Evolution of Ultrasound-Assessed Lung Aeration and Gas Exchange in Respiratory Distress Syndrome and Transient Tachypnea of the Neonate.

OBJECTIVE: To use clinical, lung ultrasound, and gas exchange data to clarify the evolution of lung aeration and function in neonates with respiratory distress syndrome (RDS) and transient tachypnea of the neonate (TTN), the most common types of neonatal respiratory failure. STUDY DESIGN: In this prospective observational cohort study, lung aeration and function were measured with a semiquantitative lung ultrasound score (LUS) and transcutaneous blood gas measurement performed at 1 hour (time point 0), 6 hours (time point 1), 12 hours (time point 2), 24 hours (time point 3) and 72 hours (time point 4) of life. Endogenous surfactant was estimated using lamellar body count (LBC). LUS, oxygenation index (OI), oxygen saturation index (OSI), and transcutaneous pressure of carbon dioxide (PtcCO2) were the primary outcomes. All results were adjusted for gestational age. RESULTS: Sixty-nine neonates were enrolled in the RDS cohort, and 58 neonates were enrolled in the TTN cohort. LUS improved over time (within-subjects, P < .001) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001). Oxygenation improved over time (within-subjects, P = .011 for OI, P < .001 for OSI) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001 for OI and OSI). PtcCO2 improved over time (within-subjects, P < .001) and was similar in the RDS and TTN cohorts at all time points. Results were unchanged after adjustment for gestational age. LBC was associated with RDS (ß = -0.2 [95% CI, -0.004 to -0.0001]; P = .037) and LUS (ß = -3 [95% CI, -5.5 to -0.5]; P = .019). CONCLUSIONS: For the first 72 hours of life, the RDS cohort had worse lung aeration and oxygenation compared with the TTN cohort at all time points. CO2 clearance did not differ between the cohorts, whereas both lung aeration and function improved in the first 72 hours of life.

DHA turnover in pregnant women using the natural abundance variation of 13C: a pilot study.

The importance of DHA intake to support fetal development and maternal health is well established. In this pilot study we applied the natural abundance approach to determine the contribution of 200 mg/day of DHA supplement to the plasma DHA pool in 19 healthy pregnant women on a free diet.Women received DHA, from pregnancy week 20 until delivery, from an algal source (N=13, Algae group) or from fish oil (N=6, Fish group) with slightly different content of 13C.We measured plasma phospholipids DHA 13C:12C ratio (reported as δ13C) prior to supplementation (T0), after 10 (T1) and 90 days (T2) and prior to delivery (T3).The δ13C of DHA in algae and fish supplements were -15.8±0.2 mUr and -25.3±0.2 mUr (p<0.001).DHA δ13C in the Algae group increased from -27.7±1.6 mUr (T0) to -21.9±2.2 mUr (T3) (p<0.001), whereas there were not significant changes in the Fish group (-27.8±0.9 mUr at T0 and -27.3±1.1 mUr at T3, p=0.09).In the Algae group 200 mg/day of DHA contributed to the plasma phospholipid pool by a median value of 53% (31-75% minimum and maximum). This estimation was not possible in the fish group.Our results demonstrate the feasibility of assessing the contribution of DHA from an algal source to the plasma DHA pool in pregnant women by the natural abundance approach. Plasma δ13C DHA did not change when consuming DHA of fish origin, with almost the same δ13C value of that of the pre-supplementation plasma δ13C DHA.

Lung Ultrasound to Monitor Extremely Preterm Infants and Predict Bronchopulmonary Dysplasia. A Multicenter Longitudinal Cohort Study.

