Bronchopulmonary Dysplasia In Preterm Infants Research Articles

O-213 Association Of E-nos Gene Polymorphism In Development Of Bronchopulmonary Dysplasia

Background and aims Bronchopulmonary dysplasia (BPD) is an importantmorbidity in premature infants with an multifactorial aetiology. In recent years, both genetic and epigenetic mechanisms were suggested to play an important role in BPD development. NO (Nitric Oxide) which is produced along with L-Citrulline by the oxidation of L-Arginine and catalysed by three different isoforms of NOS (NOSynthase), is a short-lived free radical involved indiverse physiological and pathological processes. It consists of 3 types such as neuronal NOS, endothelial NOS and inducible NOS. All the NOS genes are expressed in airway epithelial cells and they are important for physiological functions in the airways. The aim of this study was to investigate possible association between eNOS gene polymorphism and development of BPD in preterm infants. Methods One hundred and twenty two blood samples DNA isolation was carried out using the PureLink TM Genomic DNA Mini Kit and the concentration of the DNA samples was measured by nanophotometerImplen P 300. For the SNP analysis of eNOS ( rs1799983 ) optimised primers were used. Real Time Polymerase Chain Reaction (QRT-PCR) was carried out in a CFX96 thermocycler. Chi-square χ2 test, Fisher’s exact test, the odds ratio and confidence intervals were calculated for the comparisons of allelic and genotype frequencies. Results Comparison of the allele frequency distribution revealed the presence of G allele as a highly significant risk factor for development of BPD (p = 0.000*; OR 4.07, 95% CI 2.066–8.009) compared to the T allele. The distribution of the T allele in eNOS was found to be similarly distributed amongst BPD (51.9%) and healthy control groups (48.1%). This study demonstrated that the frequency of the GG genotype (25.37%) of the eNOSgene was higher in babies with BPD rather than TT (53.6%) and TG (59.4)genotype, when these genotypes were compared with the healthy control groups. No healthy infants were seen to carry the GG genotype (p = 0.000*; OR 1.89, 95% CI 1.514–2.148). The TT genotype (p = 0.019*, OR 0.39, 95% CI 0.180–0.870) also displayed a susceptibility fordeveloping BPD. Heterozygous TG genotype (p = 0.631; OR 0.63, 95% CI 0.527–2.873) was not associated with the development of BPD. Conclusion To our best of knowledge, noinvestigation of the eNOS gene polymorphism has previously been documented in BPD. Thefindings of this study demonstrated that the GG genotype in eNOS gene was highly significant for BPD.

Mice deficient in the gene for cytochrome P450 (CYP)1A1 are more susceptible than wild-type to hyperoxic lung injury: evidence for protective role of CYP1A1 against oxidative stress.

Hyperoxia contributes to acute lung injury in diseases such as acute respiratory distress syndrome in adults and bronchopulmonary dysplasia in premature infants. Cytochrome P450 (CYP)1A1 has been shown to modulate hyperoxic lung injury. The mechanistic role(s) of CYP1A1 in hyperoxic lung injury in vivo is not known. In this investigation, we hypothesized that Cyp1a1(-/-) mice would be more susceptible to hyperoxic lung injury than wild-type (WT) mice, and that the protective role of CYP1A1 is in part due to CYP1A1-mediated decrease in the levels of reactive oxygen species-mediated lipid hydroperoxides, e.g., F2-isoprostanes/isofurans, leading to attenuation of oxidative damage. Eight- to ten-week-old male WT (C57BL/6J) or Cyp1a1(-/-) mice were exposed to hyperoxia (>95% O2) or room air for 24-72 h. The Cyp1a1(-/-) mice were more susceptible to oxygen-mediated lung damage and inflammation than WT mice, as evidenced by increased lung weight/body weight ratio, lung injury, neutrophil infiltration, and augmented expression of IL-6. Hyperoxia for 24-48 h induced CYP1A expression at the mRNA, protein, and enzyme levels in liver and lung of WT mice. Pulmonary F2-isoprostane and isofuran levels were elevated in WT mice after hyperoxia for 24 h. On the other hand, Cyp1a1(-/-) mice showed higher levels after 48-72 h of hyperoxia exposure compared to WT mice. Our results support the hypothesis that CYP1A1 protects against hyperoxic lung injury by decreasing oxidative stress. Future research could lead to the development of novel strategies for prevention and/or treatment of acute lung injury.

