Neonatal Chronic Lung Disease Research Articles

Perinatal factors in non‐disabled ELBW school children and later performance

To determine the association between perinatal events and subsequent motor performance, cardiorespiratory endurance and respiratory function in non-disabled extremely low birthweight (ELBW) school children at 12 years of age. Forty-eight ELBW infants were included in this study. The Movement Assessment Battery for Children (MABC), VO(2) max score as a measure of cardiorespiratory endurance and respiratory function testing were performed and perinatal variables were extracted from the children's hospital files. Children with MABC score ≤ 15th centile were described as having suspect motor performance. Children were classified as being unfit with a VO(2) max > 1 standard deviation below the mean according to gender and age. Perinatal risk factors were explored as risk factors for motor outcome, cardiorespiratory endurance and respiratory function. MABC category was significantly related with gender (P = 0.005) and chronic neonatal lung disease (P = 0.013). Multiple regression analysis showed motor outcome at 12 years to be independently related to male gender (P = 0.03) and chronic neonatal lung disease (P = 0.045). Sixty-five percent of all the children were identified as unfit. Chronic neonatal lung disease was significantly related to cardiorespiratory endurance (P = 0.03) and predicted VO(2) max at 12 years (P = 0.05). No perinatal factors were significantly related to respiratory function variables. Male gender and chronic neonatal lung disease were associated with later motor outcome of ELBW school children. It is suggested that objective and consistent follow-up from childhood through preadolescence are important to address motor and fitness issues especially for male children born with ELBW.

Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants

Postnatal corticosteroids have been used for prevention and treatment of neonatal chronic lung disease (CLD) (also know as bronchopulmonary dysplasia), a significant cause of mortality and morbidity in preterm infants. As both dexamethasone and hydrocortisone administration within the first seven days of life is associated with an increased risk of cerebral palsy, early postnatal corticosteroid therapy is not recommended to prevent CLD. After seven days of life, dexamethasone has been shown to decrease the rate of CLD at 36 weeks' postmenstrual age with less impact on neurodevelopmental outcome. No trials have examined whether the benefits of corticosteroids outweigh the adverse effects for infants at high risk of, or with, severe CLD. While routine dexamethasone therapy of all ventilated infants is not recommended, clinicians may consider a short course of low-dose dexamethasone for individual infants at high risk of or with severe CLD. There is no evidence that hydrocortisone is an effective or safe alternative to dexamethasone and little evidence to support routine use of inhaled corticosteroids for prevention or treatment. Inhaled corticosteroids may be considered as an alternative to dexamethasone for treating individual infants with severe CLD. This revision replaces a statement published jointly with the American Academy of Pediatrics in 2002.

Experimental BPD – cells from human umbilical cord blood improve lung development in a double-hit mouse model

Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease in neonates with low gestational age and low birth weight. Besides the consequences for the neonatal period, the disease also affects the further development of the patients with lifelong consequences like persistent lung abnormalities. BPD has a multifactorial etiology with main risk factors being prematurity, low birth weight, oxygen therapy or infection. Among other symptoms, “new” BPD often presents with alveolar arrest and impaired lung development. Several studies showed improvement of lung development in rodent models using stem cells of different origin. Objectives: To investigate the effects of human umbilical cord blood cells (buffy coat), including progenitor and stem cells on the lung development in a BPD double-hit model. Methods: We established a new double-hit animal model in the mouse, combining prenatal hypoxia (4 days) and postnatal hyperoxia (13 days), thus combining lung damage with low birth weight to get closer to the multifactorial situation in humans. The mice were intraperitoneally injected with cells from human umbilical cord blood at postnatal day seven. The mRNA expression in lung tissue was analysed for SPB, SPC, VEGF, Elastin, HIF1a, mTOR, IGF1, RARα, RARβ, RARγ, CRABP1, RBP1, TGFb1, TGFb2, TGFb3. Results: The double-hit mice were smaller at birth than normal mice and developed more slowly. The lung structure in the double-hit mice was less developed compared to normal mice. Septal surface was decreased and septa were thickened. Treatment with buffy coat cells resulted in a tendency towards better growth of the pups. Lung structure was improved compared to untreated mice. Furthermore there was a tendency to a changed expression of several genes, being the most clear for mTOR. Conclusions: Treatment with human umbilical cord blood cells has an overall positive effect on growth and development in general and lung development in particular in our double-hit mouse model for BPD. Further studies are necessary in order to further improve stem cell therapy in experimental BPD.

Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome.

Clinical trials have confirmed that surfactant therapy is effective in improving the immediate need for respiratory support and the clinical outcome of premature newborns. Trials have studied a wide variety of surfactant preparations used either to prevent (prophylactic or delivery room administration) or treat (selective or rescue administration) respiratory distress syndrome (RDS). Using either treatment strategy, significant reductions in the incidence of pneumothorax, as well as significant improvement in survival, have been noted. It is unclear whether there are any advantages to treating infants with respiratory insufficiency earlier in the course of RDS. To compare the effects of early versus delayed selective surfactant therapy for newborns intubated for respiratory distress within the first two hours of life. Planned subgroup analyses included separate comparisons for studies utilizing natural surfactant extract and synthetic surfactant. We searched the Oxford Database of Perinatal Trials, MEDLINE (MeSH terms: pulmonary surfactant; text word: early; limits: age, newborn: publication type, clinical trial), PubMed, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language. For the updated search in April 2012 we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012, Issue 1) and PubMed (January 1997 to April 2012). Randomized and quasi-randomized controlled clinical trials comparing early selective surfactant administration (surfactant administration via the endotracheal tube in infants intubated for respiratory distress, not specifically for surfactant dosage) within the first two hours of life versus delayed selective surfactant administration to infants with established RDS were considered for review. Data regarding clinical outcomes were excerpted from the reports of the clinical trials by the review authors. Subgroup analyses were performed based on type of surfactant preparation, gestational age, and exposure to prenatal steroids. Data analysis was performed in accordance with the standards of the Cochrane Neonatal Review Group. Six randomized controlled trials met selection criteria. Two of the trials utilized synthetic surfactant (Exosurf Neonatal) and four utilized animal-derived surfactant preparations.The meta-analyses demonstrate significant reductions in the risk of neonatal mortality (typical risk ratio (RR) 0.84; 95% confidence interval (CI) 0.74 to 0.95; typical risk difference (RD) -0.04; 95% CI -0.06 to -0.01; 6 studies; 3577 infants), chronic lung disease (typical RR 0.69; 95% CI 0.55 to 0.86; typical RD -0.04; 95% CI -0.06 to -0.01; 3 studies; 3041 infants), and chronic lung disease or death at 36 weeks (typical RR 0.83; 95% CI 0.75 to 0.91; typical RD -0.06; 95% CI -0.09 to -0.03; 3 studies; 3050 infants) associated with early treatment of intubated infants with RDS.Intubated infants randomized to early selective surfactant administration also demonstrated a decreased risk of acute lung injury including a decreased risk of pneumothorax (typical RR 0.69; 95% CI 0.59 to 0.82; typical RD -0.05; 95% CI -0.08 to -0.03; 5 studies; 3545 infants), pulmonary interstitial emphysema (typical RR 0.60; 95% CI 0.41 to 0.89; typical RD -0.06; 95% CI -0.10 to -0.02; 3 studies; 780 infants), and overall air leak syndromes (typical RR 0.61; 95% CI 0.48 to 0.78; typical RD -0.18; 95% CI -0.26 to -0.09; 2 studies; 463 infants).A trend toward risk reduction for bronchopulmonary dysplasia (BPD) or death at 28 days was also evident (typical RR 0.94; 95% CI 0.88 to 1.00; typical RD -0.04; 95% CI -0.07 to -0.00; 3 studies; 3039 infants). No differences in other complications of RDS or prematurity were noted.Only two studies reported on infants under 30 weeks' gestation. Decreased risk of neonatal mortality and chronic lung disease or death at 36 weeks' postmenstrual age was noted. Early selective surfactant administration given to infants with RDS requiring assisted ventilation leads to a decreased risk of acute pulmonary injury (decreased risk of pneumothorax and pulmonary interstitial emphysema) and a decreased risk of neonatal mortality and chronic lung disease compared to delaying treatment of such infants until they develop worsening RDS.

