Antifungal Drug Usage in European Neonatal Units: A Multicenter Weekly Point Prevalence Study.

BACKGROUND: Data on antifungal prescribing in neonatal patients are limited to either single-center or single-country studies or to 1-day recording. Therefore, we assessed antifungal longitudinal usage in neonatal units (NUs) within Europe. METHODS: CALYPSO, a prospective weekly point prevalence study on antifungal drug usage in NUs in 18 hospitals (8 European countries), was conducted in 2020 during a 12-week period. All patients receiving systemic antifungals were included. Ward demographics were collected at the beginning; ward and patient data including indication, risk factors and antifungal regimen were weekly collected prospectively. RESULTS: Among 27 participating NUs, 15 (56%) practiced antifungal prophylaxis for neonates with birth weight <1000 g or <1500 g and additional risk factors. In total, 174 patients received antifungals with a median frequency per week of 10.5% ranging from 6.9% to 12.6%. Indication for antifungal prescribing was prophylaxis in 135/174 (78%) courses and treatment in 22% [39 courses (69% empirical, 10% preemptive, 21% targeted)]. Fluconazole was the most frequent systemic agent used both for prophylaxis (133/135) and treatment (15/39, 39%). Among neonates receiving prophylaxis, the most common risk factors were prematurity (119/135, 88%), mechanical ventilation (109/135, 81%) and central vascular catheters (89/135, 66%). However, gestational age <28 weeks was only recorded in 55/135 (41%) courses and birth weight <1000 g in 48/135 (35%). Most common reason for empirical treatment was late-onset sepsis; all 8 targeted courses were prescribed for invasive candidiasis. CONCLUSION: Antifungal usage in European NUs is driven by prophylaxis and empirical treatment with fluconazole being the most prescribed agent for both indications.

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.

Optimizing Oxygen Delivery by Low-Flow Nasal Cannula to Small Infants: A Bench Study.

BACKGROUND: In infants treated with a low-flow nasal cannula (LFNC), the oxygen concentration delivered to the lungs (i.e., the effective FiO2) is difficult to estimate. The existing mathematical formulas rely on important assumptions regarding the values of respiratory parameters and, thus, may be inaccurate. We aimed to assess oxygen delivery by LFNC to small infants using realistic simulations on a mechanical breathing model. METHODS: A mechanical breathing simulator (infant upper-airway replica, single-space breathing compartment, electric motor, microcontroller) was developed. Breathing simulations (n = 1200) were performed at various tidal volume (VT), inspiratory time (Ti), and respiratory rate (RR) combinations and different cannula flows. RESULTS: Minute ventilation (MV) was the most significant predictor of effective FiO2. FiO2 was higher at lower VT and higher Ti values. Benaron and Benitz's formula underestimated the effective FiO2 at lower MV values, while Finer's formula significantly overestimated it. A set of predictive FiO2 charts was developed based on cannula flow, infant body weight, and RR. CONCLUSIONS: The effective FiO2 delivered by LFNC to small infants critically depends on VT, Ti, and RR. However, since VT and Ti values are not available in clinical practice, the existing mathematical formulas may be inaccurate. Our novel predictive FiO2 charts could assist in optimizing oxygen delivery by LFNC using easy-to-obtain parameters, such as infant body weight and RR.

Use of neonatal lung ultrasound in European neonatal units: a survey by the European Society of Paediatric Research.

