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The distribution of ventilation during high-frequency ventilation (HFV) is asynchronous, nonhomogeneous, and frequency dependent. We hypothesized that differences in the regional distribution of ventilation at different oscillatory frequencies may affect gas exchange efficiency. We studied 15 newborn infants with a median gestational age of 28.9 (26.4–30.3) wk and body weight of 1.0 (0.8–1.4) kg. Five ventilation frequencies (5, 8, 10, 12, and 15 Hz) were tested, keeping carbon dioxide diffusion coefficient constant. The displacements of 24 passive markers placed on the infant’s chest wall were measured by optoelectronic plethysmography. We evaluated the amplitude and phase shift of displacements of single markers placed along the midline and the regional displacements of the chest wall surface. Blood gases were unaffected by frequency. Chest wall volume changes decreased from 1.6 (0.4) ml/kg at 5 Hz to 0.7 ml/kg at 15 Hz. At all frequencies, the abdomen (AB) oscillated more markedly than the ribcage (RC). The mean (SD) AB/RC ratio was 1. 95 (0.7) at 5 Hz, increased to 2.1 (1.3) at 10 Hz, and then decreased to 1.1 (0.5) at 15 Hz ( P < 0.05 vs. 10 Hz). Volume changes in the AB lagged the RC and this phase shift increased with frequency. The AB oscillated more than the RC at all frequencies. Regional oscillations were highly inhomogeneous up to 10 Hz, and they became progressively more asynchronous with increasing frequency. When the carbon dioxide diffusion coefficient is held constant, such differences in regional chest wall expansion do not affect gas exchange. NEW & NOTEWORTHY We characterized the regional distribution of chest wall displacements in infants receiving high-frequency oscillatory ventilation at different frequencies. When carbon dioxide diffusion coefficient is held constant, there is no combination of frequency and tidal volume that optimizes gas exchange. The relative displacement between different chest wall compartments is not affected by frequency. However, at high frequencies, chest wall displacements are lower, with the potential to reduce total and regional overdistension without affecting gas exchange.

Summary Background The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). Methods We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov , NCT02482766 . Findings Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57–0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7–135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111). Interpretation A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy. Funding None.

Purpose Delayed cord clamping for at least 60 s is recommended to improve neonatal outcomes. The aim of this study is to evaluate whether there are differences in cord BGA between samples collected after double clamping the cord or without clamping the cord, when blood collection occurs within 60 s from birth in both groups. Methods A cross-sectional study was carried out, collecting data from 6884 high-risk women who were divided into two groups based on the method of cord sampling (clamped vs unclamped). Results There were significant decrease in pH and BE values into unclamped group compared with the clamped group. This difference remained significant when considering pathological blood gas analysis parameters, with a higher percentage of pathological pH or BE values in the unclamped group. Conclusion Samples from the unclamped cord alter the acid–base parameters compared to collection from the clamped cord; however, this difference does not appear to be of clinical relevance. Findings could be due to the large sample size, which allowed to achieve a high power and to investigate very small numerical changes between groups, leading to a statistically significant difference in pH and BE between samples even when we could not appreciate any clinical relevant difference of pH or BE between groups. When blood gas analysis is indicated, the priority should be given to the timing of blood collection to allow reliable results, to assess newborns status at birth and intervene when needed.