Association Between Pulmonary Ureaplasma Colonization and Bronchopulmonary Dysplasia in Preterm Infants

Previous meta-analyses have reported a significant association between pulmonary colonization with Ureaplasma and development of bronchopulmonary dysplasia (BPD). However, because few studies reporting oxygen dependency at 36 weeks corrected gestation were previously available, we updated the systematic review and meta-analyses to evaluate the association between presence of pulmonary Ureaplasma and development of BPD. Five databases were searched for articles reporting the incidence of BPD at 36 weeks postmenstrual age (BPD36) and/or BPD at 28 days of life (BPD28) in Ureaplasma colonized and noncolonized groups. Pooled estimates were produced using random effects meta-analysis. Meta-regression was used to assess the influence of difference in gestational age between the Ureaplasma-positive and Ureaplasma-negative groups. The effects of potential sources of heterogeneity were also investigated. Of 39 studies included, 8 reported BPD36, 22 reported BPD28 and 9 reported both. The quality of studies was assessed as moderate to good. There was a significant association between Ureaplasma and development of BPD36 (odds ratio = 2.22; 95% confidence intervals: 1.42-3.47) and BPD28 (odds ratio = 3.04; 95% confidence intervals: 2.41-3.83). Sample size influenced the odds ratio, but no significant association was noted between BPD28 rates and difference in gestational age between Ureaplasma colonized and noncolonized infants (P = 0.96). Pulmonary colonization with Ureaplasma continues to be significantly associated with development of BPD in preterm infants at both 36 weeks postmenstrual age and at 28 days of life. This association at BPD28 persists regardless of difference in gestational age.

Inhibition of β-Catenin Signaling Improves Alveolarization and Reduces Pulmonary Hypertension in Experimental Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease of preterm infants. The development of pulmonary hypertension (PH) significantly increases the mortality and morbidity of this disease. β-Catenin signaling plays an important role in tissue development and remodeling. Aberrant β-catenin signaling is associated with clinical and experiment models of BPD. To test the hypothesis that inhibition of β-catenin signaling is beneficial in promoting alveolar and vascular development and preventing PH in experimental BPD, we examined the effects of ICG001, a newly developed pharmacological inhibitor of β-catenin, in preventing hyperoxia-induced BPD in neonatal rats. Newborn rat pups were randomized at postnatal day (P)2 to room air (RA) + DMSO (placebo), RA + ICG001, 90% FiO2 (O2) + DMSO, or O2 + ICG001. ICG001 (10 mg/kg) or DMSO was given by daily intraperitoneal injection for 14 days during continuous exposure to RA or hyperoxia. Primary human pulmonary arterial smooth muscle cells (PASMCs) were cultured in RA or hyperoxia (95% O2) in the presence of DMSO or ICG001 for 24 to 72 hours. Treatment with ICG001 significantly increased alveolarization and reduced pulmonary vascular remodeling and PH during hyperoxia. Furthermore, administering ICG001 decreased PASMC proliferation and expression of extracellular matrix remodeling molecules in vitro under hyperoxia. Finally, these structural, cellular, and molecular effects of ICG001 were associated with down-regulation of multiple β-catenin target genes. These data indicate that β-catenin signaling mediates hyperoxia-induced alveolar impairment and PH in neonatal animals. Targeting β-catenin may provide a novel strategy to alleviate BPD in preterm infants.

Biological markers in cord blood for prediction of bronchopulmonary dysplasia in premature infants

Objective: The current study aims to determine the contents of biological markers in cord blood and to investigate their feasibility as the predictive indices of bronchopulmonary dysplasia (BPD) in premature infants. Materials and Methods: Cord blood was collected from 134 premature infants that had birth weight ≤ 1500 g and gestational age (GA) ≤ 32 weeks at the time of birth. The contents of IL- 6, IL-6R, Sgp130, and MMP-9 were determined. Infants’ clinical data, as well as their mothers’ placental pathological data were also collected. Infants with BPD constituted the BPD group, whereas those without BPD comprised the non-BPD (NBPD) group. Differences in the contents of the biological markers between the groups were analyzed to investigate the correlations of these markers with BPD, and then biological markers that can serve as the predictive factors of BPD were defined. Results: GA was negatively correlated with BPD. IL-6, IL-6R, and Sgp130 in the BPD group was higher than those in the NBPD group, whereas MMP-9 in the BPD group was lower than that in the NBPD group. IL-6 was positively correlated with BPD and therefore had a predictive effect on BPD. Sgp130 had a collinear correlation with IL-6, which had a predictive effect on BPD as well. When GA was 46.125 pg/ml, the sensitivity, specificity, and area under curve were 1, 0.59, and 0.849, respectively, indicating a good predictive effect on BPD. Conclusion: IL-6 and Sgp130 can serve as the independent predictive cytokines of BPD.