OBJECTIVE: Regarding the use of lung ultrasound (LU) in neonatal intensive care units (NICUs) across Europe, to assess how widely it is used, for what indications and how its implementation might be improved. DESIGN AND INTERVENTION: International online survey. RESULTS: Replies were received from 560 NICUs in 24 countries between January and May 2023. LU uptake varied considerably (20%-98% of NICUs) between countries. In 428 units (76%), LU was used for clinical indications, while 34 units (6%) only used it for research purposes. One-third of units had <2 years of experience, and only 71 units (13%) had >5 years of experience. LU was mainly performed by neonatologists. LU was most frequently used to diagnose respiratory diseases (68%), to evaluate an infant experiencing acute clinical deterioration (53%) and to guide surfactant treatment (39%). The main pathologies diagnosed by LU were pleural effusion, pneumothorax, transient tachypnoea of the newborn and respiratory distress syndrome. The main barriers for implementation were lack of experience with technical aspects and/or image interpretation. Most units indicated that specific courses and an international guideline on neonatal LU could promote uptake of this technique. CONCLUSIONS: Although LU has been adopted in neonatal care in most European countries, the uptake is highly variable. The main indications are diagnosis of lung disease, evaluation of acute clinical deterioration and guidance of surfactant. Implementation may be improved by developing courses and publishing an international guideline.

A Case Report of Salmonella enterica Meningitis in an Infant: A Rare Entity not to Forget.

INTRODUCTION: Salmonellae are gram-negative, facultatively anaerobic Enterobacteri-aceae consisting of two species, Salmonella enterica and Salmonella bongori. Invasive diseases, such as meningitis, result in hospitalization, short and long-term complications, and high mortality rates. CASE PRESENTATION: A 4-month-old baby girl was admitted to a district hospital because of diarrhea and fever. WBC count, urinalysis, urine cultures, and stool cultures were normal. She was treated with intravenous cefuroxime for 5 days. She was discharged on oral cefprozil for 5 days. After the end of therapy, she was admitted again to the same hospital with fever, diarrhea, vomits, and irri-tability. Cerebrospinal fluid examination revealed pleocytosis, while S. enterica was isolated. Em-pirical therapy with ceftriaxone, amikacin, and dexamethasone was started. Because of intracranial hypertension signs, she was transferred to the pediatric intensive care unit of our tertiary hospital. Therapy continued with intravenous ceftriaxone. Brain MRI revealed subarachnoid space dilata-tion. Increased head circumference and pulsating bregmatic fontanel led to a new cerebral MRI, in which ventricular dilatation and extraparenchymal subdural collection were noted. Ceftriaxone was changed to cefotaxime and ciprofloxacin was added. She remained clinically well; her brain MRI, a week later, showed marked improvement, and the course of intravenous antibiotics for 5 weeks was completed. Her baseline immunodeficiency screening tests were normal and repeat MRI two months post-treatment cessation did not reveal the previous abnormalities. CONCLUSION: Invasive Salmonella diseases, such as meningitis, are very uncommon in industrial countries nowadays, and the optimal management is yet not well established. Late onset of com-plications from Salmonella meningitis warrants more thorough neurodevelopmental follow-ups.

Soluble urokinase plasminogen activator receptor (suPAR) in children with obesity or type 1 diabetes as a marker of endothelial dysfunction: a cross-sectional study.

Pediatric obesity and type 1 diabetes mellitus (T1DM) represent two common chronic diseases associated with chronic inflammation, endothelial dysfunction and long-term complications. The aim of the present study was to assess the possible diagnostic and prognostic value of soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation and impaired endothelial function, in children with the diseases. In this cross-sectional study, children and adolescents with T1DM (N = 41) or obesity (N = 37), aged < 18 years old, and without proteinuria were included, together with children of similar age and without evident morbidity that served as controls (N = 42). Serum samples were obtained during standard outpatient follow up and the urokinase-type plasminogen activator receptor (suPAR) concentrations were measured using a commercially available sandwich ELISA kit (DUP00, R&D systems). Clinical and biochemical indices that were also assessed include body mass index (BMI) z-score, Tanner stages, glycosylated haemoglobin (HbA1c), fasting lipid profile and serum creatinine. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls. Also, serum suPAR levels showed a negative correlation with age (Spearman rho -0.359, p < 0.001) and serum creatinine levels (Spearman rho -0.334, p = 0.005), and a positive correlation with BMI z-score (Spearman rho 0.354, p = 0.009) in the whole cohort.  Conclusion: Serum suPAR may be a useful predictive marker of inflammation or endothelial dysfunction for children with obesity and T1DM, as well as a promising therapeutic target. Further studies are needed in order to clarify whether the reported differences in suPAR levels could reflect a greater impairment of the inflammation status and endothelial function in children with obesity compared to children with T1DM. What is Known: • Paediatric obesity and type 1 diabetes are characterised by chronic inflammation and metabolic dysregulation. • Urokinase plasminogen activator receptor (uPAR) has been proposed as a useful biomarker for chronic inflammation and cardiovascular risk in adults. What is New: • Serum suPAR levels were increased in children and adolescents with obesity compared to those with T1DM and healthy controls; thus, obesity may affect the inflammatory status and endothelial function to a higher degree than T1DM during childhood. • Serum suPAR may serve as a diagnostic and predictive marker of inflammation and endothelial dysfunction for children and adolescents with obesity and T1DM.

