Bronchopulmonary Dysplasia In Preterm Neonates Research Articles

Multipotent adult progenitor cells prevent functional impairment and improve development in inflammation driven detriment of preterm ovine lungs

BackgroundPerinatal inflammation increases the risk for bronchopulmonary dysplasia in preterm neonates, but the underlying pathophysiological mechanisms remain largely unknown. Given their anti-inflammatory and regenerative capacity, multipotent adult progenitor cells (MAPC) are a promising cell-based therapy to prevent and/or treat the negative pulmonary consequences of perinatal inflammation in the preterm neonate. Therefore, the pathophysiology underlying adverse preterm lung outcomes following perinatal inflammation and pulmonary benefits of MAPC treatment at the interface of prenatal inflammatory and postnatal ventilation exposures were elucidated. MethodsInstrumented ovine fetuses were exposed to intra-amniotic lipopolysaccharide (LPS 5 mg) at 125 days gestation to induce adverse systemic and peripheral organ outcomes. MAPC (10 × 106 cells) or saline were administered intravenously two days post LPS exposure. Fetuses were delivered preterm five days post MAPC treatment and either killed humanely immediately or mechanically ventilated for 72 h. ResultsAntenatal LPS exposure resulted in inflammation and decreased alveolar maturation in the preterm lung. Additionally, LPS-exposed ventilated lambs showed continued pulmonary inflammation and cell junction loss accompanied by pulmonary edema, ultimately resulting in higher oxygen demand. MAPC therapy modulated lung inflammation, prevented loss of epithelial and endothelial barriers and improved lung maturation in utero. These MAPC-driven improvements remained evident postnatally, and prevented concomitant pulmonary edema and functional loss. ConclusionIn conclusion, prenatal inflammation sensitizes the underdeveloped preterm lung to subsequent postnatal inflammation, resulting in injury, disturbed development and functional impairment. MAPC therapy partially prevents these changes and is therefore a promising approach for preterm infants to prevent adverse pulmonary outcomes.

Correlation between early postnatal body weight changes and lung ultrasound scores as predictors of bronchopulmonary dysplasia in preterm infants: A secondary analysis of a prospective study.

In a cohort of extreme preterm infants, our study revealed a positive yet weak correlation between LUS and EWC, suggesting that EWC was not the major contributing to the evolving chronic lung disease. • Recent evidence links Early Weight-Changes with bronchopulmonary dysplasia in preterm neonates. • Lung ultrasound score has shown promise in early prediction of the subsequent development of bronchopulmonary dysplasia in preterm infants.No studies have examined the correlation between Early Weight-Changes and Lung ultrasound score in preterm infants during first 2 weeks after birth. • Our study demonstrated a positive and statistically significant correlation between early LUS and EWC, indicating their potential role as early predictors for the subsequent development of BPD in extreme preterm infants. • The weak correlation between the two parameters may stem from the possible restricted influence of EWC, given that it may not be the primary factor contributing to the evolving chronic lung disease.

EBNEO commentary: Umbrella review evaluating interventions to decrease risk of bronchopulmonary dysplasia in preterm neonates.

EBNEO commentary: Umbrella review evaluating interventions to decrease risk of bronchopulmonary dysplasia in preterm neonates.

Risk Calculator for Bronchopulmonary Dysplasia in Preterm Neonates: A Prospective Observational Study.

