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Background Previous research shows that a lung ultrasound score (LUS) can anticipate CPAP failure in neonatal respiratory distress syndrome. Research Question Can LUS also predict the need for surfactant replacement? Study Design and Methods Multicenter, pragmatic study of preterm neonates who underwent lung ultrasound at birth and those given surfactant by masked physicians, who also were scanned within 24 h from administration. Clinical data and respiratory support variables were recorded. Accuracy of LUS, oxygen saturation to F io 2 ratio, F io 2, and Silverman score for surfactant administration were evaluated using receiver operating characteristic curves. The simultaneous prognostic values of LUS and oxygen saturation to F io 2 ratio for surfactant administration, adjusting for gestational age (GA), were analyzed through a logistic regression model. Results Two hundred forty infants were enrolled. One hundred eight received at least one dose of surfactant. LUS predicted the first surfactant administration with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, 0.81-0.91), cut off of 9, sensitivity of 0.79 (95% CI, 0.70-0.86), specificity of 0.83 (95% CI, 0.76-0.89), positive predictive value of 0.79 (95% CI, 0.71-0.87), negative predictive value of 0.82 (95% CI, 0.75-0.89), positive likelihood ratio of 4.65 (95% CI, 3.14-6.89), and negative likelihood ratio of 0.26 (95% CI, 0.18-0.37). No significant difference was shown among different GA groups: 25 to 27 weeks’ GA (AUC, 0.91; 95% CI, 0.84-0.99), 28 to 30 weeks’ GA (AUC, 0.81; 95% CI, 0.72-0.91), and 31 to 33 weeks’ GA (AUC, 0.88; 95% CI, 0.79-0.95), respectively. LUS declined significantly within 24 h in infants receiving one surfactant dose. When comparing F io 2, oxygen saturation to F io 2 ratio, LUS, and Silverman scores as criteria for surfactant administration, only the latter showed a significantly poorer performance. The combination of oxygen saturation to F io 2 ratio and LUS showed the highest predictive power, with an AUC of 0.93 (95% CI, 0.89-0.97), regardless of the GA interval. Interpretation LUS is a reliable criterion to administer the first surfactant dose regardless of GA. Its association with oxygen saturation to F io 2 ratio significantly improves the prediction power for surfactant need.

Respiratory care of premature neonates has witnessed substantial advances in the last two decades and has played a crucial role in decreasing early mortality in this population. This review outlines advances in techniques of synchronization and modes of synchronized invasive mechanical ventilation in neonates. The use of synchronized ventilation in the neonatal population was delayed as compared to adults, mainly because of technical reasons. Coordinating the infant's respiratory effort and the onset of mechanical ventilation in the neonatal population has requested high sensitivity instruments.

BackgroundNeonatal hypoglycemia is a common disorder especially in at-risk infants and it can be associated with poor long-term neurological outcomes. Several therapeutic interventions are suggested, from the implementation of breastfeeding to the glucose intravenous administration. Oral dextrose gel massaged into the infant’s inner cheek is a recent treatment option of asymptomatic hypoglycemia, after which oral feeding is encouraged. This approach seems to reduce the admission of infants to neonatal intensive care unit (NICU) so favouring maternal bonding and breastfeeding success at discharge.MethodsIn our ward, we prospectively compared a group of near-term neonates, (Gr2,n = 308) at risk for hypoglycemia, treated with an innovative protocol based on the addition of 40% oral dextrose gel (Destrogel, Orsana®,Italy) administered by massaging gums and cheek with historical matching newborns (Gr1,n = 389) treated with a formerly used protocol, as control group. The primary outcome was occurrence of NICU admission and the requirement of intravenous glucose administration; while discharge with full breastfeeding was the secondary outcome.ResultsIn Gr1, 39/389 (10%) infants presented with asymptomatic hypoglycemia, 19/39 were transferred to the NICU, and 14/39 required intravenous glucose treatment. In Gr2, among the 30/308 infants with asymptomatic hypoglycemia managed according to the new protocol, 3/30 were transferred to the NICU and received intravenous glucose infusion. The mean duration of hospitalization respectively was 6.43 (± 6.36) and 3.73 ± 1.53 days (p p = 0.02). Considering Gr1 vs Gr2, the number of patients that were transferred to NICU was 19 (48.7%) vs 3 (10%) (p = 0.001) and the number of infants that needed intravenous glucose infusion was 14 (35.9%) vs 3 (10%) (p = 0.01), respectively.ConclusionsIn our population of near term infants, the introduction of 40% oral dextrose gel to the protocol, helped in the safe management of asymptomatic hypoglycemia and, at the same time, implemented breastfeeding.

Congenital goiter is an uncommon cause of neck swelling and it can be associated with hypothyroidism. We discuss a case of primary hypothyroidism with goiter presenting at birth. Ultrasound showed the enlargement of the gland and thyroid function tests detected marked hypothyroidism. Genetic analysis via next generation sequencing (NGS) was performed finding two mutations associated with thyroid dyshormonogenesis: c.7813 C > T, homozygous in the exon 45 of the thyroglobulin gene (TG) and c.1682 G > A heterozygous in exon 15 of the SLC26A4 gene (pendrin). Sanger sequencing of parents’ DNA samples revealed that the first mutation (c.7813 C > T) was inherited from both of them, while the second one (c.1682 G > A) was inherited from the mother. Hormone replacement therapy was started, following which a gradual decrease in the size of the goiter was seen with the normalization of hormonal levels. Normal infant growth status and neurological development were recorded during follow-up. Neonatal dyshormonogenetic goiter with hypothyroidism may represent an unusual cause of neonatal neck mass. Early identification and hormone replacement therapy are crucial for a better neurodevelopmental outcome. Genetic analysis is mandatory in order to reach a specific diagnosis and to elucidate new patterns of thyroid disorder.

Objective To compare sucrose 24% oral gel formulation to liquid formula and breastfeeding during a heel prick in neonates. Study design In this comparative effectiveness research 195 neonates >36 weeks' gestation were randomised to three groups, receiving during heel stick: (i) breastfeeding, (ii) sucrose 24% liquid with non-nutritive sucking and (iii) sucrose 24% gel with non-nutritive sucking. The pain was assessed through the Neonatal Infant Pain Scale. Results All the methods analysed has shown to be effective in reducing pain. There was an increase in odds of pain following liquid sucrose compared to breastfeeding (OR = 1.60; 95% CI: 0.82-3.3; p = 0.17). A reduction of odds of pain was showed comparing sucrose to breastfeeding (OR = 0.78; 0.38-1.6; 0.48), and comparing sucrose gel to liquid formula (OR = 0.48; 0.23-0.96; p = 0.04). Conclusion Sucrose 24% gel with non-nutritive sucking seems to be a valid alternative when breastfeeding is not possible. Further research is needed.

Background: Cardiac rhabdomyomas (CRs) are the most common cardiac tumors in newborns. Approximately 80–90% of cases are associated with tuberous sclerosis complex (TSC). In selective cases, Everolimus has resulted in a remarkable tumoral regression effect in children with TS. The optimal dosage for neonates is still unknown. Case presentation: We describe the use of Everolimus in a neonate with multiple biventricular CRs, causing subaortic obstruction, in which a low-dose treatment (0.1 mg/die), in an effort to maintain serum trough levels of 3–7 ng/mL, was successfully used off-label, without adverse effects. Conclusions: We showed that a low-dose Everolimus regimen may be an effective and safe treatment for CR regression in TS neonates, when the minimum therapeutic range was maintained.

