Supplemental Iron and Recombinant Erythropoietin for Anemia in Infants Born Very Preterm: A Survey of Clinical Practice in Europe.

OBJECTIVES: To survey practices of iron and recombinant human erythropoietin (rhEpo) administration to infants born preterm across Europe. STUDY DESIGN: Over a 3-month period, we conducted an online survey in 597 neonatal intensive care units (NICUs) of 18 European countries treating infants born with a gestational age of <32 weeks. RESULTS: We included 343 NICUs (response rate 56.3%) in the survey. Almost all NICUs (97.7%) routinely supplement enteral iron, and 74.3% of respondents to all infants born <32 weeks of gestation. We found that 65.3% of NICUs routinely evaluate erythropoiesis and iron parameters beyond day 28 after birth. Most NICUs initiate iron supplementation at postnatal age of 2 weeks and stop after 6 months (34.3%) or 12 months (34.3%). Routine use of rhEpo was reported in 22.2% of NICUs, and in individual cases in 6.9%. RhEpo was mostly administered subcutaneously (70.1%) and most frequently at a dose of 250 U/kg 3 times a week (44.3%), but the dose varied greatly between centers. CONCLUSIONS: This survey highlights wide heterogeneity in evaluating erythropoietic activity and iron deficiency in infants born preterm. Variation in iron supplementation during infancy likely reflects an inadequate evidence base. Current evidence on the efficacy and safety profile of rhEpo is only poorly translated into clinical practice. This survey demonstrates a need for standards to optimize patient blood management in anemia of prematurity.

The role of nutritional interventions in the prevention and treatment of chronic lung disease of prematurity.

Chronic lung disease of prematurity or bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Nutrition may affect incidence and severity of BPD. In this context, the Section on Nutrition, Gastroenterology and Metabolism, the Pulmonary Section of the European Society for Paediatric Research (ESPR) and SPR have joined forces to review the current knowledge on nutritional issues related to BPD. The aim of this narrative review is to discuss the clinical implications for nutritional practice. Nutrient deficiencies may influence pathogenesis of BPD. Adequate nutrition and growth can play a crucial role in the prevention of and recovery from BPD. Optimal nutrition strategy is an important principle, especially in the early postnatal period. As optimal energy intake in infants at risk of BPD or with evolving BPD is not yet defined, further research with well-designed studies on nutritional strategies for preterm infants with BPD is urgently needed. IMPACT: Based on current evidence it seems reasonable to recommend that BPD diagnosed infants should receive an energy supply ranging from 120 to 150 Kcal/kg/d. Exclusive MOM feed with adequate fortification should be encouraged as this is associated with a significant reduction in the risk of BPD. Suboptimal nutritional delivery is often seen in preterm infants with BPD compared to controls.

Meeting the need for effective and standardized neonatology training: a pan-European Master's Curriculum.

Neonatology is a pediatric sub-discipline focused on providing care for newborn infants, including healthy newborns, those born prematurely, and those who present with illnesses or malformations requiring medical care. The European Training Requirements (ETR) in Neonatology provide a framework for standardized quality and recognition of equality of training throughout Europe. The latest ETR version was approved by the Union of European Medical Specialists (UEMS) in April 2021. Here, we present the curriculum of the European School of Neonatology Master of Advanced Studies (ESN MAS), which is based on the ETR in Neonatology and aims to provide a model for effective and standardized training and education in neonatal medicine. We review the history and theory that form the foundation of contemporary medical education and training, provide a literature review on best practices for medical training, pediatric training, and neonatology training specifically, including educational frameworks and evidence-based systems of evaluation. The ESN MAS Curriculum is then evaluated in light of these best practices to define its role in meeting the need for a standardized empirically supported neonatology training curriculum for physicians, and in the future for nurses, to improve the quality of neonatal care for all infants. IMPACT STATEMENT: A review of the neonatology training literature was conducted, which concluded that there is a need for standardized neonatology training across international contexts to keep pace with growth in the field and rapidly advancing technology. This article presents the European School of Neonatology Master of Advanced Studies in Neonatology, which is intended to provide a standardized training curriculum for pediatricians and nurses seeking sub-specialization in neonatology. The curriculum is evaluated in light of best practices in medical education, neonatology training, and adult learning theory.

