The effect of clamped and unclamped umbilical cord samples on blood gas analysis.

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.

Results of a multicenter universal newborn screening program for sickle cell disease in Italy: A call to action.

BACKGROUND: Sickle cell disease (SCD) is a chronic multisystem disorder requiring comprehensive care that includes newborn screening (NBS) as the first step of care. Italy still lacks a national SCD NBS program and policy on blood disorders. Pilot single-center screening programs and a regional targeted screening have been implemented so far, but more evidence is needed in order to impact health policies. POPULATION AND METHODS: NBS was offered to parents of newborns in gynecology clinics in Padova and Monza, tertiary care university hospitals in northern Italy. High-performance liquid chromatography (HPLC) was performed as the first test on samples collected on Guthrie cards. Molecular analysis of the beta-globin gene was performed on positive samples. RESULTS: A total of 5466 newborns were enrolled; for 5439, informed consents were obtained. A similar family origin was seen in the two centers (65% Italians, 9% mixed couples, 26% immigrants). Compared with SCD NBS programs in the United States and Europe, our results show a similar incidence of SCD patients and carriers. All SCD patients had a Sub-Saharan family background; HbS carriers were 15% Caucasians (Italian, Albanians) and 10% from other areas (North Africa-India-South America); carriers of other hemoglobin variants were mainly (47%) from other areas. CONCLUSIONS: Our results demonstrate the feasibility of a multicentric NBS program for SCD, give information on HbS epidemiology in two Northern Italian Areas, and support previous European recommendation for a universal NBS program for SCD in Italy: a high incidence of patients and carriers has been detected, with a high percentage of Caucasian carriers, impossible to identify in a targeted NBS.

Relationship between Mean Airways Pressure, Lung Mechanics, and Right Ventricular Output during High-Frequency Oscillatory Ventilation in Infants.

OBJECTIVE: To characterize changes in lung mechanics and right ventricular output (RVO) during incremental/decremental continuous distending pressure (CDP) maneuvers in newborn infants receiving high-frequency oscillatory ventilation, with the aim of evaluating when open lung maneuvers are needed and whether they are beneficial. STUDY DESIGN: Thirteen infants on high-frequency oscillatory ventilation were studied with a median (IQR) gestational age of 261 (253-291) weeks and median (IQR) body weight of 810 (600-1020) g. CDP was increased stepwise from 8 cmH2O to a maximum pressure and subsequently decreased until oxygenation deteriorated or a CDP of 8 cmH2O was reached. The lowest CDP that maintained good oxygenation was considered the clinically optimal CDP. At each CDP, the following variables were evaluated: oxygenation, respiratory system reactance (Xrs), and RVO by Doppler echocardiography. RESULTS: At maximal CDP reached during the trial, 19 [1] cmH2O (mean [SEM]), oxygenation markedly improved, and Xrs and RVO decreased. During deflation, oxygenation remained stable over a wide range of CDP settings, Xrs returned to the baseline values, and RVO increased but the baseline values were not readily restored in all patients. CONCLUSION: These results suggest that Xrs and RVO are more sensitive than oxygenation to overdistension and they may be useful in clinical practice to guide open lung maneuvers.

Effect of frequency on pressure cost of ventilation and gas exchange in newborns receiving high-frequency oscillatory ventilation.

BackgroundWe 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.MethodsWe 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.ResultsBlood 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.ConclusionThere 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.

Supraglottic Atomization of Surfactant in Spontaneously Breathing Lambs Receiving Continuous Positive Airway Pressure.

