Outcome Of Bronchopulmonary Dysplasia Research Articles

Bronchopulmonary Dysplasia in Children. An Up-to-Date View of Disease Outcomes

Introduction. Bronchopulmonary dysplasia (BPD) is a chronic neonatal lung disease, with oxygen dependence by 36 weeks post conceptual age (PCA). Over the past decade, the frequency of the disease has increased. More and more modern scientific data are published that BPD has an adverse effect not just the development of the lungs, but also on the cardiovascular system. There is a large amount of information in the literature about the outcomes of BPD, but there is not enough information about the consequences of cardiovascular disorders in children with a history of BPD. Lack of clear criteria to predict and prevent to demonstrate cardiovascular disorders, were the basis for a detailed study of the literature concerning this issue.Purpose of the study based on study of the results of studies by local and foreign authors, to analyze the nature of cardiovascular disorders in children with a history of BPD, and to determine directions for more detailed scientific and practical search for a solution to this problem.Materials and methods. Research articles were searched for keywords “bronchopulmonary dysplasia” and “сardiovascular disorders” in the PubMed, UpToDate, Google Scholar databases, eLibrary.ru. At least 80 publications have been extracted from search results for simplification. Analyses of the results of studies by local and foreign authors on outcomes, BPD, including cardiovascular disorders, was carried out.Results and discussion. At the moment, the outcomes of BPD are well understood, while few information on cardiovascular disorders and possible prognosis for children who have undergone BPD.Conclusion. Cardiovascular disorders in children with a history of BPD are a pressing problem in pediatric practice. The presented literature review summarizes the information accumulated over several years on the outcomes of cardiovascular changes and determines the direction for further study of the problem, involving pediatricians and doctors of other specialties in order to identify groups at increased risk for the development of these diseases in children.

Inter‐hospital variations in the respiratory outcomes of very and extremely pre‐term infants: A cohort study in Japan

AbstractBackgroundHospital‐level and international variations exist in the management strategies of bronchopulmonary dysplasia (BPD). However, studies evaluating hospital‐level variations in the respiratory outcomes of pre‐term infants associated with differing management strategies of BPD are lacking.ObjectiveHerein, we aimed to assess inter‐hospital variations in the respiratory outcomes of BPD in very pre‐term and extremely pre‐term infants.MethodsIn this cohort study, the administrative claims and discharge summary data were extracted from 276 hospitals in Japan between April 2014 and March 2016. This study assessed neonates of a gestational age of 22–31 weeks old, who had been hospitalised for ≥7 days.The primary outcome was a BPD defined using any respiratory support, such as supplemental oxygen, high‐flow nasal cannula, CPAP, or mechanical ventilation at 36 weeks PMA. The median odds ratio (MOR) was calculated using a multilevel logistic regression model, including baseline characteristics, comorbidities, and treatment as covariates, to evaluate the inter‐hospital variation of the outcome.ResultsOf the 8143 neonates from across 132 hospitals, 53.7% were male, with a mean gestational age (standard deviation) of 28.0 (2.5)‐weeks‐old and birthweight of 1086 (386) g. Among these patients, BPD occurred in 2737 (33.6%). The MOR was 2.49, representing the median value of odds ratios when comparing two neonates with identical covariates from hospitals with high and low propensity for the outcomes to occur.ConclusionsOutcome variations in the BPD were observed among hospitals in Japan, even after adjusting for individual factors, including gestational age, birthweight, comorbidities, and treatments. Thus, in Japan, developing strategies is essential to decrease the BPD rates, while minimising inter‐hospital heterogeneity, to improve the healthcare quality for pre‐term neonates.

Plasma Proteome Profiles Associated with Early Development of Lung Injury in Extremely Preterm Infants.

