European Journal of Pediatrics最新文献

Every school on this planet should aim to become a healthy school. This is the motto of the WHO/UNICEF health promoting school strategic agenda (HPS). To address gaps and needs of children's health and educational inequalities in schools, a qualitative study was set up to synthesize experts' views and insights on school health programs and the HPS strategy in Europe. This multi-stakeholder consultation took place during an international children's health workshop in Cyprus (October 2024). Data was collected through focus group interviews with ~ 30 experts engaged in a multistakeholder consultation between academics, governmental officials, teacher liaisons, and health professionals, including WHO experts and NGOs. The consultation identified the following themes: systemic limitations in funding and sustainability of health education/promotion programs, enhanced curriculum needs for health literacy, limitations in school physical environment, rise in behavioral risk factors among children and adolescents, and growing mental health needs. A consensus was reached regarding the prerequisites and recommendations towards improving both health and educational outcomes for children; the implementation of holistic methodological frameworks, such as that of the human exposome and its exposomics tools were collectively proposed to better deploy the HPS recommendations in the school community.

Conclusion:  By adopting a holistic, multi-sectoral approach for schools and their communities (parents, teachers, authorities, the public) that embeds the exposomics tools and methodologies, future societies would ensure that educational institutions not only serve as centers for academic learning, but also as environments that nurture the physical, mental, and social wellbeing of students.

What is known: • The importance of schools and their communities, as settings to efficiently implement health education and promotion programs for children (4-19 years of age).

What is new: • The utility of the human exposome in integrating multiple children's risk factors and health services that overall impact growth and development. • Observatory infrastructures in schools would allow for the systematic monitoring and integration of children's health and of their multiple non-genetic risk factors, feeding into the health promoting school strategy.

The aim of this study was to assess the impact of caffeine and other methylxanthines on bronchiolitis-related apnea (BRA) in infants under 12 months of age, through a systematic review and meta-analysis. The review was conducted in accordance with the PRISMA guidelines. Inclusion criteria were studies published from January 1990 to August 2023, in English or French, and involving children from 35 weeks' gestational age to 1 year with BRA. Relevant articles were selected and data extracted by 2 members of the blinded investigative team. Four hundred sixty-nine articles were retrieved. Eleven studies conducted in Europe and North America were considered in the systematic review. Six studies were used in the meta-analysis. The meta-analysis showed no positive impact of caffeine on the length of non-invasive ventilation (mean difference =  - 0.26 days, 95% CI [- 1.71; 1.20], p = 0.53), invasive ventilation requirement (mean difference =  - 0.05 [- 0.24; 0.13], p = 0.44), or length of pediatric intensive care unit and hospital stay (mean difference =  - 0.62 days, 95% CI [- 9.31; 8.07], p = 0.79; mean difference = 1.60 days, 95% CI [- 3.65; 6.85], p = 0.32, respectively). However, caffeine was associated with a trend towards a decrease in the total length of respiratory support (mean difference =  - 2.63 days, 95% CI [- 5.61; 0.34], p = 0.06).

Conclusion: This study highlights the ongoing debate surrounding the role of caffeine and other methylxanthines in BRA. The general paucity of literature, its low level of quality, the heterogeneity of results, different caffeine regimens, and population definition greatly impaired the quality of the conclusions. However, by identifying gaps in the literature, this study helps build a framework for future trials.

What is known: • Apnea is a recognized complication of bronchiolitis in infants, particularly in those born preterm or at a young corrected age, and may necessitate intensive respiratory support. • While caffeine is a cornerstone therapy for apnea of prematurity, evidence supporting its use in bronchiolitis-related apnea (BRA) remains limited and inconclusive.

What is new: • This is the first systematic review with meta-analysis evaluating caffeine in BRA, showing no significant improvement in major clinical outcomes, but suggesting a possible reduction in overall respiratory support duration. • The study identifies critical methodological limitations in the existing literature, including heterogeneous apnea definitions and non-standardized caffeine dosing, and proposes a framework for future controlled studies.