We hypothesized that ventilating at the resonant frequency of the respiratory system optimizes gas exchange while limiting the mechanical stress to the lung in newborns receiving high-frequency oscillatory ventilation (HFOV). We characterized the frequency dependence of oscillatory mechanics, gas exchange, and pressure transmission during HFOV. We studied 13 newborn infants with a median (interquartile range) gestational age of 29.3 (26.4–30.4) weeks and body weight of 1.00 (0.84–1.43) kg. Different frequencies (5, 8, 10, 12, and 15 Hz) were tested, keeping carbon dioxide diffusion coefficient (DCO2) constant. Oscillatory mechanics and transcutaneous blood gas were measured at each frequency. The attenuation of pressure swings (ΔP) from the airways opening to the distal end of the tracheal tube (TT) and to the alveolar compartment was mathematically estimated. Blood gases were unaffected by frequency. The mean (SD) resonant frequency was 16.6 (3.5) Hz. Damping of ΔP increased with frequency and with lung compliance. ΔP at the distal end of the TT was insensitive to frequency, whereas ΔP at the peripheral level decreased with frequency. There is no optimal frequency for gas exchange when DCO2 is held constant. Greater attenuation of oscillatory pressure at higher frequencies offers more protection from barotrauma, especially in patients with poor compliance.

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. Propranolol 0.1% eye micro-drops administered to newborns with stage 2 ROP are well-tolerated, but not sufficiently effective. Methods: A multi-center open-label trial was conducted to assess the safety and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1 ROP. The progression of the disease was evaluated with serial ophthalmologic examinations. Hemodynamic, respiratory, biochemical parameters, and propranolol plasma levels were monitored. Demographic and perinatal characteristics, co-morbidities and co-intervention incidences, together with ROP progression, were compared with a historical control group in the same centers participating in the trial. Results: Ninety-eight newborns were enrolled and compared with the historical control group. Populations were not perfectly homogeneous (as demonstrated by the differences in the Apgar score and the different incidence rate in surfactant administration and oxygen exposure). The progression to ROP stage 2 or 3 plus was significantly lower than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI 0.297– 0.916). No adverse effects related to propranolol were observed and the mean propranolol plasma level was significantly lower than the safety cut-off of 20 ng/mL. Unexpectedly, three newborns treated with oral propranolol before the appearance of ROP, showed a ROP that was unresponsive to propranolol eye micro-drops and required laser photocoagulation treatment. Conclusion: Propranolol 0.2% eye micro-drops were well-tolerated and appeared to reduce the ROP progression expected on the basis of a comparison with a historical control group. Propranolol administered too early appears to favor a more aggressive ROP, suggesting that a β-adrenoreceptor blockade is only useful during the proliferative phase. Further randomized placebo-controlled trials are required to confirm the current results. Clinical Trial Registration The trial was registered at ClinicalTrials.gov with Identifier NCT02504944 and with EudraCT Number 2014-005472-29.

Optimization of nutritional management of preterm infants is crucial for achievement of their long-term health. Enteral nutrition is preferred to total parenteral nutrition (TPN) because the former avoids complications related to vascular catheterization, sepsis, adverse effects of TPN, and fasting. Due to the lack of ability of preterm infants to coordinate suckling, swallowing, and breathing, tube feeding is necessary for most infants less than 1500 g to ensure sufficient feeding tolerance, to support optimal growth and to reduce the risk of aspiration. Therefore, feeding by orogastric or nasogastric tube using either continuous or intermittent bolus delivery of formula or human milk is common practice for these infants. Theoretical risks and benefits of both continuous nasogastric milk feeding and intermittent bolus milk feeding have been proposed. According to the literature, continuous nutrition could be preferred in smaller infants (as those with a birthweight below 1250 g) or hemodynamically impaired infants; in stable growing infants nutrition can be administered intermittently as in healthy term infants.

Intrauterine growth restriction (IUGR) infants are thought to have impaired gut function after birth secondary to intrauterine redistribution of the blood flow, due to placental insufficiency, with a consequent reduction of gut perfusion. For this reason, infants complicated by IUGR have been considered at higher risk of feeding intolerance. Postnatal evaluation of splanchnic perfusion, through Doppler of the superior mesenteric artery, and of splanchnic oxygenation, through near infrared spectroscopy measurements, may be useful in evaluating the persistence (or not) of the redistribution of blood flow occurred in utero.

Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an “optimal” functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. In this study, 206 spontaneously breathing infants born at 24+0–27+6 weeks’ gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. ClinicalTrials.gov identifier: NCT02482766 . Registered on 1 June 2015.