The biological mediators which initiate lung injury in extremely preterm infants during early postnatal life remain largely unidentified, limiting opportunities for early treatment and diagnosis. This exploratory study used SWATH-mass spectrometry to identify bronchopulmonary dysplasia (BPD)-specific changes in protein abundance in plasma samples obtained in the first 72 hours of life from extremely preterm infants and bioinformatic analysis to identify BPD-related biological categories and pathways. Lasty, binary logistic regression analysis was used to test the BPD predictive potential of a base model alone (gestational age, birth weight, sex) and with the protein biomarker added, with bootstrap resampling used to internally validate protein predictors and adjust for overoptimism. We observed disturbance of key processes including coagulation, complement activation, development and extracellular matrix organisation in the first days of life in extremely preterm infants who were later diagnosed with BPD. In the BPD prediction analysis, 49 plasma proteins were identified which when each singularly was combined with birth characteristics had a C-index of 0.65-0.84 (optimism-adjusted C-index) suggesting predictive potential for BPD outcomes. Taken together, this study demonstrates that alterations in plasma proteins can be detected from 4 hours of age in extremely preterm infants who later develop BPD and that protein biomarkers when combined with three birth characteristics have the potential to predict BPD development within the first 72 hours of life.

Antibiotics and beyond: Unraveling the dynamics of bronchopulmonary dysplasia in very preterm infants.

Bronchopulmonary dysplasia (BPD) remains a significant challenge in neonatal care. Prenatal inflammation and neonatal sepsis contribute to the multifactorial nature of BPD. A potential association between empirical antibiotic therapy and BPD risk has been proposed due to microbiota dysbiosis in very low birth weight premature infants. A single centered retrospective cohort study of preterm infants (24-32 weeks gestation) from 2014 to 2021. The study compared groups that received empirical antibiotics in the first days of life and those that did not receive any antibiotic in the first days of life. The primary outcomes studied were BPD, death, and the combined outcome of BPD/death. Statistical analysis employed t-tests, Mann-Whitney U, Chi-square, and logistic regression. Of 454 preterm infants, 61.5% received antibiotics. This group had lower gestational age, birth weight, and Apgar scores. Antibiotic use was associated with higher incidence of BPD (35.5% vs. 10.3%), death (21.5% vs. 8.6%), and combined outcomes (54.5% vs. 18.3%). In multivariate analysis, antibiotic use independently associated with BPD (OR 2.58, p < 0.001) and combined outcome BPD/death (OR 2.06, p < 0.02). Antenatal corticosteroids provided protection against BPD, but not mortality. This study suggests an association between early empirical antibiotic use and BPD in preterm infants, emphasizing the need for judicious antibiotic practices in neonatal care.

Acetaminophen for Patent Ductus Arteriosus and Risk of Mortality and Pulmonary Morbidity.

Emerging data indicate that acetaminophen may adversely affect lung health. We examined whether acetaminophen compared with cyclooxygenase (COX) inhibitor alone for patent ductus arteriosus (PDA) is associated with mortality or respiratory morbidity in extremely preterm infants. This is a retrospective cohort study using data from the National Institute of Child Health and Human Development Neonatal Research Network. Infants were born at 22 to 28 weeks' gestation or weighing 401 to 1000 g between 2016 and 2020 and received acetaminophen, ibuprofen, and/or indomethacin for PDA closure. The primary outcome was death or grade 2 to 3 bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age. Secondary outcomes included predischarge mortality and respiratory morbidities. Risk ratios were adjusted for baseline and early postnatal factors. Additional exploratory analyses were adjusted for later postnatal covariates. Of 1921 infants, 627 (32.6%) received acetaminophen and 1294 (67.3%) received COX inhibitor only. Multidrug therapy (42.9% vs 4.7%) and surgical or catheter PDA closure (26.5% vs 19.9%) were more common among acetaminophen-exposed infants. Death or grade 2 to 3 BPD at 36 weeks' postmenstrual age was similar between infants treated with acetaminophen versus COX inhibitor only (57.1% vs 58.3%; adjusted relative risk [aRR] 0.96, 95% confidence interval [CI] 0.87-1.06). Acetaminophen was associated with increased risk of predischarge mortality (13.3% vs 10.0%) when adjusting for perinatal and early postnatal factors (aRR 1.42, 95% CI 1.02-1.93), but not in exploratory analyses that included later postnatal factors (aRR 1.28, 95% CI 0.91-1.82). Treatment with acetaminophen versus COX inhibitor alone for PDA was not associated with the composite outcome of death or BPD in extremely preterm infants. Our results support further evaluation of whether acetaminophen for PDA increases mortality.

Comparison of “IN-REC-SUR-E” and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial)

BackgroundSurfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration.MethodsIn this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks).Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR).DiscussionThis trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life.Trial registrationClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Administration time of caffeine in preterm infants: systematic review and meta-analysis.

