[Impact of different angles of pulmonary surfactant administration on bronchopulmonaryplasia and intracranial hemorrhage in preterm infants: a prospective randomized controlled study]. / ä¸åŒè§’åº¦æ³¨å ¥è‚ºè¡¨é¢æ´»æ€§ç‰©è´¨å¯¹æ—©äº§å„¿æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯å’Œé¢ å† å‡ºè¡€çš„å½±å“ï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the effects of different angles of pulmonary surfactant (PS) administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants. METHODS: A prospective study was conducted on 146 preterm infants (gestational age <32 weeks) admitted to the Department of Neonatology, Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023. The infants were randomly assigned to different angles for injection of pulmonary surfactant groups: 0° group (34 cases), 30° group (36 cases), 45° group (38 cases), and 60° group (38 cases). Clinical indicators and outcomes were compared among the groups. RESULTS: The oxygenation index was lower in the 60° group compared with the other three groups, with shorter invasive ventilation time and oxygen use time, and a lower incidence of bronchopulmonary dysplasia than the other three groups (P<0.05). The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group (P<0.05). The cure rate in the 60° group was higher than that in the 0° group and the 30° group (P<0.05). CONCLUSIONS: The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles, reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.

Lactobacillus plantarum L168 improves hyperoxia-induced pulmonary inflammation and hypoalveolarization in a rat model of bronchopulmonary dysplasia.

Alteration of gut microbiota can affect chronic lung diseases, such as asthma and chronic obstructive pulmonary disease, through abnormal immune and inflammatory responses. Previous studies have shown a feasible connection between gut microbiota and bronchopulmonary dysplasia (BPD) in preterm infants. However, whether BPD can be ameliorated by restoring the gut microbiota remains unclear. In preterm infants with BPD, we found variance in the diversity and structure of gut microbiota. Similarly, BPD rats showed gut dysbiosis, characterized by a deficiency of Lactobacillus, which was abundant in normal rats. We therefore explored the effect and potential mechanism of action of a probiotic strain, Lactobacillus plantarum L168, in improving BPD. The BPD rats were treated with L. plantarum L168 by gavage for 2 weeks, and the effect was evaluated by lung histopathology, lung function, and serum inflammatory markers. Subsequently, we observed reduced lung injury and improved lung development in BPD rats exposed to L. plantarum L168. Further evaluation revealed that L. plantarum L168 improved intestinal permeability in BPD rats. Serum metabolomics showed altered inflammation-associated metabolites following L. plantarum L168 intervention, notably a marked increase in anti-inflammatory metabolites. In agreement with the metabolites analysis, RNA-seq analysis of the intestine and lung showed that inflammation and immune-related genes were down-regulated. Based on the information from RNA-seq, we validated that L. plantarum L168 might improve BPD relating to down-regulation of TLR4 /NF-κB /CCL4 pathway. Together, our findings suggest the potential of L. plantarum L168 to provide probiotic-based therapeutic strategies for BPD.

Nesfatin-1 alleviates hyperoxia-induced bronchopulmonary dysplasia (BPD) via the nuclear factor-κB (NF-κB) p65 signaling pathway.

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease in newborns, which severely influences the health of infants and lacks effective clinical treatment strategies. The pathogenesis of BPD is correlated to enhanced inflammation and activated oxidative stress (OS). The application of antioxidants and anti-inflammatory treatment could be hot spots for BPD treatment. Nesfatin-1, a peptide with a suppressive property against inflammation, was tested herein for its potential therapeutic value in BPD. Neonatal SD rats were stimulated with hyperoxia, followed by being intraperitoneally administered with 20 µg/kg/day Nesfatin-1 for 2 weeks. Decreased RAC value in lung tissues, increased wet weight/dry weight (W/D) pulmonary ratio and bronchoalveolar lavage fluid (BALF) proteins, elevated cytokine release in BALF, increased malondialdehyde (MDA) content, and declined superoxide dismutase (SOD) activity were observed in BPD rats, all of which were sharply mitigated by Nesfatin-1. Rat epithelial type II cells (AECIIs) were handled with hyperoxia, and then cultured with 1 and 10 nM Nesfatin-1. Reduced cell viability, elevated lactate dehydrogenase production, elevated cytokine secretion, elevated MDA content, and decreased SOD activity were observed in hyperoxia-handled AECIIs, all of which were markedly alleviated by Nesfatin-1. Furthermore, activated nuclear factor-κB (NF-κB) signaling observed in both BPD rats and hyperoxia-handled AECIIs were notably repressed by Nesfatin-1. Collectively, Nesfatin-1 alleviated hyperoxia-triggered BPD by repressing inflammation and OS via the NF-κB signaling pathway.

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

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

BCL6 attenuates hyperoxia-induced lung injury by inhibiting NLRP3-mediated inflammation in fetal mouse.

BACKGROUND: The transcriptional repressor B-cell lymphoma 6 (BCL6) has been reported to inhibit inflammation. So far, experimental evidence for the role of BCL6 in bronchopulmonary dysplasia (BPD) is lacking. Our study investigated the roles of BCL6 in the progression of BPD and its downstream mechanisms. METHODS: Hyperoxia or lipopolysaccharide (LPS) was used to mimic the BPD mouse model. To investigate the effects of BCL6 on BPD, recombination adeno-associated virus serotype 9 expressing BCL6 (rAAV9-BCL6) and BCL6 inhibitor FX1 were administered in mice. The pulmonary pathological changes, inflammatory chemokines and NLRP3-related protein were observed. Meanwhile, BCL6 overexpression plasmid was used in human pulmonary microvascular endothelial cells (HPMECs). Cell proliferation, apoptosis, and NLRP3-related protein were detected. RESULTS: Either hyperoxia or LPS suppressed pulmonary BCL6 mRNA expression. rAAV9-BCL6 administration significantly inhibited hyperoxia-induced NLRP3 upregulation and inflammation, attenuated alveolar simplification and dysregulated angiogenesis in BPD mice, which were characterized by decreased mean linear intercept, increased radical alveolar count and alveoli numbers, and the upregulated CD31 expression. Meanwhile, BCL6 overexpression promoted proliferation and angiogenesis, inhibited apoptosis and inflammation in hyperoxia-stimulated HPMECs. Moreover, administration of BCL6 inhibitor FX1 arrested growth and development. FX1-treated BPD mice exhibited exacerbation of alveolar pathological changes and pulmonary vessel permeability, with upregulated mRNA levels of pro-inflammatory cytokines and pro-fibrogenic factors. Furthermore, both rAAV9-BCL6 and FX1 administration exerted a long-lasting effect on hyperoxia-induced lung injury (≥4 wk). CONCLUSIONS: BCL6 inhibits NLRP3-mediated inflammation, attenuates alveolar simplification and dysregulated pulmonary vessel development in hyperoxia-induced BPD mice. Hence, BCL6 may be a target in treating BPD and neonatal diseases.

Early metabolic markers as predictors of respiratory complications in preterm infants with bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of premature birth, exerts considerable impact on the respiratory health of infants. This study aimed to identify the role of plasma metabolites in predicting respiratory outcomes in BPD-afflicted infants. METHODS: This was a case-control study including 15 BPD premature infants and 15 gestational age and birth weight matched no-BPD preterm infants. Plasma samples, obtained at 36 weeks postmenstrual age (PMA), were subjected to a comprehensive analysis of over 300 metabolites using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The respiratory outcomes of the infants were collected with the first 2 years of corrected postnatal age. RESULTS: The analysis revealed a significant upregulation of urea and downregulation of nine metabolites in BPD infants, including oxalacetic acid, cis-aconitic acid, itaconic acid, betaine, L-asparagine, L-alanine, picolinic acid, inositol, and purine (p < 0.05). These metabolites primarily pertained to the citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolism, and alanine, aspartate, and glutamate metabolism. Furthermore, seven metabolites demonstrated substantial predictive capacity for respiratory readmissions within the first two years of corrected postnatal age, achieving an area under curve (AUC) exceeding or equal to 0.8. These included chenodeoxycholic acid, dehydrolithocholic acid, glucaric acid, D-glucuronic acid, gamma-glutamylvaline, mevalonic acid, and 3-ureidopropionic acid. CONCLUSIONS: This study identified ten distinct plasma metabolites at 36 weeks PMA that differentiate BPD infants from their non-BPD counterparts, implicating three major metabolic pathways. Additionally, seven metabolites showed strong predictive value for heightened risk of respiratory readmission within two years, underscoring their potential utility in clinical prognostication and management strategies for BPD.

Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen.

BACKGROUND: The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age. RESULTS: A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. CONCLUSIONS: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).

Diuretics use in the management of bronchopulmonary dysplasia in preterm infants: A systematic review.

AIM: Bronchopulmonary dysplasia (BPD), a respiratory complication associated with neonatal prematurity, presents opportunities for pharmacological intervention due to its contributing risk factors. Despite diuretics' controversial usage in BPD treatment and varying institutional practices, this review aims to consolidate evidence from clinical trials regarding diuretic use in BPD. METHODS: We conducted a systematic review following PRISMA guidelines, searching EMBASE, Medline, Web of Science and CINAHL databases (PROSPERO 2022: CRD42022328292). Covidence facilitated screening and data extraction, followed by analysis and formatting in Microsoft Excel. RESULTS: Among 430 screened records, 13 were included for analysis. Three studies assessed spironolactone and chlorothiazide combinations, two studied spironolactone and hydrochlorothiazide, while eight examined furosemide. All studies evaluated drug effects on dynamic pulmonary compliance and pulmonary resistance, serving as comparative measures in our review. CONCLUSION: Diuretics' effectiveness in treating bronchopulmonary dysplasia remains uncertain. The limited number of identified randomised controlled trials (RCTs) hampers high-level evidence-based conclusions when applying the Population, Intervention, Comparison, Outcome (PICO) approach. Conducting large prospective studies of good quality could provide more definitive insights, but the rarity of outcomes and eligible patients poses challenges. Further research, primarily focusing on RCTs assessing diuretics' safety and efficacy in this population, is warranted.

Hyperoxia-induced airflow restriction and Renin-Angiotensin System expression in a bronchopulmonary dysplasia mouse model.

Mechanisms underlying hyperoxia-induced airflow restriction in the pediatric lung disease Bronchopulmonary dysplasia (BPD) are unclear. We hypothesized a role for Renin-Angiotensin System (RAS) activity in BPD. RAS is comprised of a pro-developmental pathway consisting of angiotensin converting enzyme-2 (ACE2) and angiotensin II receptor type 2 (AT2), and a pro-fibrotic pathway mediated by angiotensin II receptor type 1 (AT1). We investigated associations between neonatal hyperoxia, airflow restriction, and RAS activity in a BPD mouse model. C57 mouse pups were randomized to normoxic (FiO2 = 0.21) or hyperoxic (FiO2 = 0.75) conditions for 15 days (P1-P15). At P15, P20, and P30, we measured airflow restriction using plethysmography and ACE2, AT1, and AT2 mRNA and protein expression via polymerase chain reaction and Western Blot. Hyperoxia increased airflow restriction P15 and P20, decreased ACE2 and AT2 mRNA, decreased AT2 protein, and increased AT1 protein expression. ACE2 mRNA and protein remained suppressed at P20. By P30, airflow restriction and RAS expression did not differ between groups. Hyperoxia caused high airflow restriction, increased pulmonary expression of the pro-fibrotic RAS pathway, and decreased expression of the pro-developmental in our BPD mouse model. These associated findings may point to a causal role for RAS in hyperoxia-induced airflow restriction.

