Subsequent Development Of Bronchopulmonary Dysplasia Research Articles

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.

Pulmonary Vascular Phenotypes of Prematurity: The Path to Precision Medicine

Pulmonary hypertension (PH) is associated with significant morbidities and high mortality in preterm infants, yet mechanisms contributing to the pathogenesis of PH, the impact of early pulmonary vascular disease (PVD) on the risk for BPD, the role for PH-targeted drug therapies, and long-term pulmonary vascular sequelae remain poorly understood. PVD is not a homogeneous disease, rather, PVD in the setting of prematurity includes various phenotypes as based on underlying pathophysiology, the severity of associated PH, the timing of disease onset, its contribution to hemodynamic and respiratory status, late outcomes, and other features. As with term newborns, severe hypoxemia with acute respiratory failure (HRF) in preterm infants can be due to marked elevation of pulmonary artery pressure with extrapulmonary shunt, traditionally referred to as persistent pulmonary hypertension of the newborn (PPHN). Transient and less severe levels of PH can also be observed during the early transition after birth without evidence of severe HRF, representing physiologic PH or delayed pulmonary vascular transition in preterm infants. Importantly, echocardiographic evidence of early PH has been strongly associated with the subsequent development of bronchopulmonary dysplasia (BPD), late PH, and chronic respiratory disease during infancy and early childhood. Late PH beyond the first postnatal months in preterm in neonates with established BPD is further associated with poor outcomes, especially as related to BPD severity. In addition, echocardiographic signs of PVD can further persist throughout childhood and may lead to chronic PH of variable severity and cardiac maldevelopment in prematurely born young adults. This review discusses the importance of characterizing diverse pulmonary vascular phenotypes in preterm infants to better guide clinical care and research, and to enhance the development of more precise therapeutic strategies to optimize early and late outcomes of preterm infants.

Clinical Significance of Early Pulmonary Hypertension in Preterm Infants

To characterize different phenotypes of early pulmonary hypertension (PH) in preterm infants and their respective associations with bronchopulmonary dysplasia (BPD) and survival. A prospective cohort study in a tertiary university medical center from June 2016 until March 2019. Infants with a gestational age <30weeks and/or a birth weight <1000g were included. Echocardiographic assessment for PH was performed at 3-10days after birth. Subsequent development of BPD at 36weeks postmenstrual age and mortality were assessed. Early PH was identified in 55% of 104 included infants, including 21% with persistent PH of the newborn (PPHN), 61% with flow-associated PH, and 18% PH without shunt. Only PPHN was associated with placental fetal vascular malperfusion, lower gestational age, and low Apgar score. Both PPHN and flow PH were associated with the development of BPD. Early PH was associated with poorer survival, driven by PPHN. Early PH is highly prevalent (55%) in preterm infants and associated with the development of BPD, independent of the phenotype of PH. Infants with PPHN had the poorest survival. Early PH presents in various phenotypes characterized by differences in etiology, pathophysiology, and associated long-term sequelae.

The Relationship Between Maternal and Neonatal Microbiota in Spontaneous Preterm Birth: A Pilot Study.

The newborn’s microbiota composition at birth seems to be influenced by maternal microbiota. Maternal vaginal microbiota can be a determining factor of spontaneous Preterm Birth (SPPTB), the leading cause of perinatal mortality. The aim of the study is to investigate the likelihood of a causal relationship between the maternal vaginal microbiota composition and neonatal lung and intestinal microbiota profile at birth, in cases of SPPTB. The association between the lung and/or meconium microbiota with the subsequent development of bronchopulmonary dysplasia (BPD) was also investigated. Maternal vaginal swabs, newborns’ bronchoalveolar lavage fluid (BALF) (1st, 3rd, 7th day of life) and first meconium samples were collected from 20 women and 23 preterm newborns with gestational age ≤ 30 weeks (12 = SPPTB; 11 = Medically Indicated Preterm Birth–MIPTB). All the samples were analyzed for culture examination and for microbiota profiling using metagenomic analysis based on the Next Generation Sequencing (NGS) technique of the bacterial 16S rRNA gene amplicons. No significant differences in alpha e beta diversity were found between the neonatal BALF samples of SPPTB group and the MIPTB group. The vaginal microbiota of mothers with SPPTB showed a significant difference in alpha diversity with a decrease in Lactobacillus and an increase in Proteobacteria abundance. No association was found between BALF and meconium microbiota with the development of BPD. Vaginal colonization by Ureaplasma bacteria was associated with increased risk of both SPPTB and newborns’ BPD occurrence. In conclusion, an increase in α-diversity values and a consequent fall in Lactobacillus in vaginal environment could be associated to a higher risk of SPPTB. We could identify neither a specific neonatal lung or meconium microbiota profiles in preterm infants born by SPPTB nor a microbiota at birth suggestive of subsequent BPD development. Although a strict match has not been revealed between microbiota of SPPTB mother-infant couples, a relationship cannot be excluded. To figure out the reciprocal influence of the maternal-neonatal microbiota and its potential role in the pathogenesis of SPPTB and BPD further research is needed.