Ventilation-induced increases in EGFR ligand mRNA are not altered by intra-amniotic LPS or ureaplasma in preterm lambs.

Chorioamnionitis and mechanical ventilation are associated with bronchopulmonary dysplasia (BPD) in preterm infants. Mechanical ventilation at birth activates both inflammatory and acute phase responses. These responses can be partially modulated by previous exposure to intra-amniotic (IA) LPS or Ureaplasma parvum (UP). Epidermal growth factor receptor (EGFR) ligands participate in lung development, and angiotensin converting enzyme (ACE) 1 and ACE2 contribute to lung inflammation. We asked whether brief mechanical ventilation at birth altered EGFR and ACE pathways and if antenatal exposure to IA LPS or UP could modulate these effects. Ewes were exposed to IA injections of UP, LPS or saline multiple days prior to preterm delivery at 85% gestation. Lambs were either immediately euthanized or mechanically ventilated for 2 to 3 hr. IA UP and LPS cause modest changes in the EGFR ligands amphiregulin (AREG), epiregulin (EREG), heparin binding epidermal growth factor (HB-EGF), and betacellulin (BTC) mRNA expression. Mechanical ventilation greatly increased mRNA expression of AREG, EREG, and HB-EGF, with no additional increases resulting from IA LPS or UP. With ventilation AREG and EREG mRNA localized to cells in terminal airspace. EGFR mRNA also increased with mechanical ventilation. IA UP and LPS decreased ACE1 mRNA and increased ACE2 mRNA, resulting in a 4 fold change in the ACE1/ACE2 ratio. Mechanical ventilation with large tidal volumes increased both ACE1 and ACE2 expression. The alterations seen in ACE with IA exposures and EGFR pathways with mechanical ventilation may contribute to the development of BPD in preterm infants.

Association between Red Blood Cell Transfusion and Bronchopulmonary Dysplasia in Preterm Infants

Anemia and the need for transfusion of packed red blood cells (PRBCs) are common in preterm infants. PRBC transfusion increases the oxygen carrying capacity of hemoglobin and may result in higher rates of organ dysfunction. To determine whether PRBC transfusion in preterm infants is associated with an increased incidence of bronchopulmonary dysplasia (BPD), this retrospective study was performed on neonates with birth weights ≤ 1,500 g or gestational age ≤ 32 weeks admitted from August, 2008 to November, 2013. Infants who received PRBC transfusion before the diagnosis of BPD and those who did not receive PRBC transfusion or received PRBC transfusion after diagnosis of BPD were compared for incidence of BPD and other morbidities. Of 231 preterm infants, 137 received PRBC transfusion before BPD was diagnosed (group 1) and 94 did not (group 2). The incidence of BPD was significantly higher in group 1 than in group 2 (37.2% vs. 2.1%, P < 0.00001). After adjusting for potential risk factors, the adjusted odds ratio for BPD was 9.80 (95% confidence interval, 1.70–56.36; P = 0.01). This study demonstrated an association between PRBC transfusion and BPD in preterm infants. A cautious approach to PRBC transfusion in these infants is warranted.

