Hyperhomocysteinemia has been recognized as a cardiovascular risk factor associated with endothelial dysfunction, oxidative stress, and vascular inflammation. Experimental and clinical studies suggest that elevated homocysteine levels may also influence myocardial electrophysiology and contribute to arrhythmogenesis. However, data regarding the relationship between homocysteine levels and electrocardiographic markers of atrial conduction in pediatric populations remain limited. This study aimed to evaluate the association between plasma homocysteine levels and electrocardiographic parameters, particularly P-wave dispersion, in children. This multicenter retrospective case-control study included pediatric patients evaluated in four tertiary pediatric metabolism centers between January 2023 and December 2025. A total of 47 patients with hyperhomocysteinemia (plasma total homocysteine ≥ 15 µmol/L) and 43 age- and sex-matched controls with normal homocysteine levels were included. Controls were selected from the screened population among children with available homocysteine measurements, electrocardiographic and echocardiographic evaluations, and no confirmed inherited metabolic disease or cardiac disorder. Clinical, biochemical, and electrocardiographic parameters, including maximum P-wave duration and P-wave dispersion, were retrospectively analyzed. A total of 90 participants were included, comprising 47 children with hyperhomocysteinemia and 43 healthy controls. P-wave dispersion and maximum P-wave duration were significantly higher in the hyperhomocysteinemia group compared with controls (48.96 [19.48–100.0] vs. 38.57 [10.57–71.19] ms, p < 0.001). Plasma homocysteine levels showed a moderate positive correlation with P-wave dispersion (ρ = 0.441, p < 0.001). These differences were more pronounced in children with higher homocysteine levels and in younger age groups (< 2 years and 2–14 years). In contrast, PR interval (p = 0.790) and QTc interval (p = 0.183) did not differ significantly between groups. Vitamin B12 levels were significantly lower in the hyperhomocysteinemia group (p = 0.013), while folate levels were comparable (p = 0.974). Although sodium, potassium, and magnesium levels differed significantly between groups, all values remained within normal physiological ranges. Conclusions: Children with hyperhomocysteinemia showed increased P-wave dispersion compared with controls. These findings suggest an association between elevated homocysteine levels and altered atrial conduction parameters in children. Further prospective studies are needed to determine the clinical significance of these findings.
Survival of extremely preterm infants has improved owing to advances in perinatal and neonatal care. However, bronchopulmonary dysplasia (BPD) has remained unabated, and research into preventive measures for the broader spectrum of prematurity-associated lung disease (PLD) has met with limited success. We summarize emerging therapeutic strategies with the potential to favorably influence the lifelong trajectory of lung health of preterm infants, especially the most immature. This narrative review examines recent preclinical and clinical studies on therapies for BPD prevention, focusing on mechanism-based interventions, biologic strategies, and innovative translational tools. Preclinical evidence converges on actionable targets in alveolarization, inflammatory pathways, redox and mitochondrial homeostasis, vascular and matrix remodeling. Novel molecules and drug-repurposing strategies are being tested in animal models, while patient-derived platforms may enable personalized therapeutic approaches. Mechanism-based approaches are progressing through Phase 1–2 clinical trials; pending efficacy analyses, insulin-like growth factor-1 replacement may become the first pharmacological therapy specifically approved to reduce or attenuate BPD. In parallel, cell-based therapies and extracellular vesicle strategies offer a complementary paradigm, acting through pleiotropic biological reprogramming of the injured lung. Ethical-regulatory complexity and the challenges of standardizing and scaling cell-based and cell-free therapies may limit clinical translation. Conclusion: A growing repertoire of therapies for BPD holds promise for modifying early respiratory illness and the long-term burden of PLD. Realizing this potential will benefit from both mechanism-informed combinatorial approaches and pleiotropic strategies, supported by patient-derived translational tools and adequately powered efficacy evaluations. Equally essential are tailored neonatal-first regulatory pathways linking the continuum of BPD to the later respiratory morbidity of PLD, a life-course condition with significant public health relevance beyond the neonatal period.
This study aimed to characterize menstrual irregularities in adolescents with eating disorder (ED) and assess their variation across diagnostic subtypes, clinical course, and clinical determinants. This retrospective study included postmenarcheal female adolescents with EDs and followed in an adolescent medicine clinic between 2015 and 2025. Demographic, anthropometric, clinical, and menstrual data at admission and during follow-up were extracted from medical records. The study included 491 adolescents: 178 (36.3
Acute otitis media (AOM) and respiratory tract infections are common in early childhood and are major contributors to antibiotic use. The oral probiotic Streptococcus salivarius K12 has demonstrated antimicrobial and immunomodulatory activity in vitro, and preventive effects in children with recurrent AOM. We aim to determine the efficacy of S. salivarius K12 in preventing AOM in the general infant population. We conducted a multicentre, double-blind, randomised, placebo-controlled trial in Wellington and Christchurch, New Zealand. Children were enrolled at 3–6 months of age, their households were randomised 1:1, and daily study product was given from age 6 to 24 months. The primary outcome was the rate of doctor-recorded AOM. Secondary outcomes included time to first AOM episode, respiratory infections, antibiotic prescribing and healthcare utilisation. Analyses were by intention to treat using mixed-effects negative binomial regression adjusted for region and, for the primary outcome, prior AOM, with random effects for general practice and family. A total of 428 children were randomised by household and 368 (86
Over the past two decades, the USA has observed fluctuating increases in opioid-, alcohol-, and drug-related mortality amongst children under the age of 4. Many factors contribute to mortality, and identifying preventative measures represents a critical gap in public health. This study aims to identify trends in related deaths and highlight potential target areas to combat mortality increases. Data was extracted from the Center for Disease Control and Prevention Wide-ranging Online data for Epidemiologic Research (CDC WONDER) database, and trends in crude mortality rate were analyzed for children ages 0–4 from 1999 to 2023. Results were stratified according to sex, region, race, and age; trends were assessed utilizing Joinpoint analysis software. Overall, crude mortality rates demonstrated an upward trend. Across every census region, there was an increase in mortality, noting the highest in the Midwest region. In nearly every year, rural regions are noted to have a higher crude mortality rate. Male sex was associated with a higher crude mortality rate, and the Non-Hispanic Black or African American population had the largest increase in crude mortality rate compared to other racial/ethnic groups. Conclusion: Complex factors contribute to mortality in this population, with clear disparities across geographic locations and demographic groups. These disparities highlight the need for further exploration regarding the effects of the opioid epidemic in the pediatric population. Integrating preventative measures and educational tools into medical education and healthcare systems across the country represents a notable absence in current practice, and direction for future research.
Kawasaki disease (KD) is an acute systemic vasculitis of childhood associated with profound immune dysregulation that may persist beyond the acute inflammatory phase. The long-term risks of autoimmune diseases and lymphoproliferative malignancies in children with KD remain incompletely defined. To determine whether children with KD carry increased 20-year risks of autoimmune and lymphoproliferative outcomes compared with matched controls. We conducted a retrospective matched cohort study using the Clalit Health Services database (2002–2022). Children with KD (n = 2,126) were matched 1:5 to controls (n = 10,630) by sex and birthdate (± 30 days) and followed through December 2024. Outcomes comprised psoriasis, vitiligo, hypothyroidism, type 1 diabetes mellitus (T1DM), celiac disease, inflammatory bowel disease (IBD), immune thrombocytopenia (ITP), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL). Adjusted hazard ratios (AHRs) with 95
Inflammation has been implicated in neonatal cholestasis, but associations between complete blood count (CBC)-derived inflammatory biomarkers and cholestasis remain unclear. This study evaluated these associations in preterm infants. This retrospective 1:1 matched case–control study included 284 cholestatic cases and 284 matched controls. Eight biomarkers were evaluated: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-plus-monocyte-to-lymphocyte ratio (NMLR), systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), neutrophil-to-lymphocyte-to-platelet ratio (NLPR), and prognostic nutritional index (PNI). Conditional logