Breast milk in neonate oral care: oropharyngeal effects in extremely preterm infants.

Ventilator-associated pneumonia (VAP) is a frequent nosocomial infection in neonatal intensive care units (NICU). Extremely preterm infants are at highest risk of developing VAP. Several studies indicate that oral care included in a preventive protocol effectively reduces neonatal VAP incidence. We investigated the effects of oral care with breast milk on oral immune defenses and microbiota in extremely preterm infants. Thirty infants born ≤ 30 weeks gestation hospitalized at our NICU were selected and divided into three groups: oral care with breast milk, formula, or sterile water. Effects on oral immune defenses in vivo were studied using ELISA to measure lactoferrin (LF) and secretory immunoglobulin A (sIgA) in pharyngeal aspirates before and after oral care. Different LF concentrations were tested in vitro to assess their effects on loads of selected bacterial species by culture. Effects on selected bacteria potentially responsible for VAP in vivo were studied by real-time PCR detection in pharyngeal aspirates before and after oral care. Oral care with breast milk significantly increases LF concentrations to 69.8 × 103 ng/ml (p = 0.012) and sIgA to 36.8 × 103 ng/ml (p = 0.017) in vivo. These LF concentrations considerably reduce loads of E. coli, S. epidermidis, S. aureus, and P. aeruginosa, in vitro. However, contrary to our expectation, no effect on colonization of bacteria most commonly responsible for VAP was found in vivo. CONCLUSION: In extremely preterm infants, oral care with breast milk increases local immune defense markers (LF, sIgA), which combat bacterial infections. Further clinical trials should be conducted to evaluate their effects on VAP prevention in neonates. WHAT IS KNOWN: • The population at higher risk to develop VAP are preterm infants. • Several studies indicate oral care within a preventive bundle is effective in reducing neonatal VAP incidence. WHAT IS NEW: • In extremely premature infants, oral care with breast milk causes a significant increase in local immune defences in terms of lactoferrin (LF) and secretory immunoglobulin A (sIgA). • LF concentrations obtained after oral care with breast milk decreased loads of bacteria most commonly responsible for VAP in premature infants under experimental in-vitro.

Enhanced INSURE (ENSURE): an updated and standardised reference for surfactant administration.

There is no firm consensus about the optimal technique for the administration of exogenous surfactant in preterm neonates, and different techniques may be equally effective. The intubation-surfactant-extubation (INSURE) procedure has not been fully described, and important details, such as duration and mode of ventilation, remain unclear, leading to significant clinical practice variations and influencing its suitability and feasibility. Since the first INSURE description, our knowledge in respiratory care has largely progressed, but the technique has not been updated according to current evidence-based practice. Thus, our aim is to formally describe a modern way to perform INSURE, based on the current knowledge and technology, to increase its feasibility and patients' safety. We offer ENSURE (Enhanced INSURE) as an updated and standardised technique for surfactant administration, clarifying crucial issues of the original method by applying current state-of-the-art concepts of respiratory care. We performed a cross-sectional observational study enrolling 57 preterm neonates describing ENSURE feasibility and safety.   Conclusion: ENSURE can be used as a reference technique in clinical practice, teaching and research. What is Known: • There is no consensus about the optimal method for surfactant administration. INSURE technique has been originally described many years ago without considering modern principles of neonatal respiratory care and the available state-of-the-art technology. What is New: • We here describe a modern way to perform INSURE, based on the current knowledge and technology. We called it ENSURE (Enhanced INSURE) and clarified crucial points of the original technique, in light of the current knowledge. We verified feasibility and safety of ENSURE in a cross-sectional observational study enrolling 57 preterm neonates.

Small for Gestational Age Preterm Neonates Exhibit Defective GH/IGF1 Signaling Pathway.

Objective: To investigate the impact of fetal growth restriction (FGR) on hormonal regulation of post-natal growth and glucose metabolism [via insulin and growth hormone (GH)/Insulin-like Growth factor 1 (IGF1) axis pathways] in small for gestational age (SGA) neonates. Methods: We conducted a monocentric observational prospective comparative study on 73 singleton babies born with a weight inferior to 2,000 g. We analyzed auxological (weight, height and head circumference), and hormonal (GH, IGF1, and insulin plasma concentrations) data comparing SGA and appropriate for gestational age (AGA) neonates, between day 1 and 60. Results: One third (23/73) of the neonates were SGA. Twenty-five percent (18/73) required insulin for idiopathic hyperglycemia of prematurity and were smaller in weight and head circumference at discharge. In the SGA group compared with the AGA group, GH plasma concentrations were higher at day 3 (70.1 vs. 38.0 mIU/L) and IGF1 plasma concentrations were higher at day 10 (29.0 vs. 18.7 ng/ml). Conclusions: SGA neonates displayed resistance to GH and IGF1, concomitant to insulin resistance. This could partially explain the initial defective catch-up growth and, later in life, the higher prevalence of metabolic syndrome in this population.