Early caffeine therapy for prevention of bronchopulmonary dysplasia in preterm infants

Objective: To determine if an early commencement of caffeine is associated with improved survival without bronchopulmonary dysplasia (BPD) in preterm infants.Methods: Retrospective data analysis from the Alere Neonatal Database for infants weighing ≤1250 g, and treated with caffeine within the first 10 days of life. The neonatal outcomes were compared between the infants who received early caffeine (0–2 days) with the infants who received delayed caffeine (3–10 days).Results: A total of 2951 infants met the inclusion criteria (early caffeine 1986, late caffeine 965). The early use of caffeine was associated with reduction in BPD (OR 0.69, 95% CI 0.58–0.82, p < 0.001) and BPD or death (OR 0.77, 95% CI 0.63–0.94, p = 0.01). Other respiratory outcomes also improved with the early commencement of caffeine. The frequency of severe intraventricular hemorrhage and patent ductus arteriosus was lower and the length of hospitalization was shorter in infants receiving early caffeine therapy. However, early use of caffeine was associated with an increase in the risk of nectrotizing enterocolits (NEC) (OR 1.41, 95% CI 1.04–1.91, p = 0.027).Conclusion: Early commencement of caffeine was associated with improvement in survival without BPD in preterm infants. The risk of NEC with early caffeine use requires further investigation.

Glucocorticoids Recruit Tgfbr3 and Smad1 to Shift Transforming Growth Factor-β Signaling from the Tgfbr1/Smad2/3 Axis to the Acvrl1/Smad1 Axis in Lung Fibroblasts

Glucocorticoids represent the mainstay therapy for many lung diseases, providing outstanding management of asthma but performing surprisingly poorly in patients with acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung fibrosis, and blunted lung development associated with bronchopulmonary dysplasia in preterm infants. TGF-β is a pathogenic mediator of all four of these diseases, prompting us to explore glucocorticoid/TGF-β signaling cross-talk. Glucocorticoids, including dexamethasone, methylprednisolone, budesonide, and fluticasone, potentiated TGF-β signaling by the Acvrl1/Smad1/5/8 signaling axis and blunted signaling by the Tgfbr1/Smad2/3 axis in NIH/3T3 cells, as well as primary lung fibroblasts, smooth muscle cells, and endothelial cells. Dexamethasone drove expression of the accessory type III TGF-β receptor Tgfbr3, also called betaglycan. Tgfbr3 was demonstrated to be a "switch" that blunted Tgfbr1/Smad2/3 and potentiated Acvrl1/Smad1 signaling in lung fibroblasts. The Acvrl1/Smad1 axis, which was stimulated by dexamethasone, was active in lung fibroblasts and antagonized Tgfbr1/Smad2/3 signaling. Dexamethasone acted synergistically with TGF-β to drive differentiation of primary lung fibroblasts to myofibroblasts, revealed by acquisition of smooth muscle actin and smooth muscle myosin, which are exclusively Smad1-dependent processes in fibroblasts. Administration of dexamethasone to live mice recapitulated these observations and revealed a lung-specific impact of dexamethasone on lung Tgfbr3 expression and phospho-Smad1 levels in vivo. These data point to an interesting and hitherto unknown impact of glucocorticoids on TGF-β signaling in lung fibroblasts and other constituent cell types of the lung that may be relevant to lung physiology, as well as lung pathophysiology, in terms of drug/disease interactions.

Cord blood fibroblast growth factor-10 as a possible predictor of bronchopulmonary dysplasia in preterm infants.

To evaluate fibroblast growth factor-10 (FGF-10) levels in cord blood as a possible predictor of the subsequent development of bronchopulmonary dysplasia (BPD) in preterm infants. A total of 269 preterm (≤32 weeks gestation) infants (76 infants developed BPD and 193 had no BPD) were enrolled. FGF-10 levels were measured by enzyme-linked immunosorbent assay. Preterm infants who subsequently developed BPD had significantly lower cord serum levels of FGF-10 than those who did not (p < 0.001). Cord blood levels of FGF-10 were significantly lower in infants with severe BPD than those with moderate or mild disease (p < 0.001). Logistic regression analysis demonstrated that low cord blood FGF-10 level was independently associated with the subsequent risk of BPD (OR = 0.978 [95 % CI: 0.959 - 0.997]; p = 0.02). Low cord blood FGF-10 levels may predict the subsequent development of BPD in preterm infants.

The relationship between eosinophilia and bronchopulmonary dysplasia in premature infants at less than 34 weeks' gestation.