Rationale: Lung ultrasound is useful in critically ill patients with acute respiratory failure. Given its characteristics, it could also be useful in extremely preterm infants with evolving chronic respiratory failure, as we lack accurate imaging tools to monitor them. Objectives: To verify if lung ultrasound can monitor lung aeration and function and has good reliability to predict bronchopulmonary dysplasia in extremely preterm neonates. Methods: A multicenter, international, prospective, longitudinal, cohort, diagnostic accuracy study consecutively enrolling inborn neonates with gestational age 30+6 weeks or younger. Lung ultrasound was performed on the 1, 7, 14, and 28 days of life, and lung ultrasound scores were calculated and correlated with simultaneous blood gases and work of breathing score. Gestational age-adjusted lung ultrasound scores were created, verified in multivariate models, and subjected to receiver operator characteristics (ROC) analyses to predict bronchopulmonary dysplasia at 36 weeks postmenstrual age. Measurements and Main Results: Mean lung ultrasound scores are different between infants developing (n = 72) or not developing (n = 75) bronchopulmonary dysplasia (P < 0.001 at any time point). Lung ultrasound scores significantly correlate with oxygenation metrics and work of breathing at any time point (P always < 0.0001). Gestational age-adjusted lung ultrasound scores significantly predict bronchopulmonary dysplasia at 7 (area under ROC curve, 0.826-0.833; P < 0.0001) and 14 (area under ROC curve, 0.834-0.858; P < 0.0001) days of life. Bronchopulmonary dysplasia severity and gestational age-adjusted lung ultrasound scores are significantly correlated at 7 and 14 days (P always < 0.0001). Conclusions: Lung ultrasound scores allow monitoring of lung aeration and function in extremely preterm infants. Gestational age-adjusted scores significantly predict the occurrence of bronchopulmonary dysplasia, starting from the seventh day of life.

Chorioamnionitis alters lung surfactant lipidome in newborns with respiratory distress syndrome.

BACKGROUND: Chorioamnionitis is associated with preterm delivery and morbidities; its role in lung disease is controversial. The aim of this study is to assess the effect of chorioamnionitis on metabolite and lipid profiles of epithelial lining fluid in preterm newborns with respiratory distress syndrome (RDS). METHODS: The study involved 30 newborns with RDS, born from mothers with or without histological chorioamnionitis (HCA): HCA+, N = 10; HCA-, N = 20. Patients had a gestational age ≤30 weeks; the groups were matched for age and birth weights. Tracheal aspirates were collected within 24 h after birth and analyzed using liquid chromatography/mass spectrometry-based untargeted lipidomics. RESULTS: According to Mann-Whitney U tests, 570 metabolite features had statistically significantly higher or lower concentrations (p < 0.05) in tracheal aspirates of HCA+ compared to HCA-, and 241 metabolite features were putatively annotated and classified. The most relevant changes involved higher levels of glycerophospholipids (fold change 2.42-17.69) and sphingolipids, with lower concentration of all annotated sphingomyelins in HCA+ (fold change 0.01-0.50). CONCLUSIONS: Untargeted lipidomics of tracheal aspirates suggested the production of lipid mediators in the context of an ongoing inflammatory status in HCA+ babies. However, the effect of chorioamnionitis on epithelial lining fluid composition deserves further investigations on a larger group of infants. IMPACT: Our lipidomics investigation on tracheal aspirates of preterm newborns at birth suggested that exposure to maternal histological chorioamnionitis may cause changes in epithelial lining fluid composition. This is the first description of epithelial lining fluid lipidomic profiles in preterm infants with and without exposition to chorioamnionitis. These results could provide novel link between placental membrane inflammation and newborns' respiratory outcome.

Surfactant-secreted phospholipase A2 interplay and respiratory outcome in preterm neonates.

Secreted phospholipase A2 hydrolyzes surfactant phospholipids and is crucial for the inflammatory cascade; preterm neonates are treated with exogenous surfactant, but the interaction between surfactant and phospholipase is unknown. We hypothesize that this interplay is complex and the enzyme plays a relevant role in neonates needing surfactant replacement. We aimed to: 1) identify phospholipases A2 isoforms expressed in preterm lung; 2) study the enzyme role on surfactant retreatment and function and the effect of exogenous surfactant on the enzyme system; and 3) verify whether phospholipase A2 is linked to respiratory outcomes. In bronchoalveolar lavages of preterm neonates, we measured enzyme activity (alone or with inhibitors), enzyme subtypes, surfactant protein-A, and inflammatory mediators. Surfactant function and phospholipid profile were also tested. Urea ratio was used to obtain epithelial lining fluid concentrations. Follow-up data were prospectively collected. Subtype-IIA is the main phospholipase isoform in preterm lung, although subtype-IB may be significantly expressed. Neonates needing surfactant retreatment have higher enzyme activity (P = 0.021) and inflammatory mediators (P always ≤ 0.001) and lower amounts of phospholipids (P always < 0.05). Enzyme activity was inversely correlated to surfactant adsorption (ρ = -0.6; P = 0.008; adjusted P = 0.009), total phospholipids (ρ = -0.475; P = 0.05), and phosphatidylcholine (ρ = -0.622; P = 0.017). Exogenous surfactant significantly reduced global phospholipase activity (P < 0.001) and subtype-IIA (P = 0.005) and increased dioleoylphosphatidylglycerol (P < 0.001) and surfactant adsorption (P < 0.001). Enzyme activity correlated with duration of ventilation (ρ = 0.679, P = 0.005; adjusted P = 0.04) and respiratory morbidity score at 12 mo postnatal age (τ-b = 0.349, P = 0.037; adjusted P = 0.043) but was not associated with mortality, bronchopulmonary dysplasia, or other long-term respiratory outcomes.