The importance of understanding epidemiology in order to inform financial decisions: A lesson from the Scottish Home Oxygen Service

To ensure that decisions on the future planning of the Scottish Home Oxygen Service reflect population needs by examining the epidemiology of the main conditions that require home oxygen therapy and trends in their management. Analysis of routinely available vital event and health service data supplemented by published literature. Use of linked data to provide person-based analyses. Consideration of trends in key risk factors, disease incidence, prevalence and mortality for chronic neonatal lung disease, cystic fibrosis, chronic interstitial lung disease in adults and chronic obstructive pulmonary disease. Examination of trends in management of these conditions including hospital admissions, length of stay and re-admissions. The prevalence of all the conditions studied has increased in Scotland over recent years due to a combination of increased incidence, increased survival, more active case finding and demographic changes. There have been changes in management with trends towards shorter hospital stays. The clinical need for home oxygen therapy is likely to continue to increase over the next 10-20 years. It will encompass all age groups and a complex range of conditions. Public health needs to be proactive in providing relevant needs assessment information to ensure that planning within financial constraints is appropriately informed on population needs.

Restriction of oral intake of water for aspiration lung disease in children

Primary aspiration of food and fluid is commonly seen in children with feeding and swallowing difficulties associated with a range of diseases and complex medical conditions. Respiratory sequelae and pneumonia are known to be associated with primary aspiration of ingested material, however causality between primary aspiration of specific food and fluid types and pulmonary effects in children is yet to be established in controlled trials. The relative pulmonary morbidity of aspiration of ingested food and fluid materials versus other causes of respiratory disease such as viral and bacterial causes, secondary aspiration of gastrointestinal contents and predisposing lung conditions such as chronic neonatal lung disease in a developing immune system is also unclear. Current management decisions for children who aspirate have to optimise oral nutrition and hydration, while reducing the risk of aspiration to preserve pulmonary integrity. This generally includes restricting aspirated food or fluids and providing texture-modified diets and thickened fluids. Young children frequently refuse thickened fluids providing a management dilemma for both families and health professionals. Our objective was to evaluate the efficacy of restriction of oral water ingestion on the pulmonary status of children with thin fluid aspiration demonstrated on a modified barium swallow study. The Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Airways Collaborative Review Group Specialised Register, MEDLINE, EMBASE and CINAHL databases were searched by the Cochrane Airways Group. The latest search was performed in May 2102. All randomised controlled trials comparing restriction of oral intake of water with unlimited oral water ingestion were eligible to be included. Results of searches were reviewed against a pre-determined criteria for inclusion. No eligible trials were identified for a paediatric population and thus no data were available for analysis. One trial in an adult population was identified and reported. No randomised controlled trials examining the efficacy of restriction of oral intake of water in the management of children with thin fluid aspiration were found. In a single study in an adult population with stroke, no significant differences were seen between a control group of oral water restriction and the experimental group of unlimited oral water ingestion on outcomes such as pneumonia, total oral fluid intake and dehydration. There are no trials that have adequately evaluated the pulmonary effects of allowing or restricting oral water ingestion in children known to have primary aspiration of thin fluids. Thus, there is currently an absence of evidence to support a strict approach of full restriction of oral intake of water or support a more liberal approach of allowing oral water ingestion in children with primary aspiration of thin fluids.

CFTR Regulates Early Pathogenesis of Chronic Obstructive Lung Disease in βENaC-Overexpressing Mice

BackgroundFactors determining the onset and severity of chronic obstructive pulmonary disease remain poorly understood. Previous studies demonstrated that airway surface dehydration in βENaC-overexpressing (βENaC-Tg) mice on a mixed genetic background caused either neonatal mortality or chronic obstructive lung disease suggesting that the onset of lung disease was modulated by the genetic background.MethodsTo test this hypothesis, we backcrossed βENaC-Tg mice onto two inbred strains (C57BL/6 and BALB/c) and studied effects of the genetic background on neonatal mortality, airway ion transport and airway morphology. Further, we crossed βENaC-Tg mice with CFTR-deficient mice to validate the role of CFTR in early lung disease.ResultsWe demonstrate that the C57BL/6 background conferred increased CFTR-mediated Cl− secretion, which was associated with decreased mucus plugging and mortality in neonatal βENaC-Tg C57BL/6 compared to βENaC-Tg BALB/c mice. Conversely, genetic deletion of CFTR increased early mucus obstruction and mortality in βENaC-Tg mice.ConclusionsWe conclude that a decrease or absence of CFTR function in airway epithelia aggravates the severity of early airway mucus obstruction and related mortality in βENaC-Tg mice. These results suggest that genetic or environmental factors that reduce CFTR activity may contribute to the onset and severity of chronic obstructive pulmonary disease and that CFTR may serve as a novel therapeutic target.