LISA/MIST: Complex clinical problems almost never have easy solutions.

Over the last 10 years, new techniques to administer surfactant have been promoted, based on their presumed lesser invasiveness and they have been generally called LISA (less invasive surfactant administration). We believe that the clinical potential of LISA techniques is currently overestimated. LISA lacks biological and pathophysiological background justifying its potential benefits. Moreover, LISA has been investigated in clinical trials without previous translational data and these trials are affected by significant flaws. The available data from these trials only allow to conclude that LISA is better than prolonged, unrestricted invasive ventilation with loosely described parameters, a mode of respiratory support that should be anyway avoided in preterm infants. We urge the conduction of high-quality studies to understand how to choose and titrate analgesia/sedation and optimize surfactant administration in preterm neonates. We offer a comprehensive, evidence-based review of the clinical data on LISA, their biases and the lack of physiopathology background.

Personalized Medicine for the Management of RDS in Preterm Neonates.

Continuous positive airway pressure and surfactant represent the first- and second-line treatment for respiratory distress syndrome in preterm neonates, as European and American guidelines, since 2013 and 2014, respectively, started to recommend surfactant replacement only when continuous positive airway pressure fails. These recommendations, however, are not personalized to the individual physiopathology. Simple clinical algorithms may have improved the diffusion of neonatal care, but complex medical issues can hardly be addressed with simple solutions. The treatment of respiratory distress syndrome is a complex matter and can be only optimized with personalization. We performed a review of tools to individualize the management of respiratory distress syndrome based on physiopathology and actual patients' need, according to precision medicine principles. Advanced oxygenation metrics, lung ultrasound, electrical impedance tomography, and both quantitative and qualitative surfactant assays were examined. When these techniques were investigated with diagnostic accuracy studies, reliability measures have been meta-analysed. Amongst all these tools, quantitative lung ultrasound seems the more developed for the widespread use and has a higher diagnostic accuracy (meta-analytical AUC = 0.952 [95% CI: 0.951-0.953]). Surfactant adsorption (AUC = 0.840 [95% CI: 0.824-0.856]) and stable microbubble test (AUC = 0.800 [95% CI: 0.788-0.812]) also have good reliability, but need further industrial development. We advocate for a more accurate characterization and a personalized approach of respiratory distress syndrome. With the above-described currently available tools, it should be possible to personalize the treatment of respiratory distress syndrome according to physiopathol-ogy.

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.

Surfactant Injury in the Early Phase of Severe Meconium Aspiration Syndrome.

No in vivo data are available regarding the effect of meconium on human surfactant in the early stages of severe meconium aspiration syndrome (MAS). In the present study, we sought to characterize the changes in surfactant composition, function, and structure during the early phase of meconium injury. We designed a translational prospective cohort study of nonbronchoscopic BAL of neonates with severe MAS (n = 14) or no lung disease (n = 18). Surfactant lipids were analyzed by liquid chromatography-high-resolution mass spectrometry. Secretory phospholipase A2 subtypes IB, V, and X and SP-A (surfactant protein A) were assayed by ELISA. SP-B and SP-C were analyzed by Western blotting under both nonreducing and reducing conditions. Surfactant function was assessed by adsorption test and captive bubble surfactometry, and lung aeration was evaluated by semiquantitative lung ultrasound. Surfactant nanostructure was studied using cryo-EM and atomic force microscopy. Several changes in phospholipid subclasses were detected during MAS. Lysophosphatidylcholine species released by phospholipase A2 hydrolysis were increased. SP-B and SP-C were significantly increased together with some shorter immature forms of SP-B. Surfactant function was impaired and correlated with poor lung aeration. Surfactant nanostructure was significantly damaged in terms of vesicle size, tridimensional complexity, and compactness. Various alterations of surfactant phospholipids and proteins were detected in the early phase of severe meconium aspiration and were due to hydrolysis and inflammation and a defensive response. This impairs both surfactant structure and function, finally resulting in reduced lung aeration. These findings support the development of new surfactant protection and antiinflammatory strategies for severe MAS.