Background and objectives The Neonatal Assessment Manual scorE (NAME) was developed to assist in the clinical management of infants in the neonatal ward by assessing their body’s compliance and homogeneity. The present study begins its validation process. Methods An expert panel of neonatal intensive care unit (NICU) professionals investigated the NAME face and content validity. Content validity was assessed through the content validity index (CVI). Construct validity was assessed using data collected from 50 newborns hospitalized in the NICU of “Vittore Buzzi” Children Hospital of Milan, Italy. Kendall’s τ and ordinal logistic regressions were used to evaluate the correlation between the NAME scores and infants’ gestational age, birth weight, post-menstrual age, weight at the time of assessment, and a complexity index related to organic complications. Results The CVIs for compliance, homogeneity, and the whole scale were respectively 1, 0.9, and 0.95. Construct validity analysis showed significant positive correlations between the NAME and infants’ weight and age, and a negative correlation between the NAME and the complexity index (τ = − 0.31 [95% IC: − 0.47, − 0.12], p = 0.016 and OR = 0.56 [95% IC: 0.32, 0.94], p = 0.034 for categorical NAME; τ = − 0.32 [95% IC: − 0.48, − 0.14], p = 0.005 for numerical NAME). Conclusions The NAME was well accepted by NICU professionals in this study and it demonstrates good construct validity in discriminating the infant’s general condition. Future studies are needed to test the NAME reliability and predictive capacity.

Background Adverse neurodevelopmental outcomes and MRI alterations are reported in infants born after fetal growth restriction (FGR). This study evaluates the additional role of FGR over prematurity in determining brain impairment. Methods Retrospective observational study comparing 48 FGR and 36 appropriate for gestational age infants born between 26 and 32 weeks' gestation who underwent a cerebral MRI at term equivalent age. Exclusion criteria were twins, congenital anomalies, and findings of overt brain lesions. Main outcomes were total maturation score (TMS) and cerebral areas independently measured by two neuro-radiologists and Griffiths or Bayley scale III scores at median age of 2 years. Results TMS was not significantly different between the groups. Inner calvarium and parenchyma's areas were significantly smaller in FGR cases. There were no significant differences in the average quotient scores. A positive correlation between parenchyma area and cognitive score was found (r = 0.372, p = 0.0078) and confirmed after adjusting for sex, gestational age, and birth weight (p = 0.0014). Among FGR, the subgroup with umbilical arterial Doppler velocimetry alterations had significantly worse gross motor scores (p = 0.005). Conclusions FGR plays additional role over prematurity in determining brain impairment. An early structural dimensional MRI evaluation may identify infants who are at higher risk. Impact Fetal growth-restricted infants showed smaller cerebral parenchymal areas than preterm controls. There is a positive correlation between the parenchyma area and the cognitive score. These results highlight the already known link between structure and function and add importance to the role of a structural dimensional MRI evaluation even in the absence of overt brain lesions.

The ventilatory management of the premature infant with severe respiratory failure needs to follow some essential rules

Objective To characterize respiratory function monitor (RFM) measurements of sustained inflations and intermittent positive pressure ventilation (IPPV) delivered noninvasively to infants in the Sustained Aeration of Infant Lungs (SAIL) trial and to compare vital sign measurements between treatment arms. Study design We analyzed RFM data from SAIL participants at 5 trial sites. We assessed tidal volumes, rates of airway obstruction, and mask leak among infants allocated to sustained inflations and IPPV, and we compared pulse rate and oxygen saturation measurements between treatment groups. Results Among 70 SAIL participants (36 sustained inflations, 34 IPPV) with RFM measurements, 40 (57%) were spontaneously breathing prior to the randomized intervention. The median expiratory tidal volume of sustained inflations administered was 5.3 mL/kg (IQR 1.1-9.2). Significant mask leak occurred in 15% and airway obstruction occurred during 17% of sustained inflations. Among 34 control infants, the median expiratory tidal volume of IPPV inflations was 4.3 mL/kg (IQR 1.3-6.6). Mask leak was present in 3%, and airway obstruction was present in 17% of IPPV inflations. There were no significant differences in pulse rate or oxygen saturation measurements between groups at any point during resuscitation. Conclusion Expiratory tidal volumes of sustained inflations and IPPV inflations administered in the SAIL trial were highly variable in both treatment arms. Vital sign values were similar between groups throughout resuscitation. Sustained inflation as operationalized in the SAIL trial was not superior to IPPV to promote lung aeration after birth in this study subgroup. Trial Registration Clinicaltrials.gov : NCT02139800 .

Food-protein-induced enterocolitis syndrome (FPIES)was notrecognized as a specific disorder until the 1970s(1). While the European Academy of Allergy and Clinical Immunology (EAACI) Guidelines addressed FPIES in 2014(2),it was only in 2017 that the first international consensus guidelines foritsdiagnosis and treatment werepublished (3). Acute FPIES usually presents with repetitive vomiting, diarrhea associated with pallor, lethargy, dehydration, hypotension and even shock in most severe cases.

AIM: To determine whether the use of a respiratory function monitor (RFM) during PPV of extremely preterm infants at birth, compared with no RFM, leads to an increase in percentage of inflations with an expiratory tidal volume (Vte) within a predefined target range. METHODS: Unmasked, randomised clinical trial conducted October 2013 - May 2019 in 7 neonatal intensive care units in 6 countries. Very preterm infants (24-27 weeks of gestation) receiving PPV at birth were randomised to have a RFM screen visible or not. The primary outcome was the median proportion of inflations during manual PPV (face mask or intubated) within the target range (Vte 4-8 mL/kg). There were 42 other prespecified monitor measurements and clinical outcomes. RESULTS: Among 288 infants randomised (median (IQR) gestational age 26+2 (25+3-27+1) weeks), a total number of 51,352 inflations were analysed. The median (IQR) percentage of inflations within the target range in the RFM visible group was 30.0 (18.0-42.2)% vs 30.2 (14.8-43.1)% in the RFM non-visible group (p = 0.721). There were no differences in other respiratory function measurements, oxygen saturation, heart rate or FiO2. There were no differences in clinical outcomes, except for the incidence of intraventricular haemorrhage (all grades) and/or cystic periventricular leukomalacia (visible RFM: 26.7% vs non-visible RFM: 39.0%; RR 0.71 (0.68-0.97); p = 0.028). CONCLUSION: In very preterm infants receiving PPV at birth, the use of a RFM, compared to no RFM as guidance for tidal volume delivery, did not increase the percentage of inflations in a predefined target range. TRIAL REGISTRATION: Dutch Trial Register NTR4104, clinicaltrials.gov NCT03256578.

Despite clinical improvements in neonatal intensive care units (NICUs), prematurity keeps causing several comorbidities. To enhance the management of such conditions, in previous studies we devised the Neonatal Assessment Manual scorE (NAME) model, a structured touch-based assessment that aims to evaluate how newborns respond to gentle touch-based stimuli. The present study aimed to begin assessing the NAME interrater reliability and specific agreements. At the “Vittore Buzzi” Pediatric Hospital NICU ward in Milan, Italy, we enrolled 144 newborns, 85 male and 59 female, with a mean age of 35.9 weeks (±4.1) and a weight of 2,055.3 g (±750.6). Two experienced manual professionals performed the NAME procedure on all the infants. Regarding the total sample and the analysis by sex, we found moderate and statistically significant results for the interrater reliability (p < 0.001) and the specific agreements (p < 0.05), in particular for the “Marginal” score. Furthermore, interrater reliability significantly (p < 0.05) increased as age and weight increased, whereas there was an almost constant moderate and significant (p < 0.05) agreement especially for the “Marginal” score. Therefore, we found preliminary results showing that the NAME could be a reliable diagnostic tool for assessing the newborns' general condition.

