PURPOSE:To provide an expert consensus framework for standardizing lung ultrasound training for neonatologists. METHODS:We selected an international panel of 15 neonatologist experts in lung ultrasound, based on clinical and research expertise criteria. Ten questions were proposed by the chairs to the expert panel, who assessed their priority (using a 1-9 Likert-type scale). Five subgroups of 2 to 3 experts were identified to develop the statements for each clinical question; each expert contributed to developing 2 statements with their scientific rationale. All expert panelists, including the chairs, voted on all statements using a 1 to 9 Likert-type scale. A maximum of 2 rounds of voting was agreed as part of the modified Delphi process, although consensus on all the statements was reached after the first round. The statements were classified as agreement (range 7-9), uncertainty (4-6), or disagreement (1-3) when the median score and ≥ 75% of votes laid within the specific range. RESULTS:All 10 statements reached an agreement with a median score of 9 for 9 statements and of 8.5 for 1 statement. The percentage of level of agreement ranged between 80% and 100%. CONCLUSION:This consensus provides a framework for the development of neonatal lung ultrasound training program dedicated to neonatologists.

OBJECTIVE:Children with systemic rheumatologic diseases (SRD) and autoinflammatory diseases can experience life-threatening deterioration requiring intensive care. We conducted a retrospective cohort study with 2 complementary components: (1) a descriptive analysis of clinical presentations and outcomes; and (2) an exploratory derivation of a bedside risk-stratification tool, intended as a candidate severity overlay on established pediatric intensive care unit (PICU) scoring systems rather than as a fully validated general-purpose prognostic model. DESIGN:Retrospective observational cohort study with exploratory prognostic model development. Propensity-score matching was used as a secondary, descriptive analysis to contextualize outcomes against comparable populations and is not intended to support causal inference. SETTING:Single academic pediatric intensive care unit (January 2005 to December 2015). PATIENTS:Forty children with confirmed SRD requiring PICU admission (first admission per patient) and propensity-matched controls (2:1 ratio). MEASUREMENTS AND MAIN RESULTS:Nearly two-thirds (62.2%) of patients experienced their first disease manifestation as a life-threatening crisis. Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) was associated with the majority of deaths, accounting for 83.3% of fatalities despite representing only 20% of admissions (disease-specific mortality 62.5% vs. 6.3% for other diagnoses combined, p<0.001). Backward stepwise logistic regression identified 3 predictors that were combined, with equal weighting, into the exploratory PHV Score (PRISM-HLH-Vasoactive): Pediatric Risk of Mortality III (PRISM-III) at 24 hours >20, HLH/MAS diagnosis, and requirement for ≥2 vasoactive agents. In this derivation sample the score showed encouraging discrimination [apparent area under the curve (AUC) 0.91, 95% CI 0.83-0.99; optimism-corrected AUC 0.88]; however, given the very limited event count (n=6 deaths), wide CIs, and the fact that the PHV Score partially incorporates PRISM-III, head-to-head AUC comparisons with PRISM-III (AUC 0.72), PELOD-2 (Pediatric Logistic Organ Dysfunction-2; AUC 0.68), and pediatric SOFA (Sequential Organ Failure Assessment; AUC 0.64) should be interpreted with caution and regarded as hypothesis-generating. At the optimal cutoff of ≥2 (Youden index), sensitivity was 83.3% and specificity 91.2%; predictive values are prevalence-dependent and may not generalize to centers with different case mixes. CONCLUSIONS:In this retrospective single-center cohort, HLH/MAS was associated with most PICU deaths among children with systemic rheumatologic and autoinflammatory diseases. The PHV Score is an exploratory, candidate bedside tool that appears to refine risk stratification in our cohort but requires prospective multicenter external validation.

