ObjectiveTo investigate the incidence and related factors of extrauterine growth retardation (EUGR) and “true EUGR” in very preterm infants (VPI) from different regions of China.Materials and methodsClinical data of VPI were prospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. The infants were divided into a small for gestational age (SGA) group or non-SGA group at birth, with non-SGA infants at 36 weeks of gestation or at discharge being further divided into a EUGR group or a non-EUGR group. Infants in the EUGR and non-SGA group were defined as “true EUGR.” The general information of VPI, such as maternal complications during pregnancy, use of enteral nutrition and parenteral nutrition, and complications during hospitalization were compared between the groups.ResultsAmong the 2,514 VPI included in this study, 47.3, 41.5, and 33.3% of VPI were below the 10th percentile, and 22.6, 22.4, and 16.0% of VPI were below the 3rd percentile for weight, height, and head circumference at 36 weeks of gestation or at discharge, respectively, by the percentile on the 2013 Fenton curve. The incidences of EUGR and “true EUGR” evaluated by weight were 47.3 and 44.5%, respectively. Univariate analysis showed that there were statistically significant differences in the aspects of perinatal and nutritional characteristics, treatment, and complications between the groups. Multivariate analysis showed that in non-SGA infants, the cumulative caloric intake during the first week was a protective factor for “true EUGR,” while days to reach total enteral nutrition, late initiation of human milk fortifier, and moderate to severe bronchopulmonary dysplasia were independent risk factors for “true EUGR.”ConclusionMore attention should be paid to the nutritional management of VPI to prevent “true EUGR.” Cumulative caloric intake should be ensured and increased during the first week, total enteral nutrition should be achieved as early as possible, human milk fortifier should be added early, and moderate to severe bronchopulmonary dysplasia should be prevented. These strategies are very important for reducing the incidence of “true EUGR” in VPI.