Lutein is a dietary carotenoid preferentially accumulated in the eye and the brain in early life and throughout the life span. Lutein accumulation in areas of high metabolism and oxidative stress such as the eye and the brain suggest a unique role of this ingredient during the development and maturation of these organs of common embryological origin. Lutein is naturally provided to the developing baby via the cord blood, breast milk and then infant diet. The presence of this carotenoid depends on fruit and vegetable intakes and its bioavailability is higher in breastmilk. This paper aims to review the anatomical development of the eye and the brain, explore the presence and selective deposition of lutein in these organs during pregnancy and infancy and, based on its functional characteristics, present the latest available research on the beneficial role of lutein in the pediatric population. The potential effects of lutein in ameliorating conditions associated with increase oxidative stress such as in prematurity will be also addressed. Since consumption of lutein rich foods falls short of government guidelines and in most region of the world infant formulas lack this bioactive, dietary recommendations for pregnant and breastfeeding women and their child can help to bridge the gap.

Objective Delivery room (DR) management may play an important role in the development and prevention of lung injury. Therefore, in a cohort of low birth weight infants (LBW), we investigated the effects of two different lung recruitment maneuvers, such as positive pressure ventilation (PPV) and sustained inflation (SI) on adrenomedullin (AM), a well-established lung-specific vasoactive agent. Study Design This is a prospective case-control randomized study in 44 LBW infants spontaneously breathing with respiratory failure at birth requiring respiratory support. LBW were randomized to receive PPV (n = 22) or SI (n = 22) support. AM was measured from blood in samples collected at birth from arterial artery (BLT0) and at 1-hour (BLT1) and at 24-hour (BLT2) from peripheral venous site. AM assessment in urine samples was performed at 1-hour (URT1) and at 24-hour (URT2). Results No significant differences in AM (p > 0.05) blood (T0–T2) and urine (T1, T2) levels were observed between groups. Conclusion The present data, showing the absence of any differences in AM blood and urine levels, suggest that PPV and SI are both feasible and equally effective DR maneuvers. The findings open the way to further studies evaluating the effects of PPV and SI on short-/long-term respiratory outcome through biomarkers assessment.

To compare postnatal magnetic resonance imaging (MRI) with the reference standard computed tomography (CT) in the identification of the key features for diagnosing different types of congenital lung malformation (CLM). Respiratory-triggered T2-weighted single-shot turbo spin echo (ss-TSE), respiratory-triggered T1-weighted turbo field echo (TFE), balanced fast field echo (BFFE), and T2-weighted MultiVane sequences were performed at 1.5 T on 20 patients prospectively enrolled. Two independent radiologists examined the postnatal CT and MRI evaluating the presence of cysts, hyperinflation, solid component, abnormal arteries and/or venous drainage, and bronchocele. Diagnostic performance of MRI was calculated and the agreement between the findings was assessed using the McNemar-Bowker test. Interobserver agreement was measured with the kappa coefficient. CT reported five congenital pulmonary airway malformations (CPAMs), eight segmental bronchial atresias, five bronchopulmonary sequestrations (BPS), one congenital lobar overinflation, one bronchogenic cyst, and three hybrid lesions. MRI reported the correct diagnosis in 19/20 (95%) patients and the malformation was correctly classified in 22/23 cases (96%). MRI correctly identified all the key findings described on the CT except for the abnormal vascularization (85.7% sensitivity, 100% specificity, 100% PPV, 94.1% NPV, 95% accuracy for arterial vessels; 57.1% sensitivity, 100% specificity, 100% PPV, 84.2% NPV, 87% accuracy for venous drainage). MRI can represent an effective alternative to CT in the postnatal assessment of CLM. In order to further narrow the gap with CT, the use of contrast material and improvements in sequence design are needed to obtain detailed information on vascularization, which is essential for surgical planning. • Congenital lung malformations (CLMs) can be effectively studied by MRI avoiding radiation exposure. • Crucial features of CLM have similar appearance when comparing CT with MRI. • MRI performs very well in CLM except for aberrant vessel detection and characterization.

Objective The aim of our study was to determine the outcome of fetuses with isolated mild ventriculomegaly, with prenatal imaging work-up, prenatal consultation, delivery and clinical follow-up performed in a single tertiary referring center. Methods Fetuses with isolated and non-progressive mild ventriculomegaly (10–15 mm) were included in the study. Inclusion criteria were as follows: singleton pregnancies, normal chromosomal analysis, normal serological evaluation of TORCH, fetal ultrasound and MRI excluding additional CNS or extra-CNS malformations. The prenatal consultation consisted in discussing the prognosis of ventriculomegaly, according to the literature. The postnatal follow-up protocol included a neuroradiological investigation (cranial ultrasound or MRI), neurological and pediatric examinations. The Griffiths Scales were used to assess the neurodevelopmental outcome. Results Thirty newborns were included in follow-up. The postnatal neuroradiological investigations confirmed the ventriculomegaly as an isolated finding in all cases except one. Nineteen children were available for formal neurodevelopmental testing. In our case series, 93.3% of the children had a favorable outcome or mild anomalies. Two children (6.6%) with mild ventriculomegaly were diagnosed as having rare genetic conditions. The Griffiths developmental quotients were normal (mean General Quotient 98.3) at the latest assessment (mean age 20.8 months) in all but one case. Discussion Most children in our case series had a favorable outcome, as described in the literature. Even though a large quantity of data is now available on ventriculomegaly, fetal consultation remains challenging and requires caution. The diagnostic work-up of pregnancies diagnosed with mild ventriculomegaly must be very meticulous and include TORCH evaluation, microarray, serial ultrasounds to exclude progression, and a fetal MRI. However, despite accurate screening, there are more complex conditions in which ventriculomegaly can be the only non-specific finding in fetal life, making postnatal follow up mandatory.

Monochorionic twins, resulting from a single fertilized egg giving rise to two separate embryos, are monozygotic and considered genetically identical. However, discordant phenotypes have been reported in monozygotic twins. We analyzed a retrospective cohort of 155 monochorionic pregnancies (312 twins) with major discordant structural anomalies coded by the ICD-10 system in order to describe the spectrum of anomalies, the management of the pregnancies, and the perinatal outcome. Treatment options included conservative management, selective feticide with bipolar cord coagulation, or complete termination. All survivors underwent at least 24 months of postnatal follow-up. Discordancy was complicated by twin-to-twin transfusion syndrome in eight pregnancies (5%) and by selective intrauterine growth restriction in 41 (26%). Major structural anomalies affected one system in 139 cases (90%) and multiple systems in 16 (10%). Median gestational age at diagnosis was 19.1 weeks (IQR 16.4–21.3). The most frequent single-system anomalies involved the nervous and circulatory systems. In total, 72 anomalous twins (46%) and 116 normal co-twins (74%) were delivered at a median gestational age of 34.6 weeks (IQR 31.0–36.3). Neonatal/infant death of the anomalous twin occurred in 22 cases (14%), with an overall survival rate of 32% (50/155). Surviving anomalous twins underwent major surgery in 22/50 cases (44%), four of whom (8%) now suffer from severe neurologic morbidity. This study shows that a wide spectrum of major discordant structural anomalies can be found in monochorionic pregnancies. The outcome for the anomalous twin is poor, while the survival rate for the normal co-twin was 71%, with a favorable overall prognosis.