Heterozygosity for E292V in ABCA3, lung function and COPD in 64,000 individuals.

BackgroundMutations in ATP-binding-cassette-member A3 (ABCA3) are related to severe chronic lung disease in neonates and children, but frequency of chronic lung disease due to ABCA3 mutations in the general population is unknown. We tested the hypothesis that individuals heterozygous for ABCA3 mutations have reduced lung function and increased risk of COPD in the general population.MethodsWe screened 760 individuals with extreme pulmonary phenotypes and identified three novel (H86Y, A320T, A1086D) and four previously described mutations (E292V, P766S, S1262G, R1474W) in the ABCA3 gene. We genotyped the entire Copenhagen City Heart study (n = 10,604) to assess the clinical importance of these mutations. To validate our findings we genotyped an additional 54,395 individuals from the Copenhagen General Population Study.ResultsIn the Copenhagen City Heart Study individuals heterozygous for E292V had 5% reduced FEV1 % predicted compared with noncarriers (t-test: p = 0.008), and an increased odds ratio for COPD of 1.9 (95% CI: 1.1-3.1). In contrast, the A1086D mutation was associated with increased FEV1 % predicted (p = 0.03). None of the other ABCA3 mutations associated with lung function or COPD risk in the Copenhagen City Heart Study. In the larger Copenhagen General Population Study, and in the two studies combined, E292V heterozygotes did not have reduced lung function or increased risk of COPD (p = 0.11-0.98), while this was the case for the positive controls, surfactant protein-B 121ins2 heterozygotes and α1-antitrypsin ZZ homozygotes.ConclusionOur results indicate that partially reduced ABCA3 activity due to E292V is not a major risk factor for reduced lung function and COPD in the general population. This is an important finding as 1.3% in the Danish population has partially reduced ABCA3 function due to E292V.

The EPICure Study: Association between Hemodynamics and Lung Function at 11 Years after Extremely Preterm Birth

ObjectiveTo investigate the relationship between disturbed lung function and large-artery hemodynamics in school-age children born extremely preterm (EP) (at 25 completed weeks of gestation or less).Study designThis was a cross-sectional study of participants from the EPICure study, now aged 11 years (n = 66), and 86 age- and sex-matched term-born classmates. Spirometry parameters (including forced expiratory volume in 1 second), blood pressure, and augmentation index (AIx, a composite of arterial stiffness and global wave reflections) were measured.ResultsCompared with their classmates, the EP children had significantly impaired lung function, particularly those with neonatal bronchopulmonary dysplasia. Peripheral blood pressure did not differ significantly between the 2 groups, but AIx values were on average 5% higher (95% CI, 2%-8%) in the preterm infants, remaining significant after adjustment for potential confounders. Neonatal bronchopulmonary dysplasia status was not related to AIx. Lung function and maternal smoking were independently associated with AIx; AIx increased by 2.7% per z-score reduction in baseline forced expiratory volume in 1 second and by 4.9% in those whose mothers smoked during pregnancy.ConclusionThe independent association between impaired lung function and cardiovascular physiology in early adolescence implies higher cardiovascular risk for children born EP, and suggests that prevention of chronic neonatal lung disease may be a priority in reducing later cardiovascular risk in preterm infants.

Audit of National Compliance with British Thoracic Society Guidelines for Neonatal Chronic Lung Disease