Risk Factors for Neurodevelopmental Impairment at 2- and 5-Years Corrected Age in Preterm Infants with Established Bronchopulmonary Dysplasia.

INTRODUCTION: The objective of this study was to identify risk factors for neurodevelopmental impairment (NDI) at 2- and 5-years corrected age (CA) in a cohort of preterm infants with established bronchopulmonary dysplasia (BPD). METHODS: This single-center retrospective cohort study included infants born between 2009 and 2016 at a gestational age (GA) <30 weeks with moderate or severe BPD at 36 weeks' postmenstrual age. Perinatal characteristics, (social) demographics, and comorbidities were collected from the electronic patient records. Odds ratios for NDI were calculated with univariate and multivariate logistic regression analyses adjusting for potential confounders. RESULTS: Of the 602 eligible infants, 123 infants were diagnosed with BPD. NDI was present in 30.3% and 56.1% at 2- and 5-years CA, respectively. The only independent risk factors associated with NDI in the multivariate analyses were birthweight (adjusted odds ratio [aOR] 0.74, 95% CI 0.57-0.95; aOR 0.70, 95% CI 0.54-0.91, respectively), small for GA (SGA) (aOR 3.25, 95% CI 1.09-9.61; aOR 5.44, 95% CI 1.62-18.2, respectively) at both time points, and male gender at 5-years CA (OR 2.49, 95% CI 1.11-5.57). CONCLUSION: Birthweight and SGA are independent risk factors for NDI at 2- and 5-years CA and male gender at 5-years CA in preterm infants with BPD. In contrast, well-known other risk factors for NDI in the general population of preterm infants, such as GA, maternal education, and neonatal comorbidities were not independently associated with NDI.

Bronchopulmonary dysplasia in adults: Exploring pathogenesis and phenotype.

This review highlights both the longstanding impact of bronchopulmonary dysplasia (BPD) on the health of adult survivors of prematurity and the pressing need for prospective, longitudinal studies of this population. Conservatively, there are an estimated 1,000,000 survivors of BPD in the United States alone. Unfortunately, most of the available literature regarding outcomes of lung disease due to prematurity naturally focuses on pediatric patients in early or middle childhood, and the relative amount of literature on adult survivors is scant. As the number of adult survivors of BPD continues to increase, it is essential that both adult and pediatric pulmonologists have a comprehensive understanding of the pathophysiology and underlying disease process, including the molecular signaling pathways and pro-inflammatory modulators that contribute to the pathogenesis of BPD. We summarize the most common presenting symptoms for adults with BPD and identify the critical challenges adult pulmonologists face in managing the care of survivors of prematurity. Specifically, these challenges include the wide variability of the clinical presentation of adult patients, comorbid cardiopulmonary complications, and the paucity of longitudinal data available on these patients. Adult survivors of BPD have even required lung transplantation, indicating the high burden of morbidity that can result from premature birth and subsequent lung injury. In addition, we analyze the disparate symptoms and management approach to adults with "old" BPD versus "new" BPD. The aim of this review is to assist pulmonologists in understanding the underlying pathophysiology of BPD and to improve clinical recognition of this increasingly common pulmonary disease.

Can Red Blood Cell and Platelet Transfusions Have a Pathogenic Role in Bronchopulmonary Dysplasia?