Deferred cord clamping (DCC) is the recommended method of placental transfusion for newborns who are vigorous at birth irrespective of gestational age. But there is lack of uniformity regarding the timing of DCC. The purpose of this study was to determine the effect of DCC for 3 min as compared to DCC for 1 min on clinically relevant hematological and hemodynamic parameters in preterm neonates. The primary outcome evaluated was venous hematocrit (Hct) at 48 (± 4) hrs of postnatal age. The important secondary outcomes assessed were mean blood pressure during the transitional period, venous Hct and ferritin levels at 6 weeks of age and significant neonatal morbidities. Three hundred and four (304) neonates of 30- 36 ^6/7 weeks gestation were assigned in a 1:1 ratio to either DCC for 1 min (n = 152) or DCC for 3 min (n = 152) in this stratified randomized controlled trial. For statistical analysis, the unpaired Student t and Chi square or Fisher's exact test were employed. The DCC for 3 min group had a higher mean Hct at 48 h than the DCC for 1 min group, 43.18 (5.292) vs. 41.02 (4.420), p < 0.001. Additionally, the DCC for 3 min group had a significantly higher mean blood pressure in the transitional phase and mean Hct at 12 h and 6 weeks (p < .0001). In the subgroup analysis (stratified by gestational age of 30-33⁺⁶ weeks, 34-36⁺⁶ weeks), similar differences were noted. There were no significant differences between the groups in terms of need for phototherapy, symptomatic polycythemia or other important neonatal morbidities.

Conclusion: Delaying the clamping of cord for 3 min improves blood pressure and results in higher venous hematocrit in the initial transitional phase and beyond. DCC for 3 min may be a feasible and useful placental transfusion technique in the preterm population. Larger multicentric studies are required to confirm its efficacy and safety.

Trial registration: CTRI/2024/10/075751; registration date October 23, 2024.

What is known: • DCC is universally recommended for vigorous neonates at birth but no consensus exist for its duration. • Studies on the effective duration of DCC are scarce in the preterm population.

What is new: • Delaying clamping of cord for 3 min is an effective placental transfusion strategy in preterm neonates of 30- 36 6/7 weeks gestation • DCC for 3 min can be an important strategy especially in developing countries where baseline prevalence of anemia is high.

The purpose of the study is to analyze the clinical features, treatment, and survival outcomes of Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) with positive cerebrospinal fluid (CSF) EBV-DNA in children. Patients diagnosed with EBV-HLH admitted to our center from January 2019 to August 2024 were enrolled and divided into a CSF-EBV group and a non-CSF-EBV group based on CSF EBV-DNA test results. Neurological manifestations were observed in only 33.3% (13/39) of children with CSF-EBV positivity, while 48.7% (19/39) showed abnormal brain magnetic resonance imaging findings. The CSF-EBV group had a higher blood EBV-DNA load (P = 0.002) and a lower CD4⁺/CD8⁺ ratio (P = 0.034) compared with the non-CSF-EBV group. A strong positive correlation was observed between CSF EBV-DNA load and CSF cell count (r = 0.800, P < 0.0001). Overall survival was shorter in the CSF-EBV group (P = 0.017). Multivariate Cox regression identified EBV-associated central nervous system (EBV-CNS) infection as a potential independent risk factor for poor prognosis (HR = 6.077, 95% CI: 1.345-27.435, P = 0.019). Intrathecal methotrexate and dexamethasone effectively reduced CSF viral load (P = 0.003) and cell count (P = 0.042), but did not significantly improve overall survival (P = 0.3).

Conclusion: EBV-CNS infection may be an independent risk factor for poor prognosis in pediatric EBV-HLH, underscoring the importance of CSF EBV-DNA testing, particularly in patients with high blood loads. Although intrathecal therapy effectively reduced CNS viral load and inflammation, its survival benefit requires further validation in large-scale prospective studies.

What is known: • CNS involvement is a well-established poor prognostic factor in HLH. • EBV-CNS infection is an independent prognostic risk factor in adult EBV-HLH.

What is new: • EBV-CNS infection is an independent prognostic risk factor in pediatric EBV-HLH. •While intrathecal therapy effectively reduces CSF viral load and inflammation, its survival benefit still requires further validation through large-scale prospective studies.

To describe the peculiarity of preterm neonates at 33-35 weeks gestational age (GA) with mild-to-severe hypoxic-ischaemic encephalopathy (HIE). This single-centre retrospective study compared the background characteristics, treatments, and outcomes of 30 preterm HIE neonates at 33-35 weeks GA with those of 399 HIE neonates at ≥ 36 weeks GA between 2011 and 2023. Between the 33-35 weeks and 36, 37-40, or ≥ 41 weeks GA groups, HIE severity and use of therapeutic hypothermia (TH) were not significantly different. Between the 33-35 weeks and 37-40 weeks GA groups, no TH, except for mild HIE, was significantly different (35% vs. 3%) and the incidence of moderate-to-severe magnetic resonance imaging (MRI) injury was significantly different (43% vs. 19%); the white matter injury was predominant. Moderate-to-severe MRI injury was associated with lower GA (odds ratio 0.81 [95% confidential intervals, 0.67-0.98]), but total adverse outcomes, including death before discharge and long-term outcomes over 2 years, were not significantly different among the groups and were not associated with GA.

