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BackgroundIn children with congenital heart disease (CHD), altered pulmonary circulation compromises gas exchange. Moreover, pulmonary dysfunction is a complication of cardiac surgery with cardiopulmonary bypass (CPB). No data are available on the effect of different CHDs on lung injury. The aim of this study was to analyze epithelial lining fluid (ELF) surfactant composition in children with CHD.MethodsTracheal aspirates (TAs) from 72 CHD children (age 2.9 (0.4-5.7) months) were obtained before and after CPB. We measured ELF phospholipids, surfactant proteins A and B (SP-A, SP-B), albumin, and myeloperoxidase activity. TAs from 12 infants (age 1.0 (0.9-2.9) months) with normal heart/lung served as controls.ResultsHeart defects were transposition of great arteries (19), tetralogy of Fallot (TOF, 20), atrial/ventricular septal defect (ASD/VSD, 22), and hypoplastic left heart syndrome (11). Increased levels of ELF SP-B were found in all defects, increased myeloperoxidase activity in all except the TOF, and increased levels of ELF albumin and SP-A only in ASD/VSD patients. Postoperatively, ELF findings remained unchanged except for a further increase in myeloperoxidase activity.ConclusionELF composition has distinctive patterns in different CHD. We speculate that a better knowledge of the ELF biochemical changes may help to prevent respiratory complications.

Background: Caffeine citrate is the treatment of choice for apnea of prematurity (AOP). Regulatory agencies have requested real-world data on drug utilization and safety, a postauthorization safety study, of a pharmaceutical-grade caffeine citrate, Peyona (R), to confirm its benefit for preterm infants. Objectives: To investigate the clinical use, outcomes, and safety profile of this pharmaceutical-grade caffeine citrate in the routine treatment of preterm infants with a gestational age (GA)

BACKGROUND AND OBJECTIVES The European Union Nitric Oxide trial was designed to assess the potential benefits of inhaled nitric oxide (iNO) compared with placebo in infants with respiratory failure. This follow-up study evaluated respiratory, neurodevelopmental, and other outcomes for infants entered into the European Union Nitric Oxide trial to age 2 years. METHODS: In a multicenter, randomized, double-blind study, preterm infants born at RESULTS: At 36 weeks’ postmenstrual age, 696 of 792 infants were alive; 4 in the iNO arm subsequently died before age 2 years compared with 7 in the control arm. We evaluated 95% of the survivors at 12 months and 90% at 2 years. In the iNO arm, 244 of 363 (67.2%) infants had survived without disability at age 2 years compared with 270 of 374 (72.2%) who received placebo (P = .094). Mean (SD) cognitive composite scores (Bayley Scales of Infant and Toddler Development, third edition) were 94 (13) in the iNO group and 95 (14) in the placebo group; in the iNO group, 19% scored CONCLUSIONS: At 2 years of age, low-dose (5 ppm) iNO started early (

Surfactant protein B (SP-B) plays a key role in surfactant homeostasis affecting its biophysical properties and physiological function. Recently, a method to measure SP-B amount and kinetics from tracheal aspirates (TAs) became available. The main objective of this study was to improve the critical steps of the procedure to obtain a better SP-B sensitivity. We administered a 24 h continuous infusion of 1 mg/kg/h of 1(13)C-leucine to ten newborn infants. SP-B was isolated from serial TAs and its fractional synthesis rate, secretion time, peak time and half life were derived from (13)C enrichment curves obtained by gas chromatography mass spectrometry. SP-B amount in TAs was also assessed. During the extraction step, acidification and organic solvent ratio optimization doubled the recovery of SP-B from TAs, so did the elongation of the propylation time (from 20 min to 1 h) with enhanced leucine derivatization yield. Measurement of (13)C leucine enrichments, and therefore all SP-B kinetics parameters, were successfully calculated in all TAs samples due to the increase of SP-B yield. SP-B amount was 0.29 (0.16-0.41) % of total phospholipids with a minimum value of 0.08% belonging to one of the respiratory distress syndrome (RDS) patients. In conclusion, this new procedure enables accurate determination of SP-B kinetics even in the presence of low protein amount like in preterm RDS patients.

