European Journal of Pediatrics最新文献

Kawasaki disease (KD) is an acute vasculitis affecting medium-sized vessels and characterized by fever lasting more than 5 days. Differential diagnosis of KD is challenging. Microribonucleic acids (miRNA/miR) have been widely studied as potential biomarkers for diagnosing KD. The objective of this study is to systematically review the clinical utility of miRNAs in KD. This systematic review followed the PRISMA 2020 guidelines. We included English-language, full-text observational studies enrolling adult and/or pediatric patients with KD (complete or incomplete) which quantified miRNA expression levels or genotyped single-nucleotide polymorphisms (SNPs) in miRNA genes. We searched the following databases: Embase, Medline Ultimate, PubMed, Scopus, and Web of Science. Each database was last searched on January 12, 2026. Thirty-six studies met the eligibility criteria and were included in this review. The most reproducible finding concerns miR-223 which has been repeatedly reported to be upregulated in KD patients compared with both healthy and febrile controls. Several miRNAs have been described to distinguish specific KD phenotypes, e.g., coronary artery lesion (CAL) formation and intravenous immunoglobulin (IVIG) responsiveness. The majority of investigated SNPs in miRNA genes were not associated with KD susceptibility; however, some associations were reported, including with KD phenotypes such as CAL formation.Conclusions: Multiple studies have shown dysregulation of miRNA expression in KD patients and the potential utility of miRNAs in diagnosing KD and identifying individuals at risk of CAL formation or IVIG resistance. Nevertheless, there is a need for methodological standardization in future research and for studies including multiethnic cohorts. What's Known? • No single test for Kawasaki Disease is available; it can be diagnosed in patients meeting the clinical criteria. • Microribonucleic acids are promising biomarkers in various cardiovascular conditions including Kawasaki Disease. What's New? • To the best of our knowledge, this is the first systematic review evaluating microribonucleic acids in Kawasaki Disease using PRISMA guidelines. • Studies regarding the role of microribonucleic acids in Kawasaki Disease are highly heterogeneous but several of them display significant potential as diagnostic biomarkers.

Following the SARS-CoV-2 pandemic, a significant percentage of people are now experiencing long-term symptoms, despite a continuing lack of concrete documentation of physiological and risk profiles that hinders diagnosis and treatment, particularly in pediatric contexts. This review aims to highlight the existing evidence for measurable physiological markers for post-acute sequelae of SARS-CoV-2 infection (long COVID) in children, adolescents, and young adults. Titles providing data related to measurable biomarkers distinguishing young long COVID patients from controls were compiled and analyzed. Results were displayed in table and diagram form for optimal qualitative evaluation of the relationship between markers and symptomatology within the context of each organ system. Only human studies published in English, Italian, Portuguese, German, and Spanish between the 5th of February 2025 and the 31st of December 2025 were considered, and no other time constraints were applied. Following search and criteria evaluation, nine studies were included, totaling 41 occurrences identified in diseased patients with statistically significant variation from healthy controls. Markers suggest the presence of organic manifestations based on published literature, although more data and future studies will be necessary to establish clear connections.

Conclusion: The data compiled for this review adds to the body of evidence indicating a physiological manifestation of long COVID and its consequences. Further investigation into potential risk factors, pre- and post-pubescent manifestations, and specific inflammatory and immune pathways will be necessary for a more concrete understanding of long COVID and its effects on children, adolescents, and young adults.

What is known: • Long COVID is estimated to affect a significant population of patients, despite the lack of concrete physiological diagnostic and prognostic measures. • Pediatric incidence of the disease is still largely debated, and published data are scarce.

What is new: • A total of 41 biomarker occurrences were identified by selected studies, which were consistent with expected physiology behind reported symptoms. • The body of data discussed suggests the presence of physiological phenomena behind the long-term symptoms experienced by pediatric long- COVID patients.