OBJECTIVES: To determine the short-term tolerance, efficacy, and lung deposition of supraglottic atomized surfactant in spontaneously breathing lambs receiving continuous positive airway pressure. DESIGN: Prospective, randomized animal study. SETTING: Animal research laboratory. SUBJECTS: Twenty-two preterm lambs on continuous positive airway pressure (132 ± 1 d gestational age). INTERVENTIONS: Animals receiving continuous positive airway pressure via binasal prongs at 8 cm H2O were randomized to receive atomized surfactant at approximately 60-minute of life (atom; n = 15) or not (control; n = 7). The atom group received 200 mg/kg of poractant alfa (Curosurf; Chiesi Farmaceutici SpA, Parma, Italy) over 45 minutes via a novel atomizer located in the upper pharynx that synchronized surfactant delivery with the inspiratory phase. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas, regional distribution of tidal ventilation (electrical impedance tomography), and carotid blood flow were recorded every 15 minutes until 90 minutes after stabilizing on continuous positive airway pressure. Gas exchange, respiratory rate, and hemodynamic variables, including carotid blood flow, remained stable during surfactant treatment. There was a significant improvement in arterial alveolar ratio after surfactant delivery in the atom group (p < 0.05; Sidak posttests), while there was no difference in PaCO2. Electrical impedance tomography data showed a more uniform pattern of ventilation in the atom group. In the atom group, the median (interquartile range) deposition of surfactant in the lung was 32% (22-43%) of the delivered dose, with an even distribution between the right and the left lungs. CONCLUSIONS: In our model of spontaneously breathing lambs receiving CPAP, supraglottic atomization of Curosurf via a novel device was safe, improved oxygenation and ventilation homogeneity compared with CPAP only, and provided a relatively large lung deposition suggesting clinical utility.

Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial.

BACKGROUND: Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). METHODS: A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. DISCUSSION: Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014-005472-29.

Impact of Continuous vs Bolus Feeding on Splanchnic Perfusion in Very Low Birth Weight Infants: A Randomized Trial.

OBJECTIVE: To detect changes in splanchnic perfusion and oxygenation induced by 2 different feeding regimens in infants with intrauterine growth restriction (IUGR) and those without IUGR. STUDY DESIGN: This was a randomized trial in 40 very low birth weight infants. When an enteral intake of 100 mL/kg/day was achieved, patients with IUGR and those without IUGR were randomized into 2 groups. Group A (n = 20) received a feed by bolus (in 10 minutes), then, after at least 3 hours, received the same amount of formula by continuous nutrition over 3 hours. Group B (n = 20) received a feed administered continuously over 3 hours, followed by a bolus administration (in 10 minutes) of the same amount of formula after at least 3 hours. On the day of randomization, intestinal and cerebral regional oximetry was measured via near-infrared spectroscopy and Doppler ultrasound (US) of the superior mesenteric artery was performed. Examinations were performed before the feed and at 30 minutes after the feed by bolus and before the feed, at 30 minutes after the start of the feed, and at 30 minutes after the end of the feed for the 3-hour continuous feed. RESULTS: Superior mesenteric artery Doppler US showed significantly higher perfusion values after the bolus feeds than after the continuous feeds. Near-infrared spectroscopy values remained stable before and after feeds. Infants with IUGR and those without IUGR showed the same perfusion and oxygenation patterns. CONCLUSION: According to our Doppler US results, bolus feeding is more effective than continuous feeding in increasing splanchnic perfusion. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01341236.

Intratracheal atomized surfactant provides similar outcomes as bolus surfactant in preterm lambs with respiratory distress syndrome.

BACKGROUND: 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. METHODS: 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. RESULTS: Dynamic compliance and oxygenation responses were similar in the Bolus and Atomizer groups, and both better than Control by 180 min (all P < 0.05; 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.

Discrimination of biomechanically possible and impossible hand movements at birth.

The development of human body perception has long been investigated, but little is known about its early origins. This study focused on how a body part highly relevant to the human species, namely the hand, is perceived a few days after birth. Using a preferential-looking paradigm, 24- to 48-hr-old newborns watched biomechanically possible and impossible dynamic hand gestures (Experiment 1, N = 15) and static hand postures (Experiment 2, N = 15). In Experiment 1, newborns looked longer at the impossible, compared to the possible, hand movement, whereas in Experiment 2 no visual preference emerged. These findings suggest that early in life the representation of the human body may be shaped by sensory-motor experience.