<h3>Aims</h3> The British Thoracic Society guidelines state that in infants with chronic lung disease (CLD), oxygen saturations below 90% are associated with an increased risk of apparent life threatening events (ALTE) and saturations below 92% may be associated with suboptimal growth. They recommend that, when assessing infants for the suitability of long term oxygen therapy (LTOT), pulse oximetry should be measured for 6-12 hours and that oxygen saturations should be maintained at 93% or above. This audit aims to identify national compliance with the BTS guidelines for assessing suitability of LTOT in CLD. <h3>Methods</h3> Guidelines for assessment for suitability for LTOT were obtained via telephone survey. <h3>Results</h3> 65 randomly selected English NICUs were contacted and 48 responded. 52% carry out pulse oximetry monitoring pre-discharge in infants with CLD to assess need for LTOT. Of these, target saturations were variable, 8% using 93%, 52% below and 40% above this. Although 43% monitored over the recommended time period, 48% monitored for over 12 and 2% for less than 6 hours. <h3>Conclusions</h3> Only 4% of units contacted carry out pulse oximetry to assess suitability for LTOT as per BTS guidelines. This suggests that some infants requiring LTOT may not receive this, increasing the risk of ALTE and poor growth. Others may receive unnecessary LTOT, with the associated expense and inconvenience. Local review supports this. These results suggest the need for increasing the awareness of the BTS guidelines amongst English neonatal units.

Mesenchymal stem cells and the stem cell niche: a new chapter

BONE MARROW-DERIVED mesenchymal stem/stromal cells (MSCs) are self-renewing multipotent cells with therapeutic effects in diverse models of tissue injury (27). In the rodent lung, MSCs reduce collagen deposition in the bleomycin model of pulmonary fibrosis (26) and reduce lung injury and improve survival following intrapulmonary delivery of endotoxin or Escherichia coli (10, 11) and following severe gram-negative peritonitis (18). In the hyperoxia model of bronchopulmonary dysplasia, exposure to high concentrations of oxygen during early postnatal life in rats and mice causes simplification of alveolar and lung capillary structure and reduced pulmonary capillary surface area, leading to pulmonary hypertension. Two groups reported simultaneously in 2009 that MSCs given by airway to rats (12) or by blood to mice (2) during prolonged hyperoxia in early postnatal life prevented arrested alveolar growth. However, engraftment of MSCs during hyperoxia and in other models has not accounted for the therapeutic effects, thus prompting a search for other mechanisms. MSCs are potent immunomodulators, suppressing several functions of lymphocytes, natural killer cells, and monocytes (1), and reduce inflammatory cell lung infiltrates and cytokines during sepsis and acute lung injury (11, 23, 25). In addition, MSCs have direct antibacterial effects (19), secrete epithelial growth factors (21), and can rescue epithelial cellular bioenergetics with mitochondrial transfer (14). MSCs and the Stem Cell Niche

Choriodecidual group B streptococcal inoculation induces fetal lung injury without intra-amniotic infection and preterm labor in Macaca nemestrina.

BackgroundEarly events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero.Methodology/Principal FindingsTen chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received one of two treatments: 1) choriodecidual and intra-amniotic saline (n = 5), or 2) choriodecidual inoculation of Group B Streptococcus (GBS) 1×106 colony forming units (n = 5). Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6) and fetal plasma (IL-8) were detected in GBS animals and correlated with lung injury (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (∼10 samples tested/animal), maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology.Conclusions/SignificanceA transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently without symptoms and before the onset of the fetal systemic inflammatory response syndrome.

Some ABCA3 mutations elevate ER stress and initiate apoptosis of lung epithelial cells

BackgroundABCA3 transporter (ATP-binding cassette transporter of the A subfamily) is localized to the limiting membrane of lamellar bodies, organelles for assembly and storage of pulmonary surfactant in alveolar epithelial type II cells (AECII). It transports surfactant phospholipids into lamellar bodies and absence of ABCA3 function disrupts lamellar body biogenesis. Mutations of the ABCA3 gene lead to fatal neonatal surfactant deficiency and chronic interstitial lung disease (ILD) of children. ABCA3 mutations can result in either functional defects of the correctly localized ABCA3 or trafficking/folding defects where mutated ABCA3 remains in the endoplasmic reticulum (ER).MethodsHuman alveolar epithelial A549 cells were transfected with vectors expressing wild-type ABCA3 or one of the three ABCA3 mutant forms, R43L, R280C and L101P, C-terminally tagged with YFP or hemagglutinin-tag. Localization/trafficking properties were analyzed by immunofluorescence and ABCA3 deglycosylation. Uptake of fluorescent NBD-labeled lipids into lamellar bodies was used as a functional assay. ER stress and apoptotic signaling were examined through RT-PCR based analyses of XBP1 splicing, immunoblotting or FACS analyses of stress/apoptosis proteins, Annexin V surface staining and determination of the intracellular glutathion level.ResultsWe demonstrate that two ABCA3 mutations, which affect ABCA3 protein trafficking/folding and lead to partial (R280C) or complete (L101P) retention of ABCA3 in the ER compartment, can elevate ER stress and susceptibility to it and induce apoptotic markers in the cultured lung epithelial A549 cells. R43L mutation, resulting in a functional defect of the properly localized ABCA3, had no effect on intracellular stress and apoptotic signaling.ConclusionOur data suggest that expression of partially or completely ER localized ABCA3 mutant proteins can increase the apoptotic cell death of the affected cells, which are factors that might contribute to the pathogenesis of genetic ILD.