The study of respiratory mechanics in infants requires a noninvasive accurate measurement of the lung volume changes (DeltaVL). Optoelectronic plethysmography (OEP) allows the assessment of DeltaVL through the measurement of the chest wall surface motion and it has been proved to be accurate in adults. The aim of this study was to apply OEP to newborns and to validate it by comparison to pneumotachography. Twenty term and preterm newborns (GA = 34 +/- 5 wk) in stable condition were studied during 1 to 2 min periods of quiet breathing in supine position. Airway opening flow was measured by applying a facemask connected to a pneumotachograph (PNT) and integrated to provide the DeltaVL. Chest wall volume changes were simultaneously measured by OEP. The tidal volume values measured by pneumotachography and by OEP were compared for each breath. A total of 771 breaths from all patients were considered. Bland-Altmann analysis showed a mean difference of -0.08 mL and a limit of agreement ranging from -2.98 to 2.83 mL. Linear regression analysis demonstrated good correlation between the two techniques (r = 0.95, q = 1.00 mL, m = 0.96). OEP provides accurate measurements of DeltaVL in newborns and may be useful to study respiratory mechanics and breathing patterns during spontaneous breathing and mechanical ventilation.

Near Infrared Spectroscopy (NIRS) is an emerging technique for brain oxygenation monitoring in newborns complicated by acute and chronic hypoxia. However, data regarding cerebral oxygenation normal values are still lacking and matter of debate. Therefore, we investigate whether NIRS parameters in healthy preterm/term infants are gestational age and delivery modalities dependent and correlate with standard monitoring parameters. From January to December 2007, 100 healthy newborns with gestational age from 30 to 42 weeks' gestation were evaluated. Routine laboratory variables, daily clinical and neurological evaluation and ultrasound imaging were performed. The regional cerebral oxygen saturation (rSO2) and fractional cerebral tissue oxygen extraction (FTOE) were measured by NIRS in the first 6-hours after birth. Data were recorded by MetaVision ICU X-Edition software and analyzed by SPSS statistical package. rSO2 and FTOE correlated (R=-0.77; R=0.41; P

Aerosolization of exogenous surfactant remains a challenge. This study is aimed to evaluate the efficacy of atomized poractant alfa (Curosurf) administered with a novel atomizer in preterm lambs with respiratory distress syndrome.Twenty anaesthetized lambs, 127 ± 1 d gestational age, (mean ± SD) were instrumented before birth and randomized to receive either (i) positive pressure ventilation without surfactant (Control group), (ii) 200 mg/kg of bolus instilled surfactant (Bolus group) at 10 min of life or (iii) 200 mg/kg of atomized surfactant (Atomizer group) over 60 min from 10 min of life. All lambs were ventilated for 180 min with a standardized protocol. Lung mechanics, regional lung compliance (electrical impedance tomography), and carotid blood flow (CBF) were measured with arterial blood gas analysis.Dynamic compliance and oxygenation responses were similar in the Bolus and Atomizer groups, and both better than Control by 180 min (all P0.05; two-way ANOVA). Both surfactant groups demonstrated more homogeneous regional lung compliance throughout the study period. There were no differences in CBFConclusion:In a preterm lamb model, atomized surfactant resulted in similar gas exchange and mechanics as bolus administration. This study suggests evaluation of supraglottic atomization with this system when noninvasive support is warranted.

