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.

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.

Accuracy of volume and pressure delivery by mechanical ventilators in use in neonatal intensive care units: A quality control study.

OBJECTIVE: Despite technical specifications of neonatal mechanical ventilators (MVs) guarantee clinically irrelevant discrepancies between the set and the delivered values of ventilation parameters, previous studies reported large deviations. Most studies characterized performances of a given model/brand by studying a single device, disregarding possible intramodel differences, and leaving the accuracy of the ventilation parameters effectively delivered in clinical settings unknown. The aim of this study was to evaluate the real-life accuracy of pressure and volume parameters delivered by neonatal ventilators ready to be used on patients in neonatal intensive care units (NICUs). STUDY DESIGN: In vitro study. SUBJECTS SELECTION: Neonatal ventilators (n = 33 of 8 different models) available in four European NICUs. METHODOLOGY: The MVs were connected to a test lung (resistance = 50 cmH2 O*s/L, compliance = 0.35 mL/cmH2 O) provided with pressure and flow sensors. MVs were tested over two different ventilation modes randomly: (a) pressure controlled (PC) with a peak inspiratory pressure (PIP) of 22 cmH2 O, and (b) PC with volume targeted ventilation (VTV) with a tidal volume (VT ) of 6 mL. In all tests, positive end-expiratory pressure (PEEP) was set to 6 cmH2 O, respiratory rate to 45 breaths/min, inspiratory time to 0.33 seconds, and oxygen fraction to 0.3. RESULTS: During PC the median (min-max) values delivered were: PEEP = 5.84(4.95-6.48) cmH2 O, PIP = 21.63(20.04-22.62) cmH2 O. During VTV, VT was 5.94(4.63-8.01) mL. VT was considerably variable, ranging from -22% to +33% of the set and displayed values. Differences in accuracy among devices of the same model were comparable to those found among different models. CONCLUSIONS: Our findings suggest that loss of accuracy in ventilation variables is likely related to daily use of the devices rather than weakness in the design or manufacturing process, urging the improvement of maintenance and quality control procedures to preserve the performances of neonatal MVs during their entire lifespan.

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.

Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study.

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 ß-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.

Regional distribution of chest wall displacements in infants during high-frequency ventilation.

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.

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.

Effect of continuous positive airway pressure on breathing variability in early preterm lung disease.

OBJECTIVES: In preterm infants, the application of nasal Continuous Positive Airway Pressure (nCPAP) improves lung function through several mechanisms and may interact with the control of breathing. Our aim was to evaluate the effect of increasing/decreasing nCPAP on gas exchange, breathing pattern, and its variability in preterm infants. METHODS: Fifeteen infants with mild to moderate respiratory distress syndrome (RDS) were studied on the first day of life. Infants had a mean (SD) gestational age of 30 + 4 (3 + 4) weeks + day and body weight of 1405 (606) g. nCPAP was increased every 10 min stepwise (0-4-8-10 cmH2 O) and then decreased every 20 min (8-6-4-2 cmH2 O). At each step, vital parameters, oxygenation, and chest wall volume changes (optoelectronic plethysmography) were evaluated. Tidal volume (VT ), inter-breath interval (IBI), end-expiratory lung volume (EELV) changes, and other breathing pattern parameters were computed breath-by-breath. The correlation properties of VT , IBI, and EELV were quantified by detrended fluctuation analysis, computing the scaling exponent α. RESULTS: During nCPAP, oxygenation improved and VT decreased significantly compared with no nCPAP. No significant changes in breathing pattern were observed between nCPAP levels. α of EELV was significantly higher off nCPAP than during nCPAP, suggesting that nCPAP helps stabilize EELV control mechanisms. CONCLUSIONS: In our population of preterm infants with mild to moderate RDS, in the first day of life, nCPAP improved gas exchange, VT , and EELV stability independent of nCPAP level.

Dynamic facial expressions of emotions are discriminated at birth.

The ability to discriminate between different facial expressions is fundamental since the first stages of postnatal life. The aim of this study is to investigate whether 2-days-old newborns are capable to discriminate facial expressions of emotions as they naturally take place in everyday interactions, that is in motion. When two dynamic displays depicting a happy and a disgusted facial expression were simultaneously presented (i.e., visual preference paradigm), newborns did not manifest any visual preference (Experiment 1). Nonetheless, after being habituated to a happy or disgusted dynamic emotional expression (i.e., habituation paradigm), newborns successfully discriminated between the two (Experiment 2). These results indicate that at birth newborns are sensitive to dynamic faces expressing emotions.

Effects of surfactant treatment in late preterm infants with respiratory distress syndrome.

OBJECTIVE: To evaluate surfactant effectiveness for the treatment of respiratory distress syndrome (RDS) in late preterm infants. METHODS: We performed a retrospective cohort study of infants born between 34+0 and 36+6 weeks of gestation admitted for respiratory failure in seven perinatal centers from January 2010 to December 2014. We evaluated changes of FiO2, PaO2 and a/APO2 in surfactant-treated patients, and the need and duration of MV, the duration of noninvasive respiratory support, stay in NICU and in hospital in surfactant-treated and untreated late preterm infants with RDS alone. RESULTS: We studied 562 infants with RDS, 252 (45%) were treated with surfactant and 310 (55%) were not. FiO2, PaO2 and a/APO2 significantly improved after surfactant treatment. The adjusted odds ratio for the need of MV and the adjusted differences of duration of noninvasive respiratory support, and of NICU and hospital stay were not different in the surfactant and non-surfactant groups. CONCLUSIONS: Surfactant therapy was followed by a quick and persisting significant improvement of respiratory function in late preterm infants with RDS. Surfactant did not improve short-term outcomes in our population probably because other factors such as the gestational age, occurrence of complications and poor feeding play a relevant role.

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.

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.

Enteral nutrition for preterm infants: by bolus or continuous? An update.

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.

Enteral feeding of intrauterine growth restriction preterm infants: theoretical risks and practical implications.

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.

Nutritional approach to preterm infants on noninvasive ventilation: An update.

Nutrition and pulmonary function in very-low-birth-weight infants (VLBWIs) are strictly related. Preterm infants on noninvasive ventilation may have respiratory instability that can interfere with feeding tolerance. Moreover, feeding may impair pulmonary function. These infants have nutritional requirements different from nonventilated infants. The main challenge of the nutritional support in such patients is to guarantee adequate caloric intake while avoiding episodes of feeding intolerance. The aim of this study was to review the issues and strategies of enteral feeding of preterm infants on noninvasive ventilation.

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.

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: study protocol for a randomized controlled trial.

BACKGROUND: 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. METHODS/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02482766 . Registered on 1 June 2015.

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.