To determine the incidence, risk factors, and accuracy of a previously published risk estimator in predicting Bronchopulmonary dysplasia (BPD) in a very preterm cohort from India. A single-center prospective observational study was conducted in preterm neonates born at 23-30 wk of gestation with a birth weight of 501-1249g. The incidence and risk factors of BPD were evaluated, and the accuracy of BPD prediction at six pre-specified time points using the National Institute of Child Health and Human Development (NICHD) BPD risk estimator was assessed by comparing the estimated risk with the observed rates. A total of 310 neonates with mean gestation age of 28.7±1.5 wk and birth weight of 1023.6±171.4g were enrolled in the study. The study cohort had 49.7% males and 32.3% neonates requiring resuscitation. Any BPD was observed in 54 (17.4%) neonates with severity being mild, moderate, and severe in 29 (53.7%), 17 (31.5%), and 8 (14.8%) neonates respectively. Hundred (32.3%) neonates died before discharge from the hospital. Sepsis, patent ductus arteriosus, retinopathy of prematurity, intraventricular hemorrhage, and blood transfusion were significant risk factors for the development of BPD. The calculator was accurate for the prediction of death or moderate-severe BPD on days 1 and 3 with the area under the curve of 0.82 and 0.77 respectively. The NICHD BPD estimator helped to accurately predict moderate-severe BPD early in Indian preterm infants.

N-Terminal Pro-B Type Natriuretic Peptide as a Predictive Biomarker of Bronchopulmonary Dysplasia or Death Due to Bronchopulmonary Dysplasia in Preterm Neonates: A Systematic Review and Meta-Analysis.

Emerging evidence suggests the clinical utility of N terminal pro B type natriuretic peptide (NT-proBNP) in multiple cardiac and pulmonary abnormalities both in adult and pediatric populations. To date, however, there is no consensus regarding its efficacy for the prediction and severity of bronchopulmonary dysplasia in premature neonates. The objective of the present meta-analysis was to determine differences in NT-proBNP among neonates that develop BPD or die from BPD and to evaluate if there is relative information on the diagnostic accuracy of the method. We conducted a systematic search according to the PRISMA guidelines and looked into Medline (1966-2023), Scopus (2004-2023), Clinicaltrials.gov (2008-2023), EMBASE (1980-2023), Cochrane Central Register of Controlled Trials CENTRAL (1999-2022) and Google Scholar (2004-2023) together with the reference lists from included studies. The potential risk of bias encountered in our study was evaluated using the QUADAS -2 tool. Finally, a total of 9 studies met the eligibility criteria, comprising 1319 newborns, from which 397 developed BPD and 922 were unaffected controls. The results retrieved from our meta-analysis showed that newborns suffering from BPD had notably elevated NT-proBNP levels after birth when compared with healthy neonates (SMD 2.57, 95% CI 0.41, 4.72). The summary effect of the AUC meta-analysis showed that NT-proBNP was very accurate in detecting neonates at risk of developing severe BPD or dying from the disease (AUC -0.16, 95% CI -0.23, -0.08). No studies reported data relevant to the sensitivity and/or specificity of the method in diagnosing BPD. Serum NT-proBNP levels represent a potential future biomarker with great diagnostic validity for the prediction of BPD complicating preterm deliveries. The limited amount of studies included and the significant variations in cutoff values and timing of measurement still restrict the application of NT-proBNP as an established clinical biomarker for BPD. The design of larger prospective studies will provide a more representative number of participants and will address the discrepancies in existing literature.

Azithromycin for Eradication of Ureaplasma and Prevention of Bronchopulmonary Dysplasia in Preterm Neonates in the Neonatal Intensive Care Unit.

Azithromycin has been explored as a treatment option for eradication of Ureaplasma and prevention of bronchopulmonary dysplasia (BPD) in preterm neonates. However, there is debate about the need for eradication of Ureaplasma and whether azithromycin is safe and efficacious for this indication. This literature review provides an overview of the evidence for use of azithromycin for eradication of Ureaplasma and prevention of BPD, including dosing and duration of azithromycin used in these studies. The literature search included articles published in the English language in Medline and PubMed from 1946 to January 2022. Relevant citations within identified articles were also reviewed. A total of 9 studies representing 388 neonates were included. The percentage of neonates that tested positive for Ureaplasma in these studies ranged from 18.6% to 57.1%. Azithromycin was initiated at <3 days of life in 8 studies (88.9%). Dosing was variable and ranged from 5 to 20 mg/kg/dose administered once daily, and the duration of treatment ranged from 1 to 35 days. Most studies used intravenous azithromycin. Overall, azithromycin was more efficacious than placebo at Ureaplasma eradication; however, most of these studies did not find a difference in the incidence of BPD between patients receiving azithromycin versus placebo. No adverse effects, specifically pyloric stenosis or QT interval prolongation, were noted in these studies.

