Neonatology 2014;105:357–363 DOI: 10.1159/000360654
Published online: May 30, 2014
Abstracts 29th International Workshop on Surfactant Replacement, Valencia, May 30–31, 2014
Fetal-to-Neonatal Transition under Hypoxic Conditions in Mice Pups I. Torres-Cuevasa, R. Rodrigoa, J. Kuligowskia, E. Cubellsa, J. Escobara, J. Belikb, M. Enomotob, A. Nuñeza, G. Quintása, M. Ventoa aNeonatal Research Group, Health Research Institute La Fe, Valencia, Spain; bDivision of Neonatology, The Hospital for Sick Children, University of Toronto, Ont., Canada
Background: In previous experiments postnatal transition in mice keeping intra-uterine oxygen conditions (FiO2 = 0.14) for several hours after birth caused protective changes in the redox state in lung at P1 and in lung and brain at P7 [Escobar J et al.: Redox Biol 2013; 1: 297–303]. Objectives: To assess redox response found in our model by assessing redox-related gene expression in lung and brain short- and long-term. Materials and Methods: FiO2 in pregnant mice was reduced from 0.21 (room air) to 0.14 (hypoxia) 8–12 h prior to delivery and reset to 0.21 6–8 h after birth. The control group was kept at 0.21 during the procedure. The mRNA levels of HIF1α target genes (VEGFα, EPO and Glut1), redox genes (gpx1, srnx1, nqo1, gr, trndx1, me1, pgd, g6pd), inflammatory genes (IL-1b, IL-6, TNF α), glutamatergic receptors (nr1, Vglut1 and Vglut2) and purinergic receptors (adora1) were evaluated by RT-PCR at P1 and P7. Results: We found upregulation of antioxidant enzymes gpx1, srnx1 and nqo1 in the lung of the experimental group at P7. In brain, gpx1 was the only redox gene upregulated at P1. However, we found higher mRNA levels of VEGFα and EPO at P1, and EPO, VEGFα, Vglut1 in brain at P7 in the experimental group. By contrast, brain adora1 was downregulated at both P1 and P7. Regarding inflammation, brain mRNA level of pro-inflammatory cytokines was elevated in the experimental group at P1 but seemed to recover to similar levels to the control group at P7 with the exception of IL-6 mRNA. Nonetheless, IL-6 may exert not only pro-inflammatory but also antiinflammatory properties. Conclusions: These data are in accor-
© 2014 S. Karger AG, Basel 1661–7800/14/1054–0357$39.50/0 E-Mail [email protected] www.karger.com/neo
dance with results of previous experiments [Escobar J et al.: Redox Biol 2013; 1: 297–303] and provide additional evidence supporting the suggestion that keeping newborn after birth under relatively hypoxic conditions appears to be protective. Acknowledgements: I. Torres-Cuevas is recipient of a PFIS FI12/0109 grant from the Instituto Carlos III (Ministry of Economy).
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Hyperoxia Leads to Impaired Lung Function in an Experimental Model of Respiratory Distress Syndrome E. Henckel, M. Haegerstrand-Bjorkman, B. Linderholm, T. Curstedt, K. Bohlin Neonatal Intensive Care Unit K76–78, Astrid Lindgrens Childrens Hospital at Huddinge, Karolinska University Hospital, Stockholm, Sweden
Background: Oxidative stress may play an important role in development of lung disease in the newborn infant. Immature surfactant-deficient lungs are particularly sensitive to damage from reactive oxygen species. Mechanical ventilation inactivates surfactant and hyperoxia induces lipid peroxidation. Objectives: To determine if hyperoxia increases oxidative stress and induces surfactant dysfunction leading to impairment of lung function. Materials and Methods: Surfactant-deficient preterm rabbits (n = 30) were randomized to ventilation with either room air (n = 10) or 100% oxygen (n = 11) after intratracheal surfactant administration (Curosurf®), placed in a body-plethysmograph box and ventilated with a positive end-expiratory pressure (PEEP) of 4 cm H2O and tidal volume 6 ml/kg for 2 h. Lung mechanics were monitored and bronchoalveolar lavage performed at the end of the experiment for
Downloaded by: NYU Medical Center Library 216.165.126.139 - 10/9/2014 11:11:28 PM
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Neuroprotective Effects of Docosahexaenoic Acid Given after Neonatal Asphyxia R. Solberga, M. Longinib, F. Proiettib, C. Felicib, O.D. Saugstada, G. Buonocoreb a