PurposeEosinophilia is common in premature infants, and its incidence increases with a shorter gestation period. We investigated the clinical significance of eosinophilia in premature infants born at <34 weeks gestation.MethodsWe analyzed the medical records of premature infants born at <34 weeks gestation who were admitted to the neonatal intensive care unit at Ewha Womans University Mokdong Hospital between January 2003 and September 2010. Eosinophilia was defined as an eosinophil percentage of >3% of the total leukocytes. Perinatal parameters and clinical parameters were also analyzed.ResultsOf the 261 infants born at <34 weeks gestation, 22.4% demonstrated eosinophilia at birth. The eosinophil percentage peaked in the fourth postnatal week at 7.5%. The incidence of severe eosinophilia increased after birth up to the fourth postnatal week when 8.8% of all patients had severe eosinophilia. Severity of eosinophilia was positively correlated with a lower gestational age, birth weight, and Apgar score. Respiratory distress syndrome, bronchopulmonary dysplasia, nephrocalcinosis, intraventricular hemorrhage, and sepsis were associated with a higher eosinophil percentage. The eosinophil percentage was significantly higher in infants with bronchopulmonary dysplasia from the first postnatal week and the percentage was the highest in the fourth postnatal week, with the maximal difference being 4.1% (P<0.001).ConclusionEosinophilia is common in premature infants and reaches peak incidence and severity in the fourth postnatal week. The eosinophil percentage was significantly higher in bronchopulmonary dysplasia patients from the first postnatal week. Severe eosinophilia was significantly associated with the incidence of bronchopulmonary dysplasia even after adjusting for other variables.

Avoiding Endotracheal Ventilation to Prevent Bronchopulmonary Dysplasia: A Meta-analysis

Mechanical ventilation via an endotracheal tube is a risk factor for bronchopulmonary dysplasia (BPD), one of the most common morbidities of very preterm infants. Our objective was to investigate the effect that strategies to avoid endotracheal mechanical ventilation (eMV) have on the incidence of BPD in preterm infants <30 weeks' gestational age (GA). In February 2013, we searched the databases Medline, Embase, and the Cochrane Central Register of Controlled Trials. Study selection criteria included randomized controlled trials published in peer-reviewed journals since the year 2000 that compared preterm infants <30 weeks' GA treated by using a strategy aimed at avoiding eMV with a control group in which mechanical ventilation via an endotracheal tube was performed at an earlier stage. Data were extracted and analyzed by using the standard methods of the Cochrane Neonatal Review Group. The authors independently assessed study eligibility and risk of bias, extracted data and calculated odds ratios and 95% confidence intervals, employing RevMan version 5.1.6. We identified 7 trials that included a total of 3289 infants. The combined odds ratio (95% confidence interval) of death or BPD was 0.83 (0.71-0.96). The number needed to treat was 35. The study results were remarkably homogeneous. Avoiding eMV had no influence on the incidence of severe intraventricular hemorrhage. Strategies aimed at avoiding eMV in infants <30 weeks' GA have a small but significant beneficial impact on preventing BPD.

Corticosteroids for the prevention of bronchopulmonary dysplasia in preterm infants: an overview of Cochrane reviews

AbstractBackgroundBronchopulmonary dysplasia (BPD) is an important complication associated with considerable morbidity in preterm infants. Corticosteroids in various regimens have been tried out to prevent BPD.ObjectiveTo examine the evidence from Cochrane systematic reviews regarding the effectiveness and associated complications of corticosteroids used to prevent BPD in preterm infants.MethodsThe Cochrane Database of Systematic Reviews was searched to identify reviews of corticosteroids for BPD in preterm infants. Data were extracted by one investigator, and checked by a second investigator for accuracy. Results are presented as risk ratios (RR) with 95% confidence intervals (CI). We considered &lt;8 days as early and &gt;7 days as late administration.Main resultsSix reviews (67 trials and 6535 patients) were included and covered three main comparisons: inhaled corticosteroids versus placebo, inhaled versus systemic corticosteroids and systemic corticosteroids versus placebo. Systemic corticosteroids compared with placebo significantly reduced the incidence of BPD (early: RR 0.79, 95% CI 0.71–0.88; late: RR 0.72, 95% CI 0.63–0.82), and BPD or mortality (early: RR 0.89, 95% CI 0.84–0.95; late: RR 0.72, 95% CI 0.63–0.82) at 36 weeks post‐menstrual age. Similar results were observed for these outcomes assessed at 28 days of life at which time there was additionally a reduction in mortality (late: RR 0.49, 95% CI 0.28–0.85). There was a higher incidence of cerebral palsy associated with systemic corticosteroids compared with placebo when initiated early (RR 1.45, 95% CI 1.06–1.98). No differences in neurodisability based on Bayley Mental or Psychomotor Developmental Index scores were observed for inhaled or systemic corticosteroids compared with placebo. Hypertension was significantly increased in association with systemic corticosteroids versus placebo (early: RR 1.85, 95% CI 1.55–2.22; late: RR 2.66, 95% CI 1.58–4.49) as were gastrointestinal (GI) perforations when treatment was initiated early (RR 1.81, 95% CI 1.33–2.48).Author's ConclusionSystemic corticosteroids decrease BPD and early mortality in premature infants but have a risk of complications, particularly when initiated in the first week of life. Owing to the wide range of dosing protocols, timing of initiation, doses and duration of therapy in the included reviews, it is difficult to determine, based on the evidence examined in this overview, a protocol that is both safe and effective. Further research should focus on determining the most effective dose and timing of corticosteroid administration beyond the first week of life to maximize benefit in decreasing BPD and mortality while avoiding short‐ and long‐term harms.