To assess the ideal time for caffeine administration in preterms, identifying its effects and safety. Study Design: Meta-analysis conducted including preterms <32 weeks GA or BW < 1500 g, comparing caffeine administration time: <24 x ≥24HOL, <48 x ≥48HOL, <72 x ≥72HOL. 18 studies included 76.998 patients. The median age of starting caffeine was the first 24 HOL. In the overall comparisons, there was reduction in patent ductus arteriosus (OR 0.71 [0.55, 0. 92]; low evidence), retinopathy of prematurity (OR 0.71 [0.54, 0.93]; moderate evidence), severe brain injury (OR 0.79 [0.70, 0.91]; moderate evidence), bronchopulmonary dysplasia (BPD) (OR 0.69 [0.59, 0.81]; moderate evidence), composite outcome of BPD or death (OR 0.76 [0.66, 0.88]; moderate evidence). Mortality increase was found (OR 1.20 [1.12, 1.29], very low evidence).Caffeine in the first24 HOL has benefits in reducing morbidities associated with prematurity. Mortality finding is potentially due to survival bias.

Corticosteroids for the prevention and treatment of bronchopulmonary dysplasia: an overview of systematic reviews.

Corticosteroids for the prevention and treatment of bronchopulmonary dysplasia: an overview of systematic reviews.

Risk Prediction of Severe Bronchopulmonary Dysplasia (BPD) Using the Respiratory Severity Score (RSS) in Extremely Preterm Infants: A Retrospective Study From Saudi Arabia.

Background Bronchopulmonary dysplasia (BPD) is a significant complication in extremely preterm infants. Therefore, early diagnosis of BPD is important for planning treatment strategies. In this study, we aimed to assess the predictive efficacy of the Respiratory Severity Score (RSS) in determining severe BPD or death outcomes in very preterm infants. Methodology This retrospective study included preterm infants born with a gestational age of ≤30 weeks. The inclusion criteria comprised individuals who were mechanically ventilated (<1 week) during the first four weeks of life. Any patients who died during the first seven days of life were excluded. RSS values were recorded on days 3, 14, 21, and 28 of life. Multivariate logistic regression was used to identify a correlation between RSS and patient outcomes. Results A total of 154 infants were included in the analysis, of whom 82 (53.24%) developed severe BPD and 38 (24.67%) died. RSS was higher in patients who either died or developed severe BPD compared to those who survived. The multivariate logistic regression analysis revealed that RSSs at postnatal day 14 (odds ratio (OR) = 3.970; 95% confidence interval (CI) = 1.114-14.147; p < 0.05), day 21 (OR = 6.201; 95% CI = 1.937-19.851; p < 0.05), and day 28 (OR = 8.925; 95% CI = 3.331-28.383; p < 0.05) was significantly associated with a higher risk of death or severe BPD. Conclusions The findings of the present study revealed that RSS can help predict the risk of severe BPD in very preterm infants.

Efficacy of inhaled nitric oxide in preterm infants ≤ 34weeks: a systematic review and meta-analysis of randomized controlled trials.

Background: The effect of inhaled nitric oxide (iNO) in neonates >34 weeks on improving respiration is well documented. However, the efficacy of iNO in preterm infants ≤34 weeks remains controversial. Objectives: The main purpose of this review is to assess the effectiveness and safety of iNO treatment in preterm infants ≤34 weeks. Search methods: We systematically searched PubMed, Embase and Cochrane Libraries from their inception to 1 June 2023. We also reviewed the reference lists of retrieved studies. Selection criteria: Our study involved randomized controlled trials on preterm infants ≤34 weeks, especially those receiving iNO treatment, and mainly assessed outcomes such as bronchopulmonary dysplasia (BPD) and mortality. Two authors independently reviewed these trials, extracted data, and evaluated study biases. Disagreements were resolved by consensus. We used the GRADE method to assess evidence quality. Results: Our research included a total of 17 studies involving 4,080 neonates and 7 follow-up studies. The synthesis of results showed that in neonates, iNO treatment reduced the incidence of BPD (RR: 0.92; 95% CI: 0.86-0.98). It also decreased the composite outcome of death or BPD (RR: 0.94; 95% CI: 0.90-0.98), without increasing the risk of short-term (such as intraventricular hemorrhage, periventricular leukomalacia) and long-term neurological outcomes (including Bayley mental developmental index <70, cerebral palsy and neurodevelopmental impairment). Furthermore, iNO did not significantly affect other neonatal complications like sepsis, pulmonary hemorrhage, necrotizing enterocolitis, and symptomatic patent ductus arteriosus. Subgroup analysis revealed that iNO significantly reduced BPD incidence in neonates at 36 weeks under specific intervention conditions, including age less than 3 days, birth weight over 1,000g, iNO dose of 10ppm or higher, or treatment duration exceeding 7 days (p < 0.05). Conclusion: Inhaled NO reduced the incidence of BPD in neonates at 36 weeks of gestation, and the effect of the treatment depended on neonatal age, birth weight, duration and dose of iNO. Therefore, iNO can be considered a promising treatment for the potential prevention of BPD in premature infants. More data, however, would be needed to support nitric oxide registration in this specific patient population, to minimize its off-label use.