Mechanism of Reduced Lung Injury by High-Frequency Nasal Ventilation in a Preterm Lamb Model of Neonatal Chronic Lung Disease

The mechanism underlying the potentially beneficial effects of the "gentler" modes of ventilation on chronic lung disease (CLD) of the premature infant is not known. We have previously demonstrated that alveolar parathyroid hormone-related protein-peroxisome proliferator-activated receptorγ (PTHrP-PPARγ) signaling is critically important in alveolar formation, and this signaling pathway is disrupted in hyperoxia- and/or volutrauma-induced neonatal rat lung injury. Whether the same paradigm is also applicable to CLD, resulting from prolonged intermittent mandatory ventilation (IMV), and whether differential effects of the mode of ventilation on the PTHrP-PPARγ signaling pathway explain the potential benefits of the "gentler" modes of ventilation are not known. Using a well-established preterm lamb model of neonatal CLD, we tested the hypothesis that ventilatory support using high-frequency nasal ventilation (HFNV) promotes alveolar PTHrP-PPARγ signaling, whereas IMV inhibits it. Preterm lambs managed by HFNV or IMV for 21 d following preterm delivery at 132-d gestation were studied by Western hybridization and immunofluorescence labeling for key markers of alveolar homeostasis and injury/repair. In lambs managed by IMV, the abundance of key homeostatic alveolar epithelial-mesenchymal markers was reduced, whereas it was significantly increased in the HFNV group, providing a potential molecular mechanism by which "gentler" modes of ventilation reduce neonatal CLD.

P1-373 Using epidemiological data to inform service planning: a lesson from the Scottish home oxygen service

IntroductionIncreasing demand for home oxygen in Scotland has resulted in a shortfall in the budget for this service. In 2009, discussions began to identify financial solutions. There was a lack...

Awake and asleep oxygen saturations in infants with chronic neonatal lung disease

There is uncertainty about the best method of withdrawing supplemental oxygen in babies with chronic neonatal lung disease (CNLD). Some authors advocate withdrawal of oxygen in the day, but continuing supplementation during sleep, based on early work suggesting that oxygen saturations are lower during sleep, which did not accord with our clinical impression. We re-examined the hypothesis that babies have lower saturations while asleep. We studied infants with CNLD during the day, while awake and asleep. We recorded video with simultaneous real-time capture of oxygen saturation (SpO2), heart rate and plethysmographic waveform from pulse oximetry. Behavioural state was scored using observation and video and classified as awake (feeding, active or quiet) or sleep. Thirteen infants had analysable data, although one had strikingly lower SpO2 values while awake and was excluded from analysis. The infants had a median gestation of 26 weeks and were studied at a median (range) postmenstrual age of 66 (37-130) weeks, for 229 (89-330) min. Mean SpO2 was 97.6% during sleep and 97.0% awake (p=0.011). Babies with CNLD have lower oxygen saturation while awake. There is no physiological justification for increasing oxygen during sleep, or withdrawing selectively during the daytime, although larger studies are needed to confirm this finding.

Rapid analysis of surfactant phosphatidylcholine synthesis in preterm infants utilising the incorporation of a novel stable isotope: a pilot study

While introduction of exogenous surfactant therapy has dramatically improved survival of infants born 23–28 weeks gestation, the turnover of exogenous and synthesis of endogenous surfactant components are poorly understood in...