Pulmonary hypertension in extremely preterm infants: a call to standardize echocardiographic screening and follow-up policy

Pulmonary hypertension (PH) is a frequent complication in extremely preterm born infants that seriously affects outcome. We aimed to describe the prevalence of PH in extremely preterm infants and the policy on screening and follow-up in the ten Dutch intensive care units (NICUs). We performed a retrospective cohort study at the University Medical Centre Groningen on infants with gestational age < 30 weeks and/or birthweight < 1000 g, born between 2012 and 2013. Additionally, we carried out a survey among the Dutch NICUs covering questions on the awareness of PH, the perceived prevalence, and policy regarding screening and following PH in extremely preterm infants. Prevalence of early-onset PH in our study was 26% and 5% for late-onset PH. PH was associated with poor survival and early-onset PH was associated with subsequent development of bronchopulmonary dysplasia (BPD). All the NICUs completed the questionnaire and we found that no standardized policy existed regarding screening and following PH in extremely preterm infants.Conclusion: Despite the frequent occurrence of PH and its clinically important consequences, (inter-)national standardized guidelines regarding screening and following of PH in extremely preterm infants are lacking. Standardizing screening and follow-up will enable early identification of infants with late-onset PH and allow for earlier treatment. Additionally, greater clarity is required regarding the prevalence of early PH as are new preventive treatment strategies to combat BPD.What is known? • Pulmonary hypertension (PH) substantially impairs the survival of extremely preterm infants. • PH is associated with bronchopulmonary dysplasia (BPD): Early-onset PH predicts the development of BPD. Late-onset PH is prevalent in infants with severe BPD.What is new? • Pulmonary hypertension (PH) is prevalent in preterm infants. Its consequences for morbidity and mortality justify a standardized policy aimed at early detection to improve prevention and treatment. • No structured policy exists in the Netherlands regarding screening/follow-up for PH in extremely preterm infants.

43 Pulmonary Artery dopplers for early prediction of Bronchopulmonary Dysplasia (BPD) in Extremely Low Birth Weight babies (ELBW): A forgotten tale