Umbilical cord clamping management may affect cerebral oxygenation (rSO₂C), but previous studies have only investigated effects in the first minutes of life. Our objective was to determine whether delayed cord clamping (DCC) and umbilical cord milking (UCM) differently affect cerebral oxygenation and cardiovascular function in the first 24 h of life in preterm infants. A post-hoc secondary outcome analysis of a multicentre prospective randomised clinical trial (PCI), conducted between April 2016 and February 2023 at 8 Italian neonatal intensive care units. The present ancillary study included preterm infants with 23⁺⁰-29⁺⁶ 30 weeks' gestation. One hundred and five infants received DCC and 104 UCM during resuscitation. Cerebral regional tissue oxygenation (rSO₂C) was measured by near-infrared spectroscopy (NIRS) at 3 (T_3h), 6 (T_6h), 12 (T_12h), 18 (T_18h), and 24 (T_24h) hours of life. Cardiovascular function was assessed by echocardiography within the first 24 h of life. We found that rSO₂C was higher at T_3h [79 (76-84) vs. 78% (74-82), P = 0.04)] and T_12h [79 (76-83) vs. 78% (74-80), P = 0.01] in the DCC than in the UCM group. Left ventricular output (LVO) was lower [196 (182-301) vs. 232 (182-301) ml/Kg/min, P = 0.02] in the DCC than in the UCM group, while right ventricular output (RVO) and superior vena cava (SVC) flow were similar. The need for dopamine was higher (26 vs. 23%, P = 0.02) in the in the DCC than in the UCM group.Conclusion: rSO₂C was transiently higher in preterm infants resuscitated with DCC in comparison with UCM, but this difference was not clinically relevant. The lower LVO value in the DCC group compared to the UCM group deserves further studies to be confirmed and interpreted.

Postoperative respiratory events are a common complication of tonsillectomy for pediatric obstructive sleep apnea (OSA). Despite identified risk factors, there are no validated criteria for systematic postoperative intensive care unit (ICU) admission. In France, an apnea-hypopnea index (AHI) ≥ 10 events/h is a recommended criterion. This study aimed to assess the incidence and risk factors of early postoperative respiratory complications in children undergoing tonsillectomy for OSA with planned ICU admission. We conducted an observational study of children undergoing tonsillectomy between January 2020 and December 2022, with a preoperative ICU indication. Respiratory events were defined as a need of oxygen therapy, noninvasive ventilation (NIV), or tracheal intubation. Collected data included anthropometrics, comorbidities, AHI, gas exchange parameters, and surgical details. Univariate and multivariate analyses were performed for potential risk factors associated with postoperative respiratory complications. 166 children were included (median age 3 years [IQR 2-5]). The median preoperative AHI was 25 events/hour [13-43]. Overall, 159 (96%) patients had at least one comorbidity (45 Down syndrome, 31 obesity and 25 craniofacial malformations). Thirty-four (21%) patients had a respiratory complication: 30 needed oxygen therapy, 4 required NIV. None required an intubation. Age (p < 0.001), percentage of sleep time spent with an Oxygen saturation level < 85% (T85) and < 90% (T90) (p = 0.02 and p = 0.03, respectively) and McGill Oximetry Score (p = 0.01) were significantly associated with respiratory events, whereas neither AHI nor comorbidities showed a significant association. Conclusion: This study highlights the limited value of AHI alone in predicting respiratory complications post-tonsillectomy.

This study aimed to describe the implementation and functioning of a regional hub-and-spoke model ("Gaslini Diffuso") for managing pediatric bronchiolitis in Liguria, Italy, during the 2023-2024 season, focusing on severity stratification, resource allocation, and outcomes. A retrospective observational study was conducted across one tertiary hub (IRCCS Istituto Giannina Gaslini, Genoa) and four affiliated spoke hospitals. Medical records of all patients aged 0-2 years hospitalized with bronchiolitis (ICD-9-CM 466.19) between October 2023 and March 2024 were reviewed. Demographic, clinical, microbiological, and treatment data were analyzed. Predictors of centralization to the hub were identified through multivariable logistic regression. A total of 562 patients were included (median age 95 days; 40.4% female). Most cases were mild to moderate, with 56.6% requiring respiratory support-mainly low-flow oxygen or HFNC-and only 2% requiring mechanical ventilation. Thirteen patients (2.3%) were admitted to the PICU, and no deaths occurred. Centralized patients (n = 10) were significantly younger (median 43.5 days) and had higher severity indicators, including elevated CO₂ and CRP levels, and longer respiratory support (median 5 vs. 3-4 days, p < 0.001). Independent risk factors for centralization were age < 60 days (OR 23.1, p = 0.004) and HFNC use (OR 20.5, p = 0.006). Spoke centers showed homogeneous adherence to referral criteria, though some variability in ancillary treatments persisted.