Pathogenesis of bronchopulmonary dysplasia in preterm neonates revealed by an RNA sequencing interaction network analysis.

The chronic lung condition known as bronchopulmonary dysplasia (BPD), which primarily affects newborns, especially preterm neonates, is brought on by prolonged oxygen consumption and mechanical ventilation. This case-control study sought to investigate the pathogenesis of BPD in preterm neonates by RNA sequencing (RNA-seq). First, RNA-seq samples were collected from 3 BPD and 3 healthy preterm neonates. Based on the sequencing data and microarray data sets, MERGE.57185.1, the key long non-coding RNA (lncRNA), was identified from the differentially expressed lncRNAs and the key module by a weighted gene co-expression network analysis (WGCNA), a Venn diagram, and an expression analysis. Next, the differentially expressed messenger RNAs (mRNAs) and microRNAs (miRNAs) that were strongly correlated to MERGE.57185.1 were identified in the protein-protein interaction networks and underwent a functional enrichment analysis and Spearman correlation analysis. Finally, the mRNA [i.e., eukaryotic translation initiation factor 5A (EIF5A)] and miRNA (i.e., hsa-miR-6833-5p) with the strongest correlations to MERGE.57185.1 were identified as the downstream targets. Among the 32 genes in the dark-red module and the 158 differentially expressed lncRNAs, 21 overlapping genes were identified. In the gene expression analysis, MERGE.57185.1 (an oncogene) was identified as the key lncRNA in BPD. The results of the multiple bioinformatics analysis showed that the mRNA and the miRNA with the strongest correlations to MERGE.57185.1 were hsa-miR-6833-5p (a suppressor gene) and EIF5A (an oncogene), respectively. Hsa-miR-6833-5p was lowly expressed in the BPD group, while EIF5A was highly expressed in the BPD group. This study identified 1 key upregulated lncRNA (i.e., MERGE.57185.1) in preterm neonatal BPD, and revealed the MERGE.57185.1/hsa-miR-6833-5p/EIF5A mechanism in preterm neonatal BPD from the lncRNA-miRNA-mRNA network. This key lncRNA gene could serve as a promising diagnostic biomarker for prenatal examinations.

Endothelin 1 As A Predictor Marker for Bronchopulmonary Dysplasia in Preterm Neonates with Respiratory Distress Syndrome

Endothelin 1 As A Predictor Marker for Bronchopulmonary Dysplasia in Preterm Neonates with Respiratory Distress Syndrome

The efficacy of hydrocortisone in preventing bronchopulmonary dysplasia: An integrative literature review

Introduction: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects mostly premature neonates, its pathophysiology is still uncertain, proliferative, apoptotic, and pro-inflammatory mechanisms are linked. The use of corticosteroids is an option in an attempt to prevent BPD. Objective: This literature review seeks to understand whether hydrocortisone has benefits in preventing BPD in preterm neonates. Methodology: An integrative review was carried out using Medline / Pubmed, Biblioteca Virtual da Saude (BVS), Cochrane, EMBASE, and Scielo as databases, searching for articles, between 2015 and 2021, that used only hydrocortisone for the prevention of BPD. To assess the methodological and evaluation quality, AMSTAR criteria, and GRADE system were used respectively. Results: From a total of 194 articles, 5 were included in the study, 2 studies observed a decrease in the need for mechanical ventilation, 3 had a decreased mortality rate and in 2 studies the cases of BPD were reduced with the use of hydrocortisone. One study did not show statistical significance for either mortality or BPD prevention with drug use compared with placebo. These studies showed a reduction in the need for invasive mechanical ventilation, as well as an increase in the extubation rate. The death rate for newborns who used hydrocortisone was also lower compared to the control group. Regarding the prevention of BPD, hydrocortisone showed a slight reduction in the number of cases compared to placebo, when started early (&lt;24 hours) and with a low dose) 1.2.Conclusion: The use of low-dose and early-onset of hydrocortisone was superior to placebo in preventing BPD, but hydrocortisone is still not an ideal drug for preventing BPD.

Macrolides for the prevention of bronchopulmonary dysplasia in preterm neonates

Macrolides for the prevention of bronchopulmonary dysplasia in preterm neonates

EBNEO Commentary: A network meta-analysis of postnatal corticosteroids for bronchopulmonary dysplasia: Has the most appropriate treatment been revealed?

Ramaswamy VV, Bandyopadhyay T, Nanda D, Bandiya P, Ahmed J, Garg A, Roehr CC, Nangia S. Assessment of Postnatal Corticosteroids for the Prevention of Bronchopulmonary Dysplasia in Preterm Neonates: A Systematic Review and Network Meta-analysis. JAMA Pediatr 2021; 175(6): e206826. PMID 33720274. Systemic postnatal corticosteroids (PNCs) reduce the risk of bronchopulmonary dysplasia (BPD) in preterm infants but may contribute to long-term neurodevelopmental harm. The need to identify a treatment regimen with a reassuring risk-benefit balance remains.1 In an extraordinary feat of data aggregation, Ramaswamy and colleagues include 62 randomised clinical trials (RCTs) enrolling 5559 neonates in a systematic review and network meta-analysis (NMA) to determine which of 14 distinct PNC exposures (Table) may be most appropriate.2 The authors suggest moderately early-initiated medium cumulative dose systemic dexamethasone is the best regimen. Unlike traditional pairwise meta-analyses, NMAs compare multiple interventions, adding relevance to clinical scenarios with various alternative treatment options. NMAs also allow indirect comparisons between interventions, linking them through a common comparator.3 For example, no RCTs have compared early systemic hydrocortisone (EHC) to late-initiated low-cumulative dose systemic dexamethasone (LaLdDx), but a shared comparison to placebo in separate RCTs allows a relative risk estimation. The validity of NMA results relies on specific assumptions. A critical one is that the data linked to produce indirect evidence display ‘transitivity’.3 In essence, that aggregation may be justified by similarities in key population characteristics. Tools that guide this subjective judgement include assessment of whether the populations are similar on important effect modifiers and whether the indirect comparisons could be assessed in head-to-head trials. Extending the example above, we consider the tools against the PREMILOC (EHC) and DART (LaLdDx) trials.4, 5 A meta-regression identified the baseline risk of developing BPD as an important effect modifier for the effect of PNCs on death or cerebral palsy.6 The rates of death or BPD in the control groups of PREMILOC and DART were 49% and 91%, respectively, questioning their similarity.4, 5 In turn, a hypothetical trial of EHC versus LaLdDx would presumably compare prophylactic EHC to LaLdDx only amongst infants remaining on mechanical ventilation at 14 days. Exposing subjects to LaLdDx irrespective of respiratory status would raise ethical concerns. However, the indirect comparison generated by the NMA is not of prophylactic EHC versus expectant management with rescue LaLdDx. Though we focus on EHC versus LaLdDx as an example, these concerns extend to various comparisons. One could argue that transitivity is generally violated when comparing interventions applied in distinct stages of disease progression, and that use of PNCs as prophylaxis versus treatment of evolving severe BPD are distinct indications best suited to distinct comparisons.3 Lastly, we should avoid labelling the PNC regimen most effective against BPD as ‘most appropriate’. Although a reduction in BPD with various PNC regimens is probable, the avoidance of risk for adverse long-term neurodevelopmental outcomes is uncertain, and the latter will guide appropriateness. Further, as the authors acknowledge, the quality of evidence supporting the conclusion is low. Despite these points of caution, Ramaswamy and colleagues add a rich contribution to the literature, shining a helpful light on the path forward. Conclusively arriving at best practice will require additional high-quality research, followed by cautious data synthesis that prioritises long-term outcomes of importance to patients and their families. URL: https://ebneo.org/postnatal-corticosteroids-meta-analysis. None.