Transitional circulation and hemodynamic monitoring in newborn infants.

Transitional circulation is normally transient after birth but can vary markedly between infants. It is actually in a state of transition between fetal (in utero) and neonatal (postnatal) circulation. In the absence of definitive clinical trials, information from applied physiological studies can be used to facilitate clinical decision making in the presence of hemodynamic compromise. This review summarizes the peculiar physiological features of the circulation as it transitions from one phenotype into another in term and preterm infants. The common causes of hemodynamic compromise during transition, intact umbilical cord resuscitation, and advanced hemodynamic monitoring are discussed. IMPACT: Transitional circulation can vary markedly between infants. There are alterations in preload, contractility, and afterload during the transition of circulation after birth in term and preterm infants. Hemodynamic monitoring tools and technology during neonatal transition and utilization of bedside echocardiography during the neonatal transition are increasingly recognized. Understanding the cardiovascular physiology of transition can help clinicians in making better decisions while managing infants with hemodynamic compromise. The objective assessment of cardio-respiratory transition and understanding of physiology in normal and disease states have the potential of improving short- and long-term health outcomes.

Sedation for less invasive surfactant administration in preterm infants: a systematic review and meta-analysis.

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.

Early prediction of severe retinopathy of prematurity requiring laser treatment using physiological data.

BACKGROUND: Early risk stratification for developing retinopathy of prematurity (ROP) is essential for tailoring screening strategies and preventing abnormal retinal development. This study aims to examine the ability of physiological data during the first postnatal month to distinguish preterm infants with and without ROP requiring laser treatment. METHODS: In this cohort study, preterm infants with a gestational age <32 weeks and/or birth weight <1500 g, who were screened for ROP were included. Differences in the physiological data between the laser and non-laser group were identified, and tree-based classification models were trained and independently tested to predict ROP requiring laser treatment. RESULTS: In total, 208 preterm infants were included in the analysis of whom 30 infants (14%) required laser treatment. Significant differences were identified in the level of hypoxia and hyperoxia, oxygen requirement, and skewness of heart rate. The best model had a balanced accuracy of 0.81 (0.72-0.87), a sensitivity of 0.73 (0.64-0.81), and a specificity of 0.88 (0.80-0.93) and included the SpO2/FiO2 ratio and baseline demographics (including gestational age and birth weight). CONCLUSIONS: Routinely monitored physiological data from preterm infants in the first postnatal month are already predictive of later development of ROP requiring laser treatment, although validation is required in larger cohorts. IMPACT: Routinely monitored physiological data from the first postnatal month are predictive of later development of ROP requiring laser treatment, although model performance was not significantly better than baseline characteristics (gestational age, birth weight, sex, multiple birth, prenatal glucocorticosteroids, route of delivery, and Apgar scores) alone. A balanced accuracy of 0.81 (0.72-0.87), a sensitivity of 0.73 (0.64-0.81), and a specificity of 0.88 (0.80-0.93) was achieved with a model including the SpO2/FiO2 ratio and baseline characteristics. Physiological data have potential to play a significant role for future ROP prediction and provide opportunities for early interventions to protect infants from abnormal retinal development.

Curriculum and assessment tool for less invasive surfactant administration: an international Delphi consensus study.