Approximately 800,000 newborns die annually due to birth asphyxia. The resuscitation of asphyxiated term newly born infants often occurs unexpected and is challenging for healthcare providers as it demands experience and knowledge in neonatal resuscitation. Current neonatal resuscitation guidelines often focus on resuscitation of extremely and/or very preterm infants; however, the recommendations for asphyxiated term newborn infants differ in some aspects to those for preterm infants (i.e., respiratory support, supplemental oxygen, and temperature management). Since the update of the neonatal resuscitation guidelines in 2015, several studies examining various resuscitation approaches to improve the outcome of asphyxiated infants have been published. In this review, we discuss current recommendations and recent findings and provide an overview of delivery room management of asphyxiated term newborn infants.

Background: Neonatal hypoglycemia is a common disorder especially in at-risk infants and it can be associated with poor long-term neurological outcomes. Several therapeutic interventions are suggested, from the implementation of breastfeeding to the glucose intravenous administration. Oral dextrose gel massaged into the infant’s inner cheek is a recent treatment option of asymptomatic hypoglycemia, after which oral feeding is encouraged. This approach seems to reduce the admission of infants to neonatal intensive care unit (NICU) so favouring maternal bonding and breastfeeding success at discharge. Methods: In our unit we recently implemented the protocol for the management of asymptomatic hypoglycemia with the introduction of dextrose oral gel at 40%. Therefore we compared two cohorts of near term at-risk infants with asymptomatic hypoglycemia: a historical group managed with our old protocol and the second one prospectively followed after the introduction of dextrose gel at 40%. Results: Primary outcome was occurrence of NICU admission and glucose intravenous needs; breastfeeding success was the secondary outcome. Infants in the dextrose oral gel group showed statistically lower need of NICU admission and higher prevalence of exclusive breastfeeding at discharge compared with infants of the historical group. Conclusions: In our population the introduction of dextrose oral gel at 40% to the protocol, helped in the safe management of asymptomatic hypoglycemia in near term infants and, at the same time, implemented breastfeeding.

BACKGROUND AND OBJECTIVES: The utility of a lung ultrasound score (LUS) has been described in the early phases of neonatal respiratory distress syndrome (RDS). We investigated lung ultrasound as a tool to monitor respiratory status in preterm neonates throughout the course of RDS. METHODS: Preterm neonates, stratified in 3 gestational age cohorts (25–27, 28–30, and 31–33 weeks), underwent lung ultrasound at weekly intervals from birth. Clinical data, respiratory support variables, and major complications (sepsis, patent ductus arteriosus, pneumothorax, and persistent pulmonary hypertension of the neonate) were also recorded. RESULTS: We enrolled 240 infants in total. The 3 gestational age intervals had significantly different LUS patterns. There was a significant correlation between LUS and the ratio of oxygen saturation to inspired oxygen throughout the admission, increasing with gestational age (b = −0.002 [P < .001] at 25–27 weeks; b = −0.006 [P < .001] at 28–30 weeks; b = −0.012 [P < .001] at 31–33 weeks). Infants with complications had a higher LUS already at birth (12 interquartile range 13–8 vs 8 interquartile range 12–4 control group; P = .001). In infants 25 to 30 weeks’ gestation, the LUS at 7 days of life predicted bronchopulmonary dysplasia with an area under the curve of 0.82 (95% confidence interval 0.71 to 93). CONCLUSIONS: In preterm neonates affected by RDS, the LUS trajectory is gestational age dependent, significantly correlates with the oxygenation status, and predicts bronchopulmonary dysplasia. In this population, LUS is a useful, bedside, noninvasive tool to monitor the respiratory status.

Background In preterm infants, InSurE (Intubation-Surfactant-Extubation) and LISA (less invasive surfactant administration) techniques allow for exogenous surfactant administration while reducing lung injury associated with mechanical ventilation. We compared the acute pulmonary response and lung deposition of surfactant by LISA and InSurE in surfactant-depleted adult rabbits. Methods Twenty-six spontaneously breathing surfactant-depleted adult rabbits (6-7 weeks old) with moderate RDS and managed with nasal continuous positive airway pressure were randomized to 3 groups: (1) 200 mg/kg of surfactant by InSurE; (2) 200 mg/kg of surfactant by LISA; (3) no surfactant treatment (Control). Gas exchange and lung mechanics were monitored for 180 min. After that, surfactant lung deposition and distribution were evaluated monitoring disaturated-phosphatidylcholine (DSPC) and surfactant protein C (SP-C), respectively. Results No signs of recovery were found in the untreated animals. After InSurE, oxygenation improved more rapidly compared to LISA. However, at 180' LISA and InSurE showed comparable outcomes in terms of gas exchange, ventilation parameters, and lung mechanics. Neither DSPC in the alveolar pool nor SP-C signal distributions in a frontal lung section were significantly different between InSurE and LISA groups. Conclusions In an acute setting, LISA demonstrated efficacy and surfactant lung delivery similar to that of InSurE in surfactant-depleted adult rabbits. Impact Although LISA technique is gaining popularity, there are still several questions to address. This is the first study comparing LISA and InSurE in terms of gas exchange, ventilation parameters, and lung mechanics as well as surfactant deposition and distribution. In our animal study, three hours post-treatment, LISA method seems to be as effective as InSurE and showed similar surfactant lung delivery. Our findings provide some clarifications on a fair comparison between LISA and InSurE techniques, particularly in terms of surfactant delivery. They should reassure some of the concerns raised by the clinical community on LISA adoption in neonatal units.

BackgroundThe thermal servo-controlled systems are routinely used in neonatal intensive care units (NICUs) to accurately manage patient temperature, but their role during the immediate postnatal phase has not been previously assessed.ObjectiveTo compare two modalities of thermal management (with and without the use of a servo-controlled system) immediately after birth.Study design and settingMulticentre, unblinded, randomised trial conducted 15 Italian tertiary hospitals.ParticipantsInfants with estimated birth weight +6weeks.InterventionThermal management with or without a thermal servo-controlled system during stabilisation in the delivery room.Primary outcomeProportion of normothermia at NICU admission (axillary temperature 36.5°C–37.5°C).ResultsAt NICU admission, normothermia was achieved in 89/225 neonates (39.6%) with the thermal servo-controlled system and 95/225 neonates (42.2%) without the thermal servo-controlled system (risk ratio 0.94, 95% CI 0.75 to 1.17). Thermal servo-controlled system was associated with increased mild hypothermia (36°C–36.4°C) (risk ratio 1.48, 95% CI 1.09 to 2.01).ConclusionsIn very low birthweight infants, thermal management with the servo-controlled system conferred no advantage in maintaining normothermia at NICU admission, while it was associated with increased mild hypothermia. Thermal management of preterm infants immediately after birth remains a challenge.Trial registration numberNCT03844204

Lung ultrasound imaging is reaching growing interest from the scientific community. On one side, thanks to its harmlessness and high descriptive power, this kind of diagnostic imaging has been largely adopted in sensitive applications, like the diagnosis and follow-up of preterm newborns in neonatal intensive care units. On the other side, state-of-the-art image analysis and pattern recognition approaches have recently proven their ability to fully exploit the rich information contained in these data, making them attractive for the research community. In this work, we present a thorough analysis of recent deep learning networks and training strategies carried out on a vast and challenging multicenter dataset comprising 87 patients with different diseases and gestational ages. These approaches are employed to assess the lung respiratory status from ultrasound images and are evaluated against a reference marker. The conducted analysis sheds some light on this problem by showing the critical points that can mislead the training procedure and proposes some adaptations to the specific data and task. The achieved results sensibly outperform those obtained by a previous work, which is based on textural features, and narrow the gap with the visual score predicted by the human experts., Comment: 7 pages

BACKGROUND Although short binasal prongs (SBP) are the most common interface for noninvasive ventilation, the "double-inspiratory loop cannulas" (DILC) have recently been introduced into many neonatal intensive care units. DILC show advantages over SBP, including reduced nasal trauma and increased comfort. However, their higher intrinsic resistance may compromise ventilation. Our aim was to test a new, low resistance DILC interface. METHODS A test lung was programmed to simulate preterm neonates (500-2000 g BW) with moderate-to-severe respiratory distress syndrome. The artificial nose was designed to keep prongs-to-nares leaks to around 30%. Giulia® ventilator (GINEVRI srl) was used to provide nasal continuous positive airway pressure (NCPAP) and flow synchronized nasal intermittent positive pressure ventilation (NIPPV). NCPAP was set at 4-10 cmH2 O and synchronized-NIPPV (SNIPPV) at peak inspiratory pressure, 15-20-25 cmH2 O; inspiratory time, 0.3-0.5 s; and positive end-expiratory pressure, 5-8 cmH2 O. Four sizes of Sync-flow Cannula® (GINEVRI srl) were tested. The Sync-flow Cannula® was compared with Neotech RAM® cannula and Ginevri SBP®. The outcome measures were the flow/pressure relationship through the four Sync-flow Cannula® sizes, the difference in resistance, the drop in ventilator-alveoli pressure measured by the test lung and the system response time during flow-SNIPPV. RESULTS The smaller DILC sizes had the lowest flow-pressure ratio. The resistance of the RAM® cannula was significantly higher compared to the other interfaces (p

Acute respiratory infections are very common medical emergency in early infancy, often requiring hospitalization. The most frequent respiratory infection at this stage of life is bronchiolitis, with a benign course in the majority of cases. However, especially during neonatal period, infants are at higher risk for developing complications, and ventilatory support of various degrees is needed. The two most widespread methods to provide noninvasive respiratory support are heated humidified high-flow nasal cannula and nasal continuous positive airway pressure. They are both used in neonatal intensive care unit to treat respiratory distress syndrome of the premature infants, and the main concept of recruiting and distending alveoli is valid also for respiratory failure occurring during bronchiolitis. However, there is still ongoing debate about the superiority of one method, and their real efficacy still need to be confirmed. Once respiratory failure does not respond to noninvasive ventilation, more intensive care must be provided in the form of conventional mechanical ventilation or high-frequency ventilation. There is currently no evidence of the optimal ventilation strategy to use, and a deeper comprehension of the pulmonary mechanics during bronchiolitis would be desirable to tailor ventilation according to the degree of severity. Further research is then urgently needed to better clarify these aspects. KEY POINTS: · Guidelines on the management of bronchiolitis in neonatal population are lacking.. · Noninvasive respiratory support is mostly delivered with HHHFNC and nCPAP.. · A deeper comprehension of the pulmonary mechanics during bronchiolitis is crucial to tailor invasive ventilation..

AimsThe aims of this study were to explore parents’ stress levels and negative feelings after premature births and to identify the risk factors related to parents’ stress and negative feelings during their children’s neonatal intensive care unit (NICU) stay.BackgroundPreterm birth is a multi-problematic event that may put the babies in danger for both their medical and neurophysiological conditions and could have a negative impact on both the mother–father relationship and the parent–child interactions.MethodsThe study involved 43 mothers and 38 fathers of preterm infants. All participants filled out the Parental Stressor Scale: Neonatal Intensive Care Unit and the Profile of Mood States.FindingsThe results revealed significant differences between mothers’ and fathers’ responses to preterm births in terms of both stress and negative feelings. We found that, for mothers, their own young age and the baby’s need for respiratory support were significant predictors of stress; for fathers, their own young age and the baby’s lower gestational age and worse condition at birth were significant predictors of stress and negative feelings. The NICU may be a stressful place both for mothers and fathers. Identifying which mothers and fathers are at risk immediately after their children are born could help to direct specific interventions that can reduce these parents’ stress and prevent them from negative feelings.

Despite the technological improvements in monitoring preterm infants in the neonatal intensive care unit, routine care in the neonatal ward is primarily based on manual procedures. Although manual clinical procedures play a critical role in neonatology, little attention has been paid to palpation as a clinical assessment tool. Palpation is a clinical evaluation tool that relies mostly on the senses of touch and proprioception. Based on recent studies investigating the role and clinical effectiveness of touch in full-term and preterm babies, this paper proposes an evaluative touch-based procedure—the Neonatal Assessment Manual Score (NAME) model—that could be useful in the neonatal ward and describes its rationale. The operator applies gentle light pressures to the infant's body. In essence, the touch stimulates low-threshold afferent fibers that could influence the interoceptive cerebral network and the autonomic nervous system, thus altering the blood flow and breathing rhythm. These events could change how bodily fluids distribute among body segments and hence the body volume. The volume modification could be felt manually through haptic perception owing to the high sensitivity of the fingers. On the basis of their clinical conditions and stage of development, infants will respond differently to the applied pressures. Evaluating the infant's response, the operator produces a score of “bad,” “marginal,” or “good” for communicating quickly and clearly the infant's conditions to other professionals. Because the NAME model is intended for every professional who is used to touch-based procedures, if future studies confirmed its validity and reliability in clinical practice, the NAME model could become a part of the neonatal ward routine care for better assessing and managing the infant's conditions, even during emergencies.

Importance Most preterm infants require respiratory support to establish lung aeration after birth. Intermittent positive pressure ventilation and continuous positive airway pressure are standard therapies. An initial sustained inflation (inflation time >5 seconds) is a widely practiced alternative strategy. Objective To conduct a systematic review and meta-analysis of sustained inflation vs intermittent positive pressure ventilation and continuous positive airway pressure for the prevention of hospital mortality and morbidity for preterm infants. Data Sources MEDLINE (through PubMed), Embase, the Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials were searched through June 24, 2019. Study Selection Randomized clinical trials of preterm infants born at less than 37 weeks’ gestation that compared sustained inflation (inflation time >5 seconds) vs standard resuscitation with either intermittent positive pressure ventilation or continuous positive airway pressure were included. Studies including other cointerventions were excluded. Data Extraction and Synthesis Two reviewers assessed the risk of bias of included studies. Meta-analysis of pooled outcome data used a fixed-effects model specific to rarer events. Subgroups were based on gestational age and study design (rescue vs prophylactic sustained inflation). Main Outcomes and Measures Death before hospital discharge. Results Nine studies recruiting 1406 infants met inclusion criteria. Death before hospital discharge occurred in 85 of 736 infants (11.5%) treated with sustained inflation and 62 of 670 infants (9.3%) who received standard therapy for a risk difference of 3.6% (95% CI, −0.7% to 7.9%). Although analysis of the primary outcome identified important heterogeneity based on gestational age subgroups, the 95% CI for the risk difference included 0 for each individual gestational age subgroup. There was no difference in the primary outcome between subgroups based on study design. Sustained inflation was associated with increased risk of death in the first 2 days after birth (risk difference, 3.1%; 95% CI, 0.9%-5.3%). No differences in the risk of other secondary outcomes were identified. The quality-of-evidence assessment was low owing to risk of bias and imprecision. Conclusions and Relevance There was no difference in the risk of the primary outcome of death before hospital discharge, and there was no evidence of efficacy for sustained inflation to prevent secondary outcomes. These findings do not support the routine use of sustained inflation for preterm infants after birth.