During the last few years, advances in the care of low-birth-weight and preterm neonates has stimulated research on the best dietetic program to improve survival and to reduce handicap incidence. At present, fortification of human milk with artificial formulas is the most usual dietetic solution. As yet, however, little is known about the composition of milk from mothers giving birth prematurely. The aim of this study was the quantification of different proteins in human milk during the lactation period. By use of an electrophoretic method, lactoferrin (LF), alpha-lactalbumin, beta-casein, and lysozyme concentrations were measured in milk from mothers delivering normally (TM) or prematurely (PM). LF concentration in milk from TM presented higher values in the very first days and a fast decrease to d 10. After d 10, the concentration reached a plateau. In milk from PM, the LF concentration in the first days was lower than for TM. Similar profiles of alpha-lactalbumin, beta-casein, and lysozyme concentrations were found in milk from TM and PM. A general higher variability in PM samples was observed both between different mothers and for the same woman during the lactation period. Lactation profiles for four human milk proteins are described here. No significant difference was observed (apart from LF in the very first days) between preterm and term milk samples, confirming the unsuitability of unfortified breast milk for preterm neonates.

Objective: To evaluate short-term respiratory outcomes in late preterm infants (LPI) compared with those of term infants (TI). Methods: A retrospective study conducted in a single third level Italian centre (2005–2009) to analyse the incidence and risk factors of composite respiratory morbidity (CRM), the need for adjunctive therapies (surfactant therapy, inhaled nitric oxide, pleural drainage), the highest level of respiratory support (mechanical ventilation – MV, nasal continuous positive airway pressure – N-CPAP, nasal oxygen) and the duration of pressure support (hours in N-CPAP and/or MV). Results: During the study period 14,515 infants were delivered. There were 856 (5.9%) LPI and 12,948 (89.2%) TI. CRM affected 105 LPI (12.4%), and 121 TI (0.9%), with an overall rate of 1.6%. Eighty-four LPI (9.8%) and 73 TI (0.56%) received respiratory support, of which 13 LPI (1.5%) and 16 TI (0.12%) were ventilated. The adjusted OR for developing CRM significantly increased from 3.3 (95% CI 2.0-5.5) at 37 weeks to 40.8 (95% CI 19.7-84.9%) at 34 weeks. The adjusted OR for the need of MV significantly increased from 3.4 (95% CI 1.2-10) at 37 weeks to 34.4 (95% CI 6.7-180.6%) at 34 weeks. Median duration of pressure support was significantly higher at 37 weeks (66.6 h vs 40.5 h). Twin pregnancies were related to a higher risk of CRM (OR 4.3, 95% CI 2.6-7.3), but not independent of gestational age (GA). Cesarean section (CS) was associated with higher risk of CRM independently of GA, but the OR was lower in CS with labour (2.2, 95% CI 1.4-3.4 vs 3.0, 95% CI 2.1-4.2). Conclusions: In this single third level care study late preterm births, pulmonary diseases and supportive respiratory interventions were lower than previously documented. LPI are at a higher risk of developing pulmonary disease than TI. Infants born from elective cesarean sections, late preterm twins in particular and 37 weekers too might benefit from preventive intervention.

The aims of the present study were (i) to characterize the relationship between mean airway pressure (PAW) and reactance measured at 5 Hz (reactance of the respiratory system (X RS), forced oscillation technique) and (ii) to compare optimal PAW (P opt) defined by X RS, oxygenation, lung volume (VL), and tidal volume (VT) in preterm lambs receiving high-frequency oscillatory ventilation (HFOV).Nine 132-d gestation lambs were commenced on HFOV at PAW of 14 cmH2O (P start). PAW was increased stepwise to a maximum pressure (P max) and subsequently sequentially decreased to the closing pressure (Pcl, oxygenation deteriorated) or a minimum of 6 cmH2O, using an oxygenation-based recruitment maneuver. X RS, regional V L (electrical impedance tomography), and V T were measured immediately after (t 0 min) and 2 min after (t 2 min) each PAW decrement. P opt defined by oxygenation, X RS, V L, and V T were determined.The PAW-X RS and PAW-VT relationships were dome shaped with a maximum at Pcl+6 cmH2O, the same point as P opt defined by VL. Below Pcl+6 cmH2O, X RS became unstable between t 0 min and t 2 min and was associated with derecruitment in the dependent lung. P opt, as defined by oxygenation, was lower than the P opt defined by X RS, V L, or V T.X RS has the potential as a bedside tool for optimizing PAW during HFOV.