BACKGROUND: Training and assessment of operator competence for the less invasive surfactant administration (LISA) procedure vary. This study aimed to obtain international expert consensus on LISA training (LISA curriculum (LISA-CUR)) and assessment (LISA assessment tool (LISA-AT)). METHODS: From February to July 2022, an international three-round Delphi process gathered opinions from LISA experts (researchers, curriculum developers, and clinical educators) on a list of items to be included in a LISA-CUR and LISA-AT (Round 1). The experts rated the importance of each item (Round 2). Items supported by more than 80% consensus were included. All experts were asked to approve or reject the final LISA-CUR and LISA-AT (Round 3). RESULTS: A total of 153 experts from 14 countries participated in Round 1, and the response rate for Rounds 2 and 3 was >80%. Round 1 identified 44 items for LISA-CUR and 22 for LISA-AT. Round 2 excluded 15 items for the LISA-CUR and 7 items for the LISA-AT. Round 3 resulted in a strong consensus (99-100%) for the final 29 items for the LISA-CUR and 15 items for the LISA-AT. CONCLUSIONS: This Delphi process established an international consensus on a training curriculum and content evidence for the assessment of LISA competence. IMPACT: This international consensus-based expert statement provides content on a curriculum for the less invasive surfactant administration procedure (LISA-CUR) that may be partnered with existing evidence-based strategies to optimize and standardize LISA training in the future. This international consensus-based expert statement also provides content on an assessment tool for the LISA procedure (LISA-AT) that can help to evaluate competence in LISA operators. The proposed LISA-AT enables standardized, continuous feedback and assessment until achieving proficiency.

Methylxanthine for the prevention and treatment of apnea in preterm infants.