Abstract Introduction/Background BPD is a chronic lung disease that affects ELBW babies and contributes significantly to their morbidity and mortality. The early abnormal vasoreactivity observed in babies at risk of BPD increases the pulmonary vascular resistance and can be assessed non-invasively using Time to Peak Velocity: Right Ventricular Ejection Time ratio (TPV: RVET) that is calculated from pulmonary artery doppler waveform. We postulate that screening for this condition early may be useful to predict BPD in this cohort, which may provide prognostic information as well as early clinical management of the ELBW at risk of developing BPD and therefore can potentially present a window of opportunity for therapeutic intervention. Objectives 1. To determine utility of TPV/RVET ratio in predicting the risk for BPD in ELBW babies in a tertiary center. 2. To determine utility of TPV/RVET(c) ratio in predicting the risk for BPD in ELBW babies in a tertiary center. Design/Methods This is a retrospective cohort study of ELBW babies &amp;lt;29 weeks admitted to the Neonatal Intensive Care Unit at Stollery Children Hospital (SCH) over a 4 year time period and had early echocardiograms performed between 7-21 days of life. These babies were further identified to have BPD or no BPD at 36 weeks CGA. TPV/RVET ratios were measured by two reviewers from pulmonary artery doppler waveforms and were corrected for heart rate. The predictive ability of TPV/RVET and TPV/RVET(c) for subsequent development of BPD were analyzed using ROC curve. Inter observer agreement was evaluated. Logistic regression analysis was performed to derive a model that can be used in the 2nd to 3rd weeks of life, to predict the subsequent development of BPD at 36 weeks CGA. Infants with congenital heart disease (other than PDA, persistent foramen ovale/atrial septal defect and Ventricular Septal Defects), congenital lung malformations, multiple congenital anomalies and chromosomal anomalies were excluded. Results Out of 589 ELBW babies &amp;lt;29 weeks admitted to SCH NICU, 207 infants were eligible with early echocardiograms done at a mean age of 12.6 days (SD 4.1). One-hundred-and-twenty-five babies (60.4%) were found to have BPD. Babies with BPD were of lower gestational age (25.6 Vs 26.4, p-0.0001), sicker at birth (SNAPPE II 42.3 Vs 33.2, p-0.0024), had higher incidence of PDA needing surgical ligation (18.4% Vs 4.9%, p-0.005) and had spent more days on mechanical ventilation (39.8 Vs 12.5, p&amp;lt;0.0001) than those without BPD. Both TPV, TPV/RVET and its corrected ratios were significantly lower in ELBW babies with BPD compared to non-BPD babies (p&amp;lt;0.0001). The TPV/RVET ratio (cut off 0.34) and TPV/RVET(c) (cut off 0.54) had Sensitivities [76.8% (95%CI 68.4-83.9) and 72% (95%CI 63.3-79.7)], Specificities [85.4% (95%CI 75.8- 92.2) and 84.1% (95%CI 74.4-91.3)], Positive Predictive Values [88.9% (95%CI 81.4-94.1) and 87.4% (95%CI 79.4-93.1)], Negative Predictive values [70.7% (95%CI 60.7- 79) and 66.3% (95%CI 56.4-75.3)] and ROC area [0.811 (95% CI 0.757-0.864) and 0.781 (95% CI 0.725-0.837)] respectively. Multi variant logistic regression analysis showed Odds Ratio(OR) for having BPD at TPV/RVET cut off 0.34 and TPV/RVET(c) cut off 0.54 to be 19.9(95%CI 8.19-48.34) and 16.3(95% 6.78-39.33) respectively and the OR increased by 1.07(95%CI 1.05-1.09) and 1.08(95% CI 1.05-1.10) with every additional days of mechanical ventilation respectively. TPV/RVET ratio had 92.75% inter-observer agreement with kappa 0.83. Conclusion TPV/RVET and its corrected ratio are good and reliable early screening tools for subsequent development of BPD in ELBW babies with substantial inter-observer agreement. Two variable model namely TPV/RVET&amp;lt;0.34 and mechanical ventilation or TPV/RVET(c) &amp;lt;0.54 and mechanical ventilation can be used in the 2nd to 3rd week of life to predict subsequent development of BPD at 36 weeks CGA in ELBW babies.

Early angiogenic proteins associated with high risk for bronchopulmonary dysplasia and pulmonary hypertension in preterm infants.

Early pulmonary vascular disease in preterm infants is associated with the subsequent development of bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH); however, mechanisms that contribute to or identify infants with increased susceptibility for BPD and/or PH are incompletely understood. Therefore, we tested if changes in circulating angiogenic peptides during the first week of life are associated with the later development of BPD and/or PH. We further sought to determine alternate peptides and related signaling pathways with the risk for BPD or PH. We prospectively enrolled infants with gestational age <34 wk and collected blood samples during their first week of life. BPD and PH were assessed at 36 wk postmenstrual age. Samples were assayed for each of the 1,121 peptides included in the SOMAscan scan technology, with subsequent pathway analysis. Of 102 infants in the study, 82 had BPD, and 13 had PH. Multiple angiogenic proteins (PF-4, VEGF121, ANG-1, bone morphogenetic protein 10 [BMP10], hepatocyte growth factor (HGF), ANG-2) were associated with the subsequent diagnosis of BPD; and FGF-19, PF-4, connective tissue activating peptide (CTAP)-III, and PDGF-AA levels were associated with BPD severity. Early increases in BMP10 was strongly associated with the late risk for BPD and PH. We found that early alterations of circulating angiogenic peptides and others were associated with the subsequent development of BPD. We further identified peptides that were associated with BPD severity and BPD-associated PH, including BMP10. We speculate that proteomic biomarkers during the first week of life may identify infants at risk for BPD and/or PH to enhance care and research.