Conclusions:  The Ligurian hub-and-spoke model demonstrated internal consistency between referral criteria and observed patient severity, supporting appropriate case stratification within the regional network. This integrated framework enhanced regional coordination and represents a scalable, sustainable model for pediatric respiratory disease management.

What is known: • Bronchiolitis is the leading cause of hospitalization in infants under two, with seasonal surges that may overwhelm pediatric services; management remains largely supportive. • Hub-and-spoke models have been proposed to optimize care and resource allocation, but real-world data on their clinical and organizational impact, especially post-COVID, is limited.

What is new: • This study evaluates, for the first time in Italy, the real-world implementation of a regional hub-and-spoke model (Gaslini Diffuso) for bronchiolitis management. • The model enabled effective stratification of disease severity, with high specificity in centralizing only the most critical cases, ensuring efficient use of pediatric intensive care resources.

Leukemia is the most common cancer among children, and although the treatment of the condition has significantly improved survival rates and outcomes, children of school age experience considerable and continuing challenges in the physical, psychological, and social spheres when having to undergo treatment. In this situation, teaching self-care skills becomes vital to help children patients control their condition, adhere to therapy, and positively improve their quality of life. This review examines the last decade of literature on self-care skills in school-aged children with leukemia. Current programs target medical, psychological, educational, and technology-enhanced self-care, addressing both treatment adherence and psychosocial resilience. All these interventions are promising in enhancing treatment outcomes, psychological, and real functioning. Nevertheless, some significant problems exist in the field, such as the lack of unified models, longitudinal follow-up, and culturally and resource-sensitive methods. The approach to these gaps will be creative, multi-disciplinary, and technologically oriented, which will involve families, schools, and healthcare providers in the process of self-care. In the future, integrating self-care skills training in pediatric cancer care and policy may be able to change the supportive care in childhood leukemia and equip young patients with lifelong coping skills and the capacity to remain resilient beyond therapy.

Conclusion:  Self-care skills training represents a vital component of supportive care in pediatric leukemia; however, future efforts should focus on developing unified models and multidisciplinary, family-centered approaches. Integrating self-care education into routine clinical practice and policy may strengthen long-term resilience and quality of life for childhood leukemia survivors.

What is known: • School-aged children with leukemia experience persistent physical, psychological, and social challenges during treatment, and self-care interventions are increasingly recognized as essential for improving adherence and quality of life. • Existing self-care programs mainly focus on medical management and psychosocial support, but standardized models and long-term evaluations remain limited.

What is new: • This review synthesizes the past decade of evidence on multidimensional self-care skills training (medical, psychological, educational, and technology-assisted) specifically for school-aged leukemia patients. • It identifies critical gaps including limited longitudinal follow-up and culturally adaptive approaches and proposes integrated, multidisciplinary strategies involving families, schools, and healthcare providers to enhance future pediatric oncology care.