814 Polymorphism of Surfactan Protein B Genes and the Risk of Respiratory Distress Sendrome and Chronic Lung Disease in Preterm Neonates

Objectives: To determine whether SP-B iΔ4 gene polymorphism is associated with respiratory distress syndrome (RDS) and chronic lung disease (CLD) etiology. Method: This prospective and retrospective study was performed in the neonatal intensive care unit in Turkey. In order to identify SP-B iΔ4 gene polymorphism, we analysed genomic DNA by polymerase chain reaction. Preterm neonates with a gestational age below 34 completed weeks, who were treated in our unit were included the study. The neonates with congenital anomalies and the neonates who died before the postnatal 28th day were excluded. The study was approved by the Local Committee on Investigations in Human Subjects. Total of 131 preterms and 50 healthy term infants were investigated. Premature babies were divided into 4 with respect to the development of RDS and CLD. Results: The frequency of SP-B iΔ4 gene variations did not differ between preterms (10.7%) and terms (10%). A total of 117 preterms with SP-B iΔ4 gene wild type (group A) and 14 preterms carrying the genetic variations (group B) did not differ in gestational age, gender distributionn and birth weight, RDS and CLD. In premature study supgroups, SP-B iΔ4 gene variations was 10.7% in control group (n:80), 15.8% in RDS group (n:19), 10% in RDS and CLD group (n:20) and 0% in CLD group (n:8). There wasn't any statistically significant difference between all supgroups. Conclusions: In our premature babies, we coulnd't show any association between SP-B iΔ4 gene polymorphism and RDS / CLD.

Pentoxifylline in Preterm Neonates

Sepsis, necrotizing enterocolitis (NEC), and chronic lung disease (CLD) in preterm neonates are associated with significant mortality and morbidity, including long-term neurodevelopmental impairment and socioeconomic burden. Safe and effective drugs for the prevention and treatment of these conditions are urgently needed. Pentoxifylline, a synthetic theobromine derivative, is a non-steroidal immunomodulating agent with unique hemorrheologic effects which has been used in a range of infectious, vascular, and inflammatory conditions in adults and children. The unique properties of pentoxifylline explain its potential benefits in preterm neonates with sepsis, NEC, and CLD, conditions characterized by activation of the inflammatory cytokine cascade, free radical toxicity, and impaired microcirculation. Pentoxifylline has anti-inflammatory properties resulting from inhibition of erythrocyte phosphodiesterase. It lowers blood viscosity and improves microcirculation and tissue perfusion. As a phosphodiesterase inhibitor, pentoxifylline downregulates pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Methylxanthines, including caffeine, theophylline, and theobromine are relatively non-toxic drugs; of these, theobromine is the least toxic. Pentoxifylline-related significant adverse events are thus very rare. Unlike other methylxanthines, pentoxifylline does not have significant cardiac and bronchodilating effects at therapeutic doses. Although it is contraindicated in adults with recent cerebral hemorrhage due to its effect on platelets, red blood cells, and plasma fibrinogen levels, no significant adverse effects including thrombocytopenia and bleeding have been reported in critically ill preterm neonates with sepsis or NEC after treatment with pentoxifylline. Based on data from pilot randomized trials and observational studies, our systematic review suggests that pentoxifylline may reduce mortality and/or morbidity in preterm neonates with sepsis, NEC, and CLD. Results of experimental studies also indicate that pentoxifylline may potentially be beneficial in meconium aspiration syndrome and hypoxic ischemic encephalopathy. Given the substantial burden of sepsis, NEC, and CLD in high-risk preterm neonates, and the findings of this systematic review, pentoxifylline needs to be evaluated urgently as a preventative and therapeutic agent for these conditions in randomized controlled trials that can detect minimal clinically significant effect sizes. Further clinical and experimental studies are also necessary to evaluate whether pentoxifylline is safe and effective in meconium aspiration syndrome and hypoxic ischemic encephalopathy.

Pulmonary hypertension in chronic neonatal lung disease

Pulmonary hypertension is an uncommon but significantly challenging complication of chronic neonatal lung disease [CNLD] as it occurs in the "new bronchopulmonary dysplasia [BPD]". The presence of pulmonary hypertension may be sub-clinical and is often overlooked as it is not considered in all but the more severe cases of children with CNLD. Whilst the mainstays of therapy are supplemental oxygen and time and the majority of children will have resolution of their pulmonary hypertension with lung growth, the advent of newer pharmacological treatments has offered stability and perhaps a better prognosis for more severe cases of pulmonary hypertension.