Increased serum Th2 chemokine levels are associated with bronchopulmonary dysplasia in premature infants.

Bronchopulmonary dysplasia (BPD) is one of the most common chronic inflammatory lung disease of premature infants, with serious short- and long-term consequences. Early identification of premature infants at risk of BPD is critical to preventing the pathogenesis of disease. Thus, in the present study, we recruited 126 premature infants, collected peripheral blood samples at different time points during early life, and measured the concentration of Th1 (MCP-1, IP-10, and MIG) and Th2 (eotaxin-1, eotaxin-2, and MCP-4) chemokines in serum. We found serum eotaxin-2 levels were significantly higher in the BPD group than in the non-BPD group on day 1 [1662pg/ml vs. 1221pg/ml, P< 0.05], day 7 [1533pg/ml vs. 1089pg/ml, P< 0.05], and day 14 [1246pg/ml vs. 704pg/ml, P< 0.05] after birth, and serum MCP-4 levels were also significantly higher in the BPD group than in the non-BPD group on day 1 [186pg/ml vs. 128pg/ml, P< 0.05], day 7 [199pg/ml vs. 101pg/ml, P< 0.05], and day 14 [238pg/ml vs. 106pg/ml, P< 0.05] of life.Conclusions: Increased levels of Th2 chemokines, eotaxin-2, and MCP-4, are associated with BPD in premature infants. What is Known: • The pathogenesis of BPD is multifactorial and it is difficult to predict and prevent. • Previous studies have demonstrated that inflammation plays a major role in the pathogenesis of BPD. What is New: • Increased Th2 chemokines, eotaxin-2 and MCP-4, were associated with BPD in premature infants. • Abnormal Th1/Th2 response in early life maybe associated with the subsequent development of BPD, which provide a new insight to understand the pathogenesis of the disease.

Association between serum 25 (OH) vitamin D level at birth and respiratory morbidities among preterm neonates

Objectives: To determine the association between 25-hydroxyvitamin D [25(OH)D] levels on first day of life with respiratory distress syndrome (RDS), need and duration of mechanical ventilation, and subsequent development of bronchopulmonary dysplasia (BPD) among preterm neonates.Study design: In this case–control study, serum 25(OH)D was measured on first day of life in 65 preterm neonates <34 weeks: 40 with RDS and 25 without RDS and compared between them. Serum 25(OH)D levels were categorized into normal (above 30 ng/ml), insufficiency (20–30 ng/ml), moderate deficiency (10–20 ng/ml), and severe deficiency (<10 ng/ml). Neonates with different 25(OH)D levels were compared as regard grade of RDS, initial pH, initial CO2, need and duration of mechanical ventilation, development of BPD, and mortality.Results: Only one of 65 studied preterm neonates had normal vitamin D level. Neonates with RDS had significantly lower mean serum 25(OH)D level than controls (10.6 versus 13.9 ng/dl) (p = .028). Neonates with severe 25(OH)D deficiency developed more BPD than those with moderate deficiency (29.4 versus 8.7%) but did not reach significant level (p value = .08). There is no correlation between serum 25(OH)D level and duration of mechanical ventilation. Logistic regression analysis shows that low serum 25(OH)D level is an independent risk factor for RDS.Conclusion: Low 25(OH)D level is far frequent among Egyptian preterm neonates. Vitamin D deficiency is an independent risk factor for development of RDS in preterm neonates.