BACKGROUND:Infants who are small for gestational age (SGA) have a higher prevalence and severity of bronchopulmonary dysplasia than appropriate for gestational age (AGA) infants, but the evolution of their respiratory pathophysiology characteristics is unknown. RESEARCH QUESTION:Do SGA infants with moderate to severe bronchopulmonary dysplasia (msBPD) have different pathophysiological phenotypes (in terms of lung aeration and gas exchange) compared with AGA infants with msBPD? STUDY DESIGN AND METHODS:This was a secondary analysis of the Pathophysiology Phenotypes in Infants Developing BPD (PATH-BPD) multicenter cohort. Patients were classified as SGA if their birth weight was < 10th percentile or < -2 z scores. Lung aeration was assessed with quantitative lung ultrasound. Gas exchange was considered by using the peripheral hemoglobin saturation/Fio2 ratio, the transcutaneous Pao2/Fio2 ratio, and transcutaneous partial pressure of CO2. msBPD was defined by using the NIH-2001, NICHD-2018, and Jensen definitions. Data were analyzed by using linear mixed-effect regression models. RESULTS:Of 347 enrolled neonates, 62 and 32 infants were classified as SGA using the percentile and z score threshold, respectively. Regardless of the BPD definition and the growth classification, evolution of lung aeration (β varying between -0.32 and 0.23; P varying between .379 and .575), the peripheral hemoglobin saturation/Fio2 ratio (β varying between 0.78 and 6.1; P varying between .896 and .250), the transcutaneous Pao2/Fio2 ratio (β varying between -0.64 and 2.2; P varying between .936 and .700), and transcutaneous partial pressure of CO2 (β varying between -0.63 and 0.03; P varying between .295 and .968) was similar in SGA and AGA infants with msBPD. INTERPRETATION:The evolution of lung aeration and gas exchange in SGA and AGA patients with msBPD is similar, regardless of the BPD definition and growth classification.

Background We lack data about the early evolution of lung pathophysiology in infants developing moderate-to-severe broncho-pulmonary dysplasia (msBPD). We aimed to describe lung aeration and gas exchange during the early phase of msBPD development and identify the critical moments at which they change. Methods Prospective, multicentre, cohort study performed in three European centres enrolling preterm (≤30 weeks’ gestation) infants evaluated at 10, 21, 28 days (D) of life and 34 and 36 weeks (W) post-menstrual age, while receiving as little invasive ventilation as possible. Lung aeration was assessed with quantitative lung ultrasound. Pulse oximetry and transcutaneous blood gas measurements were used to calculate the SpO2/FiO2 and PtcO2/FiO2 ratios. msBPD was defined using NIH-2001, NICHD-2018 and Jensen definitions. Findings 347 infants were studied, of which 80, 79 and 89 had msBPD, using the three definitions, respectively. Lung aeration and oxygenation were always poorer, since D10, in patients with msBPD than in those without it. The difference in lung aeration (β ranging from +0.009 (95% CI: 0; 0.01) to +0.012 (95% CI: 0.01; 0.02), depending on the used definition, p < 0.001) and carbon dioxide (β ranging from +0.01 (95% CI: 0; 0.02) to +0.014 (95% CI: 0.01; 0.02), depending on the used definition, p < 0.001) between patients with and without msBPD increased overtime. Results were similar regardless of the BPD definition. The strongest discrimination was obtained by the lung aeration evolution (β(t) = 0.227 (95% CI: 0.152, 0.302), p < 0.001) with a peak at 26 days. Interpretation Patients who develop msBPD consistently demonstrate early and typical pathophysiological phenotypes regardless of the BPD definition. These data highlight critical moments in the development of msBPD and are not captured by currently available BPD definitions. Funding Only institutional funding to support the author's working time was used.

INTRODUCTION:The latest American Academy of Pediatrics guidelines for managing jaundice in late preterm and term neonates have increased the bilirubin thresholds to start phototherapy. This was considered safe based on expert consensus, but its cost-effectiveness has not yet been evaluated. METHODS:This was a before-and-after, quality improvement and pharmaco-economical evaluation of hospital financial data from a perinatal academic referral centre. RESULTS:Implementing the new guidelines decreased hospitalizations due to phototherapy by 68.7%, 70.2%, and 60% for the total population and the late preterm and term subgroups, respectively (p < 0.001 for the three analyses). The hospitalization costs were decreased from EUR 1,289,040 to EUR 423,120 (i.e., an absolute saving of EUR 865,920, or ≈68%, for the entire population composed by late preterm and term neonates). Implementing the new treatment threshold nationwide would entail an estimated cost reduction of EUR 191,964,324. CONCLUSIONS:The new jaundice guidelines significantly decreased the use of phototherapy and associated healthcare costs.

