Search

Introduction: Acute lung injury and acute respiratory distress syndrome are characterized by acute alveolar injury, disrupted epithelial-mesenchymal signaling, oxidative stress, and surfactant dysfunction, yet currently, there is no effective treatment. We previously reported that a combination of aerosolized pioglitazone (PGZ) and synthetic lung surfactant B-YL peptide as surfactant protein B mimic prevents hyperoxia-induced neonatal rat lung injury, but this has not been tested in adult lung injury. Method: We characterize effects of hyperoxia on 1) perturbations in Wingless/Int (Wnt) and Transforming Growth Factor (TGF)-β signaling pathways, which are critical mediators of hyperoxia-induced lung injury, 2) aberrations of lung homeostasis and injury repair following 24 or 72-hour exposure of adult mice lung explants to hyperoxia, and 3) whether these hyperoxia-induced aberrations can be blocked by concomitant treatment with PGZ and B-YL combination. Results: Our study reveals that hyperoxia exposure of adult mouse lung explants causes activation of Wnt (upregulation of key Wnt signaling intermediates β-catenin and LEF-1) and TGF-β (upregulation of key TGF-β signaling intermediates TGF-β type I receptor (ALK5) and SMAD 3) signaling pathways accompanied by an upregulation of myogenic proteins (calponin and fibronectin) and inflammatory cytokines (IL-6, MCP-1, IL-1β, and TNFα), and alterations in key endothelial (VEGF-A and its receptor FLT-1 and PECAM-1) markers. All of these changes were largely prevented by PGZ+B-YL combination. Conclusions: The effectiveness of the PGZ+B-YL combination in blocking hyperoxia-induced adult mice lung injury ex-vivo sets the stage to test this promising therapeutic approach for adult lung injury in vivo.

The three-dimensional structure of the synthetic lung Surfactant Protein B Peptide Super Mini-B was determined using an integrative experimental approach, including mass spectrometry and isotope enhanced Fourier-transform infrared (FTIR) spectroscopy. Mass spectral analysis of the peptide, oxidized by solvent assisted region-specific disulfide formation, confirmed that the correct folding and disulfide pairing could be facilitated using two different oxidative structure-promoting solvent systems. Residue specific analysis by isotope enhanced FTIR indicated that the N-terminal and C-terminal domains have well defined α-helical amino acid sequences. Using these experimentally derived measures of distance constraints and disulfide connectivity, the ensemble was further refined with molecular dynamics to provide a medium resolution, residue-specific structure for the peptide construct in a simulated synthetic lung surfactant lipid multilayer environment. The disulfide connectivity combined with the α-helical elements stabilize the peptide conformationally to form a helical hairpin structure that resembles critical elements of the Saposin protein fold of the predicted full-length Surfactant Protein B structure.

Background Optimal functionality of synthetic lung surfactant for treatment of respiratory distress syndrome in preterm infants largely depends on the quality and quantity of the surfactant protein B (SP-B) peptide mimic and the lipid mixture. B-YL peptide is a 41-residue sulfur-free SP-B mimic with its cysteine and methionine residues replaced by tyrosine and leucine, respectively, to enhance its oxidation resistance. Aim Testing the structural and functional stability of the B-YL peptide in synthetic surfactant lipids after long-term storage. Methods The structural and functional properties of B-YL peptide in surfactant lipids were studied using three production runs of B-YL peptides in synthetic surfactant lipids. Each run was held at 5 °C ambient temperature for three years and analyzed with structural and computational techniques, i.e., MALDI-TOF mass spectrometry, ATR-Fourier Transform Infrared Spectroscopy (ATR-FTIR), secondary homology modeling of a preliminary B-YL structure, and tertiary Molecular Dynamic simulations of B-YL in surfactant lipids, and with functional methods, i.e., captive bubble surfactometry (CBS) and retesting in vivo surface activity in surfactant-deficient young adult rabbits. Results MALDI-TOF mass spectrometry showed no degradation of the B-YL peptide as a function of stored time. ATR-FTIR studies demonstrated that the B-YL peptide still assumed stable alpha-helical conformations in synthetic surfactant lipids. These structural findings correlated with excellent in vitro surface activity during both quasi-static and dynamic cycling on CBS after three years of cold storage and in vivo surface activity of the aged formulations with improvements in oxygenation and dynamic lung compliance approaching those of the positive control surfactant Curosurf®. Conclusions The structure of the B-YL peptide and the in vitro and in vivo functions of the B-YL surfactant were each maintained after three years of refrigeration storage.

