Mild Bronchopulmonary Dysplasia Research Articles

Not only bradycardia of prematurity – transitory sinus node dysfunction in a preterm infant

Aims: Sinus node dysfunction is rare in neonates, but can occur secondary to congenital heart disease, surgical interventions or endovascular manipulations. In addition, cardiac conduction disorders affecting the atrioventricular node are associated with maternal collagen vascular disorders. Here, we present the case of a hypotrophic preterm infant with transitory sinus node dysfunction in the context of maternal antiphospholipid antibody syndrome. Case report: Marked intrauterine growth restriction with oligohydramnios were diagnosed at 29 weeks of gestation in a 32 year old second gravida. A hypotrophic female infant was delivered via cesarean section with a birth weight of 430g (P<3, -3.3 SDS) and normal Apgar scores and umbilical pH. Respiratory complications included respiratory distress syndrome requiring CPAP therapy for 5 days and a mild bronchopulmonary dysplasia, requiring supplemental oxygen until 36 weeks of gestation. Further diagnostic measures revealed an asymptomatic antiphospholipid antibody syndrome in the mother with severe placental insufficiency as the probable cause of hypotrophy. Echocardiography on day 1 was normal. The baby developed mild apnea of prematurity treated with caffeine citrate until 34 weeks of gestation. At 36 weeks, repeated self-limiting episodes of severe bradycardia with asystolic phases lasting 5 seconds were noted. During these episodes the baby was asymptomatic, with absence of gastroesophageal reflux or neurologic events. Holter ECG confirmed a sinus arrhythmia with sinus pauses up to 4.5 seconds and initiation of an ectopic atrial or junctional rhythm, consistent with sinus node dysfunction. The infant showed persistence of sinus arrhythmia until 40 weeks of gestation. Monitor surveillance was discontinued shortly before discharge at 4 weeks of corrected age as the baby was stable. A follow-up Holter ECG at 46 weeks of gestation was normal. Discussion: Cardiac conduction disorders associated with maternal collagen vascular disease are a well-known entity, e.g. congenital heart block in neonatal lupus. However, neonatal sinus node dysfunction in the context of maternal antiphospholipid antibody syndrome has not yet been described and the association in our case is speculative. There are case reports describing maternal conduction disturbances associated with anti-phospholipid antibody syndrome. In addition, as has been previously described, transient sinus node dysfunction could be associated with immature autonomic nervous sytem activity in preterm infants.

Severity of bronchopulmonary dysplasia and increased risk of feeding desaturation and growth delay in very low birth weight preterm infants

Oral feeding has been reported to compromise breathing among preterm infants with bronchopulmonary dysplasia (BPD) during hospitalization or shortly after discharge. However, limited information was available concerning whether preterm infants with BPD remain vulnerable to feeding and growth insufficiency after a longer term of follow-up. The purpose of this study was therefore to examine the effect of severity of BPD on pulse oxygen saturation (SpO(2)) during feeding and growth in very low birth weight (VLBW) preterm infants during infancy. Seventy-two preterm infants with VLBW and 15 term infants were prospectively examined their growth and SpO(2) during feeding at 2, 4, and 6 months of corrected age. The severity of BPD was graded in VLBW infants according to the American National Institutes of Health consensus definition. In comparison to VLBW infants with mild BPD and term infants, VLBW infants with severe BPD showed significantly lower mean levels of SpO(2) during feeding at 2-6 months corrected age (P < 0.05). Those with severe BPD further exhibited higher rates of growth delay (weight < 10th percentile) throughout the study period. Among VLBW infants, severe BPD had an adverse relation with subsequent weight measures after adjustment for medical and demographic confounding variables (beta = -904 g, P = 0.03). The consensus BPD definition is useful to identify those preterm infants who are at greater risk of feeding desaturation and growth delay during infancy and close monitoring of SpO(2) during feeding should be advised.