Potential role of vitamin D receptor-related polymorphisms in bronchopulmonary dysplasia

BackgroundThe potential contribution of vitamin D and its receptor (VDR) to bronchopulmonary dysplasia (BPD) in preterm neonates is still unknown. The objective of the study was to test the relationship between VDR Taq 1 and Fok 1 gene polymorphisms and BPD in preterm neonates. VDR Fok 1 and Taq 1 gene polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.ResultNo statistically significant differences of genotypic distributions and allele frequencies of Fok 1 and Taq 1 VDR polymorphisms were detected between cases and controls. Moreover, no risk association was detected between both polymorphisms and BPD development in preterm neonates. Homozygous mutant (ff) genotype was the least frequent genotype among BPD and non-BPD groups (2.6%, 13.0% respectively) (p = 0.1). The same was detected for the mutant (CC) genotype frequency in both groups (10.5% and 15.2%, respectively). However, Taq 1 VDR polymorphism was significantly associated with the severity of BPD, as the genotypes with mutant allele C (CC +CT) were more frequent among severe cases (52.2%).ConclusionFok 1and Taq 1 VDR polymorphisms have no role in BPD development in preterm neonates. However, the presence of a mutant allele of Taq 1 VDR polymorphism may be associated with a more severe form of the disease.

Assessment of Postnatal Corticosteroids for the Prevention of Bronchopulmonary Dysplasia in Preterm Neonates

The safety of postnatal corticosteroids used for prevention of bronchopulmonary dysplasia (BPD) in preterm neonates is a controversial matter, and a risk-benefit balance needs to be struck. To evaluate 14 corticosteroid regimens used to prevent BPD: moderately early-initiated, low cumulative dose of systemic dexamethasone (MoLdDX); moderately early-initiated, medium cumulative dose of systemic dexamethasone (MoMdDX); moderately early-initiated, high cumulative dose of systemic dexamethasone (MoHdDX); late-initiated, low cumulative dose of systemic dexamethasone (LaLdDX); late-initiated, medium cumulative dose of systemic dexamethasone (LaMdDX); late-initiated, high cumulative dose of systemic dexamethasone (LaHdDX); early-initiated systemic hydrocortisone (EHC); late-initiated systemic hydrocortisone (LHC); early-initiated inhaled budesonide (EIBUD); early-initiated inhaled beclomethasone (EIBEC); early-initiated inhaled fluticasone (EIFLUT); late-initiated inhaled budesonide (LIBUD); late-initiated inhaled beclomethasone (LIBEC); and intratracheal budesonide (ITBUD). PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, World Health Organization's International Clinical Trials Registry Platform (ICTRP), and CINAHL were searched from inception through August 25, 2020. In this systematic review and network meta-analysis, the randomized clinical trials selected included preterm neonates with a gestational age of 32 weeks or younger and for whom a corticosteroid regimen was initiated within 4 weeks of postnatal age. Peer-reviewed articles and abstracts in all languages were included. Two independent authors extracted data in duplicate. Network meta-analysis used a bayesian model. Primary combined outcome was BPD, defined as oxygen requirement at 36 weeks' postmenstrual age (PMA), or mortality at 36 weeks' PMA. The secondary outcomes included 15 safety outcomes. A total of 62 studies involving 5559 neonates (mean [SD] gestational age, 26 [1] weeks) were included. Several regimens were associated with a decreased risk of BPD or mortality, including EHC (risk ratio [RR], 0.82; 95% credible interval [CrI], 0.68-0.97); EIFLUT (RR, 0.75; 95% CrI, 0.55-0.98); LaHdDX (RR, 0.70; 95% CrI, 0.54-0.87); MoHdDX (RR, 0.64; 95% CrI, 0.48-0.82); ITBUD (RR, 0.73; 95% CrI, 0.57-0.91); and MoMdDX (RR, 0.61; 95% CrI, 0.45-0.79). Surface under the cumulative ranking curve (SUCRA) value ranking showed that MoMdDX (SUCRA, 0.91), MoHdDX (SUCRA, 0.86), and LaHdDX (SUCRA, 0.76) were the 3 most beneficial interventions. ITBUD (RR, 4.36; 95% CrI, 1.04-12.90); LaHdDX (RR, 11.91; 95% CrI, 1.64-44.49); LaLdDX (RR, 6.33; 95% CrI, 1.62-18.56); MoHdDX (RR, 4.96; 95% CrI, 1.14-14.75); and MoMdDX (RR, 3.16; 95% CrI, 1.35-6.82) were associated with more successful extubation from invasive mechanical ventilation. EHC was associated with a higher risk of gastrointestinal perforation (RR, 2.77; 95% CrI, 1.09-9.32). MoMdDX showed a higher risk of hypertension (RR, 3.96; 95% CrI, 1.10-30.91). MoHdDX had a higher risk of hypertrophic cardiomyopathy (RR, 5.94; 95% CrI, 1.95-18.11). This study suggested that MoMdDX may be the most appropriate postnatal corticosteroid regimen for preventing BPD or mortality at a PMA of 36 weeks, albeit with a risk of hypertension. The quality of evidence was low.