Lung surfactant is a mixture of phospholipids and proteins that is synthesized by alveolar type 2 cells and secreted into the alveoli to reduce surface tension at the air-liquid interface. Mammalia...

Background: Despite improvements in perinatal care, bronchopulmonary dysplasia (BPD) in extremely premature infants has not decreased. Postnatal surfactant therapy provides symptomatic relief from respiratory distress syndrome, but does not translate into a reduction in BPD. Therefore, the search for effective interventions to prevent BPD continues. Objectives: Since PPAR-γ agonists have been demonstrated to promote neonatal lung maturation and injury repair, we hypothesized that a formulation of a PPAR-γ agonist, pioglitazone (PGZ) and a synthetic lung surfactant (a surfactant protein B peptide mimic, B-YL) combined would stimulate lung maturation and block hyperoxia-induced neonatal lung injury more effectively than either modality alone. Methods: One-day-old Sprague-Dawley rat pups were administered PGZ + B-YL via nebulization every 24 h for up to 72 h. The pups were exposed to either 21 or 95% O2, and then sacrificed. Their lungs were examined for markers of lung maturation (levels of PPAR-γ, SP-C and choline-phosphate cytidylyltransferase [CCT-α] and [3H]triolein uptake) and injury repair (bronchoalveolar lavage cell count and protein content, and levels of LEF-1, fibronectin, ALK5, and β-catenin) by Western blot analysis. Results: Markers of alveolar epithelial/mesenchymal maturation (PPAR-γ, SP-C, CCT-α, and triolein uptake) increased significantly in the PGZ + B-YL group, more than with either drug alone. Similarly, markers of hyperoxia-induced lung injury were blocked effectively with PGZ + B-YL treatment. Conclusions: Nebulized PPAR-γ agonist PGZ with a synthetic lung surfactant accelerates lung maturation and prevents neonatal hyperoxia-induced lung injury more than either modality alone, with the potential to provide more effective prevention of BPD.

Objective To evaluate the association of ibuprofen exposure with the risk of bronchopulmonary dysplasia (BPD) in extremely premature infants. Study design This was a retrospective study of all extremely premature infants admitted to a tertiary unit from 2016 to 2018. Results A total of 203 extremely premature infants were included in this study. The rate of BPD was significantly higher in infants with early exposure to ibuprofen (42.5%) compared to infants with no exposure (21.6%, P = 0.001). After adjusting for covariates, the risk of BPD was associated independently with ibuprofen exposure (odds ratios (OR) 2.296, 95% confidence interval (CI): 1.166–4.522, p = 0.016). Further analysis showed a trend towards higher risk of BPD in infants with successful patent ductus arteriosus (PDA) closure after ibuprofen treatment (32.3%) compared to non-treated infants (20.2%, p = 0.162). Conclusion Our findings suggest that ibuprofen exposure may contribute to the occurrence of BPD in extremely preterm infants.

Exchange transfusion (ET) is the most effective method for treatment of severe hyperbilirubinemia and is often required in Rhesus hemolytic disease of the newborn. The use of ET is also associated with adverse reactions, including severe catheter related infectious complications. We report a term neonate with Rhesus hemolytic disease of the newborn treated with an ET through an umbilical venous catheter who developed brain abscesses due to a Bacillus cereus sepsis. This severe complication has not previously been reported. We discuss possible causes for this severe infection and provide suggestions on prevention.