Obstructive lung disease in children with mild to severe BPD

Bronchopulmonary dysplasia (BPD) is a common cause of respiratory insufficiency in children born very premature. The purpose of this study was to examine the impact of the severity of BPD on pulmonary morbidity at school age, as measured by conventional spirometry and impulse oscillometry. We also studied the association between changes in lung function and structural changes in the lungs of children with BPD via High-Resolution Computed Tomography (HRCT). Finally we studied the prevalence of atopy associated with BPD. We studied 60 very low birth weight (VLBW) children, 28 with respiratory distress syndrome (RDS) who did not develop BPD ("preterm non-BPD") and 32 with RDS who developed BPD. The severity of BPD was graded as mild, moderate or severe. Follow-up at age 6-8 years consisted of spirometry, oscillometry, thoracic HRCT, allergy skin-prick test, blood samples and a questionnaire. All children with BPD showed some evidence of impaired lung function (more negative reactance, FEV1<80% predicted, greater reversibility), although less than half of these children were symptomatic. The majority of children with BPD (19/26) showed abnormalities on HRCT. There was no evidence that atopy was associated with BPD. Children with mild BPD exhibited similar impairments in respiratory mechanics and lung structure to those diagnosed with moderate BPD. The widespread involvement of the peripheral airways suggests that all children diagnosed with BPD are potentially at risk of developing chronic obstructive pulmonary disease later in life.

Relation of exhaled nitric oxide levels to development of bronchopulmonary dysplasia

Objective:To test the hypothesis that exhaled nitric oxide levels on day 28 and changes in exhaled nitric oxide levels in the neonatal period would differ according to whether infants developed...

Bronchopulmonary dysplasia in very low birth weight infants

The developments in newborn care have enabled many more very low birth weight premature infants to live. The aim of our study was to determine the risk factors for bronchopulmonary dysplasia (BPD) development by evaluating mild and moderate/severe BPD in extramural neonates with a birth weight <1501 g. A case-control study was conducted between January 1, 2004- December 31, 2006 at the Dr. Sami Ulus Children's Hospital Neonatal Intensive Care Unit. Patients with BPD and without BPD were compared. Bronchopulmonary dysplasia was diagnosed and classified according to the Bancalari criteria. One-hundred and six (106) extramural premature infants with a birth weight <1501 g and admitted to the Neonatal Unit in the first three days of life and survived for more than 28 postnatal days were included. Patients with multiple congenital anomalies and complex cardiac pathologies were excluded. The maternal and neonatal risk factors, clinical features, mechanical ventilation treatment were compared. The principal risk factors for BPD development were analyzed and followed by logistic regression test. The diagnosis was mild BPD in 27 of the 106 patients and moderate/severe BPD in 29. The incidence of BPD was 52.8%. Fifty of 106 patients had no BPD. Analysis of risk factors revealed that gestational age < or =28 weeks (p=0.019), birth weight < or =1000 g (p=0.007), hypothermia (p=0.003), acidosis (p=0.003) and hypotension (p=0.005) at admission, respiratory distress syndrome (RDS) ( p<0.001), mechanical ventilation therapy (p<0.001), surfactant therapy (p=0.005), higher amount of mean fluid therapy on 7(th) days (p=0.008), nosocomial infection (p<0.001), higher amount of mean packed red cell transfusions (p<0.001) and more than two packed red cell transfusions (p=0.033) were risk factors associated with the development of BPD. Multivariant logistic regression analysis showed acidosis at admission (OR 5.12, 95%CI 1.17-22.27, p=0.029), surfactant treatment (OR 7.53, 95%CI 2.14-26.45, p=0.002), nosocomial infections (OR 4.66, 95%CI 1.27-17.12, p=0.02) and PDA (OR 9.60, 95%CI 2.23-41.22, p=0.002) were risk factors increasing the severity of BPD. The most important risk factors for BPD development in our study were RDS and nosocomial infections while the presence of acidosis at admission, surfactant administration, nosocomial infections and the presence of PDA were the most important risk factors regarding BPD severity. Presence of acidosis at admission as a risk factor emphasized the importance of suitable transport conditions for premature infants.