Background IUGR infants are thought to have impaired gut function after birth, which may result in intestinal disturbances, ranging from temporary intolerance to the enteral feeding to full-blown NEC. In literature there is no consensus regarding the impact of enteral feeding on intestinal blood flow and hence regarding the best regimen and the best rate of delivering the enteral nutrition. Methods/design This is a randomized, non-pharmacological, single-center, cross-over study including 20 VLBW infants. Inclusion criteria * Weight at birth ranging: 700–1501 grams * Gestational age up to 25 weeks and 6 days * Written informed consent from parents or guardians Exclusion criteria * Major congenital abnormality * Patients enrolled in other trials * Significant multi-organ failure prior to trial entry * Pre-existing cutaneous disease not allowing the placement of the NIRS’ probe In the first 24 hours of life, between the 48th and 72nd hours of life, and during Minimal Enteral Feeding, all infants’ intestinal perfusion will be evaluated with NIRS and a Doppler of the superior mesenteric artery will be executed. At the achievement of an enteral intake of 100 mL/Kg/day the patients (IUGR and NON IUGR separately) will be randomized in 2 groups: Group A (n=10) will receive a feed by bolus (in 10 minutes); then, after at least 3 hours, they will receive the same amount of formula administered in 3 hours. Group B (n=10) will receive a feed administered in 3 hours followed by a bolus administration of the same amount of formula (in 10 minutes) after at least 3 hours. On the randomization day intestinal and cerebral regional oximetry will be measured via NIRS. Intestinal and celebral oximetry will be measured before the feed and 30 minutes after the feed by bolus during the 3 hours nutrition the measurements will be performed before the feed, 30 minutes from the start of the nutrition and 30 minutes after the end of the gavage. An evaluation of blood flow velocity of the superior mesenteric artery will be performed meanwhile. The infants of the Group A will be fed with continuous nutrition until the achievement of full enteral feeding. The infants of the Group B will be fed by bolus until the achievement of full enteral feeding. Discussion Evaluations of intestinal oximetry and superior mesenteric artery blood flow after the feed may help in differentiating how the feeding regimen alters the splanchnic blood flow and oxygenation and if the changes induced by feeding are different in IUGR versus NON IUGR infants. Trial registration number NCT01341236

Objective: Data comparing the effectiveness of high-frequency oscillatory ventilation and of conventional mechanical ventilation in the treatment of respiratory distress syndrome of very low birth weight infants are, to date, still matter of debate. We investigated the effects of first intention high-frequency oscillatory ventilation or conventional mechanical ventilation support on selected primary and secondary outcomes in very low birth weight infants complicated by respiratory distress syndrome in which antenatal glucocorticoid prophylaxis was not performed. Design: Multicenter randomized control trial. Setting: Three tertiary centers of neonatal intensive care units from December 2004 to December 2007. Population: Eighty-eight very low birth weight infants complicated by respiratory distress syndrome, without antenatal glucocorticoids, supported by first intention high-frequency oscillatory ventilation (n = 44) or conventional mechanical ventilation (n = 44). Interventions: All newborns were monitored by standard monitoring procedure, including routine laboratory variables, neurologic patterns, and ultrasound imaging. Primary outcomes were: the length of ventilatory support, the need of reintubation, and the length of nasal continuous positive airway pressure support in the postextubation period. Secondary outcomes were: the length of stay in neonatal intensive care unit and in hospital, death before discharge, adverse short-and long-term pulmonary and neonatal outcomes, and the need for a second dose of surfactant and of postnatal glucocorticoid treatment. Results: High-frequency oscillatory ventilation infants showed a significant lower duration (p

Osteopenia, a condition characterised by a reduction in bone mineral content, is a common disease of preterm babies between the tenth and sixteenth week of life. Prematurely born infants are deprived of the intrauterine supply of minerals affecting bone mineralization. The aetiology is multifactorial: inadequate nutrients intake (calcium, phosphorus and vitamin D), a prolonged period of total parenteral nutrition, immobilisation and the intake of some drugs. The diagnosis of metabolic bone disease is done by biochemical analysis: low serum levels of phosphorus and high levels of alkaline phosphatase are suggestive of metabolic bone disease. The disease can remain clinically silent or presents with symptoms and signs of rachitism depending on the severity of bone demineralisation. An early nutritional intervention can reduce both the prevalence and the severity of osteopenia. This article reviews the pathophysiology of foetal and neonatal bone metabolism, focuses on the nutrient requirements of premature babies and on the ways to early detect and treat osteopenia.

Objective To describe the natural course of intestinal failure with onset in the neonatal period to provide data regarding the occurrence and to provide a population-based survey regarding the spectrum of underlying diseases. Study design We performed a retrospective chart review including infants admitted to the neonatal intensive care unit of 7 Italian tertiary care centers. Intestinal failure was defined as a primary intestinal disease that induces the need of total parenteral nutrition (PN) for more than 4 weeks or the need of partial PN for more than 3 months. Results The total number of live births during the study time within the enrolled institutions was 30 353, and the number of newborns admitted to the neonatal intensive care unit was 5088. Twenty-six patients satisfied the definition of intestinal failure; thus the occurrence rate of intestinal failure was 0.1% among live-birth newborns and 0.5% among infants at high risk. The main underlying diseases leading to intestinal failure in neonatal age were congenital intestinal defects (42.3%), necrotizing enterocolitis (30.8%), severe intestinal motility disorder (11.5%), intestinal obstruction (7.7%), structural enterocyte defects (3.8%), and meconium peritonitis (3.8%). After a follow-up of 36 months, 84.6% of patients achieved intestinal competence, 1 patient was still receiving home PN, 1 patient underwent transplantation, and 2 patients died. Cholestatic liver disease was diagnosed in 54% of observed children. Conclusion An understanding of the incidence, causes, and natural history of intestinal failure would be helpful to appropriately allocate resources and to plan clinical trials.

The therapeutic approach to the management of pulmonary hypertension (PH) is based on strategies to decrease pulmonary vascular resistance (PVR) whilst ensuring optimal cardiorespiratory support to improve oxygenation. The goal is to maintain appropriate systemic blood pressure, ensure oxygen release to tissues and minimize lesions induced by oxygen and ventilation. Inhaled nitric oxide (iNO) remains the mainstay of treatment for this condition. As an inhaled agent it reaches the alveolar space and diffuses into the vascular smooth muscle of the adjacent pulmonary arteries where it causes vasodilation by increasing guanosine monophosphate (cGMP) levels without affecting systemic vascular tone. Although iNO significantly reduces the need for extracorporeal membrane oxygenation, almost 25-40% of iNO-treated infants are considered iNO non–responders. A complementary vasodilatory pathway in the lung is mediated by cyclic adenosine monophosphate (cAMP); prostacyclin stimulates adenylyl cyclase in vascular smooth muscle cells and causes an increase in intracellular cAMP and vasodilation of the systemic and pulmonary circulatory systems. If given as an inhaled drug the vasodilatory effects of prostacyclin tend to be limited to the pulmonary circulation, making this strategy appealing when acute pulmonary vasodilation is needed. [1] Inhibition of the cGMP-degrading phosphodiesterase (PDE5) and inhibition of the cAMP-degrading phosphodiesterase (PDE3) are two other promising therapies. Sildenafil is a PDE5 inhibitor, the predominant PDE isoform in the lung responsible for the breakdown of cGMP. It acts by enhancing NO-mediated vasodilation and may facilitate iNO discontinuation in infants with critical illness.[2] Milrinone is a PDE3 inhibitor with inotropic and vasodilatory effects; it improves the left ventricular cardiac function both directly and by reducing systemic afterload and exerts also important effects on the pulmonary vasculature by reducing PVR. It may be a plausible agent for treating patients with PH and impaired myocardial function. [3] One of the most potent vasoconstrictors described in the pulmonary vasculature is Endothelin-1 (ET-1). Inhibition of ET-1 mediated vasoconstriction could be achieved by administration of an endothelin receptor antagonist (Bosentan). Bosentan lowers pulmonary artery pressure and PVR in children with diverse causes of PH and may improve oxygenation in neonates with persistent pulmonary hypertension; it has also been successfully used as an adjunctive treatment for children receiving long-term prostacyclin therapy.