Enterovirus (EV) and human parechovirus (HPeV) are major causes of sepsis-like illness in infants under 90 days of age and have been identified as neurotropic. Studies about acute and long-term neurodevelopment in infants with sepsis-like illness without the need for intensive care are few. This study investigates cerebral imaging and neurodevelopmental outcome following EV and HPeV infection in these infants. We studied infants under 90 days of age who were admitted to a medium care unit with proven EV- or HPeV-induced sepsis-like illness. In addition to standard care, we did a cerebral ultrasound and cerebral magnetic resonance imaging (MRI), as well as neurodevelopmental follow-up at 6 weeks and 6 months and Bayley Scale of Infant and Toddler Development 3rd edition (BSID-III) investigation at 1 year of age. Twenty-six infants, 22 with EV and 4 with HPeV, were analysed. No abnormalities were detected at cerebral imaging. At 1 year of age, two infants had a moderate delay on both the motor and cognitive scale, one on the cognitive scale only and three others on the gross motor scale only. Conclusion: Although our study population, especially the number of HPeV positive infants is small, our study shows that these infants do not seem to develop severe neurodevelopmental delay and neurologic sequelae more often than the normal Dutch population. Follow-up to school age allows for more reliable assessments of developmental outcome and is recommended for further studies to better assess outcome. What is known: • Enterovirus and Human Parechovirus infections are a major cause of sepsis-like illness in young infants. • After intensive care treatment for EV or HPeV infection, white matter abnormalities and neurodevelopmental delay have been described. What is new: • In our ‘medium care’ population, no abnormalities at cerebral imaging after EV- or HPeV-induced sepsis-like illness have been found. • At 1 year of age, infants who had EV- or HPeV-induced sepsis-like illness do not seem to develop severe neurodevelopmental delay and neurologic sequelae more often than the normal population.

Background: Sepsis-like illness is a main cause for hospital admission in young infants. Our aim was to investigate incidence, epidemiology and clinical characteristics of enterovirus (EV) and human parechovirus (HPeV) infections in young infants with sepsis-like illness. Methods: This is a prospective observational cohort study in which infants younger than 90 days of age, presenting with sepsis-like symptoms in a secondary care children's hospital, underwent a full sepsis work-up. Clinical signs and infectious indices were recorded. EV or HPeV RNA was detected by polymerase chain reaction in plasma and/or cerebrospinal fluid (CSF). Results: Infants were diagnosed with EV, HPeV, fever of unknown origin or severe infection. EV and HPeV were detected in 132 of 353 (37%) and 52 of 353 (15%) of cases, respectively. EV and HPeV have distinct seasonability. Some differences in clinical signs and symptoms occurred between children with EV and HPeV infection but were of limited clinical value. CSF pleocytosis occurred in 44% of EV positive infants, and only in 13% of those with HPeV infection. Conclusions: EV and HPeV infections are major causes of sepsis-like illness in infants < 90 days of age. Neither clinical characteristics nor laboratory indices were predictive for EV/HPeV infection. CSF pleocytosis occurs, but not in all patients. Testing for EV and HPeV in all young infants with sepsis-like illness is strongly advised.

Aim: Survivors of neonatal chronic lung disease or bronchopulmonary dysplasia (BPD) suffer from compromised lung function and are at high risk for developing lung injury by multiple insults later in life. Because neonatal lysophosphatidic acid receptor-1 (LPAR1)-deficient rats are protected against hyperoxia-induced lung injury, we hypothesize that LPAR1-deficiency may protect adult survivors of BPD from a second hit response against lipopolysaccharides (LPS)-induced lung injury. Methods: Directly after birth, Wistar control and LPAR1-deficient rat pups were exposed to hyperoxia (90%) for 8 days followed by recovery in room air. After 7 weeks, male rats received either LPS (2 mg kg-1) or 0.9% NaCl by intraperitoneal injection. Alveolar development and lung inflammation were investigated by morphometric analysis, IL-6 production, and mRNA expression of cytokines, chemokines, coagulation factors, and an indicator of oxidative stress. Results: LPAR1-deficient and control rats developed hyperoxia-induced neonatal emphysema, which persisted into adulthood, as demonstrated by alveolar enlargement and decreased vessel density. LPAR1-deficiency protected against LPS-induced lung injury. Adult controls with BPD exhibited an exacerbated response toward LPS with an increased expression of pro-inflammatory mRNAs, whereas LPAR1-deficient rats with BPD were less sensitive to this "second hit" with a decreased pulmonary influx of macrophages and neutrophils, interleukin-6 (IL-6) production, and mRNA expression of IL-6, monocyte chemoattractant protein-1, cytokine-induced neutrophil chemoattractant 1, plasminogen activator inhibitor-1, and tissue factor. Conclusion: LPAR1-deficient rats have increased hyperoxia-induced BPD survival rates and, despite the presence of neonatal emphysema, are less sensitive to an aggravated "second hit" than Wistar controls with BPD. Intervening in LPA-LPAR1-dependent signaling may not only have therapeutic potential for neonatal chronic lung disease, but may also protect adult survivors of BPD from sequelae later in life.

