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Sepsis is a major concern in neonatology, but there are no reliable biomarkers for its early diagnosis. The aim of the study was to compare the metabolic profiles of plasma and urine samples collected at birth from preterm neonates with and without earlyonset sepsis (EOS) to identify metabolic perturbations that might orient the search for new early biomarkers. All preterm newborns admitted to the neonatal intensive care unit were eligible for this proof-of-concept, prospective case-control study. Infants were enrolled as “cases” if they developed EOS, and as “controls”if they did not. Plasma samples collected at birth and urine samples collected within 24 h of birth underwent untargeted and targeted metabolomic analysis using mass spectrometry coupled with ultra-performance liquid chromatography. Univariate and multivariate statistical analyses were applied. Of 123 eligible newborns, 15 developed EOS. These 15 newborns matched controls for gestational age and weight. Metabolomic analysis revealed evident clustering of the cases versus controls, with the glutathione and tryptophan metabolic pathways markedly disrupted in the former. In conclusion, neonates with EOS had a metabolic profile at birth that clearly distinguished them from those without sepsis, and metabolites of glutathione and tryptophan pathways are promising as new biomarkers of neonatal sepsis.

Background Among infants needing urgent transfer after birth, very preterm infants are a high-risk sub-group requiring special attention. This study aimed to assess trends in early respiratory management in a large series of very preterm infants undergoing postnatal transfer. Methods Trends in patient characteristics and early respiratory management were assessed in 798 very preterm infants who were transferred by the Eastern Veneto Neonatal Emergency Transport Service in 2000-2019. Trends were analyzed using joinpoint regression analysis and summarized as annual percentage changes (APCs). Results Proportion of neonates with birth weight less than 1 kg decreased from 33% to 16% (APC -3.82%). Use of nasal-continuous-positive-airway pressure increased (at call: APC 15.39%; during transfer: APC 15.60%), while use of self-inflating bag (at call: APC -12.09%), oxygen therapy (at call: APC -13.00%; during transfer: APC -23.77%) and mechanical ventilation (at call: APC -2.71%; during transfer: APC -2.99%) decreased. Use of oxygen concentrations at 21% increased (at call: APC 6.26%; during transfer: APC 7.14%), while oxygen concentrations above 40% decreased (at call: APC -5.73%; at transfer APC -8.89%). Surfactant administration at call increased (APC 3%-10%), while surfactant administration when arriving at referring hospital remained around 7-11% (APC 2.55%). Conclusion Relevant trends toward "gentle" approaches in early respiratory management of very preterm infants undergoing postnatal transfer occurred during the last twenty years. In addition, the proportion of transferred extremely low birth weight infants halved. Clinicians and stakeholders should consider such information when allocating assets to both hospitals and transfer services and planning regional perinatal programs.

Since February 21, 2020, SARS-CoV-2 has spread exponentially worldwide. Neonatal patients needing intensive care are considered a vulnerable population. To report the results of a policy based on multi-timepoint surveillance for SARS-CoV-2 of all neonates admitted to the neonatal intensive care unit (NICU), their parents, and all healthcare providers in a part of Italy with a high prevalence of the infection. Observational study conducted from 21 February to 21 April 2020. Intervention consisted of (a) parental triage on arrival at the neonatal ward; (b) universal testing with nasopharyngeal swabs and blood testing for SARS-CoV-2 IgM and IgG antibodies; (c) use of continuous personal protective equipment at the NICU by parents and staff. A total of 6726 triage procedures were performed on 114 parents, and 954 nasopharyngeal swabs were collected from 226 individuals. Five (2.2%) asymptomatic individuals (2 parents and 3 healthcare providers) tested positive on nasopharyngeal swabs and were kept isolated for 14 days. Of 75 admitted newborn, no one tested positive on nasopharyngeal swabs or antibody tests. Three parents presented with fever or flu-like symptoms at triage; they tested negative on swabs.Conclusion: With universal screening of neonates, parents, and staff, there were no cases of SARS-CoV-2 infection among the neonates admitted to a NICU in an area with a high incidence of SARS-CoV-2. Our experience could be usefully compared with other strategies with a view to developing future evidence-based guidelines for managing high-risk neonates in case of new epidemics. What is Known: • The novel coronavirus named SARS-CoV-2 has since spread worldwide at a remarkable rate, with more than 2.5 million confirmed cases. • Pediatric population may be less affected from COVID-19 than adult population but infants and newborn babies seem to be more vulnerable to SARS-CoV-2 infection. What is New: • Using an approach based on triage; testing with nasopharyngeal swabs and serology; and use of personal protective equipment, there were no cases of SARS-CoV-2 infection among neonates in a NICU in a high incidence of SARS-CoV-2 area. • Positive and asymptomatic individuals were identified and isolated early allowing the containment of infection's spread among healthcare providers and parents.