The study aims to evaluate the gait pattern of Wilson Disease adolescents, receiving pharmacological treatment, without clinical signs of gait problems, with instrumented gait analysis. The gait changes could be the first signs of neurological manifestations, providing information about which patients are at greater risk of developing neurological problems. Another aim of the paper was to find possible relationships between gait disturbances and biochemical markers. Twenty-seven patients underwent gait analysis with the VICON system. Captured data were processed and averaged. From them, the Gait Variable Scores and Gait Profile Score were calculated to assess the deviation from normal gait. The following biochemical parameters were included in the analysis: ALT, AST, GGTP, bilirubin, INR, and an abdominal ultrasound describing liver and spleen size. Additionally, a fibroscan measurement was performed to obtain information about liver stiffness (E value) and steatosis (CAP value). The neurological assessment was based on a review of school performance, tremor, walking, and writing problems. In all patients, the scores assessing global gait pattern and knee kinematics were increased, and in the majority of them, also the score of the ankle joint. Cluster and discriminant analysis showed that biochemical indicators of liver injury (ALT, E, and CAP value) were strong predictors of walking disturbances.

Conclusion:  The main finding of this study indicates that clinical assessment could detect abnormalities only when they are in a relatively advanced stage. It is not sensitive to the early signs of neurological problems, which could be picked up by the instrumented gait analysis.

What is known: • Wilson disease is a rare genetic disorder affecting copper metabolism. • Liver problems are its first clinical manifestations. • It is accepted that neurological manifestations in Wilson disease patients have onset between 20 and 30 years of age.

What is new: • First subtle gait pattern changes are present in adolescents, despite their pharmacological treatment. • These changes can be detected by instrumented gait analysis. • The deviations mainly concern the knee and ankle joints. • The major indicators of liver injury (ALT, E, and CAP value) were strong predictors of walking disturbances.

Chest pain occurs in approximately one-quarter of patients with FMF, the most common monogenic autoinflammatory disease characterized by recurrent attacks of fever and serositis. This study evaluated a large, genetically homogeneous pediatric FMF cohort carrying biallelic pathogenic exon 10 MEFV variants to describe their demographic, clinical, and genetic characteristics, and to compare patients with and without chest pain to better define this manifestation within the FMF spectrum. This cross-sectional single-center study included 918 pediatric FMF patients with biallelic pathogenic MEFV exon 10 variants followed between June 2016 and February 2025. Demographic, clinical, and genetic data were collected retrospectively, and comparative analyses were performed between patients with and without chest pain. The cohort included 456 females (49.7%), with a median age of onset of 4.0 years and diagnosis age of 6.0 years. The most common genotype was M694V/M694V (48.9%), and 12.4% had colchicine resistance. Chest pain occurred in 218 (23.7%) patients, all pleuritic in origin, with no pericarditis. Those with chest pain had higher annual attack frequency, more abdominal pain (95% vs. 87%, p = 0.001) and greater colchicine resistance (21.1% vs. 9.7%, p = 0.001). The M694V/M694V genotype was significantly more frequent in those with chest pain (p = 0.017). Among patients presenting with chest pain, radiologically confirmed pleural effusion was detected in 5% during at least one of their evaluated attacks, predominantly among those with colchicine resistance.

Conclusion: In this large genetically homogeneous pediatric FMF cohort, chest pain was a frequent pleuritic manifestation. Patients with chest pain showed higher attack frequency and greater colchicine resistance, particularly among M694V homozygotes. Although rare, detected pleural effusion in patients with chest pain was associated with a significantly higher rate of colchicine resistance.

What is known: • Chest pain is a recognized but variably reported manifestation of FMF, usually pleuritic in origin. • The M694V homozygous genotype is associated with more severe inflammatory phenotypes.

What is new: • In a large genetically homogeneous pediatric cohort, chest pain occurred in nearly one-quarter of patients and was linked to higher attack frequency. • Chest pain was strongly associated with colchicine resistance and more frequent in M694V/M694V patients. Additionally, a high frequency of colchicine resistance was observed in patients with detected pleural effusion.