Department of Pediatric Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway; bPediatric Neonatology Unit, University Hospital of Siena, Italy
Background: Docosahexaenoic acid (DHA) is critical for fetal neurodevelopment and a major component of membrane phospholipids. It accumulates during late pregnancy. DHA protects against oxidative damage to biomembranes and may also attenuate an inflammatory response in multiple organs after hypoxia/ischemia by regulating multiple molecular pathways and gene expression. Isoprostanes, neuroprostanes, and neurofurans have all become attractive biomarkers of oxidative damage and lipid peroxidation in brain tissue. Lately F2-dihomo-isoprostanes have also emerged as an in vivo biomarker of free radical damage to myelin in white matter. Objectives: To simultaneously measure all four biomarkers in cerebral cortex and hippocampus of newborn pigs after hypoxia and resuscitation with ambient air with or without additional treatment with DHA. Materials and Methods: Global hypoxia was induced in newborn piglets (age 12–36 h) until base excess was –20 mmol/l or mean arterial blood pressure 5 s. Results: Fifteen preterm infants with a mean age of 2.3 days were studied. Their mean gestational age at birth was 27.6 weeks. The mean number of apneas was reduced by caffeine citrate treatment without a change in duration of the apnea or a drop in heart rate. Tonic Edi was not different between the periods, but peak Edi and Nrr were significantly increased leading to increase in Editime product. Conclusions: The beneficial effect of caffeine citrate on reduction of the number of apneas is mediated through the stimulation of neural breathing with a simultaneous increase in the diaphragm energy expenditure.
where some of the clearance functions are aggregation and phagocytosis of these particle-like organisms. We have previously shown that SP-D shows differential interaction with nanoparticles and modifies the uptake into phagocytes in vitro. Objectives: Here we extend these findings by characterizing the interaction of SP-A with nanoparticles and their subsequent interaction with cell linederived macrophages and primary murine alveolar macrophages. Materials and Methods: We investigated the effects of SP-A on the phagocytic uptake of (1) unlabelled nanoparticles in macrophage-like RAW264.7 cells using Coherent Anti-stokes Raman Spectroscopy (CARS), and (2) FITC-labelled nanoparticles in alveolar macrophages isolated from SP-A knock-out mice and wildtype mice using flow cytometry. Results: SP-A enhanced uptake of unmodified polystyrene (PS) particles into macrophage-like cells but, in contrast, inhibited uptake of amine-modified polystyrene (A-PS) particles. Alveolar macrophages from SP-A–/– mice were more efficient at uptake of A-PS compared to wild-type macrophages. Conclusions: SP-A showed differential interaction with nanoparticles dependent on surface chemistry. The interaction could facilitate clearance of the particles but the particles could also sequester surfactant proteins and thereby make individuals ‘functionally deficient’ for these proteins leading to increased susceptibility towards infections and inflammatory conditions. Further research is required to investigate the potential of SP-A and SP-D therapy in nanoparticulate induced toxicity.
Protein levels of TGF-β1 and 2 were measured by ELISA. Smad2 phosphorylation was assessed by immuno-histochemistry. CTGF and Cav-1 mRNA and protein levels were determined by RT-PCR and Western blot. Results: Free TGF-β1 and -2 and total TGF-β1 levels were unchanged after LPS and/or BTM exposure, although total TGF-β2 increased in animals exposed to BTM 7 days before LPS. Smad2 phosphorylation increased 3-fold 7 days after LPS exposure. Similarly, CTGF mRNA and protein levels increased 7 days after LPS exposure as Cav-1 mRNA and protein levels decreased. BTM exposure prior to LPS prevented Smad2 phosphorylation, CTGF induction and Cav-1 down-regulation. Conclusions: This study demonstrates that the intrauterine inflammation-induced TGF-β signalling can be inhibited by antenatal glucocorticoids in fetal lungs and describes a new molecular protective effect of antenatal glucocorticoids on the immature lung of preterm infants.