Disaturated-phosphatidylcholine (DSPC) and phosphatidylglycerol (PG) are respectively the first and the third most abundant phospholipid in human alveolar surfactant. Their concentration decreases in airway surfactant of adults and infants with respiratory distress syndrome and cystic fibrosis. In this study, we used mass spectrometry (IRMS) to investigate the turnover of DSPC and PG in tracheal aspirates (TA) obtained from infants with normal or diseased lungs. We studied eight infants requiring mechanical ventilation: two with no lung disease, four with diaphragmatic hernia, one with ATP-binding cassette sub-family A member 3 heterozygote mutation and one with sepsis. Patients received deuterated water for 48 h as metabolic precursors of palmitate-DSPC and palmitate-PG. Serial TAs were obtained every 6 h for five days or until extubation. DSPC and PG were isolated from TA by column and high-performance thin layer chromatography. Deuterium enrichments of palmitate-DSPC and PG residues were measured by IRMS coupled with a gas chromatographer. Median secretion time (ST), peak time (PT) and fractional synthesis rate (FSR) were 3.7 [0.9- 13.4] h, 71.0 [52.2 - 85.2] h and 6.6 [6.3 - 11.1] %/day for DSPC and 19.3 [6.4 - 22.8] h, 49.0 [33.0 - 52.5] h and 5.8 [4.8 - 10.9] %/day for PG. This study shows that it is feasible to use deuterium derived from body water to trace simultaneously airway surfactant DSPC and PG in humans. When compared within the same patient, DSPC and PG had similar fractional synthesis rates, but PG had a shorter PT, suggesting differences in the life cycle of these essential surfactant components.

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

The objective of this study was to determine whether insulin administration would prevent the well-documented catabolic effect of dexamethasone given to preterm infants with chronic lung disease. We studied leucine metabolism in 11 very-low-birth-weight infants before dexamethasone treatment and on d 2. 4. and 7 thereafter, During the first 4 d of dexamethasone. insulin was administered i.v. at a dose of 0.5 (n = 7) or 1.0 (n = 5) lU/kg/d. Leucine turnover was not significantly different between d 0 (337 +/- 41.3 mu mol leucine/kg/h). d 2 (288 +/- 27.2 mu mol leucine/kg/h), d 4 (302 +/- 22.1 mu mol leucine/kg/h), and d 7 (321 +/- 21.2 mu mol leucine/kg/h), and neither was leucine breakdown (272 +/- 21.9 mu mol leucine/kg/h on d 0, 225 +/- 21.5 mu mol leucine/kg/h on d 2, 231 +/- 21 mu mol leucine/kg/h on d 4, and 242 +/- 17.6 mu mol ieucine/kg/h on d 7). Weight gain rates were significantly tower during the first week of dexamethasone treatment compared with the week before treatment or the second and third week. We conclude that during insulin and corticosteroid administration ill very-low-birth-weight infants, no changes were observed in leucine kinetics in contrast to previous studies, The decrease in weight gain was not reversed.

Objective: Treatment of preterm infants with respiratory distress syndrome (RDS) with exogenous surfactant has greatly improved clinical outcome. Some infants require multiple doses, and it has not been studied whether these large amounts of exogenous surfactant disturb endogenous surfactant metabolism in humans. We studied endogenous surfactant metabolism in relation to different amounts of exogenous surfactant, administered as rescue therapy for RDS. Design: Prospective clinical study. Setting: Neonatal intensive care unit in a university hospital. Patients: A total of 27 preterm infants intubated and mechanically ventilated for respiratory insufficiency, Interventions: Infants received a 24-hr infusion with the stable isotope [U-C-13]glucose starting 5.3 +/- 0.5 hrs after birth. The C-13-incorporation into palmitic acid in surfactant phosphatidylcholine (PG) isolated from serial tracheal aspirates was measured. Infants received either zero (n = 5), one (n = 4), two (n = 15), or three (n = 3) doses of Survanta (100 mg/kg) when clinically indicated. Measurements and Main Results: Using multiple regression analysis, the absolute synthesis rate (ASR) of surfactant PC from plasma glucose increased with 1.3 +/- 0.4 mg/kg/day per dose of Survanta (p = .007) (mean a SEM). The ASR of surfactant PC from glucose was increased by prenatal corticosteroid treatment with 1.3 +/- 0.4 mg/kg/day per dose corticosteroid (p = .004), and by the presence of a patent ductus arteriosus with 2.1 +/- 0.7 mg/kg/day (p = .01). Conclusion: These data are reassuring and show for the first time in preterm infants that multiple doses of exogenous surfactant for RDS are tolerated well by the developing lung and stimulate endogenous surfactant synthesis.

