Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Meckel's diverticulum perforation in a newborn positive to Sars-Cov-2.

The health emergency linked to the Sars-Cov-2 infection represented an absolutely new problem for all health professionals. In particular, the information regarding the spread of the virus in the pediatric field and its manifestations are still incomplete. In this paper we present a case of neonatal infection which, as far as we know, represents one of the few published cases and which occurred in a patient who came to our attention for acute abdomen from intestinal perforation. The perforation was caused by Meckel's diverticulum, an event considered infrequent in the first year of life and almost exceptional in the neonatal period. This case required particular management, putting pediatric surgeons in front of new and difficult to solve problems. New onset clinical events, such as this one described, represent an opportunity for sharing useful data for the creation of universal protocols for the management of patients with problems that are becoming common and of which little is known.

Factors affecting early-life intestinal microbiota development.

OBJECTIVES: This paper reviews the published evidence on early-life intestinal microbiota development, as well as the different factors influencing its development before, at, and after birth. A literature search was done using PubMed, Cochrane and EMBASE databases. A growing body of evidence indicates that the intrauterine environment is not sterile as once presumed, but that maternal-fetal transmission of microbiota occurs during pregnancy. The consecutive order of bacteria with which the gastrointestinal tract is colonized will influence the outcome of community assembly and the ecological success of individual colonizers. The genetic background of the infant may also strongly influence microbial colonization of the gastrointestinal tract. The composition and development of infant gut microbiota can be influenced by many prenatal factors, such as maternal diet, obesity, smoking status, and use of antibiotic agents during pregnancy. Mode of delivery is generally accepted as a major factor determining the initial colonization. Breast milk stimulates the most balanced microbiome development for the infant, mainly because of its high content of unique oligosaccharides. Feeding is another important factor to determine intestinal colonization. Compared with breastfed infants, formula-fed infants have an increased richness of species. Initial clinical studies show that infant formulas supplemented with specific human milk oligosaccharides (HMOs) -2´-fucosyllactose alone or in combination with lacto-n-neotetraose are structurally identical to those in breast milk. HMOs increase the proportion of infants with a high bifidobacterial-dominated gut microbiota typical of that observed in breastfed infants, lead to plasma immune marker profiles similar to those of breast-fed infants and to lower morbidity and antibiotics use. Further clinical studies with the same, others or more HMOs are needed to confirm these clinical effects. A growing number of studies have reported on how the composition and development of the microbiota during early life will affect risk factors related to health up to and during adulthood. If exclusive breastfeeding is not possible, the composition of infant formula should be adapted to stimulate the development of a bifidobacterial-dominated gut microbiota typical of that observed in breastfed infants. The main components in breast milk that stimulate the growth of specific bifidobacteria are HMOs.

Correlation between cardiorespiratory events and gastro-esophageal reflux in preterm and term infants: Analysis of predisposing factors.

BACKGROUND: The association between cardiorespiratory events (CRE) and gastro-esophageal reflux (GER) among neonates is still controversial. AIMS: To test such an association in preterm and term infants. STUDY DESIGN: Prospective observational study. SUBJECTS: Forty-seven infants with suspected GER and recurrent CRE admitted at a neonatal intensive care unit, who underwent simultaneous and synchronized 24-hour recording of heart rate (HR), peripheral oxygen saturation (SpO2) and pH-impedance monitoring (MII-pH). HR/SpO2 data were filtered to avoid artefactual episodes of hypoxia and hypoperfusion. OUTCOME MEASURES: The main outcome measure was the symptom association probability (SAP), with a 2-minute time window. Infants with positive (>95%) and negative (≤95%) SAP index tests were compared by univariate and multivariate statistics. RESULTS: Median gestational age at birth was 294/7 weeks, median age at study 36 days. We recorded 3341 GER events and 4936 CRE (4710 desaturations, 226 bradycardias); 609/4936 (12%) CRE were temporally associated with GER episodes: 338 preceded and 271 followed GER events. The SAP index was significant in 5/47 (11%) patients. The SAP index including only CRE following GER events was significant in 3/47 (6%). There was no significant difference in the number of acid, weakly acid, non-acid, pH-only events preceding or following CRE between infants with SAP-positive and SAP-negative tests. Infants with positive SAP-index tests compared to those with SAP-negative tests had lower weight gain in the three days preceding the test and tended to have lower birth weight. CONCLUSIONS: GER and CRE were associated in <11% of patients. The evaluation of ponderal growth might be helpful in predicting such an association.