Inhaled nitric oxide (iNO) for preventing prematurity-related bronchopulmonary dysplasia (BPD): 7-year follow-up of the European Union Nitric Oxide (EUNO) trial.

OBJECTIVES: Most studies of inhaled nitric oxide (iNO) for prevention of bronchopulmonary dysplasia (BPD) in premature infants have focused on short-term mortality and morbidity. Our aim was to determine the long-term effects of iNO. METHODS: A 7-year follow-up was undertaken of infants entered into a multicenter, double-blind, randomized, placebo-controlled trial of iNO for prevention of BPD in premature infants born between 24 and 28 weeks plus six days of gestation. At 7 years, survival and hospital admissions since the 2-year follow-up, home oxygen therapy in the past year, therapies used in the previous month and growth assessments were determined. Questionnaires were used to compare general health, well-being, and quality of life. RESULTS: A total of 305 children were assessed. No deaths were reported. Rates of hospitalization for respiratory problems (6.6 vs. 10.5%, iNO and placebo group, respectively) and use of respiratory medications (6.6 vs. 9.2%) were similar. Two patients who received iNO and one who received placebo had received home oxygen therapy. There were no significant differences in any questionnaire-documented health outcomes. CONCLUSIONS: iNO for prevention of BPD in very premature infants with respiratory distress did not result in long-term benefits or adverse long-term sequelae. In the light of current evidence, routine use of iNO cannot be recommended for prevention of BPD in preterm infants.

Urinary metabolomics reveals kynurenine pathway perturbation in newborns with transposition of great arteries after surgical repair.

INTRODUCTION: Transposition of the great arteries (TGA) is a cyanotic congenital heart defect that requires surgical correction, with the use of cardiopulmonary-bypass (CPB), usually within 3 weeks of life. The use of CPB in open heart surgery results in brain hypoperfusion and in a powerful systemic inflammatory response and oxidative stress. OBJECTIVE: We aimed to develop a novel untargeted metabolomics approach to detect early postoperative changes in metabolic profile following neonatal cardiac surgery. METHODS: We studied 14 TGA newborns with intact ventricular septum undergoing arterial switch operation with the use of CPB. Urine samples were collected preoperatively and at the end of the surgery and were analyzed using an untargeted metabolomics approach based on UHPLC-high resolution mass spectrometry. RESULTS: Since post surgery metabolic spectra were heavily contaminated by metabolites derived from administered drugs, we constructed a list of drugs used during surgery and their related metabolites retrieved from urine samples. This library was applied to our samples and 1255 drugs and drug metabolites were excluded from the analysis. Afterward, we detected over 39,000 unique compounds and 371 putatively annotated metabolites were different between pre and post-surgery samples. Among these metabolites, 13 were correctly annotated or identified. Metabolites linked to kynurenine pathway of tryptophan degradation displayed the highest fold change. CONCLUSIONS: This is the first report on metabolic response to cardiac surgery in TGA newborns. We developed an experimental design that allowed the identification of perturbed metabolic pathways and potential biomarkers of brain damage, limiting drugs interference in the analysis.

Tracing exogenous surfactant in vivo in rabbits by the natural variation of 13C.