Our aim was to assess the efficacy and safety of intravenous (i.v.) paracetamol vs. i.v. ibuprofen for the treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. This is a multicenter randomized controlled study. Infants with a gestational age of 25+0–31+6 weeks were randomized to receive i.v. paracetamol (15 mg/kg/6 h for 3 days) or i.v. ibuprofen (10-5-5 mg/kg/day). The primary outcome was the closure rate of hsPDA after the first treatment course with paracetamol or ibuprofen. Secondary outcomes included the constriction rate of hsPDA, the re-opening rate, and the need for surgical closure. Fifty-two and 49 infants received paracetamol or ibuprofen, respectively. Paracetamol was less effective in closing hsPDA than ibuprofen (52 vs. 78%; P = 0.026), but the constriction rate of the ductus was similar (81 vs. 90%; P = 0.202), as confirmed by logistic regression analysis. The re-opening rate, the need for surgical closure, and the occurrence of adverse effects were also similar.Conclusions: Intravenous paracetamol was less effective in closing hsPDA than ibuprofen, but due to a similar constriction effect, its use was associated with the same hsPDA outcome. These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA.Trial registration:Clinicaltrials.gov: NCT02422966, Date of registration: 04/09/2015; EudraCT no: 2013-003883-30. What is Known:• The successful closure of patent ductus arteriosus with oral paracetamol has been recently reported in several preterm infants, but only one randomized controlled study investigated the efficacy of intravenous paracetamol. What is New:• Intravenous paracetamol is less effective in closing hsPDA than ibuprofen, but have a similar constriction effect.• These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA.

Objective To compare short-term application of nasal high-frequency oscillatory ventilation (nHFOV) with nasal continuous positive airway pressure (nCPAP). Working hypothesis nHFOV improves CO2 removal with respect to nCPAP in preterm infants needing noninvasive respiratory support and persistent oxygen supply after the first 72 h of life. Study design Multicenter non-blinded prospective randomized crossover study. Patient selection Thirty premature infants from eight tertiary neonatal intensive care units, of mean ± SD 26.4 ± 1.8 weeks of gestational age and 921 ± 177 g of birth weight. Methodology Infants were randomly allocated in a 1:1 ratio to receive a starting treatment mode of either nCPAP or nHFOV delivered by the ventilator CNO (Medin, Germany), using short binasal prongs of appropriate size. A crossover design with four 1-h treatment periods was used, such that each infant received both treatments twice. The primary outcome was the mean transcutaneous partial pressure of CO2 (TcCO2 ) value during the 2-h cumulative period of nHFOV compared with the 2-h cumulative period of nCPAP. Results Significantly lower TcCO2 values were observed during nHFOV compared with nCPAP: 47.5 ± 7.6 versus 49.9 ± 7.2 mmHg, respectively, P = 0.0007. A different TcCO2 behavior was found according to the random sequence: in patients starting on nCPAP, TcCO2 significantly decreased from 50.0 ± 8.0 to 46.6 ± 7.5 mmHg during nHFOV (P = 0.001). In patients starting on nHFOV, TcCO2 slightly increased from 48.5 ± 7.8 to 49.9 ± 6.7 mmHg during nCPAP (P = 0.13). Conclusions nHFOV delivered through nasal prongs is more effective than nCPAP in improving the elimination of CO2 .

Osteopathic manipulative treatment (OMT) has been successfully tested in the context of preterm infants. No studies, however, have been conducted to investigate the OMT immediate effects on physiological measurements, such as partial oxygen saturation (SpO2) and heart rate (HR). The purpose of the present study was to assess the effect of osteopathic treatment on SpO2 and HR values and to compare it with 10 min of static touch.Ninety-six preterm infants (41 male), aged 33.5 weeks (±4.3) with mean weight at birth of 2067gr (±929) were recruited from the neonatal intensive care unit (NICU) of the Buzzi Hospital in Milan, and randomly allocated to two groups: OMT and Static Touch. Each protocol session consisted of: a) 5-min Pre-touch baseline recording, b) 10-min touch procedure, c) 5-min post-touch recording. Primary and secondary outcomes were, respectively, the baseline changes of HR and SpO2.The 2 × 2 repeated measure ANOVA for HR showed a statistically significant effect (F (1,94) = 5.34; p 0.02), revealing that the OMT group decreases the HR value at T2 (p = 0.006). In contrast, SpO2 analysis showed an increase of SpO2 value where the OMT group demonstrated higher values at T2 (p = 0.04).Results from the present study suggest that a single osteopathic intervention may induce beneficial effects on preterm physiological parameters.ClinicalTrials.gov identifier: NCT03833635 - Date: February 7, 2019.

To evaluate surfactant effectiveness for the treatment of respiratory distress syndrome (RDS) in late preterm infants.We performed a retrospective cohort study of infants born between 34We studied 562 infants with RDS, 252 (45%) were treated with surfactant and 310 (55%) were not. FiOSurfactant 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.

Background: A sustained inflation (SI) at birth in preterm babies may be ineffective unless the infants breathe. Gain in lung volume is associated with breathing during delivery room non-invasive management. Objective: To describe the breathing patterns of preterm infants during an SI and correlate to a calculated gain in lung volume. Methods: Retrospective observational study. Data collected from a respiratory function monitor during SI (25 cmH2O for 15 s then PEEP at 5 cmH2O) through a face mask in preterm infants (gestational age [GA] ≤31 weeks). Spontaneous breaths, inspiratory time (TI), inspiratory/expiratory tidal volume (Vti/Vte), and gain in lung volume were determined. Results: 30 SIs in 20 infants (mean GA 27 weeks; birth weight 825 g) were analysed and stratified in 2 groups according to spontaneous breathing: SIs without spontaneous breaths (apnoea: n = 11) and SIs with spontaneous breaths (breathing: n = 19). Mean GA was lower in the apnoea group versus the breathing group (25 vs. 27+5 weeks; p = 0.01). Mean birth weight was lower in the apnoea group versus the breathing group (683 vs. 860 g; p = ns). In the breathing group, the mean number of spontaneous breaths was 4 with a mean TI of 0.52 min, the mean Vti/kg was 5.9 mL/kg, and the mean Vte was 2.7 mL/kg. The calculated mean gain in lung volume was 7.5 mL/kg in the apnoea group and 17.8 mL/kg in the breathing group (p = 0.039). Conclusions: Actively breathing infants during an SI at birth showed a gain in lung volume higher than apnoeic infants. Spontaneous breathing during SI seems to be related to GA.

Newborns affected by congenital diaphragmatic hernia (CDH) need cardio-respiratory stabilization before undergoing surgical repair. Open lung strategy is a well-established approach to optimize lung volume in preterm infants with Respiratory Distress Syndrome (RDS), using both High Frequency Oscillatory Ventilation (HFOV) and Conventional Mechanical Ventilation (CMV). We report a case of left CDH with severe lung hypoplasia, managed applying open lung strategy in HFOV (pre-surgery period) and in Assist-Control with Volume Guarantee (post-surgery period), guided by SpO2 changes, TcPO2 and TcPCO2 monitoring. Opto-electronic plethysmography was used to measure end-expiratory chest wall volume changes (ΔEEcw) related to lung volume variations occurring during pressure changes. OEP confirmed the efficacy of using SpO2 and transcutaneous gas monitoring during this recruitment maneuver.