Semiquantitative Ultrasound Assessment of Lung Aeration Correlates With Lung Tissue Inflammation.

We studied the relationship between ultrasound-assessed lung aeration and inflammation in a particular population of ventilated preterm neonates with mild-to-moderate lung inflammation and no congenital heart defect. Lung aeration estimated by a semiquantitative lung ultrasound score significantly correlated with several inflammatory markers both at cellular (neutrophil count in bronchoalveolar lavage: ρ = 0.400, p = 0.018) and molecular level (total proteins: ρ = 0.524, p = 0.021; interleukine-8: ρ = 0.523, p = 0.021; granulocytes-macrophages colony stimulating factor: ρ = 0.493, p = 0.020; all measured in bronchoalveolar lavage and expressed as epithelial lining fluid concentrations). Lung ultrasound might detect changes in lung aeration attributable to mild-to-moderate local inflammation if cardiogenic lung edema is excluded. Thus, it is possible to describe some levels of lung inflammation with semiquantitative lung ultrasound.

Less invasive surfactant administration: a word of caution.

Surfactant is a cornerstone of neonatal critical care, and the presumed less (or minimally) invasive techniques for its administration have been proposed to reduce invasiveness of neonatal critical care interventions. These techniques are generally known as less invasive surfactant administration (LISA) and have quickly gained popularity in some neonatal intensive care units. Despite the increase in the use of LISA, we believe that the pathobiological background supporting its possible clinical benefits is unclear. Similarly, it is unclear whether there are any ignored drawbacks, as LISA has been tested in only a few trials and some physiopathological issues seem to have gone unnoticed. Active research is warranted to fill these knowledge gaps before LISA can be firmly recommended. In this Viewpoint, we provide an in-depth analysis of LISA techniques, based on physiological and pathobiological factors, followed by a critical appraisal of available clinical data, and highlight some possible future research directions.

Life-Threatening Extreme Methemoglobinemia during Standard Dose Nitric Oxide Therapy.

We report the first case of life-threatening extreme neonatal-acquired methemoglobinemia that occurred during inhaled nitric oxide (iNO) at the standard 20 ppm dose in a neonate with early onset sepsis and suprasystemic pulmonary hypertension. Life-threatening methemoglobinemia has been efficaciously treated with methylene blue and ascorbic acid, while stopping iNO and starting iloprost and sildenafil. The patient was subjected to various tests (including gene sequencing and hemoglobin electrophoresis) and did not have any known genetic cause or predisposition for methemoglobinemia. Neuroimaging and the 2-year clinical follow-up were completely normal.

Echography-Guided Surfactant Therapy to Improve Timeliness of Surfactant Replacement: A Quality Improvement Project.

OBJECTIVE: To improve time of surfactant administration with a surfactant replacement protocol based on semiquantitative lung ultrasound score (LUS) thresholds. STUDY DESIGN: Quality improvement (QI), prospective, before-after, pilot study. In a 6-month period surfactant replacement was based only on inspired oxygen fraction (FiO2) thresholds. In the second 6-month period, surfactant was given when either the FiO2 or LUS exceeded the limits. The main QI measures were the proportion of neonates receiving surfactant within the first 3 hours of life and maximal FiO2 reached before surfactant replacement. Secondary QI measures were the duration of respiratory support and ventilator-free days. Data were also collected for 1 year after the study to verify sustainability. RESULTS: Echography-guided Surfactant THERapy (ESTHER) increased the proportion of neonates receiving surfactant within the first 3 hours of life (71.4%-90%; P < .0001) and reduced the maximal FiO2 reached before surfactant replacement (0.33 [0.26-0.5]) vs 0.4 [0.4-0.55]; P = .005). The global need for surfactant did not significantly change. ESTHER also resulted in a significant decrease in duration of invasive ventilation and ventilator-free days. CONCLUSIONS: ESTHER improved the timeliness of surfactant administration and secondary QI indicators related to surfactant replacement.

A Multicenter Lung Ultrasound Study on Transient Tachypnea of the Neonate.