The transition to life after birth is characterized by major physiological changes in respiratory and hemodynamic function, which are predominantly initiated by breathing at birth and clamping of the umbilical cord. Lung aeration leads to the establishment of functional residual capacity, allowing pulmonary gas exchange to commence. This triggers a significant decrease in pulmonary vascular resistance, consequently increasing pulmonary blood flow and cardiac venous return. Clamping the umbilical cord also contributes to these hemodynamic changes by altering the cardiac preload and increasing peripheral systemic vascular resistance. The resulting changes in systemic and pulmonary circulation influence blood flow through both the oval foramen and ductus arteriosus. This eventually leads to closure of these structures and the separation of the pulmonary and systemic circulations. Most of our knowledge on human neonatal transition is based on human (fetal) data from the 1970s and extrapolation from animal studies. However, there is renewed interest in performing measurements directly at birth. By using less cumbersome techniques (and probably more accurate), our previous understanding of the physiological transition at birth is challenged, as well as the causes and consequences for when this transition fails to progress. This review will provide an overview of physiological measurements of the respiratory and hemodynamic transition at birth. Also, it will give a perspective on some of the upcoming technological advances in physiological measurements of neonatal transition in infants who are unable to make the transition without support.

In a prospective study we investigated the effect of body position on gastric residuals in 147 preterm infants with a gestational age of 28–36 weeks. Infants were cared for equally in four positions (left lateral (LLP), right lateral (RLP), supine (SP), and prone position (PP)) every 24 h. On day 4 after birth, gastric residuals were measured at 2 time-points in each position. Mean gestational age was 31.6 (2.2) weeks and birth weight 1630 (540) grams. Gastric residuals occurred more often during LLP (49%) than during RLP (39%; p p p

OBJECTIVE: Positive-pressure ventilation (PPV) using a manual ventilation device and a face mask is recommended for compromised newborn infants in the delivery room (DR). Mask ventilation is associated with airway obstruction and leak. A nasal tube is an alternative interface, but its safety and efficacy have not been tested in extremely preterm infants. METHODS: An unblinded randomized controlled trial was conducted in Australia, and the Netherlands. Infants were stratified by gestational age (24–25/26–29 weeks) and center. Immediately before birth infants were randomly assigned to receive PPV and/or continuous positive airway pressure with either a nasal tube or a size 00 soft, round silicone mask. Resuscitation protocols were standardized; respiratory support was provided using a T-piece device commencing in room air. Criteria for intubation included need for cardiac compressions, apnea, continuous positive airway pressure >7 cm H2O, and fraction of inspired oxygen >0.4. Primary outcome was endotracheal intubation in the first 24 hours from birth. RESULTS: Three hundred sixty-three infants were randomly assigned; the study terminated early on the grounds of futility. Baseline variables were similar between groups. Intubation rates in the first 24 hours were 54% and 55% in the nasal tube and face mask groups, respectively (odds ratio: 0.97; 95% confidence interval: 0.63–1.50). There were no important differences in any of the secondary outcomes within the whole cohort or between the 2 gestational age subgroups. CONCLUSIONS: In infants at

Aim The aim of this study was to examine the incidence, placental characteristics and outcome in acute peripartum twin–twin transfusion syndrome (TTTS). Material and Methods All consecutive cases of monochorionic (MC) twins admitted to our center were included in the study. We excluded cases with chronic TTTS or twin anemia polycythemia sequence. Acute peripartum TTTS was defined when the inter-twin hemoglobin difference at birth was >8 g/dL. Results A total of 241 MC twin pregnancies were included in the study. Acute peripartum TTTS was detected in six cases (2.5%, 6/241). Vaginal delivery occurred more often in the acute peripartum TTTS group compared to the control group of uncomplicated MC pregnancies, 100% (6/6) versus 57% (135/235) (P = 0.002), respectively. Acute anemia was detected only in firstborn twins. Placental angioarchitecture in acute peripartum TTTS was similar to the placentas in the control group. Conclusions The incidence of acute peripartum TTTS is low (2.5%). Birth order and mode of delivery appear to be associated with increased risk of acute peripartum TTTS.