Caffeine for preterm infants: current indications and uncertainties.

Caffeine is one of the most commonly used therapies in Neonatology, with different indications such as the treatment of apnea and the prevention of extubation failure and bronchopulmonary dysplasia. However, there are still uncertainties regarding effects on central nervous system development, time of discontinuation and dosing of the drug.

Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review.

Administration of drugs directly into the respiratory tree first was proposed a long time ago. Surfactant is the paradigmatic example of such therapies. Many other drugs have been used in the same way and further compounds are under investigation for this aim. In the last two decades, despite the wide number of drugs available for direct lung administration in critical care patients, few controlled data exist regarding their use in neonates and infants. This review will focus on drugs clinically available in a critical care setting for neonates and infants, including bronchodilators, pulmonary vasodilators, anti-inflammatory agents, mucolytics, resuscitative anti-infective agents, surfactants and other drugs. We provide an evidence-based comprehensive review of drugs available for intratracheal administration in paediatric and neonatal critical care and we examine possible advantages and risks for each proposed indication.

Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

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.

EIA and GC/MS analysis of 8-isoprostane in EBC of children with problematic asthma.

Asthmatic airways are characterised by enhanced oxidative stress, which can be studied by measuring biomarkers, such as 8-isoprostane. The aims of the present study were: 1) to measure the concentrations of 8-isoprostane in exhaled breath condensate (EBC) and urine of children with problematic and well-controlled asthma; 2) to compare the concentrations of 8-isoprostane measured by gas chromatographic/negative ion chemical ionisation mass spectrometry (GC/NICI-MS) and by an enzymatic immunoassay (EIA). We recruited 20 asthmatic allergic children, 13 with well-controlled asthma and seven with problematic asthma. They underwent exhaled nitric oxide measurements and spirometry, and both EBC and urine samples were collected. 8-isoprostane was measured in EBC by GC/NICI-MS and EIA. 8-isoprostane concentrations in EBC were significantly higher in children with problematic asthma than in children with well-controlled asthma (p = 0.01). An acceptable reproducibility emerged between GC/NICI-MS and EIA (coefficient of reproducibility 11.5 pg x mL(-1)). 8-isoprostane levels measured in urine did not correlate with those measured in EBC. We showed that 8-isoprostane in EBC was significantly increased in children with problematic asthma, suggesting a role for oxidative stress in this asthma phenotype. In addition we found an acceptable reproducibility of EIA compared to GC/NICI-MS, even if the latter method had higher accuracy.

Pulmonary surfactant kinetics of the newborn infant: novel insights from studies with stable isotopes.

Deficiency or dysfunction of the pulmonary surfactant plays a critical role in the pathogenesis of respiratory diseases of the newborn. After a short review of the pulmonary surfactant, including its role in selected neonatal respiratory conditions, we describe a series of studies conducted by applying two recently developed methods to measure surfactant kinetics. In the first set of studies, namely 'endogenous studies', which used stable isotope-labeled intravenous surfactant precursors, we have shown the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors, including plasma glucose, plasma fatty acids and body water. In the second set of studies, namely 'exogenous studies', which used a stable isotope-labeled phosphatidylcholine (PC) tracer given endotracheally, we estimated the surfactant disaturated phosphatidylcholine (DSPC) pool size and half-life. The major findings of our studies are presented here and can be summarized as follows: (a) the de novo synthesis and turnover rates of the surfactant (DSPC) in preterm infants with respiratory distress syndrome (RDS) are very low with either precursor; (b) in preterm infants with RDS, pool size is very small and half-life much longer than what has been reported in animal studies; (c) patients recovering from RDS who required higher continuous positive airway pressure pressure after extubation or reintubation have a lower level of intrapulmonary surfactant than those who did well after extubation; (d) term newborn infants with pneumonia have greatly accelerated surfactant catabolism; and (e) infants with uncomplicated congenital diaphragmatic hernia (CDH) and on conventional mechanical ventilation have normal surfactant synthesis, but those requiring extracorporeal membrane oxygenated (ECMO) do not. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases.