Optimal mean airway pressure during high-frequency oscillatory ventilation determined by measurement of respiratory system reactance.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: X RS has the potential as a bedside tool for optimizing PAW during HFOV.

Fetal hydronephrosis: natural history and risk factors for postnatal surgery.

BACKGROUND: The objective of this study was to assess the ability of prenatal ultrasound to predict an unfavorable outcome and the need for postnatal surgery in cases of fetal hydronephrosis (HY). METHODS: Antenatal HY was classified according to the renal pelvis anteroposterior (AP) diameter in the third trimester. Postnatal outcome was considered favorable in the presence of spontaneous resolution or postnatal diagnosis of HY <20 mm, and unfavorable in the presence of postnatal diagnosis of >20 mm HY or urinary tract pathologies. RESULTS: Prenatal diagnosis of HY was made in 120 fetuses (for a total of 161 abnormal renal units). The rates of postnatal urinary tract pathology were 14, 27 and 53% for antenatal HY of ≤7, 8-15 and >15 mm, respectively. An AP diameter ≥7 mm in the third trimester had a sensitivity of 100% and a specificity of 23% to predict unfavorable outcome. A formula inclusive of AP diameter and presence or absence of urinary tract anomalies can predict the need for postnatal surgery. CONCLUSIONS: The majority of infants with congenital HY have a favorable postnatal outcome. Risk of unfavorable outcome increases with the degree of dilatation of the renal pelvis and the presence of urinary tract anomalies. An AP diameter ≥7 mm in the third trimester warrants postnatal follow-up.

Assessment of dynamic mechanical properties of the respiratory system during high-frequency oscillatory ventilation*.

OBJECTIVES: 1) To investigate the possibility of estimating respiratory system impedance (Zrs, forced oscillation technique) by using high-amplitude pressure oscillations delivered during high-frequency oscillatory ventilation; 2) to characterize the relationship between Zrs and continuous distending pressure during an increasing/decreasing continuous distending pressure trial; 3) to evaluate how the optimal continuous distending pressure identified by Zrs relates to the point of maximal curvature of the deflation limb of the quasi-static pressure-volume curve. DESIGN: Prospective laboratory animal investigation. SETTING: Experimental medicine laboratory. SUBJECTS: Eight New Zealand rabbits. INTERVENTIONS: The rabbits were ventilated with high-frequency oscillatory ventilation. Zrs was measured while continuous distending pressure was increased and decreased between 2 and 26 cm H2O in 1-minute steps of 4 cm H2O. At each step, a low-amplitude (6 cm H2O) sinusoidal signal was alternated with a high-amplitude (18 cm H2O) asymmetric high-frequency oscillatory ventilation square pressure waveform. Pressure-volume curves were determined at the end of the continuous distending pressure trial. All measurements were repeated after bronchoalveolar lavage. MEASUREMENTS AND MAIN RESULTS: Zrs was estimated from flow and pressure measured at the inlet of the tracheal tube and expressed as resistance (Rrs) and reactance (Xrs). Linear correlation between the values, measured by applying the small-amplitude sinusoidal signal and the ventilator waveform, was good for Xrs (r = 0.95 ± 0.04) but not for Rrs (r = 0.60 ± 0.34). Following lavage, the Xrs-continuous distending pressure curves presented a maximum on the deflation limb, identifying an optimal continuous distending pressure that was, on average, 1.1 ± 1.7 cm H2O below the point of maximal curvature of the deflation limb of the pressure-volume curves. CONCLUSIONS: Xrs can be accurately measured during high-frequency oscillatory ventilation without interrupting ventilation and/or connecting additional devices. An optimal continuous distending pressure close to the point of maximal curvature of the deflation limb of quasi-static pressure-volume curve can be identified by measuring Zrs during a decreasing continuous distending pressure trial. Zrs might constitute a useful bedside tool for monitoring lung mechanics and improving the continuous distending pressure optimization during high-frequency oscillatory ventilation.