Background and Objectives Pregnant women with Idiopathic thrombocytopenic purpura (ITP) can deliver neonates with severe thrombocytopenia. Clear evidence declaring the pathophysiological cause of this neonatal thrombocytopenia is lacking, as antiplatelet antibodies are not always detectable in maternal serum. Severe neonatal thrombocytopenia below 50 × 109/l is reported in 8–13% of the neonates from mothers with ITP and intracranial haemorrhage (ICH) in 0–2·9%. Evidence about the optimal postnatal treatment is scarce. Our objective was to evaluate the outcome and management in neonates with passive ITP. Materials and Methods All neonates from mothers with ITP born between 1980 and 2011 were included. Platelet counts during the first 10 days, presence of ICH and postnatal treatment were recorded. Maternal characteristics were analysed as possible risk factors for severe neonatal thrombocytopenia. Results Sixty-seven neonates were included. Severe thrombocytopenia (

Stimulation of MAS oncogene receptor (MAS) or angiotensin (Ang) receptor type 2 (AT2) may be novel therapeutic options for neonatal chronic lung disease (CLD) by counterbalancing the adverse effects of the potent vasoconstrictor angiotensin II, consisting of arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH) and pulmonary inflammation. We determined the cardiopulmonary effects in neonatal rats with CLD of daily treatment during continuous exposure to 100% oxygen for 10 days with specific ligands for MAS [cyclic Ang-(1-7); 10–50 μg·kg−1·day−1] and AT2 [dKcAng-(1-7); 5–20 μg·kg−1·day−1]. Parameters investigated included lung and heart histopathology, fibrin deposition, vascular leakage, and differential mRNA expression in the lungs of key genes involved in the renin-angiotensin system, inflammation, coagulation, and alveolar development. We investigated the role of nitric oxide synthase inhibition with Nω-nitro-l-arginine methyl ester (25 mg·kg−1·day−1) during AT2 agonist treatment. Prophylactic treatment with agonists for MAS or AT2 for 10 days diminished cardiopulmonary injury by reducing alveolar septum thickness and medial wall thickness of small arterioles and preventing RVH. Both agonists attenuated the pulmonary influx of inflammatory cells, including macrophages (via AT2) and neutrophils (via MAS) but did not reduce alveolar enlargement and vascular alveolar leakage. The AT2 agonist attenuated hyperoxia-induced fibrin deposition. In conclusion, stimulation of MAS or AT2 attenuates cardiopulmonary injury by reducing pulmonary inflammation and preventing PAH-induced RVH but does not affect alveolar and vascular development in neonatal rats with experimental CLD. The beneficial effects of AT2 activation on experimental CLD were mediated via a NOS-independent mechanism.

Apnoea of prematurity is treated with noninvasive respiratory therapy and methylxanthines. For therapy unresponsive apnoea doxapram is often prescibed in preterm neonates. The duration, dosage and route of administration of doxapram together with its efficacy was evaluated in two Dutch neonatal intensive care. Outcome concerning short-term safety and neonatal morbidity were evaluated. During 5 years, 122 of 1,501 admitted newborns P<0.001), lower mean doses (P<0.003), and less days of intensive care (median 33 versus 42 days;P<0.002). No patients died during doxapram therapy. Incidence of necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, persistent ductus arteriosus, or worsening of pulmonary condition did not increase during doxapram therapy. Doxapram is frequently used for apnoea of prematurity, despite a lack of data on short-term efficacy and long-term safety. Until efficacy and safety are confirmed in prospective trials, doxapram should be used with caution.

Objective: To determine the differences in albumin levels between donors and recipients with twin anemia-polycythemia sequence (TAPS). Methods: We included all consecutive monochorionic twins with TAPS with double survivors. Each twin pair was matched for gestational age at birth with 2 control monochorionic twin pairs unaffected by TAPS or twin-twin transfusion syndrome. We measured levels of albumin, total protein, and hemoglobin on the first day of life in donors and recipients (TAPS group) and the control group. Results: A total of 25 TAPS twin pairs and 50 control twin pairs were included in the study. The median gestational age at birth was 32 weeks in both groups. In the TAPS group, median levels (IQR) of albumin in donor twins were significantly lower than in recipient twins, i.e. 28.0 g/l (24.0-32.0) versus 32.0 g/l (30.0-34.5) (p = 0.008). Median levels (IQR) of total protein in donor twins were also lower than in recipients, i.e. 44.0 g/l (36.5-49.0) versus 49.0 g/l (46.5-51.0), respectively (p = 0.004). The median (IQR) intertwin albumin difference was significantly higher in the TAPS group than in the control group, i.e. 4.0 g/l (2.5-10.5) versus 2.0 g/l (1.0-4.0) (p = 0.003). The rate of hypoalbuminemia (Conclusions: In addition to lower hemoglobin levels, donor twins with TAPS also have significantly lower albumin and total protein levels compared to recipient twins.