Most in vitro studies show that prenatal administration of corticosteroids stimulates the synthesis of surfactant phosphatidylcholine (PC), but studies in animals are controversial. Whether prenatal corticosteroids stimulate surfactant PC synthesis in humans has not been studied. We studied endogenous surfactant PC synthesis in relation to prenatal corticosteroid treatment in 27 preterm infants with respiratory distress syndrome. Infants received a 24-h infusion of the stable isotope [U-C-13]glucose, starting similar to 5 h after birth. We measured C-13-incorporation into palmitic acid in surfactant PC from serial tracheal aspirates and in plasma triglycerides and phospholipids by isotope-ratio mass spectrometry. Premature infants had received either zero (n = 11), one (n = 4), or two doses (n = 12) of prenatal betamethasone (12 mg intramuscularly). The fractional synthesis rate (FSR) of surfactant PC from glucose was 1.7 +/- 0.3%/d without corticosteroid treatment, 2.9 +/- 1.4%/d with one dose of prenatal corticosteroid, and 5.8 +/- 1.3%/d after two doses of prenatal corticosteroid. Using multiple regression analysis, we found that the FSR of surfactant PC increased by 40% (confidence interval: 7 to 82%/d, p

We studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. The newborn baboons were intubated, treated with surfactant, and ventilated for 6 d. They received a 24-h infusion with the stable isotope [U-C-13]glucose as precursor for the synthesis of palmitic acid in surfactant phosphatidylcholine (PC). Palmitic acid in surfactant PC became enriched 27 +/- 2 h after the start of the isotope infusion and was maximally enriched at 100 +/- 4 h. The fractional synthesis rate of PC palmitate in the beta group (1.5 +/- 0.2%/d) was increased by 129% above control (0.7 +/- 0.1%/d) (p

A study was undertaken to analyze the clinical presentation, pulmonary function, and pathological features in two female siblings with neonatal pulmonary surfactant metabolism dysfunction, type 3 (MIM 610921). The clinical records of the siblings were examined; the genes encoding surfactant protein B (SFTPB), surfactant protein C (SFTPC), and ATP-binding cassette transporter 3 protein (ABCA3) were analyzed with direct sequencing and Southern blotting. The infants were homozygous for a 5,983bp deletion in ABCA3 including exons 2-5 as well as the start AUG codon and a putative Golgi exit signal motif. Dense abnormalities of lamellar bodies at electron microscopy and absence of ABCA3 at immunohistochemical staining were in agreement with the presence of two null alleles. In addition, an increased lipid synthesis suggested a compensatory mechanism. The clinical course in the two sisters was influenced by different environmental factors like the time needed for molecular confirmation, the ventilatory assistance adopted, the occurrence of infections. A less aggressive clinical approach did not improve the course of the disease; the prognosis was always poor. Development of a fast molecular test, able to detect also structural variants, is needed. Pediatr Pulmonol. � 2014 Wiley Periodicals, Inc.

Meconium aspiration syndrome (MAS) is a life-threatening neonatal lung injury, whose pathophysiology has been mainly studied in animal models. In such models, pancreatic secretory phospholipase A2 (sPLA2-IB) and proinflammatory cytokines present in meconium challenge the lungs, catabolising surfactant and harming the alveoli. Locally produced phospholipases might perpetuate the injury and influence clinical pictures and therapeutic approaches. Our aim is to verify whether pulmonary phospholipase A2 (sPLA2-IIA) is involved in the damage and to determine if phospholipases and their modulators are associated with MAS clinical pictures.We studied distinct phospholipases A2 and their modulators in broncho-alveolar lavage (BAL) fluids and in meconium of five MAS neonates and in five control neonates ventilated for extrapulmonary reasons.MAS patients have higher amounts of pulmonary phospholipase (sPLA2-IIA; P = 0.016) and Clara cell secretory protein (CCSP; P = 0.032). The local production of such proteins by the lung is confirmed by their very low levels in meconium. sPLA2-IIA contributes to the higher total enzyme activity in MAS patients, as compared to controls (P = 0.008). Cytosolic phospholipase was not detected in meconium or alveolar fluid. sPLA2 activity and sPLA2-IIA concentrations are correlated with the TNFα and with the release of CCSP. sPLA2 total activity, sPLA2-IIA and TNFα concentrations in BAL fluids correlate with the oxygenation impairment and haemorrhagic lung oedema.Pulmonary sPLA2 is locally produced and contributes to the total sPLA2 activity during MAS. CCSP is also produced in trying to lower the inflammation. Both sPLA2 activity and sPLA2-IIA are significantly correlated with oxygenation impairment and haemorrhagic lung oedema.