Monitoring Doppler patterns and clinical parameters may predict feeding tolerance in intrauterine growth-restricted infants.

AIM: To detect predictors of feeding tolerance in intrauterine growth restriction (IUGR) infants with or without brain-sparing effect (BS). METHODS: We conducted a case-control study in 70 IUGR infants (35 IUGR with BS, matched for gestational age with 35 IUGR infants with no BS). BS was classified as pulsatility index (PI) ratio [umbilical artery (UAPI) to middle cerebral artery (MCAPI) (U/C ratio)] > 1. Clinical parameters of feeding tolerance - days to achieve full enteral feeding (FEF) - were compared between the IUGR with BS and IUGR without BS infants. Age at the start of minimal enteral feeding (MEF) was analysed. RESULTS: Achievement of FEF was significantly shorter in IUGR infants without BS than in IUGR with BS. IUGR with BS started MEF later than IUGR without BS infants. Significant correlation of MEF and FEF with UA PI, U/C ratio and CRIB score was found. Multiple linear regression analysis showed significant correlations with CRIB score and caffeine administration (MEF only), and sepsis (FEF only) and U/C ratio (for both). CONCLUSION: Impaired gut function can be early detected by monitoring Doppler patterns and clinical parameters.

Survey of neonatal respiratory care and surfactant administration in very preterm infants in the Italian Neonatal Network.

INTRODUCTION: Variation of respiratory care is described between centers around the world. The Italian Neonatal Network (INN), as a national group of the Vermont-Oxford Network (VON) allows to perform a wide analysis of respiratory care in very low birth weight infants. METHODS: We analyzed the dataset of infants enrolled in the INN in 2009 and 2010 and, for surfactant administration only, from 2006 to 2010 from 83 participating centers. All definitions are those of the (VON). A questionnaire analysis was also performed with a questionnaire on centers practices. RESULTS: We report data for 8297 infants. Data on ventilator practices and outcomes are outlined. Variation for both practices and outcome is found. Trend in surfactant administration is also analyzed. CONCLUSIONS. The great variation across hospitals in all the surveyed techniques points to the possibility of implementing potentially better practices with the aim of reducing unwanted variation. These data also show the power of large neonatal networks in identifying areas for potential improvement.

First intention high-frequency oscillatory and conventional mechanical ventilation in premature infants without antenatal glucocorticoid prophylaxis.

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 < .001 for all) of ventilator dependency, lower need of reintubation and of duration of nasal continuous positive airway pressure support in the postextubation period. Among secondary outcomes in the high-frequency oscillatory ventilation infants, the need of a second dose of surfactant administration, and the length of stay in the neonatal intensive care unit and in hospital were significantly lower (p < .05 for all). CONCLUSIONS: We found that high-frequency oscillatory ventilation in very low birth weight infants without antenatal glucocorticoid prophylaxis reduced the need of ventilatory support, surfactant therapy, and reintubation, and shortened neonatal intensive care unit and hospital stay, thus reducing unit and hospital costs. These data would support the usefulness of first intention high-frequency oscillatory ventilation strategy in managing in a selected population, such as very low birth weight newborns complicated by severe respiratory distress syndrome not antenatally treated with glucocorticoids.

Evaluation of splanchnic oximetry, Doppler flow velocimetry in the superior mesenteric artery and feeding tolerance in very low birth weight IUGR and non-IUGR infants receiving bolus versus continuous enteral nutrition.

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.

Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial.

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.

Measurement of total and compartmental lung volume changes in newborns by optoelectronic plethysmography.

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.

Body temperature at nursery admission in a cohort of healthy newborn infants: results from an observational cross-sectional study.