Surfactant metabolism in the neonate.

With the use of stable isotope-labeled intravenous precursors for surfactant phosphatidylcholine (PC) synthesis, it has been shown that the de novo synthesis rates in preterm infants with respiratory distress syndrome (RDS) are very low as are turnover rates. This is consistent with animal data. Surfactant therapy does not inhibit endogenous surfactant synthesis, and prenatal corticosteroids stimulate it. With the use of stable isotope-labeled PC given endotracheally, surfactant pool size was estimated. It turned out to be low in RDS, as expected. Similar studies were performed in term neonates with severe lung diseases. In general, patients with lung injury show a lower surfactant synthesis. The controversy around surfactant in congenital diaphragmatic hernia (CDH) persists: studies on CDH with and without extracorporeal membrane oxygenation yielded different results. In severe meconium aspiration syndrome surfactant synthesis was found to be decreased but surfactant pool size was maintained. It is possible and safe to study surfactant metabolism in human neonates with the use of stable isotopes. This can help in answering clinical questions and has the potential to bring new in vitro and animal findings about surfactant metabolism to the patient.

Kinetics of surfactant in respiratory diseases of the newborn infant.

Deficiency or dysfunction of pulmonary surfactant plays a critical role in the pathogenesis of respiratory diseases in the newborn. We describe the studies made by applying two recently developed methods to measure surfactant kinetics. The first allows the measurement of endogenous surfactant phosphatidylcholine (PC) synthesis and kinetics by a constant intravenous infusion of glucose or fatty acids labeled with stable isotope 13C. The second method consists of endotracheal administration of a tracer dose of 13C-labeled dipalmitoyl-phosphatidylcholine (DPPC) to measure disaturated-phosphatidylcholine (DSPC) half-life and apparent pool size. We present the results of surfactant kinetics in some of the respiratory diseases of the newborn infant.

Leucine kinetics during simultaneously administered insulin and dexamethasone in preterm infants with severe lung disease.

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) IU/kg/d. Leucine turnover was not significantly different between d 0 (337 +/- 41.3 micromol leucine/kg/h), d 2 (288 +/- 27.2 micromol leucine/kg/h), d 4 (302 +/- 22.1 micromol leucine/kg/h), and d 7 (321 +/- 21.2 micromol leucine/kg/h), and neither was leucine breakdown (272 +/- 21.9 micromol leucine/kg/h on d 0, 225 +/- 21.5 micromol leucine/kg/h on d 2, 231 +/- 21 micromol leucine/kg/h on d 4, and 242 +/- 17.6 micromol leucine/kg/h on d 7). Weight gain rates were significantly lower 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 in 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.

Endogenous surfactant turnover in preterm infants with respiratory distress syndrome studied with stable isotope lipids.

We studied surfactant kinetics on Day 1 of life in 11 preterm infants on mechanical ventilation by infusing stable isotope labeled palmitic (PA) and linoleic acid (LLA). Six infants received exogenous surfactant for the treatment of respiratory distress syndrome (RDS) and five did not meet treatment criteria because of minimal or no disease. The isotopic enrichment of plasma free PA and LLA and of surfactant phosphatidylcholine PA (PC-PA) and LLA (PC-LLA) from tracheal aspirates was measured by mass spectrometry. Significant isotopic enrichment could be measured in PC-PA and PC-LLA from all patients. The fractional synthesis rate (FSR) of PC-LLA was higher than that of PC-PA (22.7 +/- 15.9 versus 12.1 +/- 7.7% per day, p = 0.018). Half-life (HL) of PC-PA was longer than that of PC-LLA (94.7 +/- 18.8 versus 46.6 +/- 32.6 h, p = 0.028). Patients who received exogenous surfactant had longer secretion times (ST) and delayed peak times (PK) but FSR and HL were unaffected. We concluded that: (1) surfactant kinetics can be measured in preterm infants with stable isotope labeled lipids; (2) surfactant FSR and HL calculated with PA and LLA gave different results; (3) patients treated with exogenous surfactant had similar FSRs compared with the nontreated subjects but had longer ST and delayed PK; (4) FSR from plasma free fatty acids (present study) was higher than that from plasma glucose in our previous work (Bunt JEH, Zimmermann LJI, Wattimena D, van Beek R, Sauer PJJ, Carnielli VP. Am J Respir Crit Care Med 1998;157:810-814) in a comparable population of preterm infants with RDS.