Background: Infants born at 23–24 weeks' gestation have the highest risk of developing a hemodynamically significant patent ductus arteriosus (hsPDA), that is refractory to pharmacological closure requiring surgical ligation. Thus, these patients might have the greatest benefits from hsPDA closure, although previous studies on PDA closure were not focused on this population. Aim: To compare the occurrence of hsPDA, failure rate of the first course of ibuprofen in closing hsPDA, and need of surgical closure in infants born at 23+0–24+6 weeks' gestation to those in infants born at 25+0–28+6 weeks' gestation. Study design: This is a retrospective multicenter study including infants born at 23+0–28+6 weeks of gestation admitted to the neonatal care units from January 2013 to December 2017. All infants underwent echocardiographical assessment for hsPDA diagnosis and eventually pharmacological treatment, and surgical closure. Results: We studied a total of 842 infants of which 562 (67%) developed a PDA. Among those with PDA, 511 (91%) received a pharmacological treatment for a hsPDA. We found that a hsPDA occurred in 70% (106/151) of infants born at 23–24 weeks and in 59% (405/691) of infants born at 25–28 weeks of gestation (P < 0.001). Failure of closure with the first-treatment cycle (69 vs. 40%; P < 0.001) and need of surgical closure (19 vs 10%) were more frequent (P < 0.011) in infants born at 23–24 than 25–28 gestational weeks. Paracetamol vs. ibuprofen treatment and gestational age of 23–24 versus 25–28 weeks increased closure failure, while less severe RDS and maternal clinical chorioamnionitis decreased it. Conclusions: Among extremely preterm infants, infants born at 23–24 weeks of gestation have the highest risk of developing a hsPDA refractory to pharmacological treatment requiring surgical closure. Our findings support the need of individualized more careful strategies for hsPDA management in this special population.

This study evaluated the effect of a partly fermented infant formula (using the bacterial strains Bifidobacterium breve C50 and Streptococcus thermophilus 065) with a specific prebiotic mixture (short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS, 9:1)) on the incidence of gastrointestinal symptoms, stool characteristics, sleeping and crying behaviour, growth adequacy and safety. Two-hundred infants &le, 28 days of age were assigned either to experimental infant formula containing 30% fermented formula and 0.8 g/100 mL scGOS/lcFOS or to non-fermented control infant formula without scGOS/lcFOS. A group of breastfed infants served as a reference. No relevant differences in parent-reported gastrointestinal symptoms were observed. Stool consistency was softer in the experimental versus control group with values closer to the breastfed reference group. Daily weight gain was equivalent for both formula groups (0.5 SD margins) with growth outcomes close to breastfed infants. No clinically relevant differences in adverse events were observed, apart from a lower investigator-reported prevalence of infantile colic in the experimental versus control group (1.1% vs. 8.7%, p &lt, 0.02). Both study formulae are well-tolerated, support an adequate infant growth and are safe for use in healthy term infants. Compared to the control formula, the partly fermented formula with prebiotics induces stool consistencies closer to breastfed infants.

Background The delayed transition from gavage-to-nipple feeding is one of the most significant factors that may prolong hospital length of stay (LOS). Osteopathic manipulative treatment (OMT) has been demonstrated to be effective regarding LOS reduction, but no investigations have documented its clinical validity for attaining oral feeding. Objectives To assess OMT utility regarding the timing of oral feeding in healthy preterm infants. Design Preliminary propensity score-matched retrospective cohort study. Setting Data were extrapolated from the neonatal intensive care unit (NICU) of Del Ponte Hospital in Varese, Italy, during the period between March 2012 and December 2013. Interventions Two propensity score-matched groups of healthy preterm infants aged 28+0 to 33+6 were compared, observing those supported with OMT until hospital discharge and control subjects. Main outcome measures Days from birth to the attainment of oral feeding was the primary endpoint. Body weight, body length, head circumference and LOS were considered as secondary endpoints. Results Seventy premature infants were included in the study as the control group (n = 35; body weight (BW) = 1457.9 ± 316.2 g; gestational age (GA) = 31.5 ± 1.73 wk) and the osteopathic group (n = 35; BW = 1509.6 ± 250.8 g; GA = 31.8 ± 1.64 wk). The two groups had analogous characteristics at study entry. In this cohort, we observed a significant reduction in TOF (-5.00 days; p = 0.042) in the osteopathic group with a greater effect in very low birth weight infants. Conclusions These data demonstrate the utility and potential efficacy of OMT for the attainment of oral feeding. Further adequately powered clinical trials are recommended.

BACKGROUND Neonatal conjunctivitis is frequent and could benefit from daily cleansing with saline. Anyway super infections can occur and therefore antibiotics are frequently needed. Recently alternative therapies (e.g. Echinacea angustifolia) are used for neonatal conjunctivitis to try to reduce antibiotics therapy. The aim of the study was to verify if the use of gauze containing Echinacea angustifolia compared to standard sodium-chloride at the onset of conjunctivitis symptoms is effective in reducing the clinical symptoms and the risk for superinfections. METHODS The study was randomized and controlled. Neonates admitted in a tertiary level Neonatal Intensive Care Unit (NICU), with clinical signs of conjunctivitis during hospital stay, were randomized in two groups: group A (3 times daily ocular cleansing for 48 h with sterile gauze; group B (3 times daily ocular cleansing for 48 h with Iridium® baby gauze (Neoox) containing Echinacea angustifolia and pineapple sativus). An eye swab for cultural analysis was taken at time of presentation (T0) prior to treatment and at the end of ocular cleansing (T1). RESULTS Sixty-three neonates were enrolled (GrA=30 and GrB=33). At T0, eye specimen positivity was found in 16/30 (48%) in group A and in 18/33 (55%) in group B (P=0.9). No statistical differences among groups at T0 regarding culture positivity. After 48 h, babies in Gr A have significantly fewer positive swabs compared to group B (group A: 18/29, group B: 10/32; P=0.009). Neonates in group B who had negative swab at T0 had a significantly reduced risk to have positive culture at T1 (OR 0.28, CI: 0.10-0,80, P=0.01), also considering confounding factors (birth weight, gestational age, mode of delivery) (adjusted OR 0.15, CI: 0.03-0.52, P

Background: Transition immediately after birth is a complex physiological process. The neonate has to establish sufficient ventilation to ensure significant changes from intra-uterine to extra-uterine circulation. If hypoxia or bradycardia or both occur, as commonly happens during immediate transition in preterm neonates, cerebral hypoxia-ischemia may cause perinatal brain injury. The primary objective of the COSGOD phase III trial is to investigate whether it is possible to increase survival without cerebral injury in preterm neonates of less than 32 weeks of gestation by targeting cerebral tissue oxygen saturation (crSO 2 ) using specified clinical treatment guidelines during the immediate transition period after birth (the first 15 min) in addition to the routine monitoring of arterial oxygen saturation (SpO 2 ) and heart rate (HR). Methods/Design: COSGOD III is an investigator-initiated, randomized, multi-center, multi-national, phase III clinical trial. Inclusion criteria are neonates of less than 32 weeks of gestation, decision to provide full life support, and parental informed consent. Exclusion criteria are severe congenital malformations of brain, heart, lung, or prenatal cerebral injury or a combination of these. The premature infants will be randomly assigned to study or control groups. Both groups will have a near-infrared spectroscopy (NIRS) device (left frontal), pulse oximeter (right palm/wrist), and electrocardiogram placed immediately after birth. In the study group, the crSO 2 , SpO 2 , and HR readings are visible, and the infant will receive treatment in accordance with defined treatment guidelines. In the control group, only SpO 2 and HR will be visible, and the infant will receive routine treatment. The intervention period will last for the first 15 min after birth during the immediate transition period and resuscitation. Thereafter, each neonate will be followed up for primary outcome to term date or discharge. The primary outcome is mortality or cerebral injury (or both) defined as any intra-ventricular bleeding or cystic periventricular leukomalacia (or both). Secondary outcomes are neonatal morbidities. Discussion: crSO 2 monitoring during immediate transition has been proven to be feasible and improve cerebral oxygenation during immediate transition. The additional monitoring of crSO 2 with dedicated interventions may improve outcome of preterm neonates as evidenced by increased survival without cerebral injury.