OBJECTIVE: To evaluate whether transfusions in infants born preterm contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). STUDY DESIGN: We conducted a multihospital, retrospective study seeking associations between red blood cell or platelet transfusions and BPD. We tabulated all transfusions administered from January 2018 through December 2022 to infants born ≤29 weeks or <1000 g until 36 weeks postmenstrual age and compared those with BPD grade. We performed a sensitivity analysis to assess the possibility of a causal relationship. We then determined whether each transfusion was compliant with restrictive guidelines, and we estimated effects fewer transfusions might have on future BPD incidence. RESULTS: Eighty-four infants did not develop BPD and 595 did; 352 developed grade 1 (mild), 193 grade 2 (moderate), and 50 grade 3 (severe). Transfusions were given at <36 weeks to 7% of those who did not develop BPD, 46% who did, and 98% who developed severe BPD. For every transfusion the odds of developing BPD increased by a factor of 2.27 (95% CI, 1.59-3.68; P < .001). Sensitivity analyses suggested that transfusions might contribute to BPD. Fifty-seven percent of red blood cell transfusions and 68% of platelet transfusions were noncompliant with new restrictive guidelines. Modeling predicted that complying with restrictive guidelines could reduce the transfusion rate by 20%-30% and the moderate to severe BPD rate by ∼4%-6%. CONCLUSIONS: Transfusions were associated with BPD incidence and severity. Lowering transfusion rates to comply with current restrictive guidelines might result in a small but meaningful reduction in BPD rates.

Trends in bronchopulmonary dysplasia and respiratory support among extremely preterm infants in China over a decade.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is one of the most serious complications affecting extremely preterm infants. We aimed to evaluate temporal trends in BPD and administration of respiratory support among extremely preterm infants in China over a decade. METHODS: This was a retrospective study using data from a multicenter database, which included infants born less than 28 weeks' gestation discharged from 68 tertiary neonatal care centers in China between 2010 and 2019. Changes in rates and severity of BPD, as well as modalities and duration of respiratory support, were evaluated. RESULTS: Among 4808 eligible infants with gestational age (GA) of 21+6/7  to 27+6/7 weeks and a mean (SD) birth weight of 980 (177) g, no significant change of median GA was found over time. Overall, 780 (16.2%) infants died before 36 weeks' postmenstrual age, 2415 (50.2%) were classified as having no BPD, 917 (19.1%) developed Grade 1 BPD, 578 (12.0%) developed Grade 2 BPD, and 118 (2.5%) developed Grade 3 BPD. The rate of BPD increased from 20.8% in 2010 to 40.7% in 2019 (aRR for trend, 1.081; 95% confidence interval, 1.062-1.099), especially for Grade 1 and Grade 2. Although survival to discharge improved over the decade, the overall survival without BPD did not change during the study period. The use of invasive mechanical ventilation (IMV) remained unchanged. However, the use of noninvasive ventilation (NIV) increased from 71.5% in 2010 to 89.8% in 2019. Moreover, the median duration of NIV increased over time, from 17.0 (4.8, 34.0) days in 2010 to 33.0 (21.0, 44.0) days in 2019, without significant change in the duration of IMV. CONCLUSIONS: Although survival increased over the decade and respiratory support practices changed significantly between 2010 and 2019 in China, with increased use and duration of NIV, there was an increased rate of BPD and survival without BPD has not improved.

Duration of mechanical ventilation and clinical outcomes in very low birth weight infants: A single center 10-years cohort study.

BACKGROUND: Despite the important role of MV in reducing mortality in very preterm infants, its use is often associated with complications. The study was aimed to determine the duration of mechanical ventilation (MV), which significantly increased the risk of adverse outcomes in very low birth weight (VLBW) infants. METHODS: Data obtained from a prospectively created computer database were used in a retrospective cohort study. The database included information about 1980 VLBW infants <32 weeks of gestation who were cared for at the tertiary care center between January 2010 and December 2020. RESULTS: Out of 1980 VLBW infants, 1086 (55%) were ventilated sometime during the hospital stay. 678 (62.43%) of ventilated babies survived until discharge. With ROC analysis, it was identified that MV duration of 60.5 hours had 79.3% sensitivity and 64.6% specificity for the prediction of BPD with the AUC of 0.784 (95% CI 0.733-0.827; p < 0.0001). The duration of MV above 60.5 hours was a significant risk factor for bronchopulmonary dysplasia (aOR 6.005, 95% CI 3.626-9.946), death (aOR 3.610, 95% CI 2.470-5.276), bronchopulmonary dysplasia/death (aOR 4.561, 95% CI 3.328-6.252), sepsis (aOR 1.634, 95% CI 1.168-2.286), necrotizing enterocolitis (aOR 2.606, 95% CI 1.364-4.980), and periventricular leukomalacia (aOR 2.191, 95% CI 1.241-3.867). CONCLUSIONS: Duration of MV longer than 60.5 hours is an independent risk factor for adverse outcomes in VLBW infants. It is essential to increase and optimize efforts to avoid MV or extubate very preterm infants as soon as possible, before reaching the established threshold duration of invasive respiratory support.