MMP‐9 and TIMP‐1 in the cord blood of premature infants developing BPD

We investigated matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels in the cord blood of 29 premature infants who were <30 weeks gestation. One, 8, and 14 infants developed severe, moderate and mild bronchopulmonary dysplasia (BPD), respectively, and 6 did not. MMP-9 and TIMP-1 levels in the cord blood were determined by ELISA. MMP-9/TIMP-1 ratios in the cord blood of infants who developed severe or moderate BPD (n = 9) were significantly higher than those who developed mild BPD or did not develop BPD (n = 20; P = 0.015). Multivariate linear regressions demonstrated that MMP-9 levels and MMP-9/TIMP-1 ratios in the cord blood of the premature infants correlated with the oxygen supplementation period (r = 0.58, P = 0.003 and r = 0.41, P = 0.030, respectively). The MMP-9 levels and MMP-9/TIMP-1 ratios correlated with the severity of maternal chorioamnionitis (both trend P = 0.006). The MMP-9 levels and MMP-9/TIMP-1 ratios in the cord blood may be related to the pathogenesis and severity of BPD and maternal chorioamnionitis.

The effects of neonatal ventilator care or maternal chorioamnionitis on the development of bronchopulmonary dysplasia

Purpose : Advances in neonatal intensive care have improved the survival rate of low-birth-weight infants, but mild bronchopulmonary dysplasia (BPD) with the accompanying need for prolonged oxygen supplement remains problematic. Maternal chorioamnionitis and neonatal ventilator care affect the development of BPD. This study aimed to examine whether maternal chorioamnionitis or neonatal ventilator care affect the development of BPD dependently or independently. Methods : We performed a retrospective study of 158 newborn infants below 36 weeks of gestational age and 1,500 gm birth weight admitted to the neonatal intensive care unit of Daegu Fatima Hospital between January 2000 and December 2006. We analyzed the incidence of BPD according to maternal chorioamnionitis and neonatal ventilator care. Result : Histologic chorioamnionitis was observed in 50 of 158 infants (31.6%). There were no significant differences in the development of BPD (P=0.735) between the chorioamnionitis (+) and chorioamnionitis (-) groups. In the multiple regression analysis, ventilator care (OR=7.409, 95% CI=2.532-21.681) and neonatal sepsis (OR=4.897, 95% CI=1.227-19.539) affected the development of BPD rather than maternal chorioamnionitis (OR=0.461, 95% CI=0.201-1.059). Conclusion : Ventilator care or neonatal sepsis may play a role in the development of BPD rather than maternal chorioamnionitis.

The epidemiology of atypical chronic lung disease in extremely low birth weight infants

To determine the incidence and associated complications of atypical chronic lung disease (ACLD) in extremely low birth weight infants. All infants born at Johns Hopkins Hospital between 1996 and 2001, with birthweight <1000 g, gestational age <31 weeks, no major anomalies or genetic syndromes, and living at least 21 days were eligible for inclusion. Data pertaining to demographics, hospital course, diagnosis of atypical chronic lung disease, patterns of surfactant use, complications of prematurity and severity of lung disease were collected. Using inclusion criteria, 215 eligible infants were identified, of which 185 had hospital charts available for review. Twenty-eight infants (15%) met the criteria for atypical chronic lung disease. Of the remaining 157 infants, 57 patients met the criteria for mild bronchopulmonary dysplasia (BPD) (supplemental oxygen requirement at 28 days of life), 38 patients had moderate/severe BPD (supplemental oxygen requirement at both 28 days of life and 36 weeks post-menstrual age), and 38 infants did not have chronic lung disease. Infants with ACLD had much higher rates of sepsis (46%) and pneumothorax (18%) than infants in the comparison groups. Infants with respiratory distress syndrome in the first week of life, which initially resolves are still at risk for an atypical form of chronic lung disease. The prolonged respiratory support they require as a result of this type of lung disease increases their risk for complications of prematurity, which may outlast their lung disease. We speculate that inflammation secondary to infection acquired shortly after birth may be an important step in the pathogenesis of ACLD.