Daptomycin Use for Persistent Coagulase-Negative Staphylococcal Bacteremia in a Neonatal Intensive Care Unit.

During the last two decades, the incidence of late-onset sepsis (LOS) has increased due to improved survival of premature neonates. Persistent bacteremia (PB) in LOS is defined as more than two positive blood cultures obtained on different calendar days during the same infectious episode. Although rare, PB should be treated aggressively to prevent adverse outcomes. Daptomycin, a lipopeptide antibiotic, has been used in neonates with persistent coagulase-negative staphylococci (CoNS) bacteremia with promising results, but studies reporting on the efficacy and safety of the agent are scarce. The purpose of this study was to evaluate the efficacy and safety of daptomycin use for persistent CoNS bacteremia in a neonatal cohort. This is a retrospective, observational, single-center study of neonates treated with daptomycin during 2011-2022 in the Tertiary Neonatal Intensive Care Unit (NICU) of the University General Hospital of Patras, Greece. For the years 2011-2022, there were 3.413 admissions to the NICU. During the last 3 years (2020-2022)-the active epidemiological surveillance period-123 infants (out of 851 admissions, 14.4%) developed CoNS bacteremia (LOS). During the study period, twelve infants with PB were treated with daptomycin. They had a median gestational age of 32 weeks (IQR 31-34) and mean (SD) birth weight of 1.840 (867) grams. CoNS bacteremia isolates were s. epidermidis (50%), s. haemolyticus (20%), s. hominis (20%) and s. warneri (10%). The decision to start daptomycin (6 mg/kg/dose twice daily) was taken on median day 10 (ΙQR 7-15) of infection. None of the infants had focal complications or meningitis. Daptomycin therapy caused no renal, hepatic, muscular or gastrointestinal adverse events. One neonate developed seizures, and one death occurred due to multiple complications of prematurity. Most infants (11/12) were successfully treated and eventually had negative blood culture. Daptomycin monotherapy showed an adequate cure rate in premature neonates with persistent CoNS bacteremia in a tertiary NICU. In our study, daptomycin was effective and well tolerated; the safety profile, however, needs to be confirmed in larger studies and randomized controlled trials.

Flow-resistive loading and diaphragmatic muscle function in term and preterm infants.

PURPOSE: We aimed to assess diaphragmatic function in term and preterm infants with and without history of bronchopulmonary dysplasia (BPD), before and after the application of inspiratory flow resistive loading. METHODS: Forty infants of a median (range) gestational age of 34 (25-40) weeks were studied. BPD was defined as supplemental oxygen requirement for >28 days of life. Seventeen infants were term, 17 preterm without history of BPD, and six preterm with a history of BPD. The diaphragmatic pressure-time index (PTIdi) was calculated as the mean to maximum trans-diaphragmatic pressure ratio times the inspiratory duty cycle. The PTIdi was calculated before and after the application of an inspiratory-flow resistance for 120 s. Airflow was measured by a pneumotachograph and the transdiaphragmatic pressure by a dual pressure catheter. RESULTS: The median (interquartile range [IQR]) pre-resistance PTIdi was higher in preterm infants without BPD (0.064 [0.050-0.077]) compared with term infants (0.052 [0.044-0.062], p = .029) and was higher in preterm infants with BPD (0.119 [0.086-0.132]) compared with a subgroup of preterm infants without BPD (0.062 [0.056-0.072], p = .004). The median (IQR) postresistance PTIdi was higher in preterm infants without BPD (0.101 [0.084-0.132]) compared with term infants (0.067 [0.055-0.083], p < .001) and was higher in preterm infants with BPD [0.201(0.172-0.272)] compared with the preterm subgroup without BPD (0.091 [0.081-0.108],p = .004). The median (IQR) percentage change of the PTIdi after the application of the resistance was higher in preterm infants without BPD (65 [51-92] %) compared with term infants (34 [20-39] %, p < .001). CONCLUSIONS: Preterm infants, especially those recovering from BPD, are at increased risk of diaphragmatic muscle fatigue under conditions of increased inspiratory loading.

Monocyte Chemoattractant Protein-1 (MCP-1), Activin-A and Clusterin in Children and Adolescents with Obesity or Type-1 Diabetes Mellitus.

Inflammation plays a crucial role in diabetes and obesity through macrophage activation. Macrophage chemoattractant protein-1 (MCP-1), activin-A, and clusterin are chemokines with known roles in diabetes and obesity. The aim of this study is to investigate their possible diagnostic and/or early prognostic values in children and adolescents with obesity and type-1 diabetes mellitus (T1DM). METHODS: We obtained serum samples from children and adolescents with a history of T1DM or obesity, in order to measure and compare MCP-1, activin-A, and clusterin concentrations. RESULTS: Forty-three subjects were included in each of the three groups (controls, T1DM, and obesity). MCP-1 values were positively correlated to BMI z-score. Activin-A was increased in children with obesity compared to the control group. A trend for higher values was detected in children with T1DM. MCP-1 and activin-A levels were positively correlated. Clusterin levels showed a trend towards lower values in children with T1DM or obesity compared to the control group and were negatively correlated to renal function. CONCLUSIONS: The inflammation markers MCP-1, activin-A, and clusterin are not altered in children with T1DM. Conversely, obesity in children is positively correlated to serum MCP-1 values and characterized by higher activin-A levels, which may reflect an already established systematic inflammation with obesity since childhood.

Cardiopulmonary Exercise Performance of Children Born Non-Extremely Preterm.

Data on exercise tolerance of children born non-extremely preterm are sparse. We aimed to explore the cardiopulmonary exercise testing (CPET) characteristics in this population. We studied 63 children (age 7-12 years) born at 290/7-366/7 weeks of gestation (34 were late preterm, 29 were preterm) and 63 age-matched, term-born controls. All performed spirometry and CPET (cycle ergometry). There were no differences in activity levels and spirometric parameters between the group of preterm-born children and controls. A peak oxygen uptake (VO2peak) of <80% was noted in 25.4% of the term-born and 49.2% of preterm-born children (p = 0.001). Term-born participants presented similar VO2peak to late-preterm children but higher than those born at <340/7 weeks of gestation (p = 0.002). Ventilatory limitation was noted in 4.8% of term and 7.9% of preterm participants, while only one preterm child presented cardiovascular limitation. Children born before 34 weeks of gestation had higher respiratory rates and smaller tidal volumes at maximum exercise, as well as lower oxygen uptake for the level of generated work. We conclude that school-age children born at 29-34 weeks of gestation may present decreased exercise performance attributed to an altered ventilatory response to exercise and impaired O2 utilization by their skeletal muscles rather than other cardiopulmonary limiting factors.