BACKGROUND: Exposure to hypothermia is somehow unavoidable when a baby comes to life. This is the reason why any possible effort should be made by every caregiver involved during birth, from labour to transfer into the maternity ward, to reduce it. Hypothermia has widely shown to be related to several neonatal problems, and the risks are more relevant when the babies are born prematurely. METHOD: An observational study was conducted in April 2016 to assess the current practises to avoid hypothermia at birth in 20 Italian neonatal units. Each unit introduced local improvements in clinical practice and the same observational study was repeated 1 year later. RESULTS: A total of 4722 babies were analysed. An overall increase in adherence to local and international recommendations emerged from our study. Significant differences between 2016 and 2017 were found in regard to neonatal temperature at nursery entry (36.3 °C vs 36.5 °C, respectively, p < 0.0001), delayed cord clamping practice > 60″ (48.1% vs 68.1%, respectively, p < 0.0001) and skin-to-skin practice > 60' (56.3% vs 60.9, respectively, p = 0.03). Statistical correlations with the risk of hypothermia were found for delivery room (OR 0.88 (CI 95%0.83-0.94), p < 0.0001) and maternal temperature (OR 0.57 (CI 95% 0.48-0.67), p < 0.0001). CONCLUSION: Periodical assessment of the delivery room practice has shown to be effective in improving adherence to the international recommendations. Relationship between neonatal hypothermia and several other variables including the delivery room and mother temperature underlines how neonatal thermoregulation starts immediately after birth. Hence, a multi-disciplinary approach is needed to provide the optimal environment for a safe birth.

Effects of antenatal indomethacin on ductus arteriosus early closure and on adverse outcomes in preterm neonates.

Introduction: Premature birth is a leading cause of neonatal morbidity and mortality. Since gestational age at birth is the most important predictive factor of adverse neonatal outcomes, strategies to postpone premature labor are of major importance. Studies on tocolytic drugs show that COX inhibitors such as indomethacin are superior to others in terms of efficiency in delaying birth, but results concerning neonatal outcomes associated with prenatal exposure to these drugs show controversial results. Indomethacin is also used in the postnatal age for pharmacologic treatment of patent ductus arteriosus (PDA), but no data concerning the effects of antenatal exposure on postnatal ductal patency are available.Methods: In this study, we focused primarily on the association between antenatal indomethacin (AI) and postnatal patency of ductus arteriosus while our secondary aim was to highlight any possible influence of AI exposure on adverse neonatal outcomes. We performed a retrospective analysis of 241 medical records of newborns born before 33 weeks' gestation and exposed to antenatal tocolysis. Obstetrical data and neonatal outcomes of newborns exposed to AI were compared to those of neonates exposed to other tocolytic drugs. Early ductal closure (EDC) was defined when functional echocardiography performed within 24 hours of life showed a closed duct. Occurrence of intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), respiratory distress syndrome (RDS), chronic lung disease (CLD), necrotizing enterocolitis (NEC), sepsis, and PDA were compared between the groups and the diagnosis of at least one of III-IV grade IVH, PVL, CLD, sepsis, surgical NEC, or death was defined as a severe outcome.Results: The univariate analysis showed that infants in the AI group were at a higher risk of IVH, CLD, RDS, sepsis, and PDA. The incidence of severe outcomes also appeared to be higher in this group, while no effect of AI on PDA was observed. Since we noticed that infants exposed to AI had a lower gestational age and worse clinical conditions at birth when compared to the controls, we considered this as a confounding factor. To overcome this bias, we performed a multivariate analysis that evidenced no significant role of AI on the occurrence of severe outcomes. On the other hand, a possible association was confirmed for all degrees of IVH (OR: 3.16, 95% CI : [1.41; 7.05]) and sepsis (OR: 2.81, 95% CI: [1.24; 6,28]).Conclusions: The unexpected result shown by the multivariate analysis was the association between AI exposure and EDC (OR: 2.52, 95% CI: [1.02; 6.21]). This result, which has never been evidenced in previous studies, has great clinical importance. It is well known that PDA is more frequent at lower gestational ages, thus reducing the incidence of PDA could lead to an improvement of overall outcomes in extremely preterm newborns.