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Comparison of Effectiveness of Nasal Continuous Positive Airway Pressure and Nasal Intermittent Mandatory Ventilation in Early Rescue Surfactant Therapy in Preterm Infants: A Randomized Controlled Trial M.Y. Oncel, S. Arayici, F.N. Sari, N. Uras, F.E. Canpolat, S.S. Oguz, U. Dilmen
Antenatal Glucocorticoids Counteract LPS-Induced Changes in Transforming Growth Factor-β Signalling Pathway in Fetal Lung S. Kunzmanna, C.P. Speera, J.J.P. Collinsb, E. Kuypersb, M.W. Kempc, J.P. Newnhamc, S.G. Kallapurc, d, A.H. Jobec, d, B.W. Kramerb a University Children’s Hospital, University of Würzburg, Germany; bDepartment of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands; cSchool of Women’s and Infants’ Health, University of Western Australia, Perth, W.A., Australia; dCincinnati Children’s Hospital Medical Center, University of Cincinnati, Ohio, USA
Background: Antenatal glucocorticoids given to mothers at risk for preterm birth and intrauterine inflammation both affect lung development and may contribute to development of bronchopulmonary dysplasia (BPD). Transforming growth factor (TGF)-β, its activated Smad signalling pathway and its downstream mediators, like connective tissue growth factor (CTGF) and Caveolin-1 (Cav-1), are implicated in the etiology of BPD. The effects of combined exposures of inflammation and antenatal glucocorticoids on these members of the TGF-β family are unknown. Objectives: To determine if glucocorticoids alter intra-amniotic lipopolysaccharide (LPS) effects on TGF-β expression, its signaling molecule pSmad2, and CTGF and Cav-1 expression. Materials and Methods: Ovine singleton fetuses were randomized to receive either an intra-amniotic injection of LPS (10 mg) and/or maternal betamethasone (BTM) intramuscularly 7 and/or 14 days prior to delivery at 120 days gestation (term = 150 days). Saline was used for controls.
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Neonatology 2014;105:357–363 DOI: 10.1159/000360654
Neonatology Department, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey
Background: Respiratory distress syndrome is the commonest respiratory cause of significant morbidity and mortality in preterm infants, the standard of care being mechanical ventilation (MV) with surfactant therapy. Objectives: To compare the efficacy of nasal continuous positive airway pressure (NCPAP) and nasal intermittent mandatory ventilation (NIMV) in early rescue surfactant treatment in preterm infants. Materials and Methods: In this prospective randomized study, preterm infants (26–32 weeks) admitted to the neonatal intensive care unit were screened for eligibility following parental consent. The trial was approved by the local ethics committee and registered with ClinicalTrials.gov (http:// clinicaltrials.gov) under identifier NCT01741129. Infants were randomized into two groups: NCPAP and NIMV. Need for surfactant therapy was evaluated in all preterm infants. If deemed necessary, 100 mg/kg of poractant alfa (Curosurf®; Chiesi, Farmaceutici, Parma, Italy) was given using a non-invasive technique involving insertion of a 5F orogastric tube into the trachea through which surfactant was given as a bolus synchronously with spontaneous inspiration (Take Care technique). Infants in both groups were evaluated and compared with regard to short- and long-term efficacy, morbidity and mortality. Results: 200 infants (100 in each group) were enrolled. There were no significant differences between NCPAP and NIMV groups in terms of demographic characteristics. Mean gestational ages (29.1 ± 1.6 vs. 29.2 ± 1.7 weeks) and birth weights (1,175 ± 214 vs. 1,180 ± 206 g) were similar. More infants in the NCPAP group needed surfactant compared to the NIMV group (60 vs. 38%; p = 0.002). Surfactant was administered at a median age of 6 (2–96) h after admission in the NCPAP group
Abstracts, 29th International Workshop on Surfactant Replacement
Downloaded by: NYU Medical Center Library 216.165.126.139 - 10/9/2014 11:11:28 PM
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Ketamine Sedation for LASER Therapy of Retinopathy of Prematurity in Babies with Bronchopulmonary Dysplasia J. Courtneya, M. Alsousb, J. McElnayb, H.L. Hallidaya, c, D.G. Sweeta a
Regional Neonatal Intensive Care Unit, Royal Maternity Hospital, bSchool of Pharmacy, and cDepartment of Child Health, Queen’s University Belfast, Belfast, UK