BackgroundThis study examines the biophysical and preclinical pulmonary activity of synthetic lung surfactants containing novel phospholipase-resistant phosphonolipids or synthetic glycerophospholipids combined with Super Mini-B (S-MB) DATK and/or SP-Css ion-lock 1 peptides that replicate the functional biophysics of surfactant proteins (SP)-B and SP-C. Phospholipase-resistant phosphonolipids used in synthetic surfactants are DEPN-8 and PG-1, molecular analogs of dipalmitoyl phosphatidylcholine (DPPC) and palmitoyl-oleoyl phosphatidylglycerol (POPG), while glycerophospholipids used are active lipid components of native surfactant (DPPC:POPC:POPG 5:3:2 by weight). The objective of the work is to test whether these novel lipid/peptide synthetic surfactants have favorable preclinical activity (biophysical, pulmonary) for therapeutic use in reversing surfactant deficiency or dysfunction in lung disease or injury.MethodsSurface activity of synthetic lipid/peptide surfactants was assessedin vitroat 37 °C by measuring adsorption in a stirred subphase apparatus and dynamic surface tension lowering in pulsating and captive bubble surfactometers. Shear viscosity was measured as a function of shear rate on a Wells-Brookfield micro-viscometer.In vivopulmonary activity was determined by measuring lung function (arterial oxygenation, dynamic lung compliance) in ventilated rats and rabbits with surfactant deficiency/dysfunction induced by saline lavage to lower arterial PO2to ResultsSynthetic surfactants containing 5:3:2 DPPC:POPC:POPG or 9:1 DEPN-8:PG-1 combined with 3% (by wt) of S-MB DATK, 3% SP-Css ion-lock 1, or 1.5% each of both peptides all adsorbed rapidly to low equilibrium surface tensions and also reduced surface tension to ≤1 mN/m under dynamic compression at 37 °C. However, dual-peptide surfactants containing 1.5% S-MB DATK + 1.5% SP-Css ion-lock 1 combined with 9:1 DEPN-8:PG-1 or 5:3:2 DPPC:POPC:POPG had the greatestin vivoactivity in improving arterial oxygenation and dynamic lung compliance in ventilated animals with ARDS. Saline dispersions of these dual-peptide synthetic surfactants were also found to have shear viscosities comparable to or below those of current animal-derived surfactant drugs, supporting their potential ease of deliverability by instillation in future clinical applications.DiscussionOur findings support the potential of dual-peptide synthetic lipid/peptide surfactants containing S-MB DATK + SP-Css ion-lock 1 for treating diseases of surfactant deficiency or dysfunction. Moreover, phospholipase-resistant dual-peptide surfactants containing DEPN-8/PG-1 may have particular applications in treating direct forms of ARDS where endogenous phospholipases are present in the lungs.

Surfactant protein B (SP-B; 79 residues) is a member of the saposin superfamily and plays a pivotal role in lung function. The N- and C-terminal regions of SP-B, cross-linked by two disulfides, were theoretically predicted to fold as charged amphipathic helices, suggesting participation in surfactant activities. Previous studies with oxidized Super Mini-B (SMB), a construct based on the N- and C-regions of SP-B (i.e., residues 1–25 and 63–78) joined with a designer turn (-PKGG-) and two disulfides, indicated that freshly prepared SMB in lipids folded as a surface active, α-helix-hairpin. Because other peptides modeled on α-helical SP domains lost helicity and surfactant activity on storage, experiments were here performed on oxidized SMB in surfactant liposomes stored at ~2–8°C for ≤5.5 years. Captive bubble surfactometry confirmed low minimum surface tensions for fresh and stored SMB preparations. FTIR spectroscopy of fresh and stored SMB formulations showed secondary structures compatible with the peptide folding as α-helix-hairpin. A homology (I-TASSER) model of oxidized SMB demonstrated a globular protein, exhibiting a core of hydrophobic residues and a surface of polar residues. Since mass spectroscopy indicated that the disulfides were maintained on storage, the stability of SMB may be partly due to the disulfides bringing the N- and C-α-helices closer. Mass spectroscopy of stored SMB preparations showed some methionine oxidation, and also partial deacylation of surfactant phospholipids to form lyso-derivatives. However, the stable conformation and activity of stored SMB surfactant suggest that the active helix-hairpin resists these chemical changes which otherwise may lead to surfactant inhibition.