BACKGROUND: Respiratory Distress Syndrome (RDS) is a prematurity-related breathing disorder caused by a quantitative deficiency of pulmonary surfactant. Surfactant replacement therapy is effective for RDS newborns, although treatment failure has been reported. The aim of this study is to trace exogenous surfactant by 13C variation and estimate the amount reaching the lungs at different doses of the drug. METHODS: Forty-four surfactant-depleted rabbits were obtained by serial bronchoalveolar lavages (BALs), that were merged into a pool (BAL pool) for each animal. Rabbits were in nasal continuous positive airway pressure and treated with 0, 25, 50, 100 or 200 mg/kg of poractant alfa by InSurE. After 90 min, rabbits were depleted again and a new pool (BAL end experiment) was collected. Disaturated-phosphatidylcholine (DSPC) was measured by gas chromatography. DSPC-Palmitic acid (PA) 13C/12C was analyzed by isotope ratio mass spectrometry. One-way non-parametric ANOVA and post-hoc Dunn's multiple comparison were used to assess differences among experimental groups. RESULTS: Based on DSPC-PA 13C/12C in BAL pool and BAL end experiment, the estimated amount of exogenous surfactant ranged from 61 to 87% in dose-dependent way (p < 0.0001) in animals treated with 25 up to 200 mg/kg. Surfactant administration stimulated endogenous surfactant secretion. The percentage of drug recovered from lungs did not depend on the administered dose and accounted for 31% [24-40] of dose. CONCLUSIONS: We reported a risk-free method to trace exogenous surfactant in vivo. It could be a valuable tool for assessing, alongside the physiological response, the delivery efficiency of surfactant administration techniques.

Hypertriglyceridemia and Intravenous Lipid Titration During Routine Parenteral Nutrition in Small Preterm Infants.

OBJECTIVES: In case of hypertriglyceridemia (HiTG) during parenteral nutrition (PN), the 2018 European Society of Paediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an intravenous (IV) lipid titration, but its consequences in small preterm infants are largely unknown. We compared macronutrient and energy intakes, growth, diseases associated with prematurity, and neurodevelopment in small preterm infants on PN who developed (cases) or did not develop HiTG (controls, CNTR). METHODS: We retrospectively reviewed data of preterm infants with a birth weight (BW) <1250 g consecutively admitted to our neonatal intensive care unit (2004-2016) who received routine PN. HiTG infants were defined by at least 1 triglyceride (TG) measurement >250 mg/dL during the first 10 days of life. Patients with and without HiTG were match-paired for BW and gestational age. RESULTS: A total of 658 infants were analyzed and 196 (30%) had HiTG. One hundred thirty-six HiTG patients were matched with 136 CNTR. In the first 10 days of life, IV lipid, non-protein energy and total energy intakes, but not IV amino acids and carbohydrates, were significantly lower in HiTG infants. We found no differences between groups in diseases associated with prematurity. Anthropometry at 36 weeks (W), anthropometry at 2-year (Y) corrected age (CA), and neurodevelopment at 2Y CA were not different. CONCLUSIONS: Growth, diseases associated with prematurity, and neurodevelopment at 2Y CA in HiTG infants were similar to CNTR. This occurred despite a statistically significant albeit small reduction in IV lipid and non-protein energy intakes due to a strict TG monitoring and IV lipid titration at TG levels >250 mg/dL.

Influence of the type of congenital heart defects on epithelial lining fluid composition in infants undergoing cardiac surgery with cardiopulmonary bypass.

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.

Effects of early nutrition and growth on brain volumes, white matter microstructure, and neurodevelopmental outcome in preterm newborns.

BackgroundThis study aimed to investigate the effect of nutrition and growth during the first 4 weeks after birth on cerebral volumes and white matter maturation at term equivalent age (TEA) and on neurodevelopmental outcome at 2 years' corrected age (CA), in preterm infants.MethodsOne hundred thirty-one infants born at a gestational age (GA) <31 weeks with magnetic resonance imaging (MRI) at TEA were studied. Cortical gray matter (CGM) volumes, basal ganglia and thalami (BGT) volumes, cerebellar volumes, and total brain volume (TBV) were computed. Fractional anisotropy (FA) in the posterior limb of internal capsule (PLIC) was obtained. Cognitive and motor scores were assessed at 2 years' CA.ResultsCumulative fat and enteral intakes were positively related to larger cerebellar and BGT volumes. Weight gain was associated with larger cerebellar, BGT, and CGM volume. Cumulative fat and caloric intake, and enteral intakes were positively associated with FA in the PLIC. Cumulative protein intake was positively associated with higher cognitive and motor scores (all P<0.05).ConclusionOur study demonstrated a positive association between nutrition, weight gain, and brain volumes. Moreover, we found a positive relationship between nutrition, white matter maturation at TEA, and neurodevelopment in infancy. These findings emphasize the importance of growth and nutrition with a balanced protein, fat, and caloric content for brain development.

Patent ductus arteriosus in preterm infants born before 30 weeks' gestation: high rate of spontaneous closure after hospital discharge.

AimThe aim of this study was to determine the spontaneous closure rate of patent ductus arteriosus at a 2-year follow-up, following failed medical therapy and beyond initial hospital discharge, and to evaluate in-hospital spontaneous or pharmacological closure rates.Materials and methodsA retrospective evaluation was conducted in a cohort of preterm infants admitted to the Neonatal ICU of Ancona between January, 2004 and June, 2013. Inclusion criteria were gestational age between 24+0 and 29+6 weeks or birth weight 1.5 mm, a left atrium-to-aorta ratio >1.4, and/or reversal of end-diastolic flow in the aorta >30% of the anterograde. First-line treatment was intravenous ibuprofen. Intravenous indomethacin was used if ibuprofen failed. Surgical ligation was considered in haemodynamically significant patent ductus arteriosus after medical treatment. RESULTS: A total of 593 infants met the inclusion criteria, and patent ductus arteriosus was diagnosed in 317 (53.4%). Among them, 283 (89.3%) infants had haemodynamically significant patent ductus arteriosus, with pharmacological closure achieved in 228 (80.6%) infants and surgical ligation performed in 20 (7.1%). Follow-up at 24 months was available for 39 (81.3%) of 48 infants with patent ductus arteriosus at the hospital discharge: 36 (92.3%) underwent spontaneous closure, two (5.1%) underwent surgical ligation, and one (2.6%) had a patent ductus arteriosus.DiscussionA significant number of patent ductus arteriosus that fail pharmacological closure undergo spontaneous closure by the age of 2 years. This information should be taken into account when considering surgery or additional attempts of pharmacological closure.

Effects of Arachidonic and Docosohexahenoic Acid Supplementation during Gestation in Rats. Implication of Placental Oxidative Stress.

Arachidonic and docosahexaenoic acids (ARA and DHA) are important during pregnancy. However, the effects of dietary supplementation on fetal growth and oxidative stress are inconclusive. We aimed to assess the effect of high ARA and DHA diet during rat gestation on: (1) ARA and DHA availability in plasma and placenta, (2) fetal growth, and (3) placental oxidative stress, analyzing the influence of sex. Experimental diet (ED) was prepared by substituting soybean oil in the control diet (CD) by a fungi/algae-based oil containing ARA and DHA (2:1). Rats were fed with CD or ED during gestation; plasma, placenta, and fetuses were obtained at gestational day 20. DHA, ARA, and their precursors were analyzed in maternal plasma and placenta by gas chromatography/mass spectrophotometry. Fetuses and placentas were weighed, the proportion of fetuses with intrauterine growth restriction (IUGR) determined, and placental lipid and protein oxidation analyzed. ED fetuses exhibited lower body weight compared to CD, being >40% IUGR; fetal weight negatively correlated with maternal plasma ARA, but not DHA. Only ED female placenta exhibited higher lipid and protein oxidation compared to its CD counterparts; lipid peroxidation is negatively associated with fetal weight. In conclusion, high ARA during gestation associates with IUGR, through placental oxidative stress, with females being more susceptible.

Neonatal outcome of small for gestational age preterm infants.

Small for gestational age (SGA) preterm neonates (birth weight < -2 SDS) are considered to have increased risk of bronchopulmonary dysplasia (BPD) compared to appropriate for GA (AGA) neonates. It is unclear if SGA infants have increased risk for respiratory distress syndrome (RDS) and mortality. We analyzed data from 515 neonates born <30 weeks GA, 98(19%) were SGA. SGA were compared to AGA by univariate analysis and logistic regression analysis (LRA). Significant variables at univariate analysis were IUGR (67 vs 7%, p = 0.000), chorioamnionitis (1 vs 13%, p = 0.017), pre-eclampsia (62 vs 18%, p = 0.000), surfactant retreatment (47 vs 25%, p = 0.000), BPD (32 vs 20%, p = 0.015), death (30 vs 12%, p = 0.000), SatO2/FiO2 on day 3 (376 vs 433, p = 0.013), and SatO2/FiO2 ratio on day 28 (400 vs 448, p = 0.000). LRA found the following associations: regarding mortality, a decreased Sat/FiO2 ratio on day 3 (OR 1.99, 95% CI 1.26-3.16, p = 0.003); regarding BPD, surfactant retreatment (3.70, 2.11-6.49, p = 0.000), being SGA (2.69, 1.36-5.36, p = 0.005), decreasing GA (1.05, 1.03-1.08, p = 0.000), decreasing SatO2/FiO2 ratio on day 3 (1.25, 1.11-1.40, p = 0.000); and regarding severe RDS, pre-eclampsia (2.68, 1.58-4.55, p = 0.000) and decreasing GA (1.06, 1.04-1.08, p = 0.000). CONCLUSIONS: In our cohort of preterm infants, being SGA was significantly associated with BPD, but not with increased risk of mortality or RDS due to multiple pathophysiologic mechanisms. What is Known: • Small for gestational age preterm neonates are considered to have increased risk of bronchopulmonary dysplasia (BPD) compared to appropriate for GA neonates. • It is still unclear if SGA infants have increased risk for respiratory distress syndrome (RDS) and mortality. What is New: • In our cohort of 515 preterm infants (19% SGA), being SGA was significantly associated with BPD, but not with increased risk of mortality or RDS. • These results may be explained by the heterogeneity of mechanisms leading to SGA condition and by multiple mechanisms involving lung growth impairment and other factors.