BACKGROUND AND AIM: Discordant results that demand clarification have been published on diagnostic lung ultrasound (LUS) signs of transient tachypnea of the neonate (TTN) in previous cross-sectional, single-center studies. This work was conducted to correlate clinical and imaging data in a longitudinal and multicenter fashion. METHODS: Neonates with a gestational age of 34-40 weeks and presenting with TTN underwent a first LUS scan at 60-180 min of life. LUS scans were repeated every 6-12 h if signs of respiratory distress persisted. Images were qualitatively described and a LUS aeration score was calculated. Clinical data were collected during respiratory distress. RESULTS: We enrolled 65 TTN patients. Thirty-one (47.6%) had a sharp echogenicity increase in the lower lung fields (the "double lung point" or DLP sign). On admission, there was no significant difference between patients with and without DLP in Silverman scores (4 ± 1.5 vs. 4 ± 2.1; p = 0.9) or LUS scores (7.6 ± 2.6 vs. 5.6 ± 3.8; p = 0.12); PaO2/FiO2 (249 ± 93 vs. 252 ± 125; p = 0.91). All initial LUS scans (performed at the onset of distress) and 99.5% of all scans showed a regular pleural line with no consolidation, with only 1 neonate showing consolidation in the follow-up scans. The Silverman and LUS scores were significantly correlated (rho = 0.27; p = 0.02). CONCLUSION: A regular pleural line with no consolidation is a consistent finding in TTN. The presence of a DLP is not essential for the LUS diagnosis of TTN. A semi-quantitative LUS score correlates well with the clinical course and could be useful in monitoring changes in lung aeration during TTN.

Effect of cooling on lung secretory phospholipase A2 activity in vitro, ex vivo, and in vivo.

Hypothermia can modify surfactant composition and function. Secretory phospholipase A2 (sPLA2) hydrolyses surfactant phospholipids and is important in the pathobiology of several critical respiratory disorders. We hypothesize that sPLA2 activity might be influenced by the temperature partially explaining surfactant changes. This study aims to evaluate comprehensively the effect of hypothermia on sPLA2 activity. We measured sPLA2 activity at different temperatures, alone or combined with bile acids, in vitro (incubating human recombinant sPLA2-IIA and porcine sPLA2-IB), ex vivo (by cooling bronchoalveolar lavage samples from neonates with respiratory distress syndrome or no lung disease), and in vivo (using lavage samples obtained before and after 72 h of whole body cooling in neonates with hypoxic-ischemic encephalopathy). We also measured concentrations of various sPLA2 subtypes and natural sPLA2 inhibitors in in vivo cooled samples. Results were corrected for protein content and dilution. In vitro cooling did not show any effect of hypothermia on sPLA2. Ex vivo cooling did not alter total sPLA2 activity, and the addition of bile acids increased sPLA2 activity irrespective of the temperature and the type of sampled patient. In vivo hypothermia reduced median sPLA2 activity from 16.6 [15.2-106.7] IU/mg to 3.3 [2.7-8.5] IU/mg ( P = 0.026) and mean sPLA2-IIA from 1.1 (0.8) pg/µg to 0.6 (0.4) pg/µg ( P = 0.047), whereas dioleylphosphatidylglycerol increased from 8.3 (3.9)% to 12.8 (5.1)% ( P = 0.02). Whole body hypothermia decreases in vivo global sPLA2 activity in bronchoalveolar lavage fluids through the reduction of sPLA2-IIA and increment of dioleylphosphatidylglycerol. This effect is absent during in vitro or ex vivo hypothermia.

Lung Ultrasound Score Predicts Surfactant Need in Extremely Preterm Neonates.

BACKGROUND AND OBJECTIVES: There are several lung ultrasound scores (LUS) for evaluating lung aeration in critically ill adults with restrictive lung disorders. A modified LUS adapted for neonates correlates well with oxygenation and is able to be used to predict the need for surfactant in preterm neonates with respiratory distress syndrome (RDS). However, no data are available for extremely preterm neonates for whom timely surfactant administration is especially important. We hypothesized that LUS might be reliable in extremely preterm neonates with RDS who are treated with continuous positive airway pressure. We aimed to determine the diagnostic accuracy of LUS in predicting the need for surfactant treatment and re-treatment in this population. METHODS: We performed a prospective cohort diagnostic accuracy study between 2015 and 2016 in a tertiary-care academic center. Inborn neonates at ≤30 weeks' gestation with RDS treated with continuous positive airway pressure were eligible. Surfactant was given on the basis of oxygen requirement thresholds derived from European guidelines, and a LUS was not used to guide surfactant treatment. We calculated the LUS after admission and analyzed its diagnostic accuracy to predict surfactant treatment and re-treatment. RESULTS: We enrolled 133 infants; 68 (51%) received 1 dose of surfactant and 19 (14%) received 2 surfactant doses. A LUS is significantly correlated with oxygenation index (ρ = 0.6; P < .0001) even after adjustment for gestational age (P < .0001). A LUS can be used to accurately predict the need for the first surfactant dose (area under the curve = 0.94; 95% confidence interval: 0.90-0.98; P < .0001) and also the need for surfactant redosing (area under the curve = 0.803; 95% confidence interval: 0.72-0.89; P < .0001). The global accuracy for the prediction of surfactant treatment and re-treatment is 89% and 72%, respectively. CONCLUSIONS: LUS may be used to predict the need for surfactant replacement in extremely preterm neonates with RDS.