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.

Diaphragmatic muscle function in term and preterm infants.

We aimed to assess the determinants of diaphragmatic function in term and preterm infants. 149 infants (56 term; 93 preterm, of whom 14 were diagnosed with bronchopulmonary dysplasia-BPD) were studied before discharge. Diaphragmatic function was assessed by measurement of the maximum transdiaphragmatic pressure (Pdimax)-a measure of diaphragmatic strength, and the pressure-time index of the diaphragm (PTIdi)-a measure of the load-to-capacity ratio of the diaphragm. The Pdimax was higher in term than preterm infants without BPD (90.1 ± 16.3 vs 81.1 ± 11.8 cmH2O; P = 0.001). Term-born infants also had lower PTIdi compared to preterms without BPD (0.052 ± 0.014 vs 0.060 ± 0.017; P = 0.006). In term and preterm infants without BPD, GA was the most significant predictor of Pdimax and PTIdi, independently of the duration of mechanical ventilation and oxygen support. In infants with GA < 32 weeks (n = 30), the Pdimax was higher in infants without BPD compared to those with BPD (76.1 ± 11.1 vs 65.2 ± 11.9 cmH2O; P = 0.015). Preterms without BPD also had lower PTIdi compared to those with BPD (0.069 ± 0.016 vs 0.109 ± 0.017; P < 0.001). In this subgroup, GA was the only significant independent determinant of Pdimax, while BPD and the GA were significant determinants of the PTIdi.  Conclusions: Preterm infants present lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. In very preterm infants, BPD may further aggravate diaphragmatic function. What is Known: • The diaphragm of preterm infants has limited capacity to undertake the work of breathing effectively. • The maximum transdiaphragmatic pressure (a measure of diaphragmatic strength) and the pressure-time index of the diaphragm (a measure of the load-to-capacity ratio of the muscle) have not been extensively assessed in small infants. What is New: • Preterm infants have lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. • In very preterm infants, bronchopulmonary dysplasia may further impair diaphragmatic function.

Emerging role of metabolic reprogramming in hyperoxia-associated neonatal diseases.

Oxygen therapy is common during the neonatal period to improve survival, but it can increase the risk of oxygen toxicity. Hyperoxia can damage multiple organs and systems in newborns, commonly causing lung conditions such as bronchopulmonary dysplasia and pulmonary hypertension, as well as damage to other organs, including the brain, gut, and eyes. These conditions are collectively referred to as newborn oxygen radical disease to indicate the multi-system damage caused by hyperoxia. Hyperoxia can also lead to changes in metabolic pathways and the production of abnormal metabolites through a process called metabolic reprogramming. Currently, some studies have analyzed the mechanism of metabolic reprogramming induced by hyperoxia. The focus has been on mitochondrial oxidative stress, mitochondrial dynamics, and multi-organ interactions, such as the lung-gut, lung-brain, and brain-gut axes. In this article, we provide an overview of the major metabolic pathway changes reported in hyperoxia-associated neonatal diseases and explore the potential mechanisms of metabolic reprogramming. Metabolic reprogramming induced by hyperoxia can cause multi-organ metabolic disorders in newborns, including abnormal glucose, lipid, and amino acid metabolism. Moreover, abnormal metabolites may predict the occurrence of disease, suggesting their potential as therapeutic targets. Although the mechanism of metabolic reprogramming caused by hyperoxia requires further elucidation, mitochondria and the gut-lung-brain axis may play a key role in metabolic reprogramming.

The value of hematocrit for predicting bronchopulmonary dysplasia in very low birth weight preterm infants.

To determine hematocrit (HCT) and to identify independent risk factors for predicting bronchopulmonary dysplasia (BPD) in preterm infants with very low birth weight (VLBW) infants. This retrospective study included 296 premature infants with VLBW in the neonatal intensive care unit of the First Affiliated Hospital of the University of Science and Technology of China between January 2015 and December 2019. Maternal pregnant information and clinical information as well as hematological parameters of preterm babies were collected and compared. Then the maximum area under the curve of receiver operating characteristic curve was developed to estimate the predictive indicator in the blood. Finally, differential variables together with the predictive index were screened for multiple logistic regression analysis to determine independent prognostic factors for BPD. Infants were divided into a BPD group (134 cases) and a non-BPD group (162 cases). The area under the curve of HCT at postnatal 1 week was 0.737 with the sensitivity of 52.30 % and the specificity of 86.00%. Birth weight (BW) <1.12 kg, gestational age <28.4 weeks, newborn respiratory distress syndrome, mechanical ventilation ≥ 7 days, ventilation associated pneumonia, patent arterial duct, PaO2/FiO2 <300 mm Hg and HCT <0.455 at postnatal 1 week were risk factors for BPD of VLBW infants. HCT levels below 0.455 at 1 week after birth serve as a valuable indicator for the potential development of BPD.

A review of the effects of early postnatal hyperoxia exposure on the immature brain.

Preterm birth is a public health priority worldwide, with approximately 15 million premature babies born each year. Oxygen supplementation is one of the most common interventions for preterm infants. However, prolonged oxygen inhalation at supraphysiological concentrations can lead to the development of bronchopulmonary dysplasia (BPD). In addition to lifelong pulmonary sequelae, clinical evidence suggests that BPD is associated with adverse neurodevelopmental outcomes, such as motor impairment, cognitive impairment, and behavioral deficits, severely affecting the quality of life of preterm infants. However, the mechanisms underlying the combination of neurodevelopmental impairment with BPD remain unclear. Therefore, in recent years, attention has also been focused on the effects of hyperoxia on brain development in preterm infants. In this review, we outline the pathophysiological mechanisms of brain injury caused by developmental hyperoxia exposure in current animal models and briefly describe the pharmacological therapies that may be applicable to the associated brain injury. Overall, more studies are needed to assess the effects of hyperoxia on the immature brain, particularly combined analyses of the lungs and brain in the same experimental setting, to elucidate the potential causes of combined neurodevelopmental impairment in BPD.

Nutrition-based implications and therapeutics in the development and recovery of bronchopulmonary dysplasia.

Premature births account for over 10% of live births worldwide. Bronchopulmonary dysplasia (BPD) represents a severe sequela in neonates born very prematurely and remains the most common chronic neonatal lung disease, often leading to serious adverse consequences in adulthood. Nutrition plays a crucial role in lung development and repair. Ongoing research has primarily focused on the pathogenesis and prevention of BPD in preterm birth. However, infants with established BPD need specialist medical care that persists throughout their hospitalization and continues after discharge. This manuscript aims to highlight the impact of growth and nutrition on BPD and highlight research gaps to provide direction for future studies. Protective practices include ensuring adequate early energy delivery through parenteral nutrition and enteral feedings while carefully monitoring total fluid intake and the use of breast milk over formula. These nutritional strategies remain the same for infants with established BPD with the addition of limiting the use of diuretics and steroids; but if employed, monitoring carefully without compromising total energy delivery. Functional nutrient supplements with a potential protective role against BPD are revisited, despite the limited evidence of their efficacy, including vitamins, trace elements, zinc, lipids, and sphingolipids. Planning post-intensive care and outpatient longitudinal nutrition support is critical in caring for an infant with established BPD.