Single center experience with first-intention high-frequency jet vs. volume-targeted ventilation in extremely preterm neonates.

To examine whether first-intention high-frequency jet ventilation (HFVJ), compared to volume-targeted ventilation (VTV), in extremely preterm infants is associated with lower incidence of bronchopulmonary dysplasia (BPD) and other adverse clinical outcomes. We conducted a retrospective cohort study evaluating neonates with gestational age (GA) ≤28 weeks, who received first-intention HFJV (main exposure) or VTV (comparator), between 11/2020 and 3/2023, with a subgroup analysis including neonates with GA ≤26 weeks and oxygenation index (OI) >5. We identified 117 extremely preterm neonates, 24 (GA 25.2 ± 1.6 weeks) on HFJV, and 93 (GA 26.4 ± 1.5 weeks, p = 0.001) on VTV. The neonates in the HFJV group had higher oxygenation indices on admission, higher inotrope use, and remained intubated for a longer period. Despite these differences, there were no statistically significant differences in rates of BPD, survival, or other adverse outcomes between the two groups. In subgroup analysis of 18 neonates on HFJV and 39 neonates on VTV, no differences were recorded in the GA, and duration of mechanical ventilation, while neonates in the HFJV group had significantly lower rates of BPD (50% compared to 83%, p = 0.034), and no significant differences in other adverse outcomes compared to neonates in the VTV group. In neonates ≤26 weeks of GA with OI >5, HFJV was significantly associated with lower rates of BPD (OR 0.21, 95% CI 0.05-0.92), and combined BPD or death (OR 0.18, 95% CI 0.03-0.85), after adjusting for birth weight, and Arterial-alveolar gradient on admission. In extremely preterm neonates ≤26 weeks of GA with OI >5, first-intention HFJV, in comparison to VTV, is associated with lower rates of BPD.

Prophylactic sildenafil to prevent bronchopulmonary dysplasia: A systematic review and meta-analysis.

Bronchopulmonary dysplasia (BPD) persists as one of the foremost factors contributing to mortality and morbidity in extremely preterm infants. The effectiveness of administering sildenafil early on to prevent BPD remains uncertain. The aim of this study was to investigate the efficacy and safety of prophylactically administered sildenafil during the early life stages of preterm infants to prevent mortality and BPD. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and Ichushi were searched. Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. Two reviewers independently screened the title, abstract, and full text, extracted data, assessed the risk of bias, and evaluated the certainty of evidence (CoE) following the Grading of Recommendations Assessment and Development and Evaluation approach. The random-effects model was used for a meta-analysis of RCTs. This review included three RCTs (162 infants). There were no significant differences between theprophylactic sildenafil and placebo groups in mortality (risk ratio [RR]: 1.32; 95% confidence interval [CI]: 0.16-10.75; very low CoE), BPD (RR: 1.20; 95% CI: 0.79-1.83; very low CoE), and all other outcome assessed (all with very low CoE). The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials. The prophylactic use of sildenafil in individuals at risk of BPD did not indicate any advantageous effects in terms of mortality, BPD, and other outcomes, or increased side effects.

Association between plasma lysophosphatidic acid levels and bronchopulmonary dysplasia in extremely preterm infants: A prospective study.