Background: Pharmacokinetics (PK) and pharmacodynamics (PD) of ketamine (KET) for sedation were performed on 18 babies including 12 with bronchopulmonary dysplasia (BPD) undergoing LASER therapy for retinopathy of prematurity (ROP). For many years it has been practice to use KET for sedation in children, although its use in very preterm infants has not previously been formally studied. PK data are reported elsewhere. Objectives: To describe PD of KET in ex-preterm babies with BPD. Materials and Methods: The protocol was to use 10 mg/kg intramuscular (IM) KET with 1 mg/kg intravenous (IV) top-ups as required during the procedure and avoiding intubation if feasible. Data on drug dosing, level of sedation using N-PASS score and vital signs were collected prospectively during the procedure. Results: The babies were median (range) gestation 26 (24–28) weeks and birth weight 781 (360–1,068) g. Duration of ventilation was 22 (2–51) days and continuous positive airway pressure (CPAP) 73 (34–83) days. The KET study was performed at 86 (44–99) days of age at a corrected gestation of 37 (34–41) weeks and weight 2,080 (1,339–2,972) g. Prior to the procedure 4 infants were on CPAP, 6 on low flow oxygen and 2 on no respiratory support. Eight were electively ventilated, 2 required unplanned ventilation and 2 managed without ventilation. After initial IM KET dose, duration of adequate sedation was 30 (14–55) min and lowest N-PASS score –10 (–8 to –10). Number of IV top-up doses of KET was 2 (0–4). N-PASS score at re-dosing was –7 (–4 to –9). Duration of the procedure was 60 (22–120) min. All babies were extubated within 24 h. Full enteral feeds were re-established within 15 (6–24) h. Outcomes: 2 infants subsequently died of severe BPD (unrelated to the KET procedure), 7 went home on day 103 (64–120) and 3 were transferred for ongoing care on day 95 (74–100). Conclusions: KET can be used for sedation of infants with BPD for LASER therapy for ROP in the neonatal intensive care unit. Around 30 min of adequate sedation is obtained after a 10 mg/kg IM dose.
Abstracts, 29th International Workshop on Surfactant Replacement
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Safety and Effectiveness of Less Invasive Surfactant Administration in Routine Clinical Practice E. Hertinga, A. Kribsb, B. Rothb, N. Teiga, J. Wintgensa, C. Wiega, P. Gronecka, S. Avenariusa, D. Olbertza, M. Vochema, A.V.D. Wensea, U. Wellera, C. Rolla, M. Preussa, A. Zieglera, C. Härtela, W. Göpela a
Department of Pediatrics, University of Lübeck , and Department of Pediatrics, University of Cologne, Germany
b
Background: Less Invasive Surfactant Administration (LISA) to spontaneously breathing preterm infants on nasal continuous positive airway pressure reduces the rate of mechanical ventilation in randomized controlled trials. Objectives: To evaluate the effectivenes of LISA in routine clinical practice, we compared outcomes and complication rates with controls (matched pairs) in a large cohort study in the German Neonatal Network (GNN). Materials and Methods: Very low birth weight (1,000 very low birth weight infants this is the largest cohort treated with LISA reported so far. No safety concerns could be identified.
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Recent Interventions in Neonatal Care: Effects of Surfactant, Ventilators, Antenatal Steroids and INSURE on Infant Mortality from 1967 to 2011 J. Grytten, L. Monkerud, I. Skau, A. Eskild, R. Sørensen, O.D. Saugstad Community Dentistry, Oslo University, Oslo, Norway
Background: There has been a marked reduction in infant mortality in most western countries from the late 1960s. To our knowledge, there are no studies where the contribution of new interventions in neonatal care to this decrease in mortality has been estimated. Objectives: To estimate the effect of the introduction of surfactant, ventilators, antenatal steroids and INSURE (intubation, surfactant and extubation) on early neonatal mortality and infant mortality in Norway during the period 1967–2011. Materi-
Neonatology 2014;105:357–363 DOI: 10.1159/000360654