Low levels of tissue inhibitor of metalloproteinase-2 at birth may be associated with subsequent development of bronchopulmonary dysplasia in preterm infants.

PurposeBronchopulmonary dysplasia (BPD) is characterized by inflammation with proteolytic damage to the lung extracellular matrix. The results from previous studies are inconsistent regarding the role of proteinases and antiproteinases in the development of BPD. The aim of the present study was to investigate whether matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, and TIMP-1 levels in the serum of preterm infants at birth are related to the development of BPD.MethodsSerum was collected from 62 preterm infants at birth and analyzed for MMP-8, MMP-9, TIMP-2, and TIMP-1 by using enzyme-linked immunosorbent assay. MMPs and TIMPs were compared in BPD (n=24) and no BPD groups (n=38). Clinical predictors of BPD (sex, birth weight, gestational age, etc.) were assessed for both groups. The association between predictors and outcome, BPD, was assessed by using multivariate logistic regression.ResultsSex, birth weight, and mean gestational age were similar between the groups. BPD preterm infants had significantly lower TIMP-2 levels at birth compared with no BPD preterm infants (138.1±23.0 ng/mL vs. 171.8±44.1 ng/mL, P=0.027). No significant difference was observed in MMP-8, MMP-9, and TIMP-1 levels between the two groups. Multivariate logistic regression analysis indicated that the TIMP-2 levels were predictive of BPD after adjusting for sex, birth weight, gestational age, proteinuric preeclampsia, and intraventricular hemorrhage (β=-0.063, P=0.041).ConclusionLow TIMP-2 serum levels at birth may be associated with the subsequent development of BPD in preterm infants.

Carboxyhemoglobin Formation in Preterm Infants Is Related to the Subsequent Development of Bronchopulmonary Dysplasia.

Objective. To evaluate the usefulness of carboxyhemoglobin (CO-Hb) levels as a biomarker to predict the development and severity of bronchopulmonary dysplasia (BPD). Methods. Twenty-five infants born at <33 wk of gestational age or with a birth weight of <1,500 g were enrolled. CO-Hb levels were measured between postnatal days 5 and 8, 12 and 15, 19 and 22, and 26 and 29. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products, and Nε-(hexanoyl) lysine were measured between postnatal days 5 and 8 and 26 and 29. Receiver operating characteristic (ROC) analysis was used to compare the biomarkers' predictive values. Results. Compared with infants in the no-or-mild BPD group, infants with moderate-to-severe BPD exhibited higher CO-Hb levels during the early postnatal period and higher 8-OHdG levels between postnatal days 5 and 8. Using ROC analysis to predict the development of moderate-to-severe BPD, the area under the curve (AUC) for CO-Hb levels between postnatal days 5 and 8 was higher than AUCs for the urinary markers. Conclusions. CO-Hb levels during the early postnatal period may serve as a practical marker for evaluating oxidative stress and the severity of subsequently developing BPD.

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.

Endoglin in Amniotic Fluid as a Risk Factor for the Subsequent Development of Bronchopulmonary Dysplasia

Cross-talk between inflammation and angiogenesis pathways has been recently reported. The objectives of this study were to: (i) examine whether amniotic fluid (AF) concentrations of soluble endoglin (sEng), a protein with anti-angiogenic properties, change during pregnancy, parturition, or intra-amniotic infection and/or inflammation (IAI); (ii) determine whether an increase in sEng in the AF of patients with preterm labor (PTL) and preterm prelabor rupture of membranes (PROM) is associated with adverse neonatal outcomes; and (iii) investigate potential sources of sEng in AF. A cross-sectional study was conducted to include patients in the following groups: (i) mid-trimester (n=20); (ii) PTL with term delivery (n=95); (iii) PTL leading to preterm delivery with (n=40) and without IAI (n=46); (iv) preterm PROM with (n=37) and without IAI (n=37); (v) term in labor (n=48) and not in labor (n=44). AF concentrations of sEng were determined by enzyme-linked immunosorbent assay. Chorioamniotic membranes, umbilical cord blood, and AF macrophages were examined for the expression of endoglin. (i) Patients with IAI had a higher median AF concentration of sEng than those without IAI (P=0.02 for PTL and 0.06 for preterm PROM); (ii) AF concentrations of sEng in the 3rd and 4th quartiles were associated with IAI (OR 2.5 and 7.9, respectively); (iii) an AF sEng concentration ≥779.5pg/mL was associated with bronchopulmonary dysplasia (BPD) (OR 7.9); (iv) endoglin was co-localized with CD14+ macrophages in AF pellets of patients with IAI by immunofluorescence and flow cytometry; and (v) the concentration of sEng in the supernatant was significantly increased after the treatment of macrophages with endotoxin or TNF-α. Soluble endoglin participates in the host response against IAI. Activated macrophages may be a source of sEng concentrations in the AF of patients with IAI. An increase of sEng in the AF is associated with BPD and adverse neonatal outcomes.