Antimicrobial prescriptions in neonatal intensive care units (NICUs) represent a point of concern for the emergence of MDROs and for morbidity associated with prolonged antibiotic exposure (e.g., invasive candidiasis, necrotizing enterocolitis, and late-onset sepsis). Antimicrobial stewardship programs (ASPs) have shown to be a valuable tool for the prevention of resistance with the goals of optimizing clinical outcomes while decreasing unnecessary prescribing. The most frequent ASP strategies include the correct collection and interpretation of microbiological specimens, prescription of the narrowest-spectrum antibiotic appropriate for a particular case, and de-escalation or discontinuation of therapy in defined situations. A robust ASP requires everyday multidisciplinary collaboration between ID physicians, neonatologist, clinical pharmacists, clinical microbiologists, infection control professionals, hospital epidemiologists, and information services specialists. Education and clinical pathways (e.g., sepsis or surgical prophylaxis pathways) are an excellent starting point if followed by proactive interventions such as prospective audits and feedback and formulary restriction with prior antimicrobial authorization. The current review outlines the problems faced in NICU antimicrobial prescribing and presents various solutions from the literature.

Recognizing intrauterine growth restriction (IUGR) is a matter of great concern because this condition can significantly affect the newborn’s short- and long-term health. Ever since the first suggestion of the “thrifty phenotype hypothesis” in the last decade of the 20th century, a number of studies have confirmed the association between low birth weight and cardiometabolic syndrome later in life. During intrauterine life, the growth-restricted fetus makes a number of hemodynamic, metabolic, and hormonal adjustments to cope with the adverse uterine environment, and these changes may become permanent and irreversible. Despite advances in our knowledge of IUGR newborns, biomarkers capable of identifying this condition early on, and stratifying its severity both pre- and postnatally, are still lacking. We are also still unsure about these babies’ trajectory of postnatal growth and their specific nutritional requirements with a view to preventing, or at least limiting, long-term complications. In this setting, untargeted metabolomics—a relatively new field of ‘-omics’ research—can be a good way to investigate the metabolic perturbations typically associated with IUGR. The aim of this narrative review is to provide a general overview of the pathophysiological and clinical aspects of IUGR, focusing on evidence emerging from metabolomic studies. Though still only preliminary, the reports emerging so far suggest an “early” pattern of glucose intolerance, insulin resistance, catabolite accumulation, and altered amino acid metabolism in IUGR neonates. Further, larger studies are needed to confirm these results and judge their applicability to clinical practice.