Treatment with exogenous surfactant stimulates endogenous surfactant synthesis in premature infants with respiratory distress syndrome.

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-13C]glucose starting 5.3 +/- 0.5 hrs after birth. The 13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) 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 +/- 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.

The effect in premature infants of prenatal corticosteroids on endogenous surfactant synthesis as measured with stable isotopes.

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-(13)C]glucose, starting approximately 5 h after birth. We measured (13)C-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 < 0.02) per dose of corticosteroid and doubled after two doses of corticosteroid. The (13)C-enrichment of plasma triglycerides and phospholipids was not increased by corticosteroid. These data show for the first time that prenatal corticosteroid treatment stimulates surfactant synthesis in the preterm infant.

Metabolic and respiratory effects of theophylline in the preterm infant.

BACKGROUND: Methylxanthines are often administered to preterm infants for the treatment of apnoea. AIMS: To study the effects of theophylline on energy metabolism, physical activity, and lung mechanics in preterm infants. METHODS: Indirect calorimetry was performed for six hours before and after administration of a bolus of theophylline (5 mg/kg) in 18 preterm infants while physical activity was recorded with a video camera. Lung mechanics measurements were performed at baseline and 12 and 24 hours after theophylline treatment. RESULTS: Theophylline increased mean (SEM) energy expenditure by 15 (5) kJ/kg/day and augmented carbohydrate utilisation from 6.8 to 8.0 g/kg/day, but fat oxidation was unchanged. After theophylline treatment, preterm infants had faster respiration, lower transcutaneous CO2, and improved static respiratory compliance without increased physical activity. CONCLUSIONS: A bolus of 5 mg/kg theophylline increased energy expenditure independently of physical activity, increased carbohydrate utilisation, and improved respiratory compliance. The increased energy expenditure could be detrimental to the growth of the preterm infant.

Exogenous surfactant kinetics in infant respiratory distress syndrome: A novel method with stable isotopes.

Little is known about surfactant metabolism in newborn infants, since radioactive isotopes cannot be used in humans. We describe here a new method for studying exogenous surfactant pharmacokinetics in vivo. We measured surfactant half-life, pool size, and turnover time in eight preterm infants (gestational age: 30 +/- 2 wk; birth weight: 1,416 +/- 202 g) who were mechanically ventilated because of infant respiratory distress syndrome. We administered two doses of 100 mg/kg each of a natural porcine surfactant with (13)C-labeled dipalmitoylphosphatidylcholine as a tracer. The (13)C enrichment of surfactant disaturated phosphatidylcholine (DSPC) was measured in serial tracheal aspirates by gas chromatography-mass spectrometry. The DSPC half-life was 34.2 +/- 9.4 h (mean +/- SD; range: 21.8 to 45.9 h). The apparent DSPC pool sizes were 5.8 +/- 6.1 mg/kg (range: 0.1 to 17.0 mg/kg) and 17.3 +/- 13.6 mg/kg (range: 3.3 to 41.0 mg/kg) at the time of the first and second surfactant doses, respectively. We present a novel and safe method that allows the tracing of exogenous surfactant phosphatidylcholine, the major lipid component of pulmonary surfactant, in infants who receive exogenous surfactant. This method could be a valuable tool for studying: (1) therapies that enhance lung/surfactant maturation; (2) the dosing and timing of surfactant therapy in different lung diseases; and (3) the comparison of different surfactant preparations.

Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids.

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-(13)C]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 < 0.02, Mann- Whitney U test). The absolute synthesis rate of PC in the beta group [1.6 +/- 0.3 micromol/kg/d] was increased by 128% above controls [0.7 +/- 0.2 micromol/kg/d] (p < 0.02). These data show that the synthesis of endogenous surfactant from plasma glucose as precursor is a slow process. It is shown, for the first time in vivo, that prenatal glucocorticosteroids stimulate the synthesis of surfactant PC in the very premature baboon.