Cord Blood KL-6, a Specific Lung Injury Marker, Correlates with the Subsequent Development and Severity of Atypical Bronchopulmonary Dysplasia

Background: A considerable number of preterm infants may have been exposed to inflammation in utero and may be born with an inflamed lung. Objectives: To determine the impact of antenatal lung injury and inflammatory response on the pathogenesis of bronchopulmonary dysplasia (BPD) according to its clinical pattern, using KL-6 (as a lung injury marker) and C-reactive protein (CRP) (as a marker of inflammatory response). Methods: In this case-control study, a total of 74 infants (<32 weeks of gestation) including BPD with minimal early lung disease (‘atypical’; 21 infants), BPD with significant early lung disease (‘classic’; 29 infants) and the non-BPD (24 infants) groups underwent KL-6 and CRP in cord blood determinations. Results: The cord plasma KL-6 levels were significantly higher in the atypical and the total BPD groups than in the non-BPD group (median = 60.9 vs. 34.5 U/ml, p = 0.031; 43.5 vs. 34.5 U/ml, p = 0.02). However, the cord plasma CRP levels were not significantly different among the study groups. The cord plasma KL-6 levels in patients with atypical BPD were significantly higher in infants with moderate or severe BPD than in infants with mild BPD (median = 88.3 vs. 41.5 U/ml, p = 0.041) and were found to be significantly correlated with the duration of oxygen therapy (r = 0.502, p = 0.024). Conclusions: The present study shows that cord plasma KL-6, a specific lung injury marker, is increased and objectively reflects disease severity in atypical BPD.

Developmental sequelae in preterm infants having a diagnosis of bronchopulmonary dysplasia: analysis using a severity-based classification system.

To investigate the relationship between the severity-based definition of bronchopulmonary dysplasia (BPD), choice of treatment, and neurocognitive outcomes at age 3 and 8 years. This is a secondary analysis of data collected from a prospective, longitudinal sample of 99 children with a history of BPD. Children born with BPD admitted to 3 hospitals from February 1, 1989, to November 31, 1991. Ninety-nine children with BPD were longitudinally assessed at age 3 and 8 years. Three severity groups (mild, moderate, and severe) were formed based on gestational age and need for supplemental oxygen therapy. Supplemental oxygen therapy for 28 days or longer, birth weight less than 1500 g, and radiographic evidence of lung disease. Neurologic and medical outcomes; type of medical management; and language, achievement, and cognitive functioning were compared among the 3 severity groups. Severity classification of BPD was associated with poorer outcomes. Compared with children with mild or moderate BPD, children with severe BPD performed more poorly on IQ tests (Mental Development Index, 90 vs 76.4; and Psychomotor Development Index, 92.5 vs 73.9) and language measures (total, 95 vs 82) at age 3 years and performance IQ (86 vs 75) and perceptual organization (86 vs 76) at age 8 years. Severity of BPD was not associated with choice of medical management but was related to educational interventions. Children with severe BPD received more special education services (69% vs 44%) than did children with mild BPD. The severity-based classification clarifies the relationship between BPD and developmental sequelae. Children with severe BPD required more interventions at age 8 years than did children with mild or moderate BPD.

Deletion Allele of Angiotensin-Converting Enzyme is Associated with Increased Risk and Severity of Bronchopulmonary Dysplasia

To explore whether the deletion (D) allele of angiotensin-converting enzyme (ACE) is associated with the risk or severity of bronchopulmonary dysplasia (BPD) among very low birth weight (BW) infants. Infants with a BW < or = 1250 g were prospectively recruited. The D and I (insertion) alleles of ACE were determined using a polymerase chain reaction followed by restriction fragment length polymorphism analysis. Infants with DD/DI genotype of ACE had a (mean +/- SD) birth weight (938 +/- 204 g vs 925 +/- 196 g) and gestational age (28 +/- 3 weeks vs 28 +/- 2 weeks), similar to infants with II genotype of ACE (P > .05). Infants with DD/DI genotype of ACE were more likely to have BPD than infants with II genotype (47% vs 22%, P = .025). Among infants with BPD, ACE DD/DI genotype was more common among infants with moderate or severe BPD compared with infants with mild BPD (74% vs 26%, P = .012). The number of D alleles of ACE correlated directly and positively with the severity of BPD (R = 0.23, P = .045). The D allele of ACE is associated with an increased risk and severity of BPD among preterm infants.