Objective Premature infants have the highest risk of being hospitalized with respiratory syncytial virus (RSV) infections. Palivizumab is the only licensed agent for RSVhospitalization (RSVH) prophylaxis in infants born at 29 wGA. The aim of the present study was to compare the incidence of RSVH in two consecutive epidemic seasons (2015–2016 vs. 2016–2017), that is, before and after the new AIFA recommendations on palivizumab eligibility. Study Design This was a noninterventional retrospective cohort study conducted at three neonatal intensive care units (NICUs) in northern Italy. Infants born at 29 and 35 wGA between March 15, 2015 and March 14, 2017 were enrolled for this study. Electronic medical charts were reviewed and parents were interviewed by telephone. Data were collected on neonatal course during NICU stay, palivizumab administration, and hospitalizations related to respiratory infections during the 1st year of life, comparing the infants born in season 1 with season 2. Results Of 632 eligible infants, data were available for 536 (262 in season 1 and 274 in season 2). Overall, RSVH occurred 1.9 and 5.1% in infants in seasons 1 and 2, respectively (odds ratio [OR] = 2.77; 95% confidence interval [CI]: 0.98–7.8, p = 0.045). When the analysis was limited to patients not exposed to palivizumab, RSVHs were recorded for 1.8 and 5.9% infants in seasons 1 and 2, respectively (OR = 3.42; 95% CI: 0.96–12.20, p = 0.045). It is noteworthy that the incidence of hospital admissions for respiratory viruses other than RSV did not differ between the two seasons. Conclusion Restricting eligibility for palivizumab reimbursement led to a significant increase in RSVH but had no impact on hospitalizations for other respiratory viruses. Future decisions on palivizumab prescription and coverage rules should be driven by a careful assessment of the cost-benefit ratio.

Heated, humidified high-flow delivered by nasal cannulae (HHHFNC) is increasingly used for noninvasive respiratory support in preterm infants and critically ill children due to its perceived effectiveness and ease of use. Evidence from randomized controlled trials suggests that HHHFNC and continuous positive airway pressure (CPAP) are equally effective as postextubation support in preterm infants. HHHFNC is also used for weaning preterm infants from CPAP. Data on HHHFNC used as the primary support for treating respiratory distress syndrome are conflicting. HHHFNC use in preterm infants is associated with reduced nasal trauma. Inability to measure the pressure generated by HHHFNC systems is a concern because overexpansion can lead to an air leak and lung injury. Great caution is warranted when HHHFNC is used in extremely low-birth-weight infants (who were rarely included in these randomized controlled trials) because a recent retrospective study found its use is associated with a higher likelihood of bronchopulmonary dysplasia or death in this population. HHHFNC has also become popular in pediatric intensive care units and pediatric wards as a method for delivering oxygen and noninvasive respiratory support. Most published studies were conducted on infants and young children with bronchiolitis. The results of a few observational studies and two randomized trials suggest that HHHFNC therapy is effective in the treatment of bronchiolitis. This review discusses the proposed mechanisms of action behind HHHFNC, the results of observational studies, and the evidence emerging from clinical trials on the use of HHHFNC in preterm infants and children critically ill with bronchiolitis.

Despite notable advances in the survival and management of preterm infants in recent decades, chronic lung disease remains a common complication. Approximately one in three infants born preterm (< 32 weeks of gestation) are hospitalized with respiratory problems (mainly due to infections) in their first 2 years of life, and the risk of childhood wheezing is three times higher in this population. By comparison with infants born at term, there seems to be a higher incidence of respiratory morbidity in those born preterm, even in the absence of bronchopulmonary dysplasia (BPD) and in late-preterm babies. Although long-term follow-up data are still not collected systematically, there is evidence of preterm infants' respiratory symptoms, lung function impairments, and radiological abnormalities, tending to persist throughout childhood and into early adulthood. Respiratory conditions associated with preterm birth are often diagnosed and treated as asthma, but the pathophysiological patterns of BPD and asthma are very different. Future research should focus on characterizing preterm infants' pathological pulmonary features by gestational age at birth, and presence or absence of BPD. Improving our current knowledge of the respiratory disorder associated with prematurity might hopefully prompt targeted follow-up protocols, and novel prevention strategies and treatment approaches.

An ex-preterm, exclusively breastfed baby with poor postnatal growth was evaluated at 5 months of age for perianal erosive dermatitis (figure 1) and foul stools. No other cutaneous involvement was present. Investigations showed mild zinc deficiency (65 μg/dL, range 68–107). Unfortunately, no maternal blood or breast milk zinc levels were available. The dermatitis rapidly improved in six days (figure 2) on oral supplementation with zinc sulfate (2 mg/kg/day), and remained stable on zinc-enriched formula milk, without …