Placental finding among extremely preterm infants with moderate to severe bronchopulmonary dysplasia

Background: Fetal exposure to maternal inflammation has been reported with various adverse outcomes in preterm infants. Histological chorioamnionitis has been variably reported to be associated with the development of lung disease including bronchopulmonary Dysplasia (BPD). Most investigators have reported the association of acute inflammatory lesions and maternal vascular under perfusion on placental histopathology with BPD in preterm neonates. Objective: To determine if pre-specified placental abnormalities among preterm infants with moderate to severe BPD differ compared to infants with No/Mild BPD. Methods: Preterm infants, …

Effect of a new respiratory care bundle on bronchopulmonary dysplasia in preterm neonates.

The development of devices that can fix the tidal volume in high-frequency oscillatory ventilation (HFOV) has allowed for a significant improvement in the management of HFOV. At our institution, this had led to the earlier use of HFOV and promoted a change in the treatment strategy involving the use of higher frequencies (above 15 Hz) and lower high-frequency tidal volumes (VThf). The purpose of this observational study was to assess how survival without bronchopulmonary dysplasia grades 2 and 3 (SF-BPD) is influenced by these modifications in the respiratory strategy applied to preterm infants (gestational age < 32 weeks at birth) who required mechanical ventilation (MV) in the first 3 days of life. We compared a baseline period (2012–2013) against a period in which this strategy had been fully implemented (2016–2017). A total of 182 patients were exposed to MV in the first 3 days of life being a higher proportion on HFOV at day 3 in the second period 79.5% (n 35) in 2016–2017 vs 55.4% (n 31) in 2012–2013. After adjusting for perinatal risk factors, the second period is associated with an increased rate of SF-BPD (OR 2.28; CI 95% 1.072–4.878); this effect is more evident in neonates born at a gestational age of less than 29 weeks (OR 4.87; 95% CI 1.9–12.48).Conclusions : The early use of HFOV combined with the use of higher frequencies and very low VT was associated with an increase in the study population’s SF-BPD.What is Known:• High-frequency ventilation with volume guarantee improve ventilation stability and has been shown to reduce lung damage in animal models.What is New:• The strategy of an earlier use of high-frequency oscillatory ventilation combined with the use of higher frequencies and lower tidal volume is associated to an increase in survival without bronchopulmonary dysplasia in our population of preterm infants.