Cell Count Analysis from Nonbronchoscopic Bronchoalveolar Lavage in Preterm Infants.

OBJECTIVES: To establish the reference values, diagnostic accuracy, and effect of various factors on cell count in intubated preterm neonates subjected to nonbronchoscopic bronchoalveolar lavage. STUDY DESIGN: This prospective, cross-sectional, blinded study included preterm neonates ventilated for any reason who underwent nonbronchoscopic bronchoalveolar lavage if they had not previously received postnatal antibiotics or steroids. Lavage was performed before surfactant replacement, if any. A gentle ventilation policy was applied. Pneumonia was diagnosed using clinical criteria, without considering cell count. Investigators performing cell counts were blinded to the clinical data. RESULTS: There were 276 neonates enrolled; 36 had congenital or ventilator-associated pneumonia. In the 240 noninfected babies, median neutrophil count increased significantly after the first 2 days of ventilation (day 1, 2 cells per field [IQR, 0.0-9.5 cells per field]; day 2, 2 cells per field [IQR, 0-15 cells per field]; day 3, 20 cells per field [IQR, 2-99 cells per field]; day 4, 15 cells per field [IQR, 2-96 cells per field]; P < .0001). No significant difference was seen over time in infected babies. Multivariate analysis indicated pneumonia (standardized ß = 0.134; P = .033) and the time spent under mechanical ventilation before nonbronchoscopic bronchoalveolar lavage as factors significantly influencing neutrophil count (standardized ß = 0.143; P = .027). Neutrophil count was correlated with the duration of ventilation (rho = 0.28; P <.001). Neutrophil counts were higher in infected (24 cells/field [IQR, 5-78] cells/field) than in noninfected babies (4 cells/field [IQR, 1-24 cells/field]; P <.001) and had an moderate reliability for pneumonia within the first 2 days of ventilation (area under the curve, 0.745; (95% CI, 0.672-0.810; P = .002). CONCLUSIONS: We provide reference values for airway neutrophil counts in ventilated preterm neonates. Bronchoalveolar lavage neutrophils significantly increase after 2 days of ventilation. Neutrophil count has moderate accuracy to diagnose pneumonia, but only within the first 2 days of ventilation.

Lung Ultrasonography Score to Evaluate Oxygenation and Surfactant Need in Neonates Treated With Continuous Positive Airway Pressure.