Conclusion: In this study, preterm neonates at 33-35 weeks GA, some of who were unable to receive TH because of reasons, except for mild HIE, were at risk of moderate-to-severe MRI injury, but their total adverse outcome was comparable to that of preterm neonates at ≥ 36 weeks GA. Further research including mild-to-severe HIE regardless of TH are needed.

What is known: ・TH for preterm neonates at 33-35 weeks GA with moderate or severe HIE does not affect neurodevelopmental outcomes at 18 months. ・TH for preterm neonates with moderate or severe HIE may not increase neurodevelopmental impairment compared with term or near-term neonates.

What is new: ・Preterm neonates at 33-35 weeks GA with mild-to-severe HIE were at risk of moderate-to-severe MRI injury, but death and long-term outcomes over 2 years were comparable to those of preterm neonates at ≥ 36 weeks GA. ・Some preterm neonates with moderate or severe HIE did not use TH because of poor conditions.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with type 2 diabetes (T2D) in adults; however, its epidemiology in the pediatric population remains unclear. We conducted a systematic review and meta-analysis to estimate the prevalence of MASLD among children and adolescents with T2D. We systematically searched PubMed and Embase databases from inception until March 18, 2025 to identify observational studies investigating the prevalence of MASLD (diagnosed by liver biopsy, imaging methods, or blood-based biomarkers) in children and adolescents (aged ≤ 21 years) with T2D. Data from eligible studies were extracted, and meta-analysis was performed using a generalized linear mixed model. This study was registered in PROSPERO (ID CRD420251013625). Eighteen unique studies with 3926 pediatric patients with T2D were included. The pooled prevalence of MASLD in pediatric T2D was 36.61% (95% confidence interval [CI] 26.45 to 48.12), with substantial heterogeneity (I² = 97.1%). Prevalence estimates differed significantly by the diagnostic method used for MASLD (p = 0.014) but remained consistent across subgroups based on world region, median year of enrollment, and sample size. Sensitivity analysis restricted to magnetic resonance-based studies showed a high prevalence (55.0%, 95% CI 38.20 to 70.78, I² = 73.7%). The funnel plot did not reveal any significant publication bias.

Conclusions: MASLD affects over one-third of pediatric patients with T2D. These findings support early liver health screening in this high-risk group. Future research is needed to validate non-invasive tests for liver disease assessment in pediatric diabetes care.

What is known: • Type 2 diabetes (T2D) is a strong risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD). • The epidemiology of MASLD in children and adolescents with T2D remains poorly characterized.

What is new: • MASLD affects an estimated 36.61% of pediatric patients with T2D, with substantial variation according to the diagnostic modality used. • This high prevalence underscores the need for early liver health screening in pediatric T2D.

Point-of-care ultrasound (POCUS) is increasingly recognized as an essential skill in pediatric emergency medicine (PEM) globally. However, standardized POCUS training is lacking in France, and international curricula cannot be directly applied due to differences in training structures, scope of practice, and resource availability. This study aimed to develop a context-adapted, expert-informed POCUS curriculum for PEM residents in France. A three-round Delphi process was conducted between May and June 2025. Eligible experts were PEM physicians practicing POCUS routinely for at least 2 years. An online survey was created, including 77 items across five domains: ultrasound fundamentals, emergency POCUS, diagnostic POCUS, procedural POCUS, and teaching format. Each item was rated on a four-point Likert scale. Twenty-three of twenty-five experts completed all rounds. Consensus was achieved for 3/3 (100%) ultrasound fundamentals, 10/14 (71.5%) emergency skills, 8/41 (19.5%) diagnostic skills, 2/13 (15.4%) procedural skills, and 4/6 (66.6%) teaching format items. Overall, 20 core learning objectives were identified as essential for PEM residents.

Conclusion:  This national Delphi study provides the first context-adapted POCUS curriculum for pediatric emergency medicine in France. By identifying priority skills and preferred teaching modalities, it offers a structured approach to competency-based POCUS training that may be adapted to other countries facing similar challenges in pediatric emergency education.

What is known: • Point-of-care ultrasound (POCUS) is a core skill in pediatric emergency medicine. In France, however, training remains absent from the resident's curriculum. International programs cannot be directly implemented due to differences in training structures, scope of practice, and available resources.