Very few data are available on pediatrics malpracticeclaims. We report the first data obtained in Italy onpediatrics regarding a wide population study during a8 years survey. Data concerning 164 claims are pre-sented and discussed. Our data suggest how big is theproblem and they may be helpful to face it.IntroductionPediatrics is not a high-risk specialty in terms of thenumber of claims, although some of the largest financialpayouts have been for multiple disabled children withperinatal injuries and long life expectancy [1-5]. Wereport the first data obtained in Italy on pediatricsregarding a wide population study.Materials and methodsWe conducted a retrospective, descriptive analysis of anation-wide database on pediatric malpractice claims, inwhich patients alleged a permanent impairment relatedto a medical misconduct. The Italian Society of Pediatrics(Societa Italiana di Pediatria; SIP) has developed a link –thorough insurance broker Willis Italian SpA– with aninsurance company (CARIGE Assicurazioni SpA) thatinsures a wide proportion of Italian pediatricians (nearly60% out of 8000 physicians).We asked Willis to perform a query of its database,looking at malpractice claims reported between January,1

Several studies have shown that late preterm infants (LPI) are at higher risk for respiratory disorders than term infants. Objective: To evaluate occurrence of respiratory disorders, need for respiratory support, use and timing of specific adjunctive pulmonary therapies in LPI. Methods: Using electronic medical charts, we performed a retrospective analysis of all LPI (34 0/7 to 36 6/7 wks) born from January 2005 to December 2009 in a tertiary level NICU. Results: During the study period, 856/14443 infants born alive were LPI (5.9%). They accounted for 58.9% of preterm births. Majority of LPI were 36 weeks (53.9%), followed by 35 weeks (28.4%) and 34 weeks (17.8%). Transient tachypnea of the newborn (5.8%) was the most common pulmonary illness, followed by respiratory distress syndrome (4.7%), apnea (1.5%), air leak (1.3%) and persistent pulmonary hypertension (0.5%). Composite respiratory morbidity was 12.4%: A total of 69 (8.1%) patients received NCPAP only, 19 (2.2%) mechanical ventilation, 17 (2%) surfactant, 8 (0.9%) chest tube and 4 (0.5%) inhaled nitric oxide. Fig 1 shows the highest levels of respiratory support for each GA. Fig 2 shows times at which each treatment was started. Median length of positive pressure ventilation was 40.5 hours (IQR 16.9-91.6). Mortality was 0.4%. Conclusion: Compared with literature, our population showed lower incidence of mortality, respiratory disorders and need for assisted ventilation, probably due to a great proportion of more mature infants.

This work evaluated the neurodevelopmental and functional outcomes of premature infants with intraventricular hemorrhage (IVH). These outcomes were analyzed for their association with IVH severity. Methods and materials: In the years 2008 and 2009 we performed cerebral ultrasounds of all children with gestational age less than 32 weeks and/or birthweight under 1500 grams. We evaluated the motor outcome (infant cerebral palsy versus normal status) and the neurodevelopmental outcome (Griffith score at 12th month of corrected age) of all children with IVH (classificated according to Papile). Results: In 2008 and 2009 the newborn evaluated were 108 and 90 respectively (both inborn and outborn). Table The correlation between severity of IVH and occurence of PCI was of no statistical significance (p< 0,14). The mean IQ was lower in infants with IVH of first grade than in infants with IVH of second grade or more (101 and 67 respectively). This difference occurred also in all the single items of the Griffith score (106-89-102-102-108 and 61-54-72-68-82 respectively). Conclusions: Even though the difference is not of statistical significance,the PCI is more frequent in infants with severe IVH. The mean IQ correlates with the severity of the IVH. Preventing cerebral hemorrhage may reduce negative long-term outcomes.