Background: Exchange transfusion (ET) is a high-risk procedure. The type and rate of complications in neonatal red cell alloimmune hemolytic disease exclusively are not clear. Objectives: Our aim was to study the type and rate of complications associated with ET in a large series of neonates with hemolytic disease of the fetus and newborn (HDFN) due to red cell alloimmunization. Methods: All neonates with HDFN due to red cell alloimmunization admitted to our center between January 2001 and June 2011 were eligible for this study. We recorded the number and rate of complications during admission in the group of neonates treated with ET (ET group) and not treated with ET (no-ET group). Multivariate logistic regression analysis was performed to measure the independent risk of complications of ET treatment. Results: A total of 347 infants with red cell alloimmune hemolytic disease were included; 39% (134/347) were treated with at least one ET (ET group), and 61% (213/347) did not require ET (no-ET group). Comparison between the ET group and no-ET group showed that ET treatment was independently associated with proven sepsis [8 vs. 1%, respectively; odds ratio (OR) 8.3, 95% confidence interval (CI) 1.7–40.3; p = 0.009], leukocytopenia (88 vs. 23%, respectively; OR 36.0, 95% CI 17.5–73.8; p < 0.001), severe thrombocytopenia (platelet count 9/l; 63 vs. 8%, respectively; OR 31.4, 95% CI 14.0–70.4; p < 0.001), hypocalcemia (22 vs. 1%, respectively; OR 27.4, 95% CI 5.9–126.8; p < 0.001) and hypernatremia (8 vs. 0%, respectively; p < 0.001). There were no neonatal deaths in the ET group. Conclusion: ET in neonates with HDFN is associated with an increased risk of sepsis, leukocytopenia, thrombocytopenia, hypocalcemia and hypernatremia.

BACKGROUND: Neonates with Rhesus c (Rh c) hemolytic disease of the fetus and newborn (HDFN) are often managed in the same way as neonates with Rhesus D (Rh D) HDFN, although evidence to support this policy is limited. The objective of this study was to evaluate neonatal outcome in severe Rh c HDFN compared to Rh D HDFN. STUDY DESIGN AND METHODS: A retrospective study of (near-)term neonates with severe Rh c (n = 22) and Rh D HDFN (n = 103; without additional antibodies) admitted to the Leiden University Medical Center between January 2000 and October 2011 was conducted. The need for intrauterine transfusions (IUTs), phototherapy, exchange transfusions (ETs), and top-up transfusions up to 3 months of age were recorded and compared between both groups. RESULTS: Although there was a trend for a slightly more severe antenatal course for Rh D HDFN reflected by an earlier need for and higher number of IUTs (median [interquartile range], 2 [1.5-4] vs. 2 [1-2] in Rh c HDFN; p = 0.070), no significant differences were found for the postnatal course between Rh c and Rh D group in days of phototherapy (mean, Days 4.8 and 4.6, respectively; p = 0.569), need for ET (50% vs. 44%, respectively; p = 0.589), and top-up transfusions (62% vs. 78%, respectively; p = 0.128). CONCLUSION: Postnatal outcome in neonates with severe Rh c HDFN is similar compared to neonates with severe Rh D hemolytic disease in terms of days of phototherapy, need for ET, and need for top-up transfusions. These results justify a similar postnatal management of neonates with Rh D and Rh c HDFN.