The association between hypertensive disorders in pregnancy and bronchopulmonary dysplasia: a systematic review

Whether hypertensive disorders in pregnancy (HDP) are the risk factors of bronchopulmonary dysplasia (BPD) is controversial. A systematic review was made to determine the association between HDP and BPD in preterm infants. We searched PubMed, Embase, Cochrane Library, ScienceDirect, Web of Science, with no language limitation, and reviewed the reference lists of the selected articles to identify additional relevant publications and contacted the authors of relevant studies for further information. The data were extracted independently by 2 reviewers who used a predetermined data extraction form. Studies were combined with an odds ratio (OR) using a random-effects model. Meta-regression and subgroup analysis were used to explore potential confounders. Funnel plots, Egger's test and Begg's test were used to investigate the publication bias. The Trim and Fill method was used to control the publication bias. A total of 787 studies were identified and only 15 studies (20 779 patients) were included. The pooled unadjusted OR showed that HDP was significantly associated with BPD (P=0.04; OR=1.29, 95% CI=1.01-1.65). Heterogeneity was substantial (I(2)=74%) and might be partially explained by different variables in maternal complications between the control groups across the studies. The pooled adjusted OR suggested the same conclusion that HDP was a risk factor for BPD (P=0.01; OR=1.59, 95% CI=1.11-2.26). Funnel plot and Egger's test showed that there were publication bias of unadjusted estimate of association between HDP and BPD. Unadjusted analyses showed that the rate of BPD was slightly higher in the infants exposed to HDP, and adjusted analyses confirmed this finding. But this result should be interpreted cautiously because substantial heterogeneity and publication bias were identified in this review.

Could mean platelet volume predict developing of bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome

Introduction: some studies have suggested correlation between MPV index and inflammatory diseases such as rheumatoid arthritis in adults. Though bronchopulmonary dysplasia is also an inflammatory disease which develops in preterm neonates with Respiratory distress syndrome, we decided to study the possible correlation between the mean platelet volume (MPV) and the occurrence of bronchopulmonary dysplasia (BPD) Subject & Methods: We reviewed the medical records of 280 infant with the diagnosis of RDS admitted to the neonatal intensive care unit of the Mahdieh obstetrics and gynecology Hospital of Tehran and Amir general Hospital of semnan from April 2008 to April 2012. Infants who have been expired before first month of life were excluded. Enrolled infants were divided into BPD and no-BPD groups (30 with and 250 without BPD). MPV was determined during first three days of life in all cases. Results: MPV measured during first three days of life was significantly( p=0.017) higher in the BPD than in the no-BPD group (10.8-0.96 versus 9.65-0.91 fL)but Platelet count at the same time were similar in the BPD and no-BPD groups, and MPV increment was associated with BPD development risk( (OR=1.6, 95%CI: 2.38-1.08, p=0.019) . Conclusion: We concluded that higher MPV in the first three days of life is a probable risk factor for the development of BPD in preterm infants with RDS. This might be attributed to the fact that high MPV could prone the neonate to inflammatory and oxidative lung damage. Keywords: oxidative lung damage; supplemental oxygen therapy; Neonatal intensive care unit; Preterm neonates; Platelet