Endogenous surfactant metabolism in critically ill infants measured with stable isotope labeled fatty acids.

Little is known about endogenous surfactant metabolism in infants, because radioactive isotopes used for this purpose in animals cannot be used in humans. We developed a novel and safe method to measure the endogenous surfactant kinetics in vivo in humans by using stable isotope labeled fatty acids. We infused albumin-bound [U-13C]palmitic acid (PA) and [U-13C]linoleic acid (LLA) for 24 h in eight critically ill infants (mean+/-SD: weight: 3.7+/-1.3 kg: age: 51.3+/-61.6 d) who required mechanical ventilation. The 13C enrichment of PA and LLA in surfactant phosphatidylcholine (PC), obtained from tracheal aspirates, was measured by gas chromatography combustion interface-isotope ratio mass spectrometry. We measured a significant incorporation of both 13C-PA and 13C-LLA into surfactant PC. PC-PA and PC-LLA became enriched after 8.7+/-4.9 h (range: 3.4-17.3) and 10.0+/-7.2 h (range: 3.0-22.4), respectively; the times at maximum enrichment were 49.2+/-8.9 and 45.6+/-19.3 h, respectively. The fractional synthesis rate of surfactant PC-PA ranged from 0.4 to 3.4% per h, whereas the fractional synthesis rate of PC-LLA ranged from 0.5 to 3.8% per h. The surfactant PC-PA and PC-LLA half-lives ranged from 16.8 to 177.7 and 23.8 to 144.4 h, respectively. This method provides new data on surfactant metabolism in infants requiring mechanical ventilation. We found that synthesis of surfactant from plasma PA and LLA is a slow process and that there were marked differences in PC kinetics among infants. This variability could be related to differences in lung disease and could affect the clinical course of the respiratory failure.

[Use and efficacy of treatment with porcine surfactant in newborns with birth weight < or = 1000 g: experience in 3 years]. / Utilizzazione ed efficacia della terapia con surfactant suino nel neonato con peso neonatale < or = 1000 g: esperienza di un triennio.

OBJECTIVE: Evaluate the clinical response to the first and subsequent doses of natural surfactant for the treatment of respiratory distress syndrome (RDS) in extremely low birth weight infants (ELBWI). METHODS: Retrospective chart review of all ELBWI admitted to Neonatal Intensive Care Unit of Padova from July 1995 to December 1998 who received porcine surfactant for the treatment of RDS. Data collection included: (a) standard clinical variables (birth weight, gestational age, maternal steroid treatment, etc) (b) surfactant dosing), and (c) response to surfactant treatment as assessed by changes in the fraction of inspiratory oxygen (F1O2) and by the Oxygenation Index (OI). Outcome data (d) which included: death, duration of mechanical ventilation, duration of oxygen therapy, days in hospital stay, OI at 3,7 and 21 days of age, oxygen dependency at 28 days and at 36 week post conception were also collected. Data were analyzed by group comparison tests when comparing the groups that received one (S1), two (S2) or three (S3) surfactant doses and by multiple regression for the "predictors" of the response to surfactant treatment and for the "predictors" of outcome. RESULTS: Ninety-four ELBWI were evaluated. F1O2 at 12 hours after surfactant was reduced by more than one/third in 62% of the infants after the first dose, in 54% of the second doses and 61% of the third doses (non significant). S1, S2 and S3 groups had similar demographics and birth characteristics but the OI differed at 3 and 7 days (1.73 +/- 1.39, 3.34 +/- 2.15 and 6.45 +/- 5.23 at day 3 and 1.42 +/- 1.27, 1.98 +/- 1.83 and 4.03 +/- 3.91 at day 6 for S1, S2 and S3 respectively, p = 0.003). The response of exogenous was not found to be a significant predictor in our multiple regression model for major outcome variables such as oxygen dependency at 28 d or 36 wk. CONCLUSIONS: In ELBWI in spite of the high percentages of good clinical response to the first, to the second and even to the third surfactant dose, response to surfactant treatment did not predict major general and respiratory outcomes.