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compared to 6 (2–48) h in the NIMV group (p = 0.129). MV rates were significantly higher in the NCPAP group (29 vs. 13%; p = 0.005). Median time to intubation was 6 (2–96) h in the NCPAP group compared to 24 (4–60) h in the NIMV (p = 0.552), with median durations of MV of 3 (1–25) days and 2 (1–7) days, respectively (p = 0.342). Severe chronic lung disease (CLD) developed in 16 infants (16%) from the NCPAP group compared to 7 (7%) in the NIMV group (p = 0.046). Other short- and long-term morbidity and mortality rates were similar. Conclusions: Fewer infants required surfactant therapy in the NIMV group compared to the NCPAP group. NIMV compared with NCPAP decreased the requirement of MV and incidence of severe CLD in preterm infants
Published online: May 30, 2014
Abstracts 29th International Workshop on Surfactant Replacement, Valencia, May 30–31, 2014
Fetal-to-Neonatal Transition under Hypoxic Conditions in Mice Pups I. Torres-Cuevasa, R. Rodrigoa, J. Kuligowskia, E. Cubellsa, J. Escobara, J. Belikb, M. Enomotob, A. Nuñeza, G. Quintása, M. Ventoa aNeonatal Research Group, Health Research Institute La Fe, Valencia, Spain; bDivision of Neonatology, The Hospital for Sick Children, University of Toronto, Ont., Canada
Background: In previous experiments postnatal transition in mice keeping intra-uterine oxygen conditions (FiO2 = 0.14) for several hours after birth caused protective changes in the redox state in lung at P1 and in lung and brain at P7 [Escobar J et al.: Redox Biol 2013; 1: 297–303]. Objectives: To assess redox response found in our model by assessing redox-related gene expression in lung and brain short- and long-term. Materials and Methods: FiO2 in pregnant mice was reduced from 0.21 (room air) to 0.14 (hypoxia) 8–12 h prior to delivery and reset to 0.21 6–8 h after birth. The control group was kept at 0.21 during the procedure. The mRNA levels of HIF1α target genes (VEGFα, EPO and Glut1), redox genes (gpx1, srnx1, nqo1, gr, trndx1, me1, pgd, g6pd), inflammatory genes (IL-1b, IL-6, TNF α), glutamatergic receptors (nr1, Vglut1 and Vglut2) and purinergic receptors (adora1) were evaluated by RT-PCR at P1 and P7. Results: We found upregulation of antioxidant enzymes gpx1, srnx1 and nqo1 in the lung of the experimental group at P7. In brain, gpx1 was the only redox gene upregulated at P1. However, we found higher mRNA levels of VEGFα and EPO at P1, and EPO, VEGFα, Vglut1 in brain at P7 in the experimental group. By contrast, brain adora1 was downregulated at both P1 and P7. Regarding inflammation, brain mRNA level of pro-inflammatory cytokines was elevated in the experimental group at P1 but seemed to recover to similar levels to the control group at P7 with the exception of IL-6 mRNA. Nonetheless, IL-6 may exert not only pro-inflammatory but also antiinflammatory properties. Conclusions: These data are in accor-
© 2014 S. Karger AG, Basel 1661–7800/14/1054–0357$39.50/0 E-Mail [email protected] www.karger.com/neo
dance with results of previous experiments [Escobar J et al.: Redox Biol 2013; 1: 297–303] and provide additional evidence supporting the suggestion that keeping newborn after birth under relatively hypoxic conditions appears to be protective. Acknowledgements: I. Torres-Cuevas is recipient of a PFIS FI12/0109 grant from the Instituto Carlos III (Ministry of Economy).
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Hyperoxia Leads to Impaired Lung Function in an Experimental Model of Respiratory Distress Syndrome E. Henckel, M. Haegerstrand-Bjorkman, B. Linderholm, T. Curstedt, K. Bohlin Neonatal Intensive Care Unit K76–78, Astrid Lindgrens Childrens Hospital at Huddinge, Karolinska University Hospital, Stockholm, Sweden
Background: Oxidative stress may play an important role in development of lung disease in the newborn infant. Immature surfactant-deficient lungs are particularly sensitive to damage from reactive oxygen species. Mechanical ventilation inactivates surfactant and hyperoxia induces lipid peroxidation. Objectives: To determine if hyperoxia increases oxidative stress and induces surfactant dysfunction leading to impairment of lung function. Materials and Methods: Surfactant-deficient preterm rabbits (n = 30) were randomized to ventilation with either room air (n = 10) or 100% oxygen (n = 11) after intratracheal surfactant administration (Curosurf®), placed in a body-plethysmograph box and ventilated with a positive end-expiratory pressure (PEEP) of 4 cm H2O and tidal volume 6 ml/kg for 2 h. Lung mechanics were monitored and bronchoalveolar lavage performed at the end of the experiment for
Downloaded by: NYU Medical Center Library 216.165.126.139 - 10/9/2014 11:11:28 PM