Validation of the National Institutes of Health Consensus Definition of Bronchopulmonary Dysplasia

A number of definitions of bronchopulmonary dysplasia (BPD), or chronic lung disease, have been used. A June 2000 National Institute of Child Health and Human Development/National Heart, Lung, and Blood Institute Workshop proposed a severity-based definition of BPD for infants <32 weeks' gestational age (GA). Mild BPD was defined as a need for supplemental oxygen (O2) for > or =28 days but not at 36 weeks' postmenstrual age (PMA) or discharge, moderate BPD as O2 for > or =28 days plus treatment with <30% O2 at 36 weeks' PMA, and severe BPD as O2 for > or =28 days plus > or =30% O2 and/or positive pressure at 36 weeks' PMA. The objective of this study was to determine the predictive validity of the severity-based, consensus definition of BPD. Data from 4866 infants (birth weight < or =1000 g, GA <32 weeks, alive at 36 weeks' PMA) who were entered into the National Institute of Child Health and Human Development Neonatal Research Network Very Low Birth weight (VLBW) Infant Registry between January 1, 1995 and December 31, 1999, were linked to data from the Network Extremely Low Birth Weight (ELBW) Follow-up Program, in which surviving ELBW infants have a neurodevelopmental and health assessment at 18 to 22 months' corrected age. Linked VLBW Registry and Follow-up data were available for 3848 (79%) infants. Selected follow-up outcomes (use of pulmonary medications, rehospitalization for pulmonary causes, receipt of respiratory syncytial virus prophylaxis, and neurodevelopmental abnormalities) were compared among infants who were identified with BPD defined as O2 for 28 days (28 days definition), as O2 at 36 weeks' PMA (36 weeks' definition), and with the consensus definition of BPD. A total of 77% of the neonates met the 28-days definition, and 44% met the 36-weeks definition. Using the consensus BPD definition, 77% of the infants had BPD, similar to the cohort identified by the 28-days definition. A total of 46% of the infants met the moderate (30%) or severe (16%) consensus definition criteria, identifying a similar cohort of infants as the 36-weeks definition. Of infants who met the 28-days definition and 36-weeks definition and were seen at follow-up at 18 to 22 months' corrected age, 40% had been treated with pulmonary medications and 35% had been rehospitalized for pulmonary causes. In contrast, as the severity of BPD identified by the consensus definition worsened, the incidence of those outcomes and of selected adverse neurodevelopmental outcomes increased in the infants who were seen at follow-up. The consensus BPD definition identifies a spectrum of risk for adverse pulmonary and neurodevelopmental outcomes in early infancy more accurately than other definitions.