International Guidelines provide a standardised approach to newborn resuscitation in the DR and, in their most recent versions, recommendations dedicated to management of ELBWI were progressively increased. It is expected that introduction in clinical practice and dissemination of the most recent evidence should be more consistent in academic than in non-academic hospitals. The aim of the study was to compare adherence to the International Guidelines and consistency of practice in delivery room management of extremely low birth weight infants between academic and non-academic institutions.A questionnaire was sent to the directors of all Italian level III centres between April and August 2012.There was a 92% (n = 98/107) response rate. Apart from polyethylene wrapping to optimise thermal control, perinatal management approach was comparable between academic and non-academic centres.There were minor differences in management of extremely low birth weight infants between Italian academic and non-academic institutions, apart from thermal management. Although there was a good, overall adherence to the International Guidelines for Neonatal Resuscitation, temperature management was not in accordance with official recommendations and every effort has to be done to improve this aspect.

We read with interest the paper by O'Shea et al .1 Faces of preterm infants were photographed and analysed by using a software; they then were compared with the size of the most commonly available face masks (Laerdal 0/0 and Fisher&Paykel Infant Resuscitation Masks ‘small’ and ‘extra small’). Authors concluded that the smallest size of some brands of mask is …

A female infant was born at 27+5 weeks of gestation through emergency caesarean section, performed because of an acute increase of a compressive thoracic malformation diagnosed at the 20th gestational week. At birth, two enormous violaceous masses extending to thorax and superior limbs were observed (figure 1). The infant was immediately intubated and transfused because of severe anaemia. A compressive bandage on masses was performed to decrease the risk of bleeding. Angio-CT confirmed the presence of voluminous masses surrounding the …

To evaluate whether a polyethylene total body wrapping (covering both the body and head) is more effective than conventional treatment (covering up to the shoulders) in reducing perinatal thermal losses in very preterm infants.This was a multicenter, prospective, randomized, parallel 1:1, unblinded, controlled trial of infants29 weeks' gestation age, comprising two study groups: experimental group (total body group; both the body and head covered with a polyethylene occlusive bag, with the face uncovered) and control group (only the body, up to the shoulders, covered with a polyethylene occlusive bag). The primary outcome was axillary temperature on neonatal intensive care unit admission immediately after wrap removal.One hundred randomly allocated infants (50 in the total body group and 50 controls) completed the study. Mean axillary temperature on neonatal intensive care unit admission was similar in the two groups (36.5±0.6°C total body vs 36.4±0.8°C controls; P=.53). The rate of moderate hypothermia (temperature36°C) was 12% in the total body group and 20% in the control group (P=.41). Three subjects in each group (6.0%) had an axillary temperature37.5°C on admission, and one subject in control group had an axillary temperature38°C.Total body wrapping is comparable with covering the body up to the shoulders in preventing postnatal thermal losses in very preterm infants.

Objectives Reflex anal dilatation (RAD) is considered as a possible sign of anal abuse,however studies evaluating its prevalence in non-abused children are limited. The aim of this study was to evaluate the prevalence of RAD in a convenience sample of children with no suspicion of abuse admitted to a Pediatric Emergency Department (PED). Methods Prospective observational study including children admitted to the PED of Padova, Italy, between January and June 2011. Patients with no suspicion of abuse and for whom ano-genital examination was part of their medical evaluation were included. Children were excluded if in critical clinical conditions or if any suspicion of abuse arose during medical evaluation. Presence/absence of RAD and of factors favoring its appearance were recorded for each patient. Results Two-hundred and thirty children (median age of 12 months, interquartile range 5–35 months) were finally included. A positive RAD was reported in 14 (6.1%, CI 95% 3.4–10). Only 3 patients (1.3%, CI 95% 0.3–3.7) showed a positive RAD in the absence of any predisposing factor. Conclusions RAD is an infrequent sign in non-abused children and it is particularly rare in the absence of any predisposing factor. Case-control studies are necessary to better clarify its diagnostic relevance.