Lysophosphatidic acid (LPA) is implicated in bronchopulmonary dysplasia (BPD) pathogenesis, but clinical evidence is lacking. This study aimed to investigate LPA levels in preterm infants with and without BPD and explore LPA as a biomarker for predicting BPD occurrence. Premature infants with a gestational age of <28 weeks or a birth weight of <1000 g were enrolled. Blood samples were collected at postnatal day (PD) 7, 28, and postmenstrual age (PMA) 36 weeks, and plasma LPA levels were measured using a commercial ELISA kit. Receiver operating characteristic curve (ROC) curve analysis determined the PD 28 cutoff for LPA, and multivariable regression analyzed LPA's independent contribution to BPD and exploratory outcomes. Among the 91 infants enrolled in this study, 35 were classified into the non-BPD group and 56 into the BPD group. Infants with BPD had higher plasma LPA levels at PD 28 (6.467 vs. 4.226 μg/mL, p = 0.034) and PMA 36 weeks (2.330 vs. 1.636 μg/mL, p = 0.001). PD 28 LPA level of 6.132 μg/mL was the cutoff for predicting BPD development. Higher PD 28 LPA levels (≥6.132 μg/mL) independently associated with BPD occurrence (OR 3.307, 95% CI 1.032-10.597, p = 0.044). Higher LPA levels correlated with longer oxygen therapy durations [regression coefficients (β) 0.147, 95% CI 0.643-16.133, p = .034]. Infants with BPD had higher plasma LPA levels at PD 28 and PMA 36 weeks. Higher PD 28 LPA levels independently associated with an increased BPD risk.

Ambient Air Pollution and Outpatient Morbidities in Bronchopulmonary Dysplasia.

Rationale: Bronchopulmonary dysplasia (BPD) is the most common long-term complication of prematurity. Although socioeconomic status is associated with BPD morbidities, the drivers of this association are poorly understood. In the United States, ambient air pollution (AAP) exposure is linked to both race/ethnicity and socioeconomic status. Furthermore, AAP exposure is known to have a detrimental effect on respiratory health in children. Objectives: To assess if AAP exposure is linked to BPD morbidity in the outpatient setting. Methods: Participants with BPD were recruited from outpatient clinics at Johns Hopkins University and the Children's Hospital of Philadelphia between 2008 and 2021 (N = 800) and divided into low, moderate, and high AAP exposure groups, based on publicly available U.S. Environmental Protection Agency data. Clinical data were obtained by chart review and caregiver questionnaires. Results: Non-White race, home ventilator use, and lower median household income were associated with higher degrees of air pollution exposure. After adjustment for these factors, moderate and high air pollution exposure were associated with requiring systemic steroids (odds ratio, 1.78 and 2.17, respectively) compared with low air pollution. Similarly, high air pollution exposure was associated with emergency department visits (odds ratio, 1.59). Conclusions: This study demonstrates an association between AAP exposure and BPD morbidity after initial hospital discharge. AAP exposure was closely linked to race and median household income. As such, it supports the notion that AAP exposure may be contributing to health disparities in BPD outcomes. Further studies directly measuring exposure and establishing a link between biomarkers of exposure and outcomes are prerequisites to developing targeted interventions protecting this vulnerable population.

Systemic corticosteroids for the prevention of bronchopulmonary dysplasia, a network meta-analysis.

Systemic corticosteroids for the prevention of bronchopulmonary dysplasia, a network meta-analysis.

Heterogeneity of Treatment Effects of Hydrocortisone by Risk of Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants in the National Institute of Child Health and Human Development Neonatal Research Network Trial

Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death. To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death. This secondary post hoc analysis used data from the NICHD NRN Hydrocortisone Trial, which was a double-masked, placebo-controlled, randomized clinical trial conducted in 19 US academic centers. The NICHD HRN Hydrocortisone Trial enrolled infants born at a gestational age of less than 30 weeks who received mechanical ventilation for at least 7 days, including at the time of enrollment, and who were aged 14 to 28 postnatal days. Infants were enrolled between August 22, 2011, and February 4, 2018, with follow-up between 22 and 26 months of corrected age completed on March 29, 2020. Data were analyzed from September 13, 2021, to March 25, 2023. Infants were randomized to 10 days of hydrocortisone or placebo treatment. Infants' baseline risk of grades 2 to 3 BPD or death was estimated using the NICHD Neonatal BPD Outcome Estimator. Differences in absolute and relative treatment effects by baseline risk were evaluated using interaction terms in models fitted to the efficacy outcome of grades 2 to 3 BPD or death and the safety outcome of moderate or severe NDI or death by follow-up. Among the 799 infants included in the analysis (421 boys [52.7%]), the mean (SD) gestational age was 24.9 (1.5) weeks, and the mean (SD) birth weight was 715 (167) g. The mean estimated baseline risk for grades 2 to 3 BPD or death was 54% (range, 18%-84%) in the study population. The interaction between treatment group and baseline risk was not statistically significant on a relative or absolute scale for grades 2 to 3 BPD or death; the size of the effect ranged from a relative risk of 1.13 (95% CI, 0.82-1.55) in quartile 1 to 0.94 (95% CI, 0.81-1.09) in quartile 4. Similarly, the interaction between treatment group and baseline risk was not significant on a relative or absolute scale for moderate or severe NDI or death; the size of the effect ranged from a relative risk of 1.04 (95% CI, 0.80-1.36) in quartile 1 to 0.99 (95% CI, 0.80-1.22) in quartile 4. In this secondary analysis of a randomized clinical trial, the effect of hydrocortisone vs placebo was not appreciably modified by baseline risk for grades 2 to 3 BPD or death. ClinicalTrials.gov Identifier: NCT01353313.

Nasal high flow therapy for primary respiratory support in preterm infants.

Nasal high flow therapy for primary respiratory support in preterm infants.

Inhaled nitric oxide in premature infants for preventing bronchopulmonary dysplasia: a meta-analysis

BackgroundThe effectiveness of nitric oxide (NO) in reducing the risk of bronchopulmonary dysplasia (BPD) remains debatable. In this study, we performed a meta-analysis to guide clinical decision-making regarding the significance of inhaled NO (iNO) on the potential occurrence and outcomes of BPD in premature infants.MethodsData from clinical randomized controlled trials (RCTs) published in PubMed, Embase, Cochrane Library, Wanfang, China National Knowledge Infrastructure (CNKI) and Chinese Scientific Journal Database VIP databases for premature infants were searched from inception to March 2022. Review Manager 5.3 statistical software was used for heterogeneity analysis.ResultsOf the 905 studies retrieved, 11 RCTs met the screening criteria of this study. Our analysis showed that the iNO group was associated with a significantly lower incidence of BPD than the control group (relative risk [RR] = 0.91, 95% confidence interval (CI) 0.85-0.97, P = 0.006). We also observed no significant difference in the incidence of BPD between the two groups at the initial dose of 5 ppm (ppm) (P = 0.09) but those treated with 10 ppm iNO had a significantly lower incidence of BPD (RR = 0.90, 95%CI 0.81-0.99, P = 0.03). However, it should be noted that although the iNO group had an increased risk for necrotizing enterocolitis (NEC) (RR = 1.33, 95%CI 1.04-1.71, P = 0.03), cases treated with an initial dose of 10 ppm revealed no significant difference in the incidence of NEC compared with the control group (P = 0.41), while those treated with an initial dosage of 5 ppm of iNO had a significantly greater NEC rates than the control group (RR = 1.41, 95%CI 1.03-1.91, P = 0.03). Further, we observed no statistically significant differences in the incidence of in-hospital mortality, intraventricular hemorrhage (IVH) (Grade 3/4) or periventricular leukomalacia (PVL) and pulmonary hemorrhage (PH) between the two treatment groups.ConclusionsThis meta-analysis of RCTs showed that iNO at an initial dosage of 10 ppm seemed more effective in reducing the risk of BPD than conventional treatment and iNO at an initial dosage of 5 ppm in preterm infants at a gestational age of ≤34 weeks who required respiratory support. However, the incidence of in-hospital mortality and adverse events between the overall iNO group and Control were similar.

Prevention for moderate or severe BPD with intravenous infusion of autologous cord blood mononuclear cells in very preterm infants-a prospective non-randomized placebo-controlled trial and two-year follow up outcomes.