What is new: • This national Delphi study establishes the first context-adapted POCUS curriculum for pediatric emergency medicine in France, identifying 20 core learning objectives and consensus-based teaching modalities to support structured, competency-based training.

Preterm infants are susceptible to metabolic disruptions due to physiologically immature development, and early metabolic dysregulation may contribute to neurodevelopmental impairments that persist throughout infancy and beyond. This study aims to investigate the associations between preterm birth, neonatal metabolism, and later neurodevelopment, and to explore the potential mediating role of neonatal metabolism. In this prospective birth cohort of 9023 in China, linear regression analyses were employed in discovery and validation sets to identify metabolites associated with preterm birth. Metabolites were then categorized as extremely high (> 90th percentile) or low (< 10th percentile), and their associations with preterm birth were assessed using meta-analysis and logistic regression. Among 2086 infants with neurodevelopmental assessments at 1 year old, we applied restricted cubic splines and linear regression to evaluate associations between extreme metabolite levels and neurodevelopment. Mediation analysis was then performed to assess the potential mediating effects of neonatal metabolism. Preterm birth was associated with extremely low levels of four metabolites and extremely high levels of seven metabolites (e.g., 17-hydroxyprogesterone, alanine, and multiple carnitines/acylcarnitines), indicating perturbed neonatal metabolic profiles. Moreover, extremely high levels of free carnitine (C0) were associated with poorer cognition (β = -0.47; 95% CI -0.75, -0.19) and receptive communication (β = -0.32; 95% CI -0.61, -0.03), with C0 accounting for 10.3% of the relative effect on cognition and 7.2% on receptive communication among preterm infants.

Conclusion:  Preterm infants exhibit metabolic perturbations linked to suboptimal neurodevelopment at 1 year of age, offering compelling evidence for the biological mechanism underlying preterm birth outcomes.

What is known: • Preterm birth is known to disrupt neonatal metabolism and to adversely affect neurodevelopment, but the underlying biological mechanisms remain controversial.

What is new: • Preterm infants are prone to extreme metabolic perturbations, which are associated with subsequent suboptimal neurodevelopmental outcomes. • Free carnitine acted as a potential biomarker of the effects of preterm birth on suboptimal cognition and receptive communication.

Acute mastoiditis (AM) is the most common intratemporal complication of acute otitis media in children. This multicenter study aimed to describe the epidemiological, clinical, microbiological, and radiological features of pediatric AM in four Italian regions and to identify factors associated with radiologic complications. This retrospective, observational cohort study included all patients under 18 years hospitalized with AM in the pediatric departments of Bari, Forlì, Macerata, and Pescara between January 2022 and May 2025. Demographic, clinical, microbiological, imaging, and management data were extracted from medical records using a standardized form and analyzed descriptively. Logistic regression explored associations between clinical variables and radiologic complications. A total of 118 hospitalizations (117 children; median age 4 years, IQR 2-7.8; 56% males) were analyzed. The estimated annual hospitalization rate was approximately 23 per 100 000 children. Otalgia (70%), postauricular swelling (57%), and erythema (56%) were common presenting features. Clinical complications occurred in 25 (21%) patients, and surgery was required in 13 (11%). Microbiological testing was positive in 38 (32%) episodes, most frequently identifying Streptococcus pyogenes or Pseudomonas aeruginosa. Imaging was performed in 70 (59%) episodes, revealing radiologic complications in 20 (17%; 28.5% of imaged). In multivariable analysis, auricular protrusion was independently associated with a lower likelihood of radiologic complications (p = 0.018), whereas no other clinical variable independently predicted radiologic complications.

Conclusion: AM remains a relevant cause of hospitalization in Italian children. Most patients respond well to medical therapy, whereas surgical intervention is required for complicated presentations. The significant protective role of auricular protrusion supports the selective use of imaging and suggests a conservative management approach in most cases.

What is known: • Acute mastoiditis (AM) is the most frequent intratemporal complication of acute otitis media in children. • Despite antibiotic and vaccine advances, AM remains a relevant cause of pediatric hospitalizations. • Most children respond to medical therapy, but some require surgical drainage.

What is new: • This multicenter study provides the first post-pandemic overview of pediatric AM across four Italian regions. • Radiologic complications occurred in 17% of cases; auricular protrusion independently predicted a lower risk of severe imaging findings. • The findings highlight a post-pandemic rebound of AM and support conservative, standardized management.