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Neuroprotective Effects of Docosahexaenoic Acid Given after Neonatal Asphyxia R. Solberga, M. Longinib, F. Proiettib, C. Felicib, O.D. Saugstada, G. Buonocoreb a
Department of Pediatric Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway; bPediatric Neonatology Unit, University Hospital of Siena, Italy
Background: Docosahexaenoic acid (DHA) is critical for fetal neurodevelopment and a major component of membrane phospholipids. It accumulates during late pregnancy. DHA protects against oxidative damage to biomembranes and may also attenuate an inflammatory response in multiple organs after hypoxia/ischemia by regulating multiple molecular pathways and gene expression. Isoprostanes, neuroprostanes, and neurofurans have all become attractive biomarkers of oxidative damage and lipid peroxidation in brain tissue. Lately F2-dihomo-isoprostanes have also emerged as an in vivo biomarker of free radical damage to myelin in white matter. Objectives: To simultaneously measure all four biomarkers in cerebral cortex and hippocampus of newborn pigs after hypoxia and resuscitation with ambient air with or without additional treatment with DHA. Materials and Methods: Global hypoxia was induced in newborn piglets (age 12–36 h) until base excess was –20 mmol/l or mean arterial blood pressure 5 s. Results: Fifteen preterm infants with a mean age of 2.3 days were studied. Their mean gestational age at birth was 27.6 weeks. The mean number of apneas was reduced by caffeine citrate treatment without a change in duration of the apnea or a drop in heart rate. Tonic Edi was not different between the periods, but peak Edi and Nrr were significantly increased leading to increase in Editime product. Conclusions: The beneficial effect of caffeine citrate on reduction of the number of apneas is mediated through the stimulation of neural breathing with a simultaneous increase in the diaphragm energy expenditure.
where some of the clearance functions are aggregation and phagocytosis of these particle-like organisms. We have previously shown that SP-D shows differential interaction with nanoparticles and modifies the uptake into phagocytes in vitro. Objectives: Here we extend these findings by characterizing the interaction of SP-A with nanoparticles and their subsequent interaction with cell linederived macrophages and primary murine alveolar macrophages. Materials and Methods: We investigated the effects of SP-A on the phagocytic uptake of (1) unlabelled nanoparticles in macrophage-like RAW264.7 cells using Coherent Anti-stokes Raman Spectroscopy (CARS), and (2) FITC-labelled nanoparticles in alveolar macrophages isolated from SP-A knock-out mice and wildtype mice using flow cytometry. Results: SP-A enhanced uptake of unmodified polystyrene (PS) particles into macrophage-like cells but, in contrast, inhibited uptake of amine-modified polystyrene (A-PS) particles. Alveolar macrophages from SP-A–/– mice were more efficient at uptake of A-PS compared to wild-type macrophages. Conclusions: SP-A showed differential interaction with nanoparticles dependent on surface chemistry. The interaction could facilitate clearance of the particles but the particles could also sequester surfactant proteins and thereby make individuals ‘functionally deficient’ for these proteins leading to increased susceptibility towards infections and inflammatory conditions. Further research is required to investigate the potential of SP-A and SP-D therapy in nanoparticulate induced toxicity.
Protein levels of TGF-β1 and 2 were measured by ELISA. Smad2 phosphorylation was assessed by immuno-histochemistry. CTGF and Cav-1 mRNA and protein levels were determined by RT-PCR and Western blot. Results: Free TGF-β1 and -2 and total TGF-β1 levels were unchanged after LPS and/or BTM exposure, although total TGF-β2 increased in animals exposed to BTM 7 days before LPS. Smad2 phosphorylation increased 3-fold 7 days after LPS exposure. Similarly, CTGF mRNA and protein levels increased 7 days after LPS exposure as Cav-1 mRNA and protein levels decreased. BTM exposure prior to LPS prevented Smad2 phosphorylation, CTGF induction and Cav-1 down-regulation. Conclusions: This study demonstrates that the intrauterine inflammation-induced TGF-β signalling can be inhibited by antenatal glucocorticoids in fetal lungs and describes a new molecular protective effect of antenatal glucocorticoids on the immature lung of preterm infants.