178 Pulmonary Function at one Year of Age in Premature Infants with Bronchopulmonary Dysplasia

Background: Bronchopulmonary dysplasia (BPD) was recently classified as mild, moderate or severe in step with oxygen (O2) or positive pressure (PP) requirement at 36 wks post conceptional age (PCA).Objective: To assess pulmonary function at one year of age of premature infants born before 32 wks PCA in step with initial BPD severity. Patients and methods: 25 infants (mean GA±SD = 27.6±1.9 wks; birthweight = 851±174g) with BPD (i.e., O2 requirement for more than 28 days) were classified as mild BPD if weaned of O2 and PP at 36 wks PCA (group1; n=8) and moderate to severe if not (group2, n=16). At 14.3±3.5 months of age (i.e.; 11.7±3.6 months corrected age) functional residual capacity (FRC) was assessed with the nitrogen washout method and the partial forced expiratory flow (Vmax FRC) with the jacket method. Values were expressed as percentage of predicted normal values.Results: Vmax FRC and FRC of the population studied were 42.6±26.5% and 77.4±14.9% of predicted normal values, respectively. 4 infants (16.7%) had pure restrictive disease (i.e.; FRC < 80% of predicted values), 8 (33,3%) had pure obstructive disease (i.e.; Vmax FRC < 80% of predicted values) and 11 (45%) had both diseases. There was no statistical correlation between any measurements of pulmonary function and birthweight, GA, duration of mechanical ventilation nor duration of oxygen therapy. There was no significant difference in pulmonary function at 1 year of age between the 2 groups.Conclusion: Infants with a history of BDP exhibited very frequent severe pulmonary function abnormalities at one year of age characterized by airflow obstruction, restrictive disease or both. These abnormalities were no predicted by initial BPD severity.

Developmental Regulation of p66Shc Is Altered by Bronchopulmonary Dysplasia in Baboons and Humans

The p66(Shc) adapter protein antagonizes mitogen-activated protein, or MAP, kinase, mediates oxidative stress, and is developmentally regulated in fetal mouse lungs. To determine if p66(Shc) is similarly regulated in primates and in bronchopulmonary dysplasia (BPD), which results from oxidative injury to immature lungs. Normal and injured lungs from humans and baboons were evaluated by Western analysis and immunohistochemistry. In baboons, p66(Shc) decreased 80% between 125 and 175 days' gestation (p = 0.025), then doubled after term delivery at 185 days (p = 0.0013). In the hyperoxic 140-day fetal baboon BPD model, p66(Shc) expression persisted, and its localization shifted from the epithelium of gestational controls to the mesenchyme of diseased lungs, coincident with expression of proliferating cell nuclear antigen and cleaved poly(adenyl ribose) polymerase, a marker of apoptosis. Treatment with the antibombesin antibody 2A11 attenuated BPD, reduced cell proliferation, increased p66(Shc) expression 10.5-fold, and preserved epithelial p66(Shc) localization. p66(Shc) also decreased during normal human lung development, falling 87% between 18 and 24 weeks' gestation (p = 0.02). p66(Shc) was expressed throughout 18-week human lungs, became restricted to scattered epithelial cells by 24 weeks, and localized to isolated mesenchymal cells after term delivery. In contrast, p66(Shc) remained prominent in the epithelium of lungs with acute injury or mild BPD, and in the mesenchyme of lungs with severe disease. p66(Shc) localized to tissues expressing proliferating cell nuclear antigen and cleaved poly(adenyl ribose) polymerase. p66(Shc) expression, cell proliferation, and apoptosis are concomitantly altered during lung development and in BPD.

Lung function at term reflects severity of bronchopulmonary dysplasia

To test whether infants with bronchopulmonary dysplasia (BPD) express the same functional impairments at term as healthy, preterm infants, and whether clinical severity of BPD is qualitatively or quantitatively related. Prospective measurements on a consecutive sample of 50 infants with BPD and 19 healthy preterm controls in a university hospital. BPD infants were classified as "severe," "moderate," or "mild," according to their need for oxygen. A multiple-breath nitrogen wash-out method was used to assess functional residual capacity (FRC) and gas mixing efficiency. Mechanical variables were estimated by the occlusion test. Infants with severe BPD had lower FRC, less efficient gas mixing, and higher specific conductance than those with mild and moderate BPD, and the preterm controls. Mild and moderate BPD did not differ in any property from each other but differed from controls in the same variables. The elastic properties of the respiratory system appeared unaffected by BPD. The ventilatory impairments in BPD were of the same nature as in healthy preterm infants when compared with term infants, but their magnitude was related to the clinical severity of the BPD. Gas mixing efficiency together with FRC appears to be useful to assess lung development in BPD.

Is the New Definition of Bronchopulmonary Dysplasia More Useful?