BACKGROUND: Very preterm infants often require respiratory support and are therefore exposed to an increased risk of chronic lung disease and later neurodevelopmental disability. Although methylxanthines are widely used to prevent and treat apnea associated with prematurity and to facilitate extubation, there is uncertainty about the benefits and harms of different types of methylxanthines. OBJECTIVES: To assess the effects of methylxanthines on the incidence of apnea, death, neurodevelopmental disability, and other longer-term outcomes in preterm infants (1) at risk for or with apnea, or (2) undergoing extubation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and three trial registers (November 2022). SELECTION CRITERIA: We included randomized trials in preterm infants, in which methylxanthines (aminophylline, caffeine, or theophylline) were compared to placebo or no treatment for any indication (i.e. prevention of apnea, treatment of apnea, or prevention of re-intubation). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods and GRADE to assess the certainty of evidence. MAIN RESULTS: We included 18 studies (2705 infants), evaluating the use of methylxanthine in preterm infants for: any indication (one study); prevention of apnea (six studies); treatment of apnea (five studies); and to prevent re-intubation (six studies). Death or major neurodevelopmental disability (DMND) at 18 to 24 months. Only the Caffeine for Apnea of Prematurity (CAP) study (enrolling 2006 infants) reported on this outcome. Overall, caffeine probably reduced the risk of DMND in preterm infants treated with caffeine for any indication (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.78 to 0.97; risk difference (RD) -0.06, 95% CI -0.10 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 16, 95% CI 10 to 50; 1 study, 1869 infants; moderate-certainty evidence). No other trials reported DMND. Results from the CAP trial regarding DMND at 18 to 24 months are less precise when analyzed based on treatment indication. Caffeine probably results in little or no difference in DMND in infants treated for prevention of apnea (RR 1.00, 95% CI 0.80 to 1.24; RD -0.00, 95% CI -0.10 to 0.09; 1 study, 423 infants; moderate-certainty evidence) and probably results in a slight reduction in DMND in infants treated for apnea of prematurity (RR 0.85, 95% CI 0.71 to 1.01; RD -0.06, 95% CI -0.13 to 0.00; NNTB 16, 95% CI 7 to > 1000; 1 study, 767 infants; moderate-certainty evidence) or to prevent re-intubation (RR 0.85, 95% CI 0.73 to 0.99; RD -0.08, 95% CI -0.15 to -0.00; NNTB 12, 95% CI 6 to >1000; 1 study, 676 infants; moderate-certainty evidence). Death. In the overall analysis of any methylxanthine treatment for any indication, methylxanthine used for any indication probably results in little or no difference in death at hospital discharge (RR 0.99, 95% CI 0.71 to 1.37; I2 = 0%; RD -0.00, 95% CI -0.02 to 0.02; I2 = 5%; 7 studies, 2289 infants; moderate-certainty evidence). Major neurodevelopmental disability at 18 to 24 months. In the CAP trial, caffeine probably reduced the risk of major neurodevelopmental disability at 18 to 24 months (RR 0.85, 95% CI 0.76 to 0.96; RD -0.06, 95% CI -0.10 to -0.02; NNTB 16, 95% CI 10 to 50; 1 study, 1869 infants; moderate-certainty evidence), including a reduction in the risk of cerebral palsy or gross motor disability (RR 0.60, 95% CI 0.41 to 0.88; RD -0.03, 95% CI -0.05 to -0.01; NNTB 33, 95% CI 20 to 100; 1 study, 1810 infants; moderate-certainty evidence) and a marginal reduction in the risk of developmental delay (RR 0.88, 95% CI 0.78 to 1.00; RD -0.05, 95% CI -0.09 to -0.00; NNTB 20, 95% CI 11 to > 1000; 1 study, 1725 infants; moderate-certainty evidence). Any apneic episodes, failed apnea reduction after two to seven days (< 50% reduction in apnea) (for infants treated with apnea), and need for positive-pressure ventilation after institution of treatment. Methylxanthine used for any indication probably reduces the occurrence of any apneic episodes (RR 0.31, 95% CI 0.18 to 0.52; I2 = 47%; RD -0.38, 95% CI -0.51 to -0.25; I2 = 49%; NNTB 3, 95% CI 2 to 4; 4 studies, 167 infants; moderate-certainty evidence), failed apnea reduction after two to seven days (RR 0.48, 95% CI 0.33 to 0.70; I2 = 0%; RD -0.31, 95% CI -0.44 to -0.17; I2 = 53%; NNTB 3, 95% CI 2 to 6; 4 studies, 174 infants; moderate-certainty evidence), and may reduce receipt of positive-pressure ventilation after institution of treatment (RR 0.61, 95% CI 0.39 to 0.96; I2 = 0%; RD -0.06, 95% CI -0.11 to -0.01; I2 = 49%; NNTB 16, 95% CI 9 to 100; 9 studies, 373 infants; low-certainty evidence). Chronic lung disease. Methylxanthine used for any indication reduces chronic lung disease (defined as the use of supplemental oxygen at 36 weeks' postmenstrual age) (RR 0.77, 95% CI 0.69 to 0.85; I2 = 0%; RD -0.10, 95% CI -0.14 to -0.06; I2 = 18%; NNTB 10, 95% CI 7 to 16; 4 studies, 2142 infants; high-certainty evidence). Failure to extubate or the need for re-intubation within one week after initiation of therapy. Methylxanthine used for the prevention of re-intubation probably results in a large reduction in failed extubation compared with no treatment (RR 0.48, 95% CI 0.32 to 0.71; I2 = 0%; RD -0.27, 95% CI -0.39 to -0.15; I2 = 69%; NNTB 4, 95% CI 2 to 6; 6 studies, 197 infants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Caffeine probably reduces the risk of death, major neurodevelopmental disability at 18 to 24 months, and the composite outcome DMND at 18 to 24 months. Administration of any methylxanthine to preterm infants for any indication probably leads to a reduction in the risk of any apneic episodes, failed apnea reduction after two to seven days, cerebral palsy, developmental delay, and may reduce receipt of positive-pressure ventilation after institution of treatment. Methylxanthine used for any indication reduces chronic lung disease (defined as the use of supplemental oxygen at 36 weeks' postmenstrual age).

Neonates and COVID-19: state of the art : Neonatal Sepsis series.

The SARS-CoV-2 pandemic has had a significant impact worldwide, particularly in middle- and low-income countries. While this impact has been well-recognized in certain age groups, the effects, both direct and indirect, on the neonatal population remain largely unknown. There are placental changes associated, though the contributions to maternal and fetal illness have not been fully determined. The rate of premature delivery has increased and SARS-CoV-2 infection is proportionately higher in premature neonates, which appears to be related to premature delivery for maternal reasons rather than an increase in spontaneous preterm labor. There is much room for expansion, including long-term data on outcomes for affected babies. Though uncommon, there has been evidence of adverse events in neonates, including Multisystem Inflammatory Syndrome in Children, associated with COVID-19 (MIS-C). There are recommendations for reduction of viral transmission to neonates, though more research is required to determine the role of passive immunization of the fetus via maternal vaccination. There is now considerable evidence suggesting that the severe visitation restrictions implemented early in the pandemic have negatively impacted the care of the neonate and the experiences of both parents and healthcare professionals alike. Ongoing collaboration is required to determine the full impact, and guidelines for future management. IMPACT: Comprehensive review of current available evidence related to impact of the COVID-19 pandemic on neonates, effects on their health, impact on their quality of care and indirect influences on their clinical course, including comparisons with other age groups. Reference to current evidence for maternal experience of infection and how it impacts the fetus and then neonate. Outline of the need for ongoing research, including specific areas in which there are significant gaps in knowledge.