AIM This study compared how non-invasive respiratory support (NRS) was provided in neonatal units in Italy and the UK. METHODS An NRS questionnaire was sent to tertiary neonatal centres, identified by national societies, from November 2015 to May 2016. RESULTS Responses were received from 49/57 (86%) UK units and 103/115 (90%) Italian units. NRS was started in the delivery room by 61% of UK units and 85% of Italian units. In neonatal intensive care units, 33% of UK units used nasal high-flow therapy (HFT) as primary support, compared to 3% in Italy. Nasal continuous positive airway pressure (CPAP) was used in 57% of UK units and 90% of Italian units. The commonest starting flow rate on nasal HFT for term and preterm infants was 6 L/min in the UK, while Italian units mainly used this flow for term infants. In the UK, 67% of units decreased nasal HFT by 1 L/min per day. In Italy, infants on nasal CPAP were weaned by 1 cm H2 O per day in 39% of units. CONCLUSION The way that NRS was managed for very preterm infants differed between the UK and Italy, reflecting a lack of evidence on optimal NRS and the use of local protocols.

Background: Few studies evaluated the efficacy of pharmacological therapy for gastro-esophageal reflux disease (GERD) in newborns, whose safety has been questioned. Esophageal basal impedance (BI) is a marker of mucosal integrity, and treatment with proton pump inhibitors significantly increases BI in infants; however, no correlation with clinical improvement was reported. Aims: To evaluate the relationship between BI and other esophageal pH-impedance parameters and clinical response to therapy in newborns with GERD. Study design: Multicenter retrospective study. Subjects: Infants who received omeprazole or ranitidine for GERD. Outcome measures: Complete response to therapy was defined as symptom decrease by ≥50% compared to baseline, partial response as symptom decrease

Application of nasal continuous positive airway pressure (nCPAP) in the delivery room is a valid alternative to mechanical ventilation in the management of respiratory failure of preterm infants, with reduced occurrence of bronchopulmonary dysplasia and death. nCPAP at birth is still burdened by a high failure rate. Sustained inflation appears to be an intriguing approach to allow the respiratory transition at birth by clearing the lung fluid, thus obtaining an adequate functional residual capacity. This may enhance nCPAP success. Sustained inflation reduces the need for mechanical ventilation in the first 72 h of life, with no changes in the incidence of bronchopulmonary dysplasia and death. The efficacy of sustained inflation seems to be related to the presence of open glottis with active breathing of the infant. Further studies are needed to recommend the application of sustained inflation during delivery room management of preterm infants at risk of respiratory distress or with clinical signs of respiratory failure.

IMPORTANCE: Treatment options for a symptomatic pneumothorax in newborns include needle aspiration (NA) and chest drain (CD) insertion. There is little consensus as to the preferred treatment, reflecting a lack of evidence from clinical trials. OBJECTIVE: To investigate whether treating pneumothoraces diagnosed on chest radiography (CR) in newborns receiving respiratory support with NA results in fewer infants having CDs inserted within 6 hours of diagnosis. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted from October 7, 2013, to December 21, 2016. The setting was 5 tertiary European neonatal intensive care units. Infants receiving respiratory support (endotracheal ventilation, continuous positive airway pressure, or supplemental oxygen >40%) who had a pneumothorax on CR that clinicians deemed needed treatment were eligible for inclusion. INTERVENTIONS: Infants were randomly assigned (1:1) to drainage using NA or CD insertion, stratified by center and gestation at birth (

In the 1990s, the most relevant pillars in the treatment of neonatal respiratory distress syndrome (RDS) have been improvements in ventilation strategies, the introduction of exogenous surfactant replacement therapy, and the use of antenatal steroids. Lately, in addition to the standard INSURE (INtubation–SURfactant administration–Extubation) method to administer surfactant, a new technique has been gaining increasing popularity. It is the so-called less invasive surfactant administration (LISA) method, which has shown promising results in preventing bronchopulmonary dysplasia development and in reducing mortality in preterm neonates. The rationale behind this technique is to avoid positive pressure ventilation and the endotracheal tube, being surfactant delivered through a thin catheter while the neonate is maintained on continuous positive airway pressure. Given the paucity of large-scale randomized trials on LISA method to prove its effects on short- and long-term outcomes, some questions still remain unanswered. Then, uncertainty regarding the feasibility of this maneuver needs to be better clarified before gaining wide acceptance in routine clinical practice. In our report, we aim at hypothesizing the main mechanisms behind the efficacy of LISA, considering it as a single maneuver in a comprehensive approach for RDS management in the delivery room.

Background: Non-invasive ventilation (NIV) significantly changed the management of respiratory distress syndrome (RDS) in preterm infants. Further perspectives for neonatologists regard the assessment of different NIV strategies in terms of availability, effectiveness, and failure.Objective: The aim of the present study is to evaluate the effectiveness of three different NIV strategies: nasal continuous positive airway pressure (N-CPAP), nasal synchronized intermittent positive pressure ventilation (N-SIPPV), and nasal bilevel-CPAP (BiPAP), as first intention treatment for RDS in very low birth-weight infants (VLBW).Methods: A multicenter retrospective study was conducted in three neonatal intensive care unit (NICUs) that enrolled 191 VLBW infants complicated by RDS, who received, as first intention treatment for RDS, three different NIV approaches (N-CPAP: n=66; N-SIPPV: n=62, BiPAP: n=63). We evaluated the performance of different NIV strategies by primary (failure within the first 5 d of life) and some selected secondary end-points.Results: The incidence of NIV failure was significantly higher in the N-CPAP group (22/66) versus N-SIPPV/BiPAP groups (11/62; 11/63) (p

The development of a proper neonatal microbiota is of great importance, especially for the effects that dysbiosis has in acute and chronic diseases’ onset. The microbiota, particularly the intestinal one, plays a crucial role in maintaining the health of the host, preventing colonization by pathogenic bacteria and significantly influencing the development and maturation of a normal gastrointestinal mucosal immunity. Several factors may interfere with the physiological development of microbiota, such as diseases during pregnancy, type of delivery, maternal nutrition, type of neonatal feeding, use of antibiotics, exposition to hospital environment (e.g., neonatal intensive care unit) and genetic factors. Thanks to a proper maternal and neonatal supplementation with specific functional nutrients, it is now possible to correct dysbiosis, thus reducing the risks for the newborn’s health. In this review of the literature, we give an overview of the studies highlighting the composition of the maternal, fetal and neonatal microbiota, the factors potentially responsible for dysbiosis and the use of functional nutrients to prevent diseases’ onset.