Addition of SNAP to perinatal risk factors improves the prediction of bronchopulmonary dysplasia or death in critically ill preterm infants

BackgroundBronchopulmonary dysplasia (BPD) is the most common serious pulmonary morbidity in premature infants. The score for neonatal acute physiology (SNAP) is a physiologic severity index for neonatal intensive care and correlates well with neonatal mortality and clinical outcomes. The prognostic value of the SNAP score for BPD in preterm infants remains to be clarified. The aim of the study was to determine whether SNAP can predict the development of BPD or death, and to investigate the contribution of SNAP to the predictive accuracy of other potential perinatal risk factors for the adverse outcome in critically ill preterm infants.MethodsWe conducted a study in 160 critically ill preterm infants with less than 33 gestational weeks. The original SNAP score was prospectively calculated based on 28 items collected during the first 24 hours of admission. The potential perinatal risk factors were assessed during the first 72 hours of life. Major outcome measures were BPD and mortality before the time of BPD screening.ResultsOf the 160 infants, 17 died and 41 developed BPD. The SNAP score was significantly associated with BPD or death (odds ratio [OR] =1.28; 95% confidence interval [CI], 1.16-1.41; p <0.001), even after adjustment for gestational age (OR =1.27; 95% CI, 1.13-1.41; p <0.001). High SNAP score was an independent predictor of BPD or death (area under the curve [AUC] =0.78; 95% CI, 0.70-0.85; p <0.001), with additional predictive value when combined with other perinatal risk factors. Multivariate regression analysis resulted in a final model, including SNAP, gestational age, apnea of prematurity, patent ductus arteriosus, and surfactant use as independent risk factors, with a higher predictive accuracy compared with individual components (AUC =0.92; 95% CI, 0.87-0.96; p <0.001).ConclusionsSNAP is associated with adverse outcome of BPD or death. High SNAP scores are predictive of BPD or death in critically ill preterm infants, and add prognostic value to other perinatal risk factors.

Early biomarkers as predictors for bronchopulmonary dysplasia in preterm infants: a systematic review

Bronchopulmonary dysplasia (BPD) is usually diagnosed in preterm infants at least 28 days after birth. Great interest lies in the potential to identify biomarkers that predict development of the disease and future neurodevelopmental outcomes. We have reviewed the existing literature on early biomarkers as predictors for BPD in preterm infants. Two reviewers independently searched the databases of PubMed, EMBASE, and Google Scholar for studies pertaining to biomarkers for BPD. Studies were assessed using Quality Assessment of Diagnostic Accuracy Studies criteria. We identified 46 relevant articles that are summarized in the review. These studies assessed over 30 potential biomarkers. Sensitivity and specificity of biomarkers were reported or could be calculated for only 16 articles, and ranged from 0 to 100 %. Based on the nine highest quality studies, serum KL-6, CC16, neutrophil gelatinase-associated lipocalin, and end-tidal carbon monoxide (etCO) perform extremely well in predicting the early diagnosis of established BPD, highlighting these biomarkers as promising candidates for future research. Published data from studies on serum biomarkers and etCO suggest that biomarkers may have great potential to predict the subsequent BPD and neurodevelopmental outcomes. These biomarkers need validation in larger studies, and the generalizability of biomarkers for predicting BPD, as well as the neurodevelopmental outcomes, needs to be further explored.

Bronchopulmonary dysplasia in preterm infants managed with non-invasive ventilation or surfactant and a brief period of mechanical ventilation: a 6-year cohort study

Objective: Non-invasive ventilation (NIV) is increasingly used as first-line management of respiratory distress syndrome in preterm infants to avoid the lung-damaging effects of mechanical ventilation (MV). We hypothesised that even a short period of MV following surfactant treatment would increase the rate of bronchopulmonary dysplasia (BPD).Methods: Retrospective study including preterm infants <30 weeks gestational age over a six-year period if they required surfactant followed by MV not longer than 24 h (SURF&MV group) or if managed exclusively with NIV (NIV group). Baseline and morbidity variables such as gestation, birth weight, sex, place of birth, antenatal steroids, sepsis, pneumothorax, intraventricular haemorrhage, necrotising enterocolitis, and patent ductus arteriosus were analysed in a multivariate model for potential confounding.Results: 289 infants were included: 150 in the NIV group and 139 in the SURF&MV group. Seventeen infants in the NIV group and 23 in the SURF&MV group developed BPD (odds ratio: 1.55; 95% confidence interval (CI): 0.79–3.05; p = 0.202). After adjusting for potential confounders, the odds ratio was 1.09 for the SURF&MV group to develop BPD (95% CI: 0.52–2.28; p = 0.812).Conclusion: The rate of BPD did not differ between infants managed with NIV or with surfactant administration followed by ≤24 h of MV after adjusting for confounding factors.

