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More and more very low birth weight (VLBW) infants around the world survive nowadays, with consequently larger numbers of children developing prematurity-related morbidities, especially bronchopulmonary dysplasia (BPD). BPD is a multifactorial disease and its rising incidence in recent years means that general pediatricians are much more likely to encounter a child born extremely preterm, possibly with BPD, in their clinical practice. Short- and long-term sequelae in VLBW patients may affect not only pulmonary function (principally characterized by an obstructive pattern), but also other aspect including the neurological (neurodevelopmental and neuropsychiatric disorders), the sensorial (earing and visual impairment), the cardiological (systemic and pulmonary hypertension, reduced exercise tolerance and ischemic heart disease in adult age), nutritional (feeding difficulties and nutritional deficits), and auxological (extrauterine growth restriction). For the most premature infants at least, a multidisciplinary follow-up is warranted after discharge from the neonatal intensive care unit in order to optimize their respiratory and neurocognitive potential, and prevent respiratory infections, nutritional deficiencies or cardiovascular impairments. Conclusion: The aim of this review is to summarize the main characteristics of preterm and BPD infants, providing the general pediatrician with practical information regarding these patients’ multidisciplinary complex follow-up. We explore the current evidence on respiratory outcomes and their management that actually does not have a definitive available option. We also discuss the available investigations, treatments, and strategies for prevention and prophylaxis to improve the non-respiratory outcomes and the quality of life for these children and their families, a critical aspect not always considered. This comprehensive approach, added to the increased needs of a VLBW subjects, is obviously related to very high health-related costs that should be beared in mind. What is Known:• Every day, a general pediatrician is more likely to encounter a former very low birth weight infant.• Very low birth weight and prematurity are frequently related not only with worse respiratory outcomes, but also with neurological, sensorial, cardiovascular, renal, and nutritional issues. What is New:• This review provides to the general pediatrician a comprehensive approach for the follow-up of former premature very low birth weight children, with information to improve the quality of life of this special population.

Background: Sedation to preterm neonates receiving less invasive surfactant administration (LISA) for respiratory distress syndrome is controversial. Methods: Systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies (OS) to evaluate the effect of sedative drugs for LISA on respiratory outcomes and adverse effects. Results: One RCT (78 neonates) and two OS (519 neonates) were analyzed in pairwise meta-analysis and 30 studies (2164 neonates) in proportion-based meta-analysis. Sedative drugs might not affect the duration of the procedure [RCT: mean difference (MD) (95% CI); −11 (−90; 67) s; OS: MD 95% CI: −60 (−178; 58) s; low certainty of evidence (CoE)]. Evidence for success at the first attempt and rescue intubation was uncertain (very low CoE). The risk of nasal intermittent positive pressure ventilation [RCT: 1.97 (1.38–2.81); OS: RR, 95% CI: 2.96 (1.46; 6.00), low CoE], desaturation [RCT: RR, 95% CI: 1.30 (1.03; 1.65), low CoE], and apnea [OS: RR, 95% CI: 3.13 (1.35; 7.24), very low CoE] might be increased with sedation. Bradycardia, hypotension, and mechanical ventilation were comparable between groups (low CoE). Conclusions: Use of sedative drugs for LISA temporarily affects the newborn’s breathing. Further trials are warranted to explore the use of sedation for LISA. Impact: The effect of sedative drugs (analgesics, sedatives, anesthetics) compared to the effect of no-sedation for LISA in preterm infants with RDS is underexplored.This systematic review and meta-analysis assesses the impact of sedative drugs compared to no-sedation for LISA on short-term pulmonary outcomes and potential adverse events.Sedative drugs for LISA temporarily affect the newborn’s breathing (desaturation, apnea) and increase the need for nasal intermittent positive pressure ventilation. For most outcomes, certainty of evidence is low/very low.