Multisystem inflammatory syndrome in children (MIS-C): A nationwide collaborative study in the Greek population.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe hyperinflammatory condition that may occur following SARS-CoV-2 infection. This retrospective, descriptive study of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) in 12 tertiary care centers from 3/11/2020 to 12/31/2021. Demographics, clinical and laboratory characteristics, treatment and outcomes are described. Among 145 patients (95 males, median age 8.2 years) included, 123 met the WHO criteria for MIS-C, while 112 (77%) had serological evidence of SARS-CoV-2 infection. Fever was present in 99%, gastrointestinal symptoms in 77%, mucocutaneous involvement in 68% and respiratory symptoms in 28%. Fifty-five patients (38%) developed myocarditis, 29 (20%) pericarditis and 19 (13%) coronary aneurysms. Among the above cases 11/55 (20%), 1/29 (3.4%) and 5/19 (26.3%), respectively, cardiac complications had not fully resolved at discharge. Underlying comorbidities were reported in 18%. Median CRP value was 155 mg/l, ferritin 535 ng/ml, PCT 1.6 ng/ml and WBC 14.2 × 109/mm3. Most patients had elevated troponin (41.3%) and/or NT-pro-BNP (49.6%). Intravenous immunoglobulin plus corticosteroids were used in 117/145 (80.6%), monotherapy with IVIG alone in 13/145 (8.9%) and with corticosteroids alone in 2/145 (1.3%). Anti-IL1 treatment was added in 15 patients (10.3%). Thirty-three patients (23%) were admitted to the PICU, 14% developed shock and 1 required ECMO. Mortality rate was 0.68%. The incidence of MIS-C was estimated at 0.69/1000 SARS-CoV-2 infections. Patients who presented with shock had higher levels of NT-pro-BNP compared to those who did not (p < 0.001). Acute kidney injury and/or myocarditis were associated with higher risk of developing shock. CONCLUSION: MIS-C is a novel, infrequent but serious disease entity. Cardiac manifestations included myocarditis and pericarditis, which resolved in most patients before discharge. Timely initiation of immunomodulatory therapy was shown to be effective. NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. Further research is required to elucidate the pathogenesis, risk factors and optimal management, and long-term outcomes of this clinical entity. WHAT IS KNOWN: • MIS-C is an infrequent but serious disease entity. • Patients with MIS-C present with multi-organ dysfunction, primarily involving the gastrointestinal and cardiovascular systems. WHAT IS NEW: • NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. • Acute kidney injury and/or myocarditis were associated with higher risk of developing shock.

Knowledge and attitudes of medical students about clinical aspects of congenital cytomegalovirus infection in newborns: A nationwide cross-sectional study in Greece.

Introduction: Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide causing severe morbidity in newborns, infants, and children. Despite the clinical importance of congenital CMV (cCMV) infection, studies conducted so far indicate that there is limited awareness in the medical community in the field. The aim of this study was to assess Greek medical students' knowledge on cCMV infection. Methods: We performed a questionnaire-based nationwide cross-sectional study. A convenience sample of medical students from seven medical schools was enrolled. Results: Of the 562 respondents, 54,8% considered themselves undereducated on cCMV infection. However, almost half of the participants could correctly recognize some basic principles of cCMV infection including ways of transmission, diagnosis and treatment, while there were aspects of cCMV infection with knowledge deficit. The year of study had a positive impact on the level of knowledge with students of higher years of study being of more sufficient education on the specific topic. Conclusion: Overall, our study indicates a discrepancy between self-reported awareness and the level of knowledge among medical students in Greece. Further educational opportunities about cCMV should be offered, particularly in areas of the curriculum involving the care of women and children. Establishing medical students' solid background on the disease burden and educating them about preventative strategies for at-risk populations, should be the main pillars of such efforts in order to promote confidence in managing these cases in their future professional careers.

The effects of cerebral oximetry in mechanically ventilated newborns: a protocol for the SafeBoosC-IIIv randomised clinical trial.