Objective To evaluate compliance with neonatal resuscitation guidelines during resuscitation of preterm infants by video recording of delivery room management and monitoring physiologic parameters. Methods The delivery room management of preterm infants at birth was recorded by an independent researcher. Physiological parameters (airway pressures, gas flow, tidal volume, heart rate and oxygen saturation) were measured, use of supplemental oxygen was noted and a video of the resuscitation was recorded. All signals were digitised and recorded using specially designed software. The delivery room management was then evaluated and compared with the local resuscitation guidelines. Results Thirty-four infants were included with a mean (SD) gestational age of 30.6 (3.2) weeks and birth weight of 1292 (570) g. Time from birth to initial evaluation was longer than recommended (65 (15) s). Respiratory support was started at 70 (23) s. In 7/34 infants (21%), interventions were performed according to guidelines. In 25/34 infants (74%), one or more respiratory interventions were not performed according to guidelines. In 10/34 infants (29%), one or more non-respiratory interventions (mainly related to the prevention of heat loss) were not performed according to guidelines. The presence and adequacy of spontaneous breathing was difficult to judge clinically. In almost all occasions (96%) the information from the respiratory function monitor was not used. Conclusions Neonatal caregivers often deviate from resuscitation guidelines. Respiratory function monitoring parameters were often not used during resuscitation. A difficult part of neonatal resuscitation is subjectively assessing spontaneous breathing.

Aim: To give new insights into how an infant responded to naloxone, given afteracquiring a maternal opiate by recording the breathing pattern directly after birth. Method: A respiratory recording is presented of an infant during resuscitation in thedelivery room after receiving naloxone for respiratory depression, resulting from maternalremifentanyl use. Results: The infant was born apneic and bradycardic. Normal resuscitation manoeu-vres had no effect on the respiratory drive. Directly after administration of naloxone, a tac-hypneic breathing pattern with sporadic expiratory breaking manoeuvres was observed. Conclusion: The immediate tachypnoea is most likely a direct effect of the naloxonecausing an immediate ‘rebound response’ after the release of the opiate-induced inhibitionof the respiratory drive.INTRODUCTIONNaloxone is the N-ally1 derivative of oxymorphone and actsby competitively binding opiate receptors. Although otheropiate antagonists have partial agonistic activity compara-ble to opiates, naloxone has little or no agonistic activity onopiate receptors (1,2). Naloxone administration to neonatesexposed to maternal opioids during labour has beencommon practice for neonatologists in the last 30 years.However, the efficacy of this treatment has not been clearlydemonstrated. In a systematic review, it was concluded thatnaloxone administration to newborns exposed to maternalopiates increased alveolar ventilation compared to controlnewborns (3). However, the significance of this finding isunclear because the newborns reviewed in these studies didnot appear to have respiratory depression requiring ventila-tory support (3). International guidelines state that focusneeds to remain on effective ventilation and airway supportfor the persistently apneic newborn (4). We describe thebreathing pattern of an apneic infant at birth, exposed tomaternally acquired opiates, after the administration of nal-oxone.PATIENTAND METHODSRecording physiological parameters, including respiratoryfunction monitoring, and video recording is consideredstandard care in our neonatal unit of Leiden UniversityMedical Center, the Netherlands. The recordings are usedfor audit, teaching and research and are obtained using aMasimo SET pulse oximeter (Masimo, Irvine, CA, USA), aFlorian respiratory monitor (Acutronic Medical SystemsAG, Hirzel, Switzerland) and a digital video recorder.Informed consent of the parents was received after delivery.The mother, G1P0, was admitted at 35 weeks and 2 daysof gestation with HELLP syndrome. One day after admis-sion, she experienced severe abdominal pain. Ultrasoundexamination revealed a large liver haematoma. The obstetri-cians decided to deliver the baby by emergency caesareansection. To prevent liver rupture and massive bleeding, themother had to be kept hemodynamically stable. Therefore,general anaesthesia with remifentanyl was given. Remifen-tanyl was administered by continuous intravenous infusion,starting with a dosage of 3.3 lg⁄min 23 min before delivery.Ten minutes before delivery, the dose was increased to20 lg⁄min.The infant (birthweight, 2415 g) was born apneic, hypo-tonic and bradycardic (heart rate, 60 bpm). The infant wasresuscitated using a T-piece infant resuscitator (Neopuff;Abbreviations

Objective To evaluate the incidence and severity of and risk factors for thrombocytopenia at birth in neonates with red cell alloimmunization. Study design All neonates with haemolytic disease of the foetus/newborn (HDFN) due to red cell alloimmunization admitted to our centre between January 2000 and September 2010 were included in this retrospective study. We measured platelet counts at birth and determined the incidence of thrombocytopenia (platelet count