Necrotizing enterocolitis (NEC) is the main gastrointestinal emergency of preterm infants for whom bowel rest and parenteral nutrition (PN) is essential. Despite the improvements in neonatal care, the incidence of NEC remains high (11% in preterm newborns with a birth weight

The objective of this study is to assess the effect of neonatal procedures on glucose variability in very preterm infants. Preterm infants (≤ 32 weeks gestation and/or birthweight ≤ 1500 g) were started on continuous glucose monitoring (CGM) on day 2 of birth and monitored for 5 days. Minimally invasive (heel stick, venipunctures) and non-invasive (nappy change, parental presence) procedures were recorded. CGM data were analyzed 30 min before and after each procedure. The primary outcome was the coefficient of glucose variation (CV = SD/mean) before and after the procedure; SD and median glucose were also evaluated. We analyzed 496 procedures in 22 neonates (GA 30.5 weeks [29–31]; birthweight 1300 g [950–1476]). Median glucose did not change before and after each procedure, while CV and SD increased after heel prick (p = 0.017 and 0.030), venipuncture (p = 0.010 and 0.030), and nappy change (p Conclusions: Non-invasive and minimally invasive procedures increase glucose variability in the absence of changes of mean glucose. What is Known:• Minimally invasive procedures - including nappy change - may increase neonatal stress in preterm infants. What is New:• Continuous glucose monitoring provides a quantitative measure of neonatal stress during neonatal care procedures demonstrating an increase of glucose variability.

Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal emergency in preterm neonates. Research on early predictive biomarkers is fundamental. This is a systematic review of studies applying untargeted metabolomics and gut microbiota analysis to evaluate the differences between neonates affected by NEC (Bell’s stage II or III), and/or by spontaneous intestinal perforation (SIP) versus healthy controls. Five studies applying metabolomics (43 cases, 95 preterm controls) and 20 applying gut microbiota analysis (254 cases, 651 preterm controls, 22 term controls) were selected. Metabolomic studies utilized NMR spectroscopy or mass spectrometry. An early urinary alanine/histidine ratio >4 showed good sensitivity and predictive value for NEC in one study. Samples collected in proximity to NEC diagnosis demonstrated variable pathways potentially related to NEC. In studies applying untargeted gut microbiota analysis, the sequencing of the V3–V4 or V3 to V5 regions of the 16S rRNA was the most used technique. At phylum level, NEC specimens were characterized by increased relative abundance of Proteobacteria compared to controls. At genus level, pre-NEC samples were characterized by a lack or decreased abundance of Bifidobacterium. Finally, at the species level Bacteroides dorei, Clostridium perfringens and perfringens-like strains dominated early NEC specimens, whereas Clostridium butyricum, neonatale and Propionibacterium acnei those at disease diagnosis. Six studies found a lower Shannon diversity index in cases than controls. A clear separation of cases from controls emerged based on UniFrac metrics in five out of seven studies. Importantly, no studies compared NEC versus SIP. Untargeted metabolomics and gut microbiota analysis are interrelated strategies to investigate NEC pathophysiology and identify potential biomarkers. Expression of quantitative measurements, data sharing via biorepositories and validation studies are fundamental to guarantee consistent comparison of results.

The biochemical variations occurring in intrauterine growth restriction (IUGR), when a fetus is unable to achieve its genetically determined potential, are not fully understood. The aim of this study is to compare the urinary metabolomic profile between IUGR and non-IUGR very preterm infants to investigate the biochemical adaptations of neonates affected by early-onset-restricted intrauterine growth.Neonates born32 weeks of gestation admitted to neonatal intensive care unit (NICU) were enrolled in this prospective matched case-control study. IUGR was diagnosed by an obstetric ultra-sonographer and all relevant clinical data during NICU stay were captured. For each subject, a urine sample was collected within 48 h of life and underwent untargeted metabolomic analysis using mass spectrometry ultra-performance liquid chromatography. Data were analyzed using multivariate and univariate statistical analyses.Among 83 enrolled infants, 15 IUGR neonates were matched with 19 non-IUGR controls. Untargeted metabolomic revealed evident clustering of IUGR neonates versus controls showing derangements of pathways related to tryptophan and histidine metabolism and aminoacyl-tRNA and steroid hormones biosynthesis.Neonates with IUGR showed a distinctive urinary metabolic profile at birth. Although results are preliminary, metabolomics is proving to be a promising tool to explore biochemical pathways involved in this disease.Very preterm infants with intrauterine growth restriction (IUGR) have a distinctive urinary metabolic profile at birth. Metabolism of glucocorticoids, sexual hormones biosynthesis, tryptophan-kynurenine, and methionine-cysteine pathways seem to operate differently in this sub-group of neonates. This is the first metabolomic study investigating adaptations exclusively in extremely and very preterm infants affected by early-onset IUGR. New knowledge on metabolic derangements in IUGR may pave the ways to further, more tailored research from a perspective of personalized medicine.