BACKGROUND: The SafeBoosC project aims to test the clinical value of non-invasive cerebral oximetry by near-infrared spectroscopy in newborn infants. The purpose is to establish whether cerebral oximetry can be used to save newborn infants' lives and brains or not. Newborns contribute heavily to total childhood mortality and neonatal brain damage is the cause of a large part of handicaps such as cerebral palsy. The objective of the SafeBoosC-IIIv trial is to evaluate the benefits and harms of cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. METHODS/DESIGN: SafeBoosC-IIIv is an investigator-initiated, multinational, randomised, pragmatic phase-III clinical trial. The inclusion criteria will be newborns with a gestational age more than 28 + 0 weeks, postnatal age less than 28 days, predicted to require mechanical ventilation for at least 24 h, and prior informed consent from the parents or deferred consent or absence of opt-out. The exclusion criteria will be no available cerebral oximeter, suspicion of or confirmed brain injury or disorder, or congenital heart disease likely to require surgery. A total of 3000 participants will be randomised in 60 neonatal intensive care units from 16 countries, in a 1:1 allocation ratio to cerebral oximetry versus usual care. Participants in the cerebral oximetry group will undergo cerebral oximetry monitoring during mechanical ventilation in the neonatal intensive care unit for as long as deemed useful by the treating physician or until 28 days of life. The participants in the cerebral oximetry group will be treated according to the SafeBoosC treatment guideline. Participants in the usual care group will not receive cerebral oximetry and will receive usual care. We use two co-primary outcomes: (1) a composite of death from any cause or moderate to severe neurodevelopmental disability at 2 years of corrected age and (2) the non-verbal cognitive score of the Parent Report of Children's Abilities-Revised (PARCA-R) at 2 years of corrected age. DISCUSSION: There is need for a randomised clinical trial to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. TRIAL REGISTRATION: The protocol is registered at www. CLINICALTRIALS: gov (NCT05907317; registered 18 June 2023).

Diaphragmatic muscle function in term and preterm infants.

We aimed to assess the determinants of diaphragmatic function in term and preterm infants. 149 infants (56 term; 93 preterm, of whom 14 were diagnosed with bronchopulmonary dysplasia-BPD) were studied before discharge. Diaphragmatic function was assessed by measurement of the maximum transdiaphragmatic pressure (Pdimax)-a measure of diaphragmatic strength, and the pressure-time index of the diaphragm (PTIdi)-a measure of the load-to-capacity ratio of the diaphragm. The Pdimax was higher in term than preterm infants without BPD (90.1 ± 16.3 vs 81.1 ± 11.8 cmH2O; P = 0.001). Term-born infants also had lower PTIdi compared to preterms without BPD (0.052 ± 0.014 vs 0.060 ± 0.017; P = 0.006). In term and preterm infants without BPD, GA was the most significant predictor of Pdimax and PTIdi, independently of the duration of mechanical ventilation and oxygen support. In infants with GA < 32 weeks (n = 30), the Pdimax was higher in infants without BPD compared to those with BPD (76.1 ± 11.1 vs 65.2 ± 11.9 cmH2O; P = 0.015). Preterms without BPD also had lower PTIdi compared to those with BPD (0.069 ± 0.016 vs 0.109 ± 0.017; P < 0.001). In this subgroup, GA was the only significant independent determinant of Pdimax, while BPD and the GA were significant determinants of the PTIdi.  Conclusions: Preterm infants present lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. In very preterm infants, BPD may further aggravate diaphragmatic function. What is Known: • The diaphragm of preterm infants has limited capacity to undertake the work of breathing effectively. • The maximum transdiaphragmatic pressure (a measure of diaphragmatic strength) and the pressure-time index of the diaphragm (a measure of the load-to-capacity ratio of the muscle) have not been extensively assessed in small infants. What is New: • Preterm infants have lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. • In very preterm infants, bronchopulmonary dysplasia may further impair diaphragmatic function.

Cerebral oximetry monitoring versus usual care for extremely preterm infants: a study protocol for the 2-year follow-up of the SafeBoosC-III randomised clinical trial.

BACKGROUND: In the SafeBoosC-III trial, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the incidence of death or severe brain injury in extremely preterm infants at 36 weeks' postmenstrual age, as compared with usual care. Despite an association between severe brain injury diagnosed in the neonatal period and later neurodevelopmental disability, this relationship is not always strong. The objective of the SafeBoosC-III follow-up study is to assess mortality, neurodevelopmental disability, or any harm in trial participants at 2 years of corrected age. One important challenge is the lack of funding for local costs for a trial-specific assessment. METHODS: Of the 1601 infants randomised in the SafeBoosC-III trial, 1276 infants were alive at 36 weeks' postmenstrual age and will potentially be available for the 2-year follow-up. Inclusion criteria will be enrollment in a neonatal intensive care unit taking part in the follow-up study and parental consent if required by local regulations. We aim to collect data from routine follow-up programmes between the ages of 18 and 30 months of corrected age. If no routine follow-up has been conducted, we will collect informal assessments from other health care records from the age of at least 12 months. A local co-investigator blinded to group allocation will classify outcomes based on these records. We will supplement this with parental questionnaires including the Parent Report of Children's Abilities-Revised. There will be two co-primary outcomes: the composite of death or moderate or severe neurodevelopmental disability and mean Bayley-III/IV cognitive score. We will use a 3-tier model for prioritisation, based on the quality of data. This approach has been chosen to minimise loss to follow-up assuming that little data is better than no data at all. DISCUSSION: Follow-up at the age of 2 years is important for intervention trials in the newborn period as only time can show real benefits and harms later in childhood. To decrease the risk of generalisation and data-driven biased conclusions, we present a detailed description of the methodology for the SafeBoosC-III follow-up study. As funding is limited, a pragmatic approach is necessary. TRIAL REGISTRATION: ClinicalTrials.gov NCT05134116 . Registered on 24 November 2021.

Diabetic Ketoacidosis in Children and Adolescents; Diagnostic and Therapeutic Pitfalls.

Diabetic ketoacidosis (DKA) represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM) primarily and, occasionally, Type 2 Diabetes Mellitus (T2DM) in children and adolescents. It is characterized by the biochemical triad of hyperglycaemia, ketonaemia and/or ketonuria, and acidaemia. Clinical symptoms include dehydration, tachypnoea, gastrointestinal symptoms, and reduced level of consciousness, precipitated by a variably long period of polyuria, polydipsia, and weight loss. The present review aims to summarize potential pitfalls in the diagnosis and management of DKA. A literature review was conducted using the Pubmed/Medline and Scopus databases including articles published from 2000 onwards. Diagnostic challenges include differentiating between T1DM and T2DM, between DKA and hyperosmolar hyperglycaemic state (HHS), and between DKA and alternative diagnoses presenting with overlapping symptoms, such as pneumonia, asthma exacerbation, urinary tract infection, gastroenteritis, acute abdomen, and central nervous system infection. The mainstays of DKA management include careful fluid resuscitation, timely intravenous insulin administration, restoration of shifting electrolyte disorders and addressing underlying precipitating factors. However, evidence suggests that optimal treatment remains a therapeutic challenge. Accurate and rapid diagnosis, prompt intervention, and meticulous monitoring are of major importance to break the vicious cycle of life-threatening events and prevent severe complications during this potentially fatal medical emergency.

Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Early Diagnosis of Late-Onset Neonatal Sepsis Using a Sepsis Prediction Score.

Sepsis represents a common cause of morbidity in the Neonatal Intensive Care Unit (NICU). Our objective was to assess the value of clinical and laboratory parameters in predicting septicemia (positive blood culture) in NICU infants. In the first part of the present study (derivation cohort) we retrospectively reviewed the clinical files of 120 neonates with symptoms of suspected sepsis and identified clinical and laboratory parameters associated with proven sepsis on the day the blood culture was taken, as well as 24 h and 48 h earlier. These parameters were combined into a sepsis prediction score (SPS). Subsequently (validation study), we prospectively validated the performance of the SPS in a cohort of 145 neonates. The identified parameters were: temperature instability, platelet count < 150,000/mm3, feeding volume decrease > 20%, changes in blood glucose > 50%, CRP > 1 mg/dL, circulatory and respiratory deterioration. In the retrospective cohort, on the day the blood culture was obtained, a SPS ≥ 3 could predict sepsis with 82.54% sensitivity, 85.96% specificity, 5.88 PLR (Positive Likelihood Ratio), 0.20 NLR (Negative Likelihood Ratio), 86.67% PPV (Positive Predictive Value), 81.67% NPV (Negative Predictive Value) and 84.17% accuracy. In the prospective cohort, on the day the blood culture was obtained, a SPS ≥ 3 could predict sepsis with 76.60% sensitivity, 72.55% specificity, 2.79 PLR, 0.32 NLR, 83.72% PPV, 62.71% NPV and 75.17% accuracy. We concluded that this combination of clinical and laboratory parameters may assist in the prediction of septicemia in NICUs.