Melatonin Supplementation as Adjuvant Therapy for the Prevention of Bronchopulmonary Dysplasia in Neonates

Background: Neonatal bronchopulmonary dysplasia (BPD) is a chronic chest disease caused by prolonged ventilation and oxygenation which leads to neonatal disability.Methods: It was a prospective randomized clinical trial (RCT) (Study ID: TCTR20191211004) which was conducted in Tanta University Hospital (TUH) from July 2016 to March 2018 on 100 preterm neonates who exhibited severe respiratory distress (RD) on mechanical ventilation (MV). The studied neonates were assigned to two groups: group one which received melatonin supplementation and group two which did not. Urinary β2-microglobulin (B2M) and serum Krebs von den Lungen-6 (KL-6) levels were measured 3 and 10 days after hospitalization. The length of neonates’ stay in incubator was determined, and the number of newborns with established BPD was calculated.Results: Significant decreases were detected in urinary B2M and serum KL-6 levels of neonates in group one who received melatonin, as compared to their counterparts in group two who did not take melatonin (P< 0.05). In addition, there was a significant decline in the length of incubator stay of neonates in group one, in comparison to that of newborns in group two (P<0.05). Moreover, neonates in group one who received melatonin displayed a significant decline in the development of established cases of BPD, as compared to group two who did not take melatonin (P<0.05).Conclusion: As evidenced by the obtained results, melatonin supplementation could be used as adjuvant therapy for the prevention of BPD in preterm neonates. Nonetheless, further studies involving a larger number of neonates must be performed on this topic in order to recommend melatonin administration for ventilated premature neonates who are susceptible to the development of neonatal BPD.

Serum activity of MMP-2 and MMP-9 and stromielisin-1 concentration as predictors in the pathogenesis of bronchopulmonary dysplasia in preterm neonates

Aim: Bronchopulmonary dysplasia (BPD) is one of the most severe respiratory diseases, mainly related to premature neonates. Previous studies indicated the role of matrix metalloproteinases (MMPs) in the development of BPD. The aim of the study was to determine the relationship between MMP-2, MMP-3, MMP-9 with their tissue inhibitors (TIMP-1 TIMP-2) and BPD occurrence in premature neonates. Material/Methods: Eighty-one patients, divided into four study groups, numbered from 1 to 4, depending on gestational age (25–28; 29–32; 33–36; 37–40 weeks), were enrolled. Venous blood was collected between 5 and 7 days after birth. The activity of MMP-2 and MMP-9 were determined with usage of gelatin zymography, whereas MMP-3, TIMP-1 and TIMP-2 was determined using the immunoassay ELISA. Results: BPD was diagnosed in 50% of patients from group 1 and 11% from group 2. The increase of MMP-2 activity in Group 2, and a decrease in MMP-2/TIMP-2 ratio was noticed in Group 1 compared to Group 2 and 4. A significantly lower incidence of BPD in patients with higher (above the median) values for MMP-2/TIMP-2 (OR = 0.02, CI = 0.00 – 0.55; p &lt;0.05) was noticed in Group 1. The decreased occurrence of BPD in patients with higher MMP-3 concentration, higher MMP-9 activity and the higher value of MMP-9/TIMP-1 did not reach statistical significance. Conclusions: It has been shown that elevated activity of collagenolytic enzyme in serum, especially MMP-2, may have the effect of decreasing the risk of bronchopulmonary dysplasia in premature neonates.

Hyperoxia causes miR199a-5p-mediated injury in the developing lung.