Higher CPAP levels improve functional residual capacity at birth in preterm rabbits.

BACKGROUND: Preterm infants are commonly supported with 4-8 cm H2O continuous positive airway pressures (CPAP), although higher CPAP levels may improve functional residual capacity (FRC). METHODS: Preterm rabbits delivered at 29/32 days (~26-28 weeks human) gestation received 0, 5, 8, 12, 15 cm H2O of CPAP or variable CPAP of 15 to 5 or 15 to 8 cm H2O (decreasing ~2 cm H2O/min) for up to 10 min after birth. RESULTS: FRC was lower in the 0 (6.8 (1.0-11.2) mL/kg) and 5 (10.1 (1.1-16.8) mL/kg) compared to the 15 (18.8 (10.9-22.4) mL/kg) cm H2O groups (p = 0.003). Fewer kittens achieved FRC > 15 mL/kg in the 0 (20%), compared to 8 (36%), 12 (60%) and 15 (73%) cm H2O groups (p = 0.008). While breathing rates were not different (p = 0.096), apnoea tended to occur more often with CPAP < 8 cm H2O (p = 0.185). CPAP belly and lung bulging rates were similar whereas pneumothoraces were rare. Lowering CPAP from 15 to 5, but not 15 to 8 cm H2O, decreased FRC and breathing rates. CONCLUSION: In all, 15 cm H2O of CPAP improved lung aeration and reduced apnoea, but did not increase the risk of lung over-expansion, pneumothorax or CPAP belly immediately after birth. FRC and breathing rates were maintained when CPAP was decreased to 8 cm H2O. IMPACT: Although preterm infants are commonly supported with 4-8 cm H2O CPAP at birth, preclinical studies have shown that higher PEEP levels improve lung aeration. In this study, CPAP levels of 15 cm H2O improved lung aeration and reduced apnoea in preterm rabbit kittens immediately after birth. In all, 15 cm H2O CPAP did not increase the risk of lung over-expansion (indicated by bulging between the ribs), pneumothorax, or CPAP belly. These results can be used when designing future studies on CPAP strategies for preterm infants in the delivery room.

Non-invasive ventilatory support in neonates: An evidence-based update.

Non-invasive ventilatory support (NIV) is considered the gold standard in the care of preterm infants with respiratory distress syndrome (RDS). NIV from birth is superior to mechanical ventilation (MV) for the prevention of death or bronchopulmonary dysplasia (BPD), with a number needed to treat between 25 and 35. Various methods of NIV are available, some of them extensively researched and with well proven efficacy, whilst others are needing further research. Nasal continuous positive airway pressure (nCPAP) has replaced routine invasive mechanical ventilation (MV) for the initial stabilization and the treatment of RDS. Choosing the most suitable form of NIV and the most appropriate patient interface depends on several factors, including gestational age, underlying lung pathophysiology and the local facilities. In this review, we present the currently available evidence on NIV as primary ventilatory support to preventing intubation and for secondary ventilatory support, following extubation. We review nCPAP, nasal high-flow cannula, nasal intermittent positive airway pressure ventilation, bi-level positive airway pressure, nasal high-frequency oscillatory ventilation and nasal neurally adjusted ventilatory assist modes. We also discuss most suitable NIV devices and patient interfaces during resuscitation of the newborn in the delivery room.

Neonatal Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for neonatal life support includes evidence from 7 systematic reviews, 3 scoping reviews, and 12 evidence updates. The Neonatal Life Support Task Force generally determined by consensus the type of evidence evaluation to perform; the topics for the evidence updates followed consultation with International Liaison Committee on Resuscitation member resuscitation councils. The 2020 CoSTRs for neonatal life support are published either as new statements or, if appropriate, reiterations of existing statements when the task force found they remained valid. Evidence review topics of particular interest include the use of suction in the presence of both clear and meconium-stained amniotic fluid, sustained inflations for initiation of positive-pressure ventilation, initial oxygen concentrations for initiation of resuscitation in both preterm and term infants, use of epinephrine (adrenaline) when ventilation and compressions fail to stabilize the newborn infant, appropriate routes of drug delivery during resuscitation, and consideration of when it is appropriate to redirect resuscitation efforts after significant efforts have failed. All sections of the Neonatal Resuscitation Algorithm are addressed, from preparation through to postresuscitation care. This document now forms the basis for ongoing evidence evaluation and reevaluation, which will be triggered as further evidence is published. Over 140 million babies are born annually worldwide (https://ourworldindata.org/grapher/births-and-deaths-projected-to-2100). If up to 5% receive positive-pressure ventilation, this evidence evaluation is relevant to more than 7 million newborn infants every year. However, in terms of early care of the newborn infant, some of the topics addressed are relevant to every single baby born.

Pulmonary hypertension in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a major complication in prematurely born infants. Pulmonary hypertension (PH) associated with BPD (BPD-PH) is characterized by alveolar diffusion impairment, abnormal vascular remodeling, and rarefication of pulmonary vessels (vascular growth arrest), which lead to increased pulmonary vascular resistance and right heart failure. About 25% of infants with moderate to severe BPD develop BPD-PH that is associated with high morbidity and mortality. The recent evolution of broader PH-targeted pharmacotherapy in adults has opened up new treatment options for infants with BPD-PH. Sildenafil became the mainstay of contemporary BPD-PH therapy. Additional medications, such as endothelin receptor antagonists and prostacyclin analogs/mimetics, are increasingly being investigated in infants with PH. However, pediatric data from prospective or randomized controlled trials are still sparse. We discuss comprehensive diagnostic and therapeutic strategies for BPD-PH and briefly review the relevant differential diagnoses of parenchymal and interstitial developmental lung diseases. In addition, we provide a practical framework for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH from the 2018 World Symposium on Pulmonary Hypertension, and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies. Finally, current gaps of knowledge and future research directions are discussed. IMPACT: PH in BPD substantially increases mortality. Treatment of BPD-PH should be conducted by an interdisciplinary team and follow our new treatment algorithm while still kept tailored to the individual patient. We discuss recent developments in BPD-PH, make recommendations on diagnosis, monitoring and treatment of PH in BPD, and address current gaps of knowledge and potential research directions. We provide a practical framework, including a new treatment algorithm, for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH (2018 WSPH) and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies for BPD-PH.

Paediatric research in the times of COVID-19.

The COVID-19 pandemic poses many direct and indirect consequences for children's health and associated research. Direct consequences include participation of children in COVID-19 research trials, pausing other research in children and the potential implications of a global economic downturn on future research funding. Collaborative and networked research together with streamlined research processes and use of remote technology have been central to efforts by clinicians and scientists around the world and have proved essential for reducing COVID-19 morbidity and mortality. IMPACT: Maintain streamlined and efficient approaches to research governance and data sharing to facilitate high-quality collaborative research. Ensure early inclusion of children in trials of therapies for diseases that affect all age groups. Paediatric Research Societies should co-ordinate effective processes to define key research questions and develop multinational clinical trials for diagnostics, therapeutics and preventative strategies for infants, children and young people.

Stimulating and maintaining spontaneous breathing during transition of preterm infants.

Most preterm infants breathe at birth, but need additional respiratory support due to immaturity of the lung and respiratory control mechanisms. To avoid lung injury, the focus of respiratory support has shifted from invasive towards non-invasive ventilation. However, applying effective non-invasive ventilation is difficult due to mask leak and airway obstruction. The larynx has been overlooked as one of the causes for obstruction, preventing face mask ventilation from inflating the lung. The larynx remains mostly closed at birth, only opening briefly during a spontaneous breath. Stimulating and supporting spontaneous breathing could enhance the success of non-invasive ventilation by ensuring that the larynx remains open. Maintaining adequate spontaneous breathing and thereby reducing the need for invasive ventilation is not only important directly after birth, but also in the first hours after admission to the NICU. Respiratory distress syndrome is an important cause of respiratory failure. Traditionally, treatment of RDS required intubation and mechanical ventilation to administer exogenous surfactant. However, new ways have been implemented to administer surfactant and preserve spontaneous breathing while maintaining non-invasive support. In this narrative review we aim to describe interventions focused on stimulation and maintenance of spontaneous breathing of preterm infants in the first hours after birth.

T-piece resuscitator or self-inflating bag during neonatal resuscitation: a scoping review.

BACKGROUND: To identify the evidence for administering positive pressure ventilation (PPV) to infants at birth by either T-piece resuscitator (TPR) or self-inflating bag (SIB), and to determine whether a full systematic review (SR) is warranted. METHODS: Guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews, eligible studies included peer-reviewed human studies, prospectively or retrospectively comparing a TPR vs. SIB for administering PPV at birth. Databases searched were OVID Medline, PubMed, Embase and the Cochrane Central Register of Controlled Trials. Review Manager software was used for the data analysis. RESULTS: Following electronic literature search and review, data from four eligible studies (3 RCT and 1 observational study), enrolling a total of 2889 patients, were included. Studies differed regarding the investigated populations, reported outcomes and came from different geographical areas. In particular for preterm infants, use of TPR for providing PPV may improve survival, result in fewer intubations at birth and decrease the incidence of bronchopulmonary dysplasia. CONCLUSIONS: This scoping review identified two new studies with substantive new evidence, pointing towards improved survival, decreased bronchopulmonary dysplasia and fewer intubations at birth, in particular among preterm infants treated with TPR. Full SR of the literature is advised. IMPACT: This scoping review identified studies comparing TPR vs. SIB for respiratory support of newborn infants previously not included in the International Liaison Committee on Resuscitation (ILCOR) recommendations. Our review found substantive new evidence highlighting that device choice may impact the outcomes of compromised newborn infants'. This scoping review stipulates the need for full SR and updated meta-analysis of studies investigating supportive equipment for stabilizing infants at birth in order to inform ILCOR treatment recommendations.

International comparison of guidelines for managing neonates at the early phase of the SARS-CoV-2 pandemic.

BACKGROUND: The COVID-19 pandemic threatens global newborn health. We describe the current state of national and local protocols for managing neonates born to SARS-CoV-2-positive mothers. METHODS: Care providers from neonatal intensive care units on six continents exchanged and compared protocols on the management of neonates born to SARS-CoV-2-positive mothers. Data collection was between March 14 and 21, 2020. We focused on central protocol components, including triaging, hygiene precautions, management at delivery, feeding protocols, and visiting policies. RESULTS: Data from 20 countries were available. Disease burden varied between countries at the time of analysis. In most countries, asymptomatic infants were allowed to stay with the mother and breastfeed with hygiene precautions. We detected discrepancies between national guidance in particular regarding triaging, use of personal protection equipment, viral testing, and visitor policies. Local protocols deviated from national guidance. CONCLUSIONS: At the start of the pandemic, lack of evidence-based guidance on the management of neonates born to SARS-CoV-2-positive mothers has led to ad hoc creation of national and local guidance. Compliance between collaborators to share and discuss protocols was excellent and may lead to more consensus on management, but future guidance should be built on high-level evidence, rather than expert consensus. IMPACT: At the rapid onset of the COVID19 pandemic, all countries presented protocols in place for managing infants at risk of COVID19, with a certain degree of variations among regions. A detailed review of ad hoc guidelines is presented, similarities and differences are highlighted. We provide a broad overview of currently applied recommendations highlighting the need for international context-relevant coordination.

European consensus recommendations for neonatal and paediatric retrievals of positive or suspected COVID-19 patients.

BACKGROUND: The 2020 novel coronavirus (SARS-Cov-2) pandemic necessitates tailored recommendations addressing specific procedures for neonatal and paediatric transport of suspected or positive COVID-19 patients. The aim of this consensus statement is to define guidelines for safe clinical care for children needing inter-facility transport while making sure that the clinical teams involved are sufficiently protected from SARS-CoV-2. METHODS: A taskforce, composed of members of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) Transport section and the European Society for Paediatric Research (ESPR), reviewed the published literature and used a rapid, two-step modified Delphi process to formulate recommendations regarding safety and clinical management during transport of COVID-19 patients. RESULTS: The joint taskforce consisted of a panel of 12 experts who reached an agreement on a set of 17 recommendations specifying pertinent aspects on neonatal and paediatric COVID-19 patient transport. These included: case definition, personal protective equipment, airway management, equipment and strategies for invasive and non-invasive ventilation, special considerations for incubator and open stretcher transports, parents on transport and decontamination of transport vehicles. CONCLUSIONS: Our consensus recommendations aim to define current best-practice and should help guide transport teams dealing with infants and children with COVID-19 to work safely and effectively. IMPACT: We present European consensus recommendations on pertinent measures for transporting infants and children in times of the coronavirus (SARS-Cov-2 /COVID-19) pandemic. A panel of experts reviewed the evidence around transporting infants and children with proven or suspected COVID-19. Specific guidance on aspects of personal protective equipment, airway management and considerations for incubator and open stretcher transports is presented. Based on scant evidence, best-practice recommendations for neonatal and paediatric transport teams are presented, aiming for the protection of teams and patients. We highlight gaps in knowledge and areas of future research.

Enteral Feeding Strategies in Preterm Neonates ≤32 weeks Gestational Age: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Critical aspects of time of feed initiation, advancement, and volume of feed increment in preterm neonates remain largely unanswered. METHODS: Medline , Embase, CENTRAL and CINAHL were searched from inception until 25th September 2020. Network meta-analysis with the Bayesian approach was used. Randomized controlled trials (RCTs) evaluating preterm neonates ≤32 weeks were included. Feeding regimens were divided based on the following categories: initiation day: early (<72 h), moderately early (72 h-7 days), and late (>7 days); advancement day: early (<72 h), moderately early (72 h-7 days), and late (>7 days); increment volume: small volume (SV) (<20 mL/kg/day), moderate volume (MoV) (20-< 30 mL/kg/day), and large volume (≥30 mL/kg/day); and full enteral feeding from the first day. Sixteen regimens were evaluated. Combined outcome of necrotizing enterocolitis (NEC) stage ≥ II or mortality before discharge was the primary outcome. RESULTS: A total of 39 studies enrolled around 6,982 neonates. Early initiation (EI) with moderately early or late advancement using MoV increment enteral feeding regimens appeared to be most efficacious in decreasing the risk of NEC or mortality when compared to EI and early advancement with SV increment (risk ratio [95% credible interval]: 0.39 [0.12, 0.95]; 0.34 [0.10, 0.86]) (GRADE-very low). CONCLUSIONS: Early initiated, moderately early, or late advanced with MoV increment feeding regimens might be most appropriate in decreasing the risk of NEC stage ≥II or mortality. In view of the certainty of evidence being very low, adequately powered RCTs evaluating these 2 strategies are warranted.

[Newborn resuscitation and support of transition of infants at birth]. / Versorgung und Reanimation des Neugeborenen nach der Geburt: Leitlinien des European Resuscitation Council 2021.

The European Resuscitation Council has produced these newborn life support guidelines, which are based on the International Liaison Committee on Resuscitation (ILCOR) 2020 Consensus on Science and Treatment Recommendations (CoSTR) for Neonatal Life Support. The guidelines cover the management of the term and preterm infant. The topics covered include an algorithm to aid a logical approach to resuscitation of the newborn, factors before delivery, training and education, thermal control, management of the umbilical cord after birth, initial assessment and categorisation of the newborn infant, airway and breathing and circulation support, communication with parents, considerations when withholding and discontinuing support.