Validation of a non-invasive pressure-time index of the inspiratory muscles in spontaneously breathing newborn infants.

To validate the pressure-time index of the inspiratory muscles as a non-invasive index of inspiratory muscle function in spontaneously breathing infants by comparing it against the gold-standard pressure-time index of the diaphragm. Prospective observational cohort study of consecutive infants breathing unsupported in room air in a tertiary neonatal intensive care unit, studied prior to discharge from neonatal care. The invasive pressure-time index of the diaphragm was calculated using a transdiaphragmatic dual-pressure catheter that measured transdiaphragmatic pressure by subtraction of the oesophageal from the gastric pressure. The non-invasive pressure-time index of the inspiratory muscles was calculated using pressure measurements at the level of the mouth via a differential pressure transducer connected to a face mask. Both indices were calculated as the product of the ratio of the mean inspiratory pressure divided by the maximum inspiratory pressure and the ratio of the inspiratory time divided by the total time of a respiratory cycle. One hundred and thirty infants (79 male) were included with a mean (SD) gestational age of 35.2 (3.2) weeks, studied at a median (IQR) postnatal age of 9 (6-20) days. The mean (SD) pressure-time index of the diaphragm was 0.063 (0.019) and the mean (SD) pressure-time index of the inspiratory muscles was 0.065 (0.023). The correlation coefficient for the two indices was 0.509 (p < 0.001). The mean (SD) absolute difference between the pressure-time index of the inspiratory muscles and pressure-time index of the diaphragm was 0.002 (0.021). In convalescent infants, the non-invasive pressure-time index of the inspiratory muscles had a moderate degree of correlation with the invasively derived pressure time index of the diaphragm measured with a transdiaphragmatic catheter.

Preterm newborns exposed to early-onset preeclampsia have altered postnatal Tumor Necrosis Factor-related apoptosis-inducing ligand trends versus controls.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein with anti-atherogenic and vasoprotective effects that has never been studied in newborns exposed to preeclampsia. Our aim was to examine TRAIL serum concentrations in such neonates after birth and during the transitional period. METHODS: Serum TRAIL levels were measured on the first and fifth day of life (DOL1 and DOL5, respectively) in 38 newborns exposed to early-onset preeclampsia and 38 controls born of normotensive mothers. RESULTS: TRAIL values on DOL1 and DOL5 did not differ between cases and controls. However, from DOL1 to DOL5 TRAIL levels increased in controls (from 20.54 ± 7.35 to 23.93 ± 11.02 pg/ml, p = 0.044) but decreased in those exposed to preeclampsia (from 25.58 ± 15.74 to 20.53 ± 10.72 pg/ml, p = 0.035). Overall, the relative change of TRAIL values from DOL1 to DOL5 was positively related to birth weight (beta coefficient 0.234, p = 0.042) and inversely related to preeclampsia (beta coefficient -0.241, p = 0.036). CONCLUSION: Newborns exposed to early-onset preeclampsia present a decrease in serum TRAIL levels during the transitional period. This pattern is exactly the opposite from what is observed in neonates born to normotensive mothers, and most likely points towards a defective mechanism of extrauterine adaptation related to preeclampsia exposure in utero. IMPACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels during the transitional period do not differ between infants exposed to early-onset preeclampsia and controls The pattern of change of TRAIL levels after birth is different; TRAIL decreases in newborns exposed to preeclampsia but increases in controls The decrease of TRAIL levels during the transitional period points towards a defective mechanism of extrauterine adaptation and an altered cardiometabolic profile in newborns exposed to early-onset preeclampsia.