Bronchopulmonary dysplasia (BPD) is the primary severe complication of preterm birth. Severe BPD was associated with higher risks of mortality, more postnatal growth failure, long term respiratory and neurological developmental retardation. Inflammation plays a central role in alveolar simplification and dysregulated vascularization of BPD. There is no effective treatment to improve BPD severity in clinical practice. Our previous clinical study showed autologous cord blood mononuclear cells (ACBMNCs) infusion could reduce the respiratory support duration safely and potential improved BPD severity. Abundant preclinical studies have reported the immunomodulation effect as an important mechanism underlying the beneficial results of stem cell therapies in preventing and treating BPD. However, clinical studies assessing the immunomodulatory effect after stem cells therapy were rare. This study was to investigate the effect of ACBMNCs infusion soon after birth on prevention for severe BPD and long term outcomes in very preterm neonates. The immune cells and inflammatory biomarkers were detected to investigate the underlying immunomodulatory mechanisms. This single-center, prospective, investigator-initiated, non-randomized trial with blinded outcome assessment aimed to assess the effect of a single intravenous infusion of ACBMNCs in preventing severe BPD (moderate or severe BPD at 36 weeks of gestational age or discharge home) in surviving very preterm neonates less than 32 gestational weeks. Patients admitted to the Neonatal Intensive Care Unit (NICU) of Guangdong Women and Children Hospital from July 01, 2018 to January 1, 2020 were assigned to receiving a targeted dosage of 5×107cells/kg ACBMNC or normal saline intravenously within 24h after enrollment. Incidence of moderate or severe BPD in survivors were investigated as the primary short term outcome. Growth, respiratory and neurological development were assessed as long term outcomes at corrected age of 18-24 month-old. Immune cells and inflammatory biomarkers were detected for potential mechanism investigation. The trial was registered at ClinicalTrials.gov (NCT02999373). Six-two infants were enrolled, of which 29 were enrolled to intervention group, 33 to control group. Moderate or severe BPD in survivors significantly decreased in intervention group (adjusted p=0.021). The number of patients needed to treat to gain one moderate or severe BPD-free survival was 5 (95% confidence interval: 3-20). Survivors in the intervention group had a significantly higher chance to be extubated than infants in the control group (adjusted p=0.018). There was no statistical significant difference in total BPD incidence (adjusted p=0.106) or mortality (p=1.000). Incidence of developmental delay reduced in intervention group in long term follow-up (adjusted p=0.047). Specific immune cells including proportion of T cells (p=0.04) and CD4+ T cells in lymphocytes (p=0.03), and CD4+ CD25+ forkhead box protein 3 (FoxP3)+ regulatory T cells in CD4+ T cells increased significantly after ACBMNCs intervention (p＜0.001). Anti-inflammatory factor IL-10 was higher (p=0.03), while pro-inflammatory factor such as TNF-a (p=0.03) and C reactive protein (p＜0.001) level was lower in intervention group than in control group after intervention. ACBMNCs could prevent moderate or severe BPD in surviving very premature neonates and might improve neurodevelopmental outcomes in long term. An immunomodulatory effect of MNCs contributed to the improvement of BPD severity. This work was supported by National Key R&D Program of China (2021YFC2701700), National Natural Science Foundation of China (82101817, 82171714, 8187060625), Guangzhou science and technology program (202102080104).

Respiratory outcomes after delivery room stabilisation with a new respiratory support system using nasal prongs.

To study if stabilisation using a new respiratory support system with nasal prongs compared to T-piece with a face mask is associated with less need for mechanical ventilation and bronchopulmonary dysplasia. A single-centre follow-up study of neonates born <28 weeks gestation at Karolinska University Hospital, Stockholm included in the multicentre Comparison of Respiratory Support after Delivery (CORSAD) trial and randomised to initial respiratory support with the new system versus T-piece. Data on respiratory support, neonatal morbidities and mortality were collected up to 36 weeks post-menstrual age. Ninety-four infants, 51 female, with a median (range) gestational age of 25 +2 (23 +0, 27 +6) weeks and days, were included. Significantly fewer infants in the new system group received mechanical ventilation during the first 72h, 24 (52.2%) compared with 35 (72.9%) (p= 0.034) and during the first 7 days, 29 (63.0%) compared with 39 (81.3%) (p= 0.045) in the T-piece group. At 36 weeks post-menstrual age, 13 (28.3%) in the new system and 13 (27.1%) in the T-piece group were diagnosed with bronchopulmonary dysplasia. Stabilisation with the new system was associated with less need for mechanical ventilation during the first week of life. No significant difference was seen in the outcome of bronchopulmonary dysplasia.