To determine the incidence of bronchopulmonary dysplasia (BPD) in low birth weight (LBW) infants <1251 g managed with early bubble nasal continuous positive airway pressure (NCPAP) and a gentle ventilation strategy using the newly proposed definition for BPD and the previous definitions. Needs for supplemental oxygen and positive pressure (positive pressure ventilation or NCPAP) during initial hospitalization were evaluated in 266 inborn LBW infants (birth weight <1251 g). The data were categorized in three weight groups, <751, 751 to 1000 and 1001 to 1250 g and the incidence of BPD was computed in survivors based on oxygen need at 28 days, 36 weeks postmenstrual age (PMA) and the new severity of BPD criteria, that is, mild BPD: need for supplemental oxygen > or =28 days, but not at 36 weeks PMA; moderate BPD: need for supplemental oxygen > or =28 days and <30% at 36 weeks PMA and severe BPD: need for supplemental oxygen > or =28 days, and >30% at 36 weeks PMA and/or positive pressure at 36 weeks PMA. Further, BPD-associated comorbidities and short-term outcome data during hospitalization were compared among the groups, defined by severity of BPD. Among LBW infants <1251 g, the incidences of BPD at 28 days and 36 weeks PMA were 21.1 and 7.4% respectively. Using the newly defined criteria, the incidences of mild, moderate and severe BPD were 13.5, 4.8 and 2.6%, respectively. In total, 64.6% of these infants had mild BPD and 70.8% weighed <751 g at birth. Associated comorbidities correlated significantly with grades of underlying pulmonary disease. Also, significantly longer hospital stay, discharge at a higher PMA and lower growth velocity was observed with increasing grades of BPD. The new system for grading the severity of BPD offers a better description of underlying pulmonary disease and correlates with the infant's maturity, growth and overall severity of illness. Whether it will have a role in predicting long-term outcome remains to be determined.

Increased lung water and tissue damage in bronchopulmonary dysplasia

To test the hypothesis that high and asymmetrical water content persists in infants with bronchopulmonary dysplasia (BPD) and that this is associated with nonuniform lung damage. Magnetic resonance imaging was used to assess lung water content in 20 infants and tissue injury in 35 infants of 23 to 33 weeks' gestational age (15 with severe BPD, 13 with mild BPD, and 7 without BPD). Relative proton density provided an index of water content and distribution. The location and extent of focal densities and cyst-like appearances indicating lung damage were defined. Proton density was significantly higher in dependent regions. Average proton density, proton density gradient, and severity of lung damage were greater in infants with severe BPD. Indicators of damage were greatest in dorsal lung regions. BPD was associated with a higher lung water burden and gravity-dependent atelectasis and/or alveolar flooding. Lesions were more common in dorsal lung regions in infants with severe lung damage. Infants with BPD have increased lung water and are susceptible to gravity-induced collapse and/or alveolar flooding in the dependent lung. Focal tissue damage appears to be distributed inhomogenously.

Polymorphism of tumor necrosis factor-alpha and risk and severity of bronchopulmonary dysplasia among very low birth weight infants.

Preterm infants with bronchopulmonary dysplasia (BPD) exhibit prolonged elevation of inflammatory indices in their tracheal aspirates. Tumor necrosis factor-alpha (TNF-alpha) is a central mediator of the inflammatory response. The adenine-containing alleles of TNF-alpha-308 and lymphotoxin-alpha+250 have been associated with increased levels of TNF-alpha, whereas the adenine allele of TNF-alpha-238 produces lower levels of TNF-alpha after stimulation. High levels of TNF-alpha may promote chronic inflammation by overwhelming counter-regulatory mechanisms and may lead to the development of BPD. Low levels of TNF-alpha may decrease the risk and/or severity of BPD. To determine whether alleles of TNF-alpha play a role in the susceptibility and/or severity of BPD among very low birth weight infants. Infants with birth weights of < or =1250 g were included. Genotypic analyses (polymerase chain reaction-restriction fragment length polymorphism assays) were performed with DNA extracted from whole-blood samples. Infants who developed BPD (fraction of inspired oxygen at postconceptional age of 36 weeks of >0.21, n = 51) had a younger gestational age (mean +/- SD: 27 +/- 4 vs 29 +/- 2 weeks) and lower birth weight (853 +/- 184 vs 997 +/- 193 g) than did infants without BPD (n = 69). The genotypic distributions of lymphotoxin-alpha+250 and TNF-alpha-308 were comparable among the groups of infants. However, the AA and GA TNF-alpha-238 genotypes were much less likely to occur among infants with BPD than among infants without BPD. The adenine allele of TNF-alpha-238 was absent among infants with severe BPD and occurred significantly less often among infants with moderate or severe BPD, compared with infants with mild BPD. The number of adenine alleles of TNF-alpha-238 was correlated inversely with the severity of BPD (r = -.341). The adenine allele of TNF-alpha-238 may reduce the risk and severity of BPD.