Correlation of urinary inflammatory and oxidative stress markers in very low birth weight infants with subsequent development of bronchopulmonary dysplasia

Currently, bronchopulmonary dysplasia (BPD) occurs almost exclusively in pre-term infants. In addition to prematurity, other factors like oxygen toxicity and inflammation can contribute to the pathogenesis. This study aimed to compare urinary inflammatory and oxidative stress markers between the no/mild BPD group and moderate/severe BPD group and between BPD cases with significant early lung disease like respiratory distress syndrome (RDS) (‘classic’ BPD) and with minimal early lung disease (‘atypical’ BPD). A total of 60 patients who were a gestational age < 30 weeks or a birth weight < 1250 g were included. Urine samples were obtained on the 1st, 3rd and 7th day of life and measured the levels of leukotriene E4 (LTE4) and 8-hydroxydeoxyguanosine (8-OHdG). The 8-OHdG values on the 3rd day showed significant correlation to duration of mechanical ventilation. The 8-OHdG levels on the 7th day were the independent risk factor for developing moderate/severe BPD. In ‘classic’ BPD, the 8-OHdG values on the 3rd day were higher than those of ‘atypical’ BPD. In ‘atypical’ BPD, the LTE4 values on the 7th day were higher than the values in ‘classic’ BPD. These results suggest that oxidative DNA damage could be the crucial mechanism in the pathogenesis of current BPD and the ongoing inflammatory process could be an important mechanism in ‘atypical’ BPD.

Angiopoietin-1 and Endostatin Levels in Cord Plasma Predict the Development of Bronchopulmonary Dysplasia in Preterm Infants

To determine whether angiopoietin-1 and endostatin levels in the cord blood could predict the subsequent development of bronchopulmonary dysplasia (BPD) in preterm infants. A total of 102 preterm (gestational age ≤ 32 weeks) infants (28 infants developed BPD and 74 had no BPD) were enrolled in the study. Cord plasma levels of angiopoietin-1 and endostatin were measured by enzyme-linked immunosorbent assay. Preterm infants who subsequently developed BPD had significantly lower cord plasma levels of angiopoietin-1 than those who did not (p < 0.001). Our results showed that cord plasma levels of endostatin were significantly higher in infants with BPD than in those without (p < 0.001). In infants with BPD, angiopoietin-1 levels in cord plasma correlated negatively with endostatin (r = -0.48; p = 0.008). In preterm infants, low-angiopoietin-1 and high-endostatin levels in cord plasma at birth predict the subsequent development of BPD.

The use of culture-independent tools to characterize bacteria in endo-tracheal aspirates from pre-term infants at risk of bronchopulmonary dysplasia

Although premature infants are increasingly surviving the neonatal period, up to one-third develop bronchopulmonary dysplasia (BPD). Despite evidence that bacterial colonization of the neonatal respiratory tract by certain bacteria may be a risk factor in BPD development, little is known about the role these bacteria play. The aim of this study was to investigate the use of culture-independent molecular profiling methodologies to identify potential etiological agents in neonatal airway secretions. This study used terminal restriction fragment length polymorphism (T-RFLP) and clone sequence analyses to characterize bacterial species in endo-tracheal (ET) aspirates from eight intubated pre-term infants. A wide range of different bacteria was identified in the samples. Forty-seven T-RF band lengths were resolved in the sample set, with a range of 0-15 separate species in each patient. Clone sequence analyses confirmed the identity of individual species detected by T-RFLP. We speculate that the identification of known opportunistic pathogens including S. aureus, Enterobacter sp., Moraxella catarrhalis, Pseudomonas aeruginosa and Streptococcus sp., within the airways of pre-term infants, might be causally related to the subsequent development of BPD. Further, we suggest that culture-independent techniques, such as T-RFLP, hold important potential for the characterization of neonatal conditions, such as BPD.