Objectives To compare the efficacy of intra‐tracheal (IT) surfactant/budesonide (SB) with that of surfactant alone (S) in reducing the rate of bronchopulmonary dysplasia (BPD) at 36 weeks post‐menstrual age (PMA), we included extremely preterm very low birth weight (VLBW) infants with severe respiratory distress syndrome (RDS) in our tertiary neonatal level of care unit (Padua, Italy). Study Design A retrospective chart review of two cohorts of extremely preterm VLBW neonates (

Bronchopulmonary dysplasia (BPD) still carries a heavy burden of morbidity and mortality in survivors of extreme prematurity. The disease is characterized by simplification of the alveolar structure, involving a smaller number of enlarged alveoli due to decreased septation and a dysmorphic pulmonary microvessel growth. These changes lead to persistent abnormalities mainly affecting the smaller airways, lung parenchyma, and pulmonary vasculature, which can be assessed with lung function tests and imaging techniques. Several longitudinal lung function studies have demonstrated that most preterm‐born subjects with BPD embark on a low lung function trajectory, never achieving their full airway growth potential. They are consequently at higher risk of developing a chronic obstructive pulmonary disease‐like phenotype later in life. Studies based on computer tomography and magnetic resonance imaging, have also shown that in these patients there is a persistence of lung abnormalities like emphysematous areas, bronchial wall thickening, interstitial opacities, and mosaic lung attenuation also in adult age. This review aims to outline the current knowledge of pulmonary and vascular growth in survivors of BPD and the evidence of their lung function and imaging up to adulthood.

The aim of this review was threefold: (a) to retrieve all SARS-CoV-2 evidences published by Italian neonatologists working in maternity centers and NICUs during the pandemic; (b) to summarize current evidence for the management of term and preterm infants with a SARS-CoV-2-related illness; and (c) to provide an update for dealing with the second wave of COVID-19 and discuss open questions. A review was conducted using MEDLINE/PubMed and the national COVID-19 registry of the Italian Society of Neonatology including citations from December 1, 2019 to October 28, 2020. Sixty-three articles were included. Collected data were divided into the following topics: (a) antenatal management, (b) management in delivery room, (c) postnatal management, (d) mother–baby dyad and breastfeeding management, (e) neonatal emergency transport system reorganization, (f) parents’ management and perspective during SARS-CoV-2 pandemic, and (g) future perspective. Evidences have evolved over the pandemic period and the current review can be useful in the management of the mother–neonate dyad during SARS-CoV-2 future waves. Italian neonatologists have played an active role in producing official guidelines and reporting data that have contributed to improve the care of neonates. A joint European action plan is mandatory to face COVID-19 in neonates with more awareness. Impact A joint European action plan is mandatory to face COVID-19 in neonates with more awareness. This review summarizes the available evidences from neonatal COVID-19 management in Italy analyzing all the published paper in this specific field of interest. The current review can be useful in the management of the mother–neonate dyad during the SARS-CoV-2 future waves.

Necrotizing enterocolitis (NEC), the first cause of short bowel syndrome (SBS) in the neonate, is a serious neonatal gastrointestinal disease with an incidence of up to 11% in preterm newborns less than 1500 g of birth weight. The rate of severe NEC requiring surgery remains high, and it is estimated between 20–50%. Newborns who develop SBS need prolonged parenteral nutrition (PN), experience nutrient deficiency, failure to thrive and are at risk of neurodevelopmental impairment. Prevention of NEC is therefore mandatory to avoid SBS and its associated morbidities. In this regard, nutritional practices seem to play a key role in early life. Individualized medical and surgical therapies, as well as intestinal rehabilitation programs, are fundamental in the achievement of enteral autonomy in infants with acquired SBS. In this descriptive review, we describe the most recent evidence on nutritional practices to prevent NEC, the available tools to early detect it, the surgical management to limit bowel resection and the best nutrition to sustain growth and intestinal function.