IMPORTANCE: Lung ultrasonography (LUS) is a bedside technique useful to diagnose neonatal respiratory problems, but, to our knowledge, no data are available about its use for monitoring lung function or eventually guiding surfactant therapy. OBJECTIVE: To determine the diagnostic accuracy of a neonatal-adapted LUS score to evaluate oxygenation and predict need for surfactant administration. DESIGN, SETTING, AND PARTICIPANTS: Prospective diagnostic accuracy study following STARD (Standards for the Reporting of Diagnostic Accuracy Studies) guidelines at a tertiary level academic neonatal intensive care unit in 2014. All neonates admitted to the neonatal intensive care unit with signs of respiratory distress were eligible, and 130 neonates were enrolled. The LUS score was calculated in the first hours of life under continuous positive airway pressure. The transcutaneous partial pressure of oxygen (Ptco2) to fraction of inspired oxygen (Fio2) ratio, alveolar-arterial gradient, oxygenation index, and arterial to alveolar ratio were calculated within 30 minutes from LUS, using transcutaneous blood gas monitoring. Surfactant was administered according to 2013 European guidelines. MAIN OUTCOMES AND MEASURES: Correlation between LUS score and indices of oxygenation and prediction of surfactant administration. RESULTS: Among the 130 neonates in this study, the LUS score was significantly correlated with all indices of oxygenation, independent from gestational age (GA) (Ptco2 to Fio2 ratio: GA ≥ 34 weeks: ρ = -0.57; GA <34 weeks: ρ = -0.62; P < .001; alveolar-arterial gradient: GA ≥ 34 weeks: ρ = 0.62; GA <34 weeks: ρ = 0.59; P < .001; oxygenation index: GA ≥ 34 weeks: ρ = 0.63; GA <34 weeks: ρ = 0.69; P < .001; and arterial to alveolar ratio: GA ≥ 34 weeks: ρ = -0.60; GA <34 weeks: ρ = -0.56; P < .001). The LUS score predicted the need for surfactant better in preterm babies with a GA less than 34 weeks (area under the curve = 0.93; 95% CI, 0.86-0.99; P < .001) than in term and late-preterm neonates with a GA of 34 weeks or greater (area under the curve = 0.71; 95% CI, 0.54-0.90; P = .02); the areas under the curve for these 2 GA subgroups are significantly different (P = .02). In babies with a GA less than 34 weeks, a LUS score cutoff of 4 predicted surfactant administration with 100% sensitivity and 61% specificity, yielding a posttest probability of 72%. CONCLUSIONS AND RELEVANCE: The LUS score is well correlated with oxygenation status in both term and preterm neonates, and it shows good reliability to predict surfactant administration in preterm babies with a GA less than 34 weeks under continuous positive airway pressure.

Continuous Positive Airway Pressure and the Burden of Care for Transient Tachypnea of the Neonate: Retrospective Cohort Study.

OBJECTIVES: Transient tachypnea of the neonate (TTN) is the commonest neonatal respiratory disorder. Given TTN physiopathology, continuous positive airway pressure (CPAP) could be indicated for its treatment, but no data are available. Our aim is to clarify if CPAP might reduce the TTN burden of care. DESIGN: Retrospective multicenter cohort study enrolling 42 full-term TTN babies treated with CPAP and 40 with oxygen supplementation. RESULTS: CPAP-treated infants show shorter intensive care unit stay (CPAP, 2.5 ± 2 vs. Oxygen, 4.4 ± 2.6 days; adjß, -2.1 [95% confidence interval (CI): -3.1; -1]); p < 0.001) and lower maximal oxygen fraction (adjß, -4.7 [95% CI: -7.7; -1.7]; p = 0.003). Air leak incidence was similar between the groups (adjOR, 0.36 [95% CI: 0.1; 1.1); p = 0.08). Patients' comfort as per EDIN score was also unchanged. Given the shorter length of intensive care, the use of CPAP for treating TTN would spare on average around 7,000 Euros/infant. CONCLUSION: CPAP seems a useful therapeutics for TTN, as it may reduce the burden of care without increasing air leaks or patients' discomfort.

Natural evolution of patent ductus arteriosus in the extremely preterm infant.

OBJECTIVE: The persistence of the patent ductus arteriosus (PDA) is frequently encountered in very preterm infants. Neither preventive nor curative treatments of PDA have been shown to improve the outcome of these infants. Since no consensus on optimal treatment of PDA is established, we evaluated the rate of spontaneous PDA closure in infants born before 28 weeks of gestation. PATIENTS AND METHODS: We studied a retrospective cohort of 103 infants (gestational age 24-27 weeks) admitted to our neonatal intensive care unit from 1 June 2008 to 31 July 2010. Maternal and neonatal characteristics were collected. The PDA was defined by the persistence of ductal patency after 72 h and was followed up by regular echocardiography. RESULTS: Twelve infants died within the first 72 h and were excluded from the analysis. Among 91 infants analysed, 8 (9%) closed their ductus arteriosus before 72 h and the ductus could not be determined patent in 13. Of the 70 infants with a PDA still persistent, one underwent surgical ligation and echocardiography showed spontaneous closure in 51 (73%) of them. In the remaining 18 infants, the date of PDA closure could not be determined either because of their death (n=11) or due to discharge (n=7). Overall, a spontaneous closure of the ductus arteriosus was observed in 59 of the 91 infants. CONCLUSIONS: We have to question whether exposure to the risks of therapeutic interventions targeted for ductal closure is warranted since a PDA closes spontaneously in at least 73% of infants born before 28 weeks.