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Comparison of Effectiveness of Nasal Continuous Positive Airway Pressure and Nasal Intermittent Mandatory Ventilation in Early Rescue Surfactant Therapy in Preterm Infants: A Randomized Controlled Trial M.Y. Oncel, S. Arayici, F.N. Sari, N. Uras, F.E. Canpolat, S.S. Oguz, U. Dilmen
Antenatal Glucocorticoids Counteract LPS-Induced Changes in Transforming Growth Factor-β Signalling Pathway in Fetal Lung S. Kunzmanna, C.P. Speera, J.J.P. Collinsb, E. Kuypersb, M.W. Kempc, J.P. Newnhamc, S.G. Kallapurc, d, A.H. Jobec, d, B.W. Kramerb a University Children’s Hospital, University of Würzburg, Germany; bDepartment of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands; cSchool of Women’s and Infants’ Health, University of Western Australia, Perth, W.A., Australia; dCincinnati Children’s Hospital Medical Center, University of Cincinnati, Ohio, USA
Background: Antenatal glucocorticoids given to mothers at risk for preterm birth and intrauterine inflammation both affect lung development and may contribute to development of bronchopulmonary dysplasia (BPD). Transforming growth factor (TGF)-β, its activated Smad signalling pathway and its downstream mediators, like connective tissue growth factor (CTGF) and Caveolin-1 (Cav-1), are implicated in the etiology of BPD. The effects of combined exposures of inflammation and antenatal glucocorticoids on these members of the TGF-β family are unknown. Objectives: To determine if glucocorticoids alter intra-amniotic lipopolysaccharide (LPS) effects on TGF-β expression, its signaling molecule pSmad2, and CTGF and Cav-1 expression. Materials and Methods: Ovine singleton fetuses were randomized to receive either an intra-amniotic injection of LPS (10 mg) and/or maternal betamethasone (BTM) intramuscularly 7 and/or 14 days prior to delivery at 120 days gestation (term = 150 days). Saline was used for controls.
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Neonatology 2014;105:357–363 DOI: 10.1159/000360654
Neonatology Department, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey
Background: Respiratory distress syndrome is the commonest respiratory cause of significant morbidity and mortality in preterm infants, the standard of care being mechanical ventilation (MV) with surfactant therapy. Objectives: To compare the efficacy of nasal continuous positive airway pressure (NCPAP) and nasal intermittent mandatory ventilation (NIMV) in early rescue surfactant treatment in preterm infants. Materials and Methods: In this prospective randomized study, preterm infants (26–32 weeks) admitted to the neonatal intensive care unit were screened for eligibility following parental consent. The trial was approved by the local ethics committee and registered with ClinicalTrials.gov (http:// clinicaltrials.gov) under identifier NCT01741129. Infants were randomized into two groups: NCPAP and NIMV. Need for surfactant therapy was evaluated in all preterm infants. If deemed necessary, 100 mg/kg of poractant alfa (Curosurf®; Chiesi, Farmaceutici, Parma, Italy) was given using a non-invasive technique involving insertion of a 5F orogastric tube into the trachea through which surfactant was given as a bolus synchronously with spontaneous inspiration (Take Care technique). Infants in both groups were evaluated and compared with regard to short- and long-term efficacy, morbidity and mortality. Results: 200 infants (100 in each group) were enrolled. There were no significant differences between NCPAP and NIMV groups in terms of demographic characteristics. Mean gestational ages (29.1 ± 1.6 vs. 29.2 ± 1.7 weeks) and birth weights (1,175 ± 214 vs. 1,180 ± 206 g) were similar. More infants in the NCPAP group needed surfactant compared to the NIMV group (60 vs. 38%; p = 0.002). Surfactant was administered at a median age of 6 (2–96) h after admission in the NCPAP group
Abstracts, 29th International Workshop on Surfactant Replacement
Downloaded by: NYU Medical Center Library 216.165.126.139 - 10/9/2014 11:11:28 PM
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Ketamine Sedation for LASER Therapy of Retinopathy of Prematurity in Babies with Bronchopulmonary Dysplasia J. Courtneya, M. Alsousb, J. McElnayb, H.L. Hallidaya, c, D.G. Sweeta a
Regional Neonatal Intensive Care Unit, Royal Maternity Hospital, bSchool of Pharmacy, and cDepartment of Child Health, Queen’s University Belfast, Belfast, UK