One Extra Gram of Protein to Preterm Infants From Birth to 1800 g: A Single-Blinded Randomized Clinical Trial.

OBJECTIVE: The aim of the study was to evaluate the effect on growth and neurodevelopment of increasing amino acid (AA) during parenteral nutrition and protein intake during enteral nutrition in extremely low birth-weight infants starting from birth to day of reaching 1800 g body weight. METHODS: We randomized preterm infants with birth weight 500 to 1249 g either to a high AA/protein intake (HiP [high protein]: parenteral nutrition = 3.5 AA, enteral nutrition = 4.6 protein g ·â€Škg ·â€Šday) or to a standard of care group (StP [standard protein]: parenteral nutrition = 2.5 AA, enteral nutrition = 3.6 protein g ·â€Škg ·â€Šday). The primary outcome was weight gain from birth to 1800 g. RESULTS: TWO:: hundred twenty-six patients were screened, 164 completed the study and were analyzed (82 StP and 82 HiP). Cumulative AA/protein intake from birth to 1800 g was 178 ±â€Š42 versus 223 ±â€Š45 g/kg in the StP versus HiP group respectively, P < 0.0001.Blood urea was higher in HiP than in StP group both during parenteral and enteral nutrition (P = 0.004).Weight gain from birth to 1800 g was 12.3 ±â€Š1.6 in StP and 12.6 ±â€Š1.7 g ·â€Škg ·â€Šday in HiP group (P = 0.294). We found no difference in any growth parameters neither during hospital stay nor at 2 years corrected age. Bayley III score at 24 months corrected age was 93.8 ±â€Š12.9 in StP group and 94.0 ±â€Š13.9 in the HiP group, P = 0.92. CONCLUSIONS: Increasing AA/protein intake both during parenteral and enteral nutrition does not improve growth and neurodevelopment of small preterm infants 500 to 1249 g birth weight.

Surfactant protein B and A concentrations are increased in neonatal pneumonia.

BACKGROUND: Term newborns with pneumonia show a reduced pulmonary compliance due to multiple and ill-defined factors. Surfactant proteins' (SPs) changes could have a role in the reduced compliance but the matter is still unsettled. The aim of this study was to clarify the meaning of SPs changes during pneumonia in term newborns. METHODS: In 28 term ventilated newborns, 13 with pneumonia and 15 with no lung disease, we measured SP-B, SP-A, disaturated-phosphatidylcholine (DSPC), and total phospholipids (PL) concentrations in tracheal aspirates at intubation and close to extubation. We also measured DSPC kinetics using (U-(13)C-PA)dipalmitoyl-phosphatidylcholine. RESULTS: At baseline, SP-B, expressed as % of PL, was significantly different between the groups, being 3.5-fold higher in pneumonia than controls. Conversely, SP-A did not vary between the groups. At extubation, SP-B and SP-A concentrations had decreased significantly in newborns with pneumonia, while there was no significant change in controls. DSPC t1/2 was significantly shorter in the pneumonia group (11.8 (5.5-19.8) h vs. 26.6 (19.3-63.6) h, P = 0.011). CONCLUSION: In term newborns with pneumonia, SP-B increases with respect to PL, and DSPC is turned over at a faster rate. Disease's resolution is associated with the restoration of the normal ratio between SP-B and PL.

Surfactant protein C metabolism in human infants and adult patients by stable isotope tracer and mass spectrometry.