The most important action in the resuscitation of a newborn in the delivery room is to establish effective assisted ventilation. The face mask and endotracheal tube are the devices used to achieve this goal. Laryngeal mask airways that fit over the laryngeal inlet have been shown to be effective for ventilating newborns at birth and should be considered as an alternative to facemask ventilation or endotracheal intubation among newborns weighing >2,000 g or delivered ≥34 weeks’ gestation. A recent systematic review and meta-analysis of supraglottic airways in neonatal resuscitation reported the results of four randomized controlled trials (RCTs) stating that fewer infants in the group using laryngeal mask airways required endotracheal intubation (1.5%) compared to the group using face masks (12.0%). However, there were methodological concerns over all the RCTs including the fact that the majority of the operators in the trials were anesthesiologists. Our hypothesis is based on the assumption that ventilating newborns needing positive pressure ventilation with a laryngeal mask airway will be more effective than ventilating with a face mask in a setting where neonatal resuscitation is performed by midwives, nurses, and pediatricians. The primary aim of this study will be to assess the effectiveness of the laryngeal mask airway over the face mask in preventing the need for endotracheal intubation. This will be an open, prospective, randomized, single center, clinical trial. In this study, 142 newborns weighing >1,500 g or delivered ≥34 weeks gestation needing positive pressure ventilation at birth will be randomized to be ventilated with a laryngeal mask airway (LMA SupremeTM, LMA Company, UK - intervention group) or with a face mask (control group). Primary outcome: Proportion of newborns needing endotracheal intubation. Secondary outcomes: Apgar score at 5 minutes, time to first breath, onset of the first cry, duration of resuscitation, death or moderate to severe hypoxic-ischemic encephalopathy within 7 days of life. ClinicalTrials.gov identifier: NCT01963936 (October 11, 2013).

Commentary on: BOOST II UK Collaborative Group; BOOST II Australia Collaborative Group; BOOST II New Zealand Collaborative Group, et al. Oxygen saturation and outcomes in preterm infants. N Engl J Med 2013;368:2094–104.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] The goal of oxygen therapy is to deliver sufficient oxygen to the tissues while minimising oxygen toxicity and oxidative stress. Although many extremely preterm infants receive supplemental oxygen for prolonged periods, the optimal oxygen saturation has not yet been defined. The Benefits Of Oxygen Saturation Targeting (BOOST) II randomised controlled trial (RCT) aimed to evaluate the effects of targeting an oxygen saturation of 85–89%, as compared with a range of 91–95%, on disability-free survival at 2 years in infants born before 28 weeks’ gestation. During the study period, two major changes were made to the original study protocol; first, in the midst of the UK and Australian trials, … [1]: {openurl}?query=rft.jtitle%253DN%2BEngl%2BJ%2BMed%26rft.issn%253D0028-4793%26rft.volume%253D368%26rft.spage%253D2094%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa1302298%26rft_id%253Dinfo%253Apmid%252F23642047%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa1302298&link_type=DOI [3]: /lookup/external-ref?access_num=23642047&link_type=MED&atom=%2Febmed%2F19%2F1%2F20.atom [4]: /lookup/external-ref?access_num=000319574200007&link_type=ISI

Background High fidelity simulation has been executed to allow the evaluation of technical and non-technical skills of health caregivers. Our objective was to assess technical and non-technical performances of low level hospitals health caregivers who attended a Neonatal Resuscitation course using high fidelity simulation in a standard-setting scenario. Methods Twenty-three volunteers were asked to manage a simple scenario (infant with secondary apnea) after the course. Technical and non-technical skills were assessed by using previously published scores. Performances were assessed during the scenario and after 2 months by filmed video recordings. Results Sixteen (69.5%) participants failed to pass the minimum required technical score. Staff experience and participation in previous courses were associated to higher score in technical and non-technical skills, while working in level I or II hospitals did not affect the scores. Previous experience in neonatal resuscitation requiring positive pressure ventilation was associated to better non-technical performance. Technical and non-technical scores were significantly correlated (r = 0.67, p = 0.0005). Delayed and direct evaluation of technical skills provided the same scores. Conclusions A neonatal resuscitation course, performed by using a high fidelity simulation manikin, had a limited impact on technical and non-technical skills of participants working in low level hospitals. Training programs should be tailored to the participants’ professional background and to the more relevant sessions.