Coronavirus disease 2019 (COVID-19), caused by the novel SARS-CoV-2 virus, is rapidly spreading across the world. As the number of infections increases, those of infected pregnant women and children will rise as well. Controversy exists whether COVID-19 can be transmitted in utero and lead to disease in the newborn. As this chance cannot be ruled out, strict instructions for the management of mothers and newborn infants are mandatory. This perspective aims to be a practical support tool for the planning of delivery and neonatal resuscitation of infants born by mothers with suspected or confirmed COVID-19 infection.

This document provides recommendations for monitoring and treatment of children in whom bronchopulmonary dysplasia (BPD) has been established and who have been discharged from the hospital, or who were >36 weeks of postmenstrual age. The guideline was based on predefined Population, Intervention, Comparison and Outcomes (PICO) questions relevant for clinical care, a systematic review of the literature and assessment of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. After considering the balance of desirable (benefits) and undesirable (burden, adverse effects) consequences of the intervention, the certainty of the evidence, and values, the task force made conditional recommendations for monitoring and treatment of BPD based on very low to low quality of evidence. We suggest monitoring with lung imaging using ionising radiation in a subgroup only, for example severe BPD or recurrent hospitalisations, and monitoring with lung function in all children. We suggest to give individual advice to parents regarding daycare attendance. With regards to treatment, we suggest the use of bronchodilators in a subgroup only, for example asthma-like symptoms, or reversibility in lung function; no treatment with inhaled or systemic corticosteroids; natural weaning of diuretics by the relative decrease in dose with increasing weight gain if diuretics are started in the neonatal period; and treatment with supplemental oxygen with a saturation target range of 90–95%. A multidisciplinary approach for children with established severe BPD after the neonatal period into adulthood is preferable. These recommendations should be considered until new and urgently needed evidence becomes available.

Respiratory diseases account for about 25% of all pediatric consultations, and 10% of these are for asthma. The other main pediatric respiratory diseases, in terms of incidence, are bronchiolitis, acute bronchitis and respiratory infections. Oral corticosteroids, in particular prednisolone, are often used to treat acute respiratory diseases given their anti-inflammatory effects. However, the efficacy of treatment with oral corticosteroids differs among the various types of pediatric respiratory diseases. Notably, also the adverse effects of corticosteroid treatment can differ depending on dosage, duration of treatment and type of corticosteroid administered — a case in point being growth retardation in long-course treatment. A large body of data has accumulated on this topic. In this article, we have reviewed the data and guidelines related to the role of oral corticosteroids in the treatment and management of pediatric bronchiolitis, wheezing, asthma and croup in the attempt to provide guidance for physicians. Also included is a section on the management of acute respiratory failure in children.

Objective Bronchopulmonary dysplasia (BPD) is a serious complication associated with preterm birth. A growing body of evidence suggests a role for prenatal factors in its pathogenesis. Metabolomics allows simultaneous characterization of low molecular weight compounds and may provide a picture of such a complex condition. The aim of this study was to evaluate whether an unbiased metabolomic analysis of amniotic fluid (AF) can be used to investigate the risk of spontaneous preterm delivery (PTD) and BPD development in the offspring. Study design We conducted an exploratory study on 32 infants born from mothers who had undergone an amniocentesis between 21 and 28 gestational weeks because of spontaneous preterm labor with intact membranes. The AF samples underwent untargeted metabolomic analysis using mass spectrometry combined with ultra-performance liquid chromatography. The data obtained were analyzed using multivariate and univariate statistical data analysis tools. Results Orthogonally Constrained Projection to Latent Structures-Discriminant Analysis (oCPLS2-DA) excluded effects on data modelling of crucial clinical variables. oCPLS2-DA was able to find unique differences in select metabolites between term (n = 11) and preterm (n = 13) deliveries (negative ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.65; positive ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.70), and between PTD followed by the development of BPD (n = 10), and PTD without BPD (n = 11) (negative data set: R2 = 0.48, mean AUC ROC in prediction = 0.73; positive data set: R2 = 0.55, mean AUC ROC in prediction = 0.71). Conclusions This study suggests that amniotic fluid metabolic profiling may be promising for identifying spontaneous preterm birth and fetuses at risk for developing BPD. These findings support the hypothesis that some prenatal metabolic dysregulations may play a key role in the pathogenesis of PTD and the development of BPD.