Hyperoxia-induced acute lung injury (HALI) is characterized by increased permeability and infiltration of inflammatory cells, impairment of alveolar development, and compromised lung function. Recent evidence has determined that microRNAs (miRs) are implicated in hyperoxia-induced lung injury, including bronchopulmonary dysplasia (BPD). However, the expression profile and functional role of miR199a-5p in developing lungs have not been reported. The present study was undertaken to explore the role of miR199a-5p in developing mice lungs and human neonates. We exposed neonatal mice for 7 days, mouse lung epithelial cells (MLE12), mouse lung endothelial cells (MLECs), and macrophages (RAW246.7), to hyperoxia at different time points. Our results demonstrated enhanced miR199a-5p expression in hyperoxia-exposed mice lungs and cells, as well as in tracheal aspirates of infants developing BPD, with significant reduction in the expression of its target, caveolin-1. Next, we observed that miR199a-5p-mimic worsens HALI as evidenced by increased inflammatory cells, cytokines, and lung vascular markers. Conversely, miR199a-5p-inhibitor treatment attenuated HALI. Thus, our findings suggest that miR199a-5p is a potential target for attenuating HALI pathophysiology in the developing lung. Moreover, miR199a-5p-inhibitor could be part of a novel therapeutic strategy for improving BPD in preterm neonates.

Bronchopulmonary dysplasia in neonates born to mothers with preeclampsia: Impact of small for gestational age.

Background and objectivesSmall for gestational age and preeclampsia have both been described as risk factors for bronchopulmonary dysplasia in preterm neonates, but their respective role in the occurrence of bronchopulmonary dysplasia is debated. We evaluated the relation between small for gestational age and bronchopulmonary dysplasia in neonates born to mothers with preeclampsia. We hypothesized that low birth weight is still associated with bronchopulmonary dysplasia in this homogeneous population.MethodsRetrospective single-center cohort study including 141 neonates born between 24 and 30 weeks’ gestation to mothers with preeclampsia. The main outcome measure was moderate to severe bronchopulmonary dysplasia at 36 weeks’ postmenstrual age. Neonates born small for gestational age (birthweight < 10th percentile on the AUDIPOG curves) were compared to those with appropriate birthweight for gestational age by bivariable analyses and logistic regression models, estimating odds ratios (ORs) and 95% confidence intervals (CIs).ResultsBronchopulmonary dysplasia rates were 61.5% (32/52) and 27.4% (20/73) for small for gestational age and appropriate birthweight for gestational age neonates (p < .001). On adjustment for gestational age and other confounding factors, the risk of moderate to severe bronchopulmonary dysplasia was greater for small for gestational age than appropriate birthweight for gestational age neonates (adjusted OR = 5.9, 95% CI [2.2–15.4]), as was the composite outcome death or moderate to severe bronchopulmonary dysplasia (adjusted OR = 4.7, 95% CI [1.9–11.3]).ConclusionsSmall for gestational age was associated with bronchopulmonary dysplasia in very preterm neonates born to mothers with preeclampsia.Registration numberCNIL no. 1747084.

Evaluating the use of corticosteroids in preventing and treating bronchopulmonary dysplasia in preterm neonates.

Approximately 15 million babies worldwide are born premature, and complications of prematurity are one of the leading causes of death in neonates. Neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD) are two of the most common and serious consequences of prematurity. Synthetic corticosteroids, including dexamethasone, have been central in efforts to treat and prevent BPD. There is strong evidence to show that prenatal corticosteroids reduce infant mortality and the incidence of NRDS, leading to their widespread use in obstetric units. However, data suggest that they are not as effective in reducing the incidence of BPD as NRDS, which may be due to the multifactorial pathogenesis of BPD. On the other hand, the use of postnatal corticosteroids in preterm infants is much more controversial. They have been shown to improve lung function and help in reducing the need for mechanical ventilation. These benefits, however, are associated with a range of adverse short- and long-term effects. This review will discuss the benefits and consequences of corticosteroids in treating BPD and will examine alternative treatments and future research that may improve the understanding of BPD and inform clinical practice.