Background: Pharmacokinetics (PK) and pharmacodynamics (PD) of ketamine (KET) for sedation were performed on 18 babies including 12 with bronchopulmonary dysplasia (BPD) undergoing LASER therapy for retinopathy of prematurity (ROP). For many years it has been practice to use KET for sedation in children, although its use in very preterm infants has not previously been formally studied. PK data are reported elsewhere. Objectives: To describe PD of KET in ex-preterm babies with BPD. Materials and Methods: The protocol was to use 10 mg/kg intramuscular (IM) KET with 1 mg/kg intravenous (IV) top-ups as required during the procedure and avoiding intubation if feasible. Data on drug dosing, level of sedation using N-PASS score and vital signs were collected prospectively during the procedure. Results: The babies were median (range) gestation 26 (24–28) weeks and birth weight 781 (360–1,068) g. Duration of ventilation was 22 (2–51) days and continuous positive airway pressure (CPAP) 73 (34–83) days. The KET study was performed at 86 (44–99) days of age at a corrected gestation of 37 (34–41) weeks and weight 2,080 (1,339–2,972) g. Prior to the procedure 4 infants were on CPAP, 6 on low flow oxygen and 2 on no respiratory support. Eight were electively ventilated, 2 required unplanned ventilation and 2 managed without ventilation. After initial IM KET dose, duration of adequate sedation was 30 (14–55) min and lowest N-PASS score –10 (–8 to –10). Number of IV top-up doses of KET was 2 (0–4). N-PASS score at re-dosing was –7 (–4 to –9). Duration of the procedure was 60 (22–120) min. All babies were extubated within 24 h. Full enteral feeds were re-established within 15 (6–24) h. Outcomes: 2 infants subsequently died of severe BPD (unrelated to the KET procedure), 7 went home on day 103 (64–120) and 3 were transferred for ongoing care on day 95 (74–100). Conclusions: KET can be used for sedation of infants with BPD for LASER therapy for ROP in the neonatal intensive care unit. Around 30 min of adequate sedation is obtained after a 10 mg/kg IM dose.
Abstracts, 29th International Workshop on Surfactant Replacement
12
Safety and Effectiveness of Less Invasive Surfactant Administration in Routine Clinical Practice E. Hertinga, A. Kribsb, B. Rothb, N. Teiga, J. Wintgensa, C. Wiega, P. Gronecka, S. Avenariusa, D. Olbertza, M. Vochema, A.V.D. Wensea, U. Wellera, C. Rolla, M. Preussa, A. Zieglera, C. Härtela, W. Göpela a
Department of Pediatrics, University of Lübeck , and Department of Pediatrics, University of Cologne, Germany
b
Background: Less Invasive Surfactant Administration (LISA) to spontaneously breathing preterm infants on nasal continuous positive airway pressure reduces the rate of mechanical ventilation in randomized controlled trials. Objectives: To evaluate the effectivenes of LISA in routine clinical practice, we compared outcomes and complication rates with controls (matched pairs) in a large cohort study in the German Neonatal Network (GNN). Materials and Methods: Very low birth weight (1,000 very low birth weight infants this is the largest cohort treated with LISA reported so far. No safety concerns could be identified.
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Recent Interventions in Neonatal Care: Effects of Surfactant, Ventilators, Antenatal Steroids and INSURE on Infant Mortality from 1967 to 2011 J. Grytten, L. Monkerud, I. Skau, A. Eskild, R. Sørensen, O.D. Saugstad Community Dentistry, Oslo University, Oslo, Norway
Background: There has been a marked reduction in infant mortality in most western countries from the late 1960s. To our knowledge, there are no studies where the contribution of new interventions in neonatal care to this decrease in mortality has been estimated. Objectives: To estimate the effect of the introduction of surfactant, ventilators, antenatal steroids and INSURE (intubation, surfactant and extubation) on early neonatal mortality and infant mortality in Norway during the period 1967–2011. Materi-
Neonatology 2014;105:357–363 DOI: 10.1159/000360654
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compared to 6 (2–48) h in the NIMV group (p = 0.129). MV rates were significantly higher in the NCPAP group (29 vs. 13%; p = 0.005). Median time to intubation was 6 (2–96) h in the NCPAP group compared to 24 (4–60) h in the NIMV (p = 0.552), with median durations of MV of 3 (1–25) days and 2 (1–7) days, respectively (p = 0.342). Severe chronic lung disease (CLD) developed in 16 infants (16%) from the NCPAP group compared to 7 (7%) in the NIMV group (p = 0.046). Other short- and long-term morbidity and mortality rates were similar. Conclusions: Fewer infants required surfactant therapy in the NIMV group compared to the NCPAP group. NIMV compared with NCPAP decreased the requirement of MV and incidence of severe CLD in preterm infants