Background and aims: HIE severity and MRI findings are predictors of neurological outcome in asphyxiated neonates. Mild hypothermia may reduce the severity of basal ganglia and thalamus lesions, which are predictive of abnormal outcome. Moreover hypothermia does not induce any unexpected cerebral lesions. We compare MRI lesions with HIE grade and neurological outcome. Methods: From December 2006 in S. Gerardo Hospital NICU, mild hypothermia (selective head cooling) is the standard of care for the hypoxicischemic newborns. Patient's selection and treatment were done according to the protocols employed in the published randomized trials. The treated neonates were 26, 12 infants had hypoxicischemic encephalopathy (HIE) grade II and 14 had HIE grade III. MRI (T1-T2 and diffusion-weighted sequences) was performed within 15 days of life and classified according to the Mercury's classification. The neurological outcome was assessed at 12 months. Results: MRI showed cerebral lesions in 71% (mostly mild). Unexpected MRI lesions weren't seen. There is no correlation between severity of HIE and MRI lesions; moreover there is not correlation between the severity of MRI cerebral lesions and motor delay or cerebral palsy. Conclusions: in our population of cooled infants, neurological outcome is not associated with the degree of HIE and the severity of MRI lesions.

Background and aim: Optoelectronic plethysmography (OEP) allows the measurement of lung volume changes through the assessment of chest wall surface motion. It has been shown that it provides an accurate estimation of total and compartmental (rib cage and abdomen) lung volume changes in adults during spontaneous breathing and mechanical ventilation and in spontaneously breathing infants (REF). The aim of the present study is to evaluate the accuracy of OEP in infants during continuous positive airways pressure (CPAP). Methods: 5 infants (GA=27.9±3.6, PNA=3.8±3.6, BW=1077±461) were studied for ∼ 2 minutes at CPAP 0, 4 and 8 cmH2O. Flow was measured at the inlet of a full-face mask by a mesh-type pneumotacograph connected to a differential pressure transducer. Chest wall volume changes were measured by OEP (DVOEP) and compared with lung volume changes obtained by integrating the flow signal (DVPNT). Results: We analysed a total of 602 breaths at 0 cmH2O, 523 at 4 cmH2O, and 150 at 8 cmH2O. The mean difference between DVOEP and DVPNT for all newborns was -0.45±3.92% of Vt at 0 cm H2O, -4.25±9.04% at 4 cmH2O and -8.31±3.87% at 8 cmH2O. Pooling data points from all infants and all pressure levels, Bland-Altman and linear regression analysis showed good agreement between the two measurement techniques (see Fig). Conclusions: OEP can be used to assess lung volume changes and breathing pattern noninvasively in newborns supported by CPAP.

Several cases of fetal intraventricular hemorrage (IVH) have been reported using prenatal ultrasonography (US). However the clinical and prognostic significance of these lesions has not been established. To this aim, four cases of fetal IVH are presented. Methods: US was performed with a high resolution, real-time scanner with a 5.0 Mhz-phased array. MRI studies were obtained using T1 and T2 weighted sections at 4-5 mm intervals.

To confirm the hypothesis that I modifies G pharmacokinetic with high risk of toxicity, we studied 48 neonates (mean gestational age (GA) 28.3 w., birth-weight 1125 g, postnatal age 4.5 d.) affected by respiratory problems and treated with following schedule ol G administration: 2.5 mg(Kg/dose every 24 h for GA