Endostatin Concentration in Cord Plasma Predicts the Development of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants

Endostatin is an antiangiogenic growth factor. Together with proangiogenic growth factors it acts to shape the developing vasculature. Dysregulation of angiogenesis is a component in the pathogenesis of bronchopulmonary dysplasia. Our goal was to study whether the concentration of circulating endostatin at birth is associated with the development of bronchopulmonary dysplasia in very low birth weight infants. Endostatin concentration was measured in cord plasma from 92 very low birth weight infants (gestational age < 32 weeks; birth weight < 1500 g) and 48 healthy term infants (gestational age > 37 weeks; birth weight > 2500 g). Endostatin concentration in very low birth weight infants was lower than in healthy term infants. Within the very low birth weight group no correlation existed between endostatin concentration and gestational age or relative birth weight. Very low birth weight infants who subsequently developed bronchopulmonary dysplasia had higher cord endostatin than those who did not. Higher endostatin concentration was associated with higher odds for bronchopulmonary dysplasia. Adjusted for gestational age, the odds for bronchopulmonary dysplasia were higher. Circulating endostatin in term infants was higher than in very low birth weight infants, suggesting a temporal pattern for fetal endostatin concentration. In very low birth weight infants a high concentration of circulating endostatin at birth is associated with the subsequent development of bronchopulmonary dysplasia.

Lung protective ventilatory strategies in very low birth weight infants

Respiratory distress syndrome (RDS) is the most common respiratory diagnosis in preterm infants. Surfactant therapy and mechanical ventilation using conventional or high-frequency ventilation have been the standard of care in the management of RDS. Bronchopulmonary dysplasia (BPD) continues to remain as a major morbidity in very low birth weight infants despite these treatments. There is no significant difference in pulmonary outcome when an optimal lung volume strategy is used with conventional or high-frequency ventilation. Lung injury is directly related to the duration of invasive ventilation via the endotracheal tube. Studies using noninvasive ventilation, such as nasal continuous positive airway pressure and noninvasive positive pressure ventilation, have shown to decrease postextubation failures as well as a trend toward reduced risk of BPD. Lung protective ventilatory strategy may involve noninvasive ventilation as a primary therapy or following surfactant administration in very preterm infants with RDS. Initial steps in the management of preterm infants may also include sustained inflation to establish functional residual capacity, followed by noninvasive ventilation to minimize lung injury and subsequent development of BPD.

05/01407 Carbon nanofibers for composite applications: Hammel, E. et al. Carbon, 2004, 42, (5–6), 1153–1158

We show that smellprints of volatile organic components measured with an electronic nose (Cyranose 320; Smiths Detection Group Ltd, Watford, United Kingdom) differ between tracheal aspirates from preterm neonates with or without laboratory-confirmed bloodstream infections and with or without subsequent development of bronchopulmonary dysplasia. Tracheal aspirate smellprints could be useful noninvasive diagnostic markers for preterm neonates.

05/01402 Studies of the relationship between mineral matter and grinding properties for low-rank coals: Ural, S. and Akyildiz, M. International Journal of Coal Geology, 2004, 60, (1), 81–84

We show that smellprints of volatile organic components measured with an electronic nose (Cyranose 320; Smiths Detection Group Ltd, Watford, United Kingdom) differ between tracheal aspirates from preterm neonates with or without laboratory-confirmed bloodstream infections and with or without subsequent development of bronchopulmonary dysplasia. Tracheal aspirate smellprints could be useful noninvasive diagnostic markers for preterm neonates.