Early changes of pulmonary mechanics to predict the severity of bronchopulmonary dysplasia in ventilated preterm infants

Objectives: To verify whether early pulmonary mechanics measurements are useful to predict subsequent bronchopulmonary dysplasia (BPD) and its severity. Methods: Pulmonary mechanics were studied at 3, 5, 7 and 10 days of age in 52 preterm infants with birth weight < 1250 g, affected by respiratory distress syndrome and ventilated for more than 72 h. Pulmonary function was assessed using a previously standardized method based on the measurement of airflow with a Fleisch OO pneumotachograph and airway pressure with a model P7D differential pressure transducer. At 28 days pulmonary outcome was classified into three groups: no BPD, mild BPD (oxygen dependency and hazy lung on X-ray) and severe BPD (oxygen dependency and Northway stage 3/4). Results: Of the 52 infants, 39 survived to 28 days: no BPD (11 infants), mild BPD (16 infants) and severe BPD (12 infants). The no-BPD group had significantly higher gestational age and birth weight, fewer males and a lower incidence of patent ductus arteriosus than both BPD groups, while no differences were detected between the BPD groups. Lung compliance was significantly higher in the mild-BPD group than in the severe-BPD group at 7 and 10 days of life (p < 0.01 and p < 0.001, respectively). The corresponding odds ratio confirmed that ventilated infants with lower lung compliance values had a significantly higher probability of developing severe BPD. Respiratory system resistance did not show any predictive value. Conclusions: Our findings indicate that low lung compliance values determined on the 7th and 10th days of life are a reliable predictive tool of the severity of later BPD.

Early changes of pulmonary mechanics to predict the severity of bronchopulmonary dysplasia in ventilated preterm infants

Objectives: To verify whether early pulmonary mechanics measurements are useful to predict subsequent bronchopulmonary dysplasia (BPD) and its severity.Methods: Pulmonary mechanics werestudied at 3, 5, 7 and 10 days of age in 52 preterm infants with birth weight < 1250 g, affected by respiratory distress syndrome and ventilated for more than 72 h. Pulmonary function was assessed usinga previously standardized method based on the measurement of airflow with a Fleisch OO pneumotachograph and airway pressure with a model P7D differential pressure transducer. At 28 days pulmonary outcomewas classified into three groups: no BPD, mild BPD (oxygen dependency and hazy lung on X-ray) and severe BPD (oxygen dependency and Northway stage 3/4).Results: Of the 52 infants, 39 survivedto 28 days: no BPD (11 infants), mild BPD (16 infants) and severe BPD (12 infants). The no-BPD group had significantly higher gestational age and birth weight, fewer males and a lower incidence of patentductus arteriosus than both BPD groups, while no differences were detected between the BPD groups. Lung compliance was significantly higher in the mild-BPD group than in the severe-BPD group at 7 and 10days of life (p < 0.01 and p < 0.001, respectively). The corresponding odds ratio confirmed that ventilated infants with lower lung compliance values had a significantly higher probabilityof developing severe BPD. Respiratory system resistance did not show any predictive value.Conclusions: Our findings indicate that low lung compliance values determined on the 7th and 10th daysof life are a reliable predictive tool of the severity of later BPD.