Objective. To evaluate the relationships between electrical cardiometry-derived index of contractility (ICON TM ) and standardized echocardiography measurements of left ventricular function. Study design. Prospective pilot cohort study recruiting preterm neonates after the transitional period without cardiovascular or respiratory failure. ICON TM , ejection (EF) and shortening fraction (SF) were simultaneously considered. EF and SF were calculated offline by a single investigator with formal expertise in echocardiography and unaware of the ICON TM values. Results. ICON TM weakly but significantly correlated with EF (ρ = 0.236, p = 0.009) and SF (ρ = 0.232, p = 0.011). Differences between ICON TM and EF or SF were positive (i.e. the ICON TM index overestimated both EF and SF) and increased at higher values. Multivariable models confirmed the significant associations between ICON TM , EF and SF after adjustment for gestational and postnatal age. Conclusions. These findings suggest that ICON™ could be used as a continuous monitoring tool without replacing echocardiographic measures.

Introduction Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity, characterised by impaired alveolarisation and pulmonary vascular development. BPD has been associated with an increased risk of respiratory morbidity, neurodevelopmental impairment and death, intensifying a lifelong health and economic burden. The current standard of neonatal care is primarily supportive, with no approved therapies to restore lung development, promote maturation and lung growth or prevent long-term sequelae. Therefore, there is a critical unmet need for novel interventions, particularly in high-risk, extremely premature (EP) infants. In EP infants, serum insulin-like growth factor-1 (IGF-1) levels decrease rapidly and remain low for the first weeks after birth relative to the corresponding foetal levels in utero.Methods and analysis OHB-607, a recombinant human IGF-1 combined with its binding protein-3, may replenish IGF-1 during this period of deficiency and support lung and vascular maturation. OHB-607 is being investigated as a first-line therapy to prevent severe BPD in EP infants in a Phase 2b, multicentre, open-label, randomised trial. Here, we present the Phase 2b study protocol. Target enrolment is 338 EP infants. To mimic physiological IGF-1 levels in utero, OHB-607 will be administered starting within 24 hours of birth until 29+6 weeks postmenstrual age (PMA) via continuous intravenous infusion. The primary endpoint is the incidence of severe BPD, based on the modified National Institute of Child Health and Human Development criteria, or death by 36 weeks PMA. Key secondary endpoints include weaning from respiratory support at 12 months corrected age and BPD severity (Grade 2/3) by the 2019 Neonatal Research Network definition. Other secondary endpoints include other complications of prematurity, neurodevelopmental outcomes and family and infant well-being and social functioning through 24 months’ corrected age, and pharmacokinetic and dynamic impact of OHB-607 on the multisystem consequences of prematurity, and overall safety in modifying the natural history of BPD and its consequences.Ethics and dissemination Findings will be disseminated via local and international congresses and publications.Trial registration number ClinicalTrials.gov (NCT03253263), Clinicaltrialsregister.eu (EudraCT: 2018-001393-16), Euclinicaltrials.eu (EUCT: 2024-515914-41-00) and Pmda.go.jp (PMDA: jRCT2031240339).

INTRODUCTION:Bronchopulmonary dysplasia (BPD) remains a major complication of prematurity. We aimed to assess whether intratracheal administration of budesonide mixed with surfactant reduces mortality and BPD in preterm infants. METHODS:We conducted a systematic review and meta-analysis of randomised and observational studies enrolling preterm neonates. PubMed, Scopus, and Web of Science were searched from inception to October 2025 without language or year restrictions. Studies comparing bolus administration of bovine or porcine surfactant mixed with budesonide versus surfactant alone were included. Random-effects meta-analyses using inverse variance weighting were performed to estimate risk ratios (RRs) with 95% confidence intervals (CIs). Certainty of evidence was assessed using GRADE. RESULTS:Twenty randomised and five observational studies were included. Surfactant-budesonide combination therapy reduced mortality (RR: 0.83, 95% CI: 0.69-0.99; 18 studies, 5,117 infants) and BPD (RR: 0.84, 95% CI: 0.75-0.94; 25 studies, 5,732 infants). Mortality reduction was observed when all studies were pooled, with no significant difference between study designs. Prenatal steroid exposure was associated with greater mortality reduction. Reduction in BPD remained significant when restricted to randomised trials, irrespective of surfactant type. Sensitivity analyses excluding studies at high risk of bias yielded similar results. Certainty of evidence was moderate for both outcomes. CONCLUSION:Surfactant combined with budesonide may reduce mortality and BPD in preterm infants. However, the evidence remains insufficient to recommend the combination as generalised primary treatment for all preterm neonates. Future studies should incorporate pathophysiological phenotyping to identify infants most likely to benefit.

In the sentence beginning with "High-frequency ventilation (HFV) maintains functional residual capacity and minimizes ventilator-induced lung injury by delivering subdead-space tidal volumes at supraphysiologic frequencies. Its performance depends on airway size and lung mechanics, making it effective in preterm infants with low compliance. HFV modalities include high-frequency jet ventilation, delivering rapid gas pulses with passive exhalation to improve gas exchange and support lung stabilization, especially in air-leak syndromes; high-frequency oscillatory ventilation, providing bidirectional oscillations at constant mean airway pressure, enabling alveolar recruitment while limiting volutrauma and atelectrauma, with volume-guarantee strategies enhancing stability and protection; and less common percussive or flow-interruption ventilation with limited neonatal evidence…" please link the citations to the references as appropriate.

BACKGROUND:Mechanical power estimates the amount of energy delivered to ventilated lungs, but there are no available data for neonates. This study aimed to provide a real-world description of power and investigate its relationship with clinical variables in neonates. METHODS:This was a cross-sectional study enrolling neonates of any gestational age. Patients were classified as recovering from respiratory distress syndrome, affected by neonatal acute respiratory distress syndrome, or with evolving bronchopulmonary dysplasia. Simultaneously collected ventilation and oxygenation data, as well as ultrasound-assessed lung aeration, were used; power was calculated with four different equations. RESULTS:A total of 100 (55 males) neonates (32 with respiratory distress syndrome, 30 with neonatal acute respiratory distress syndrome, 10 with evolving bronchopulmonary dysplasia, and 28 controls with no lung disease) were studied. Distributions of power and energy ( i.e. , power for a single breath) for the whole population were given (median power ranging between (interquartile range [25th, 75th percentile]) 0.28 [0.18, 0.39] and 0.39 [0.29, 0.54] J · min -1 · kg -1 , median energy ranging between 7.1 [4.9, 9.1] and 9.5 [6.8, 12.3] mJ/kg). Median power (difference varying between 0.21 and 0.9 J · min -1 · kg -1 [ P was always less than 0.001], depending on the equation used) and energy (difference varying between 0.9 and 3 mJ/kg [ P was always less than 0.001], depending on the equation used) were higher in neonates with respiratory failure than in controls. Components of power due to dynamic and static strain showed similar differences. Power correlated with oxygenation (adjusted ρ between 0.18 [95% CI, 0.02 to 0.34] and 0.22 [95% CI, 0.06 to 0.38]; P varying between 0.032 and 0.045) and lung aeration impairment (ρ between 0.25 [95% CI, 0.07 to 0.41] and 0.27 (95% CI, 0.08 to 0.43); P varying between 0.009 and 0.013, depending on the equation used). CONCLUSIONS:Mechanical power, its components due to dynamic and static strain, and energy are higher in neonates with respiratory disorders than in controls. Mechanical power and its components are correlated with impairment of oxygenation and lung aeration.

OBJECTIVES:To update evidence-based management recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with sepsis or septic shock. DESIGN:A panel of 68 international experts, representing 13 international organizations, as well as six methodologists, was convened. A formal conflict-of-interest policy was developed at the onset of the process and applied throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and subgroup leads as well as within subgroups, served as an integral part of the guideline development process. METHODS:New priority topics and recommendations from the prior guideline iteration were used to identify Population, Intervention, Control, and Outcomes (PICO) questions likely to have new or updated evidence. We conducted a systematic review to identify the best available evidence, summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or conditional, or as a good practice statement. "In our practice," statements were included when evidence was inconclusive to issue a recommendation but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS:The panel provided 61 statements on the management of children with sepsis or septic shock. Overall, five were strong recommendations, 24 were conditional recommendations, and ten were good practice statements. For 22 PICO questions, no recommendations could be made, but, for seven of these, "in our practice" statements were provided. Compared with the 2020 guidelines, 20 recommendations were new, 13 were updated for clarity and/or new evidence, six were reviewed but not changed, and 22 were carried forward based on consensus of the panel that new evidence was not available. Only three recommendations were based on high or moderate certainty of evidence. CONCLUSIONS:Updated management guidelines were issued by a panel of international experts for the best care of children with sepsis or septic shock, acknowledging that most aspects of care continue to have relatively low quality of evidence.