Single Nucleotide Polymorphism in Toll-like Receptor 6 Is Associated With a Decreased Risk for Ureaplasma Respiratory Tract Colonization and Bronchopulmonary Dysplasia in Preterm Infants

Ureaplasma spp. respiratory tract colonization is a risk factor for bronchopulmonary dysplasia (BPD) in preterm infants, but differences in host susceptibility have not been elucidated. We hypothesized that variants in genes regulating the innate immune response are associated with altered risk for Ureaplasma spp. respiratory colonization and BPD in preterm infants. Twenty-four tag single nucleotide polymorphisms (SNPs) from Toll-like receptor (TLR)1, TLR2, TLR4 and TLR6 were assayed in 298 infants <33 weeks gestation who had serial respiratory cultures for Ureaplasma spp. and were evaluated for BPD. The majority of subjects (N = 205 [70%]) were African-American. One hundred ten (37%) were Ureaplasma positive. Four SNPs in TLR2 and TLR6 were significantly associated with Ureaplasma respiratory tract colonization. Single SNPs in TLR2, TLR4 and TLR6 were associated with BPD. TLR6 SNP rs5743827 was associated with both a decreased risk for Ureaplasma respiratory tract colonization and decreased risk for BPD (odds ratio: 0.54 [0.34-0.86] and odds ratio: 0.54 [0.31-0.95], respectively). There was a significant additive interaction between Ureaplasma colonization and genotype at TLR6 SNP rs5743827 (Padditive = 0.023), with an attributable proportion due to interaction of 0.542. Polymorphisms in host defense genes may alter susceptibility to Ureaplasma infection and severity of the inflammatory response contributing to BPD. These observations implicate host genetic susceptibility as a major factor in BPD pathogenesis in Ureaplasma-infected preterms.

Risk factors of bronchopulmonary dysplasia in preterm infants with different severities

Objective To improve the prevention and treatment of bronchopulmonary dysplasia(BPD) in preterm infants, and the clinical risk factors of premature neonates with different severities of BPD were investigated. Methods A total of 139 cases among preterm infants who were admitted to NICU in the Third Affiliated Hospital of Zhengzhou University from Jan.2007 to Dec.2011 were analyzed retrospectively.The history of birth and mother pregnancy, clinical treatment, prognosis and complication of mild, moderate and severe BPD according to clinical diagnostic criteria were analyzed, respectively. Results Of the total 139 premature neonates, 61 cases were diagnosed as mild BPD, 48 cases as moderate BPD and 30 cases as severe BPD.No significant differences were found in gender, birth times, fertilization, delivery mode, the percentage of fetal distress and neonatal resuscitation, maternal age, the percen-tage of pregnancy-induced hypertension, the percentage of antenatal corticosteroids administration and postnatal pulmonary surfactant and combined with patent ducts arteries among the different groups(all P>0.05). With the increasing severity of BPD, the birth weight and gestational age were decreasing, the percentage of the infants with Apgar 1 minute score ≤7, premature rupture of membranes≥8 hours, maternal perinatal infection, meconium-stained amniotic fluid were increasing(all P<0.05). And mechanical ventilation, the time of using oxygen, and the percentage of trachea cannula intubation ≥2 times, indwelling gastric tube and red blood cells transfusing, the positive rate of sputum cultures and the blood culture were also increased with the increasing severity of BPD(all P<0.05). Conclusions Preventing of preterm delivery, control and reduce antenatal and postnatal infection, shorten the duration of mechanical ventilation and usage of oxygen are key factors to reduce BPD and severities in neonatal infants. Key words: Bronchopulmonary dysplasia; Clinical risk factor; Preterm infant