Surfactant protein C (SP-C) is deemed as the surfactant protein most specifically expressed in type II alveolar epithelial cells and plays an important role in surfactant function. SP-C turnover in humans and its meaning in the clinical context have never been approached. In this study, we used mass spectrometry to investigate SP-C turnover in humans. We studied four infants and eight adults requiring mechanical ventilation. All patients had no lung disease. Patients received a 24-h continuous infusion of (13)C-leucine as precursor of SP-C, and serial tracheal aspirates and plasma samples were obtained every 6 h till 48 h. SP-C was isolated from tracheal aspirates by sorbent-phase chromatography. (13)C-leucine SP-C enrichment could be successfully measured in three infant and in four adult samples by using mass spectrometry coupled with a gas chromatographer. Median SP-C fractional synthesis rate, secretion time, and peak time were 15.7 (14.1-27.5)%/day, 6.0 (4.7-11.5) h, and 24 (20-27) h. In conclusion, this study shows that it is feasible to accurately determine SP-C turnover in humans by stable isotopes.

rhBSSL improves growth and LCPUFA absorption in preterm infants fed formula or pasteurized breast milk.

OBJECTIVES: Preterm infants often experience suboptimal growth, which can affect organ development. The aim of this study was to improve growth by treatment with bile salt-stimulated lipase (BSSL), naturally present in breast milk, but lost after pasteurization, and absent in formula. METHODS: Two clinical trials were performed with a predefined analysis of combined data to investigate the effects of recombinant human BSSL (rhBSSL) treatment on growth velocity and fat absorption in preterm infants. The studies were randomized and double-blinded comparing 7-day treatment with rhBSSL and placebo, administered in pasteurized breast milk or formula, using a crossover design. RESULTS: Sixty-three infants were evaluated for safety. At randomization, the mean (standard deviation) weight was 1467 (193) g and mean postmenstrual age was 32.6 (0.5) weeks. Sixty and 46 infants were evaluated for growth velocity and fat absorption, respectively. rhBSSL treatment significantly improved mean growth velocity by 2.93 g · kg · day (P<0.001) compared with placebo (mean 16.86 vs 13.93 g · kg · day) and significantly decreased the risk of suboptimal growth (<15 g · kg · day) (30% vs 52%, P=0.004). rhBSSL significantly increased absorption of the long-chain polyunsaturated fatty acids, docosahexaenoic acid, and arachidonic acid by 5.76% (P=0.013) and 8.55% (P=0.001), respectively, but had no significant effect on total fat absorption. The adverse-event profile was similar to placebo. CONCLUSIONS: In preterm infants fed pasteurized breast milk or formula, 1 week of treatment with rhBSSL was well tolerated and significantly improved growth and long-chain polyunsaturated fatty acid absorption compared to placebo. This publication presents the first data regarding the use of rhBSSL in preterms and the results have led to further clinical studies.

Growth and fatty acid profiles of VLBW infants receiving a multicomponent lipid emulsion from birth.

OBJECTIVES: Very-low-birth-weight (VLBW) infants are dependent on parenteral nutrition after birth. A parenteral lipid emulsion with a multicomponent composition may improve growth and neurodevelopment and may prevent liver injury, which is often observed in association with long-term parenteral nutrition with pure soybean oil. Our aim was to evaluate the safety and efficacy of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triacylglycerol, 25% olive oil, and 15% fish oil compared with a conventional pure soybean oil emulsion in VLBW infants. METHODS: We conducted a double-blind randomized controlled trial in VLBW infants randomized to parenteral nutrition with the multicomponent (study group) or pure soybean oil emulsion (control group) from birth at a dose of 2 to 3 g · kg(-1) · day(-1) until the infants were receiving full enteral nutrition. We assessed efficacy by growth rates and measuring plasma fatty acid profiles (representative subset). Safety was evaluated by assessing hematologic and biochemical parameters, potentially harmful phytosterol concentrations (same subset), and clinical neonatal outcome parameters. RESULTS: Ninety-six infants were included (subsets n = 21). The multicomponent emulsion was associated with higher weight and head circumference z scores during admission. Plasma eicosapentaenoic acid and docosahexaenoic acid concentrations were higher in the study group. The hematological, biochemical, and neonatal outcomes were not different between groups, whereas the plasma concentrations of phytosterols were higher in the control group. CONCLUSIONS: The multicomponent lipid emulsion was well tolerated and associated with improved growth and higher plasma fatty acid profiles in VLBW infants in comparison with the pure soybean oil emulsion.