Very preterm neonates admitted to the neonatal intensive care unit (NICU) face daily stressors that activate their hypothalamic-pituitary-adrenal (HPA) axis, triggering cortisol release and potentially affecting their outcomes. We examined the relationship between NICU stressors, urinary cortisol levels, and short-term outcomes in very preterm neonates. This study was part of a multicenter cohort study (HIPPO) including 446 neonates (gestational age < 29 weeks) across all Dutch NICUs. Data on daily stress exposure for the first 28 days and outcomes were prospectively collected, along with urine samples on postnatal days 8 (T1) and 28 (T2) to determine cortisol levels as markers of the stress response. Urinary samples were available for 391 (88%) neonates. In general, the most preterm born neonates had the highest cortisol levels, though highly variable with similar stress exposure. At T1, cortisol levels rose with increasing stress exposure in neonates born after gestational ages ≥ 27 weeks but decreased in the most preterm. At T2, cortisol levels tended to rise with stress exposure across all gestational ages. Though cortisol levels were higher in neonates that died or developed intraventricular hemorrhage, bronchopulmonary dysplasia or retinopathy of prematurity, cortisol was not independently associated with any of these outcomes.

Conclusion: High cortisol levels are linked to neonatal morbidity and mortality, but not independently, since urinary cortisol levels are moderated by gestational age. To protect preterm infants' future, it is key to understand their responses to stress in order to develop and evaluate stress protection strategies.

What is known: • Very preterm neonates in the neonatal intensive care unit (NICU) are exposed to high levels of stress on a daily basis. • Stress exposure and altered cortisol responses in very preterm neonates have both been linked to adverse outcomes.

What is new: • This study reveals gestational age-dependent effects of stress exposure on very preterm neonates' cortisol levels. • In general, high cortisol was associated with morbidity and mortality. • This study provides insight in hypothalamic-pituitary-adrenal axis development and highlights the importance of reducing stress.

Drowning-associated pneumonia (DAP) is the most common infectious complication in drowning patients admitted to the pediatric intensive care unit (PICU). We aim to describe the clinical features, emergency interventions, microbiological characteristics, and antibacterial treatment strategies for children who have drowned, ando analyze the correlation between these factors and their prognosis. This retrospective study enrolled 141 children admitted to the PICU following freshwater drowning between 2019 and 2024. The cohort was stratified by the occurrence of DAP, with comparisons conducted on baseline characteristics, clinical outcomes, pathogen spectrum, and treatment. A logistic regression model was employed to identify risk factors for 28-day post-discharge mortality. Among the 141 pediatric patients admitted to the PICU due to drowning, 71 were diagnosed with DAP and 70 without (Non-DAP). No significant differences were found in the frequency distributions between the two groups when comparing time intervals from submersion to chest compressions and the duration of chest compressions, using a 5-minute cutoff (P > 0.05). Although the DAP group experienced significantly longer hospital and PICU stays, they demonstrated a markedly lower mortality rate at discharge (18.31% vs 41.43%, P = 0.003) and 28-day post-discharge (22.54% vs. 47.14%, P = 0.002) compared to the Non-DAP group. The Pediatric Risk of Mortality (PRISM) score  and hypoxic-ischemic encephalopathy (HIE) were independent risk factors, while a longer length of hospital stay was served as a protective factor for 28-day post-discharge mortality. Microbiological analysis showed that the most commonly detected pathogens were Staphylococcus aureus and Mycoplasma pneumoniae, Candida albicans and rhinovirus. Combination therapy was significantly more frequent in the DAP group (63.38% vs 41.51%), and the use of linezolid was significantly higher in this group than in the Non-DAP group (36.62% vs. 8.57%, P = 0.001).

Conclusions:  DAP is a frequently observed complication in PICU patients following drowning incidents, but it is not associated with increased mortality among these children. Staphylococcus aureus is a frequently identified pathogen in pediatric DAP, underscoring the need for empirical antibiotic therapy to cover Gram-positive bacteria.

What is known: • Drowning is a leading cause of pediatric ICU admission. • Drowning-associated pneumonia is common and poses diagnostic challenges, prompting the use of empiric broad-spectrum antibiotics.

What is new: • In this pediatric cohort, DAP was associated with longer hospital and PICU stays, but not with increase mortality. • Staphylococcus aureus was the most prevalent pathogen, underscoring the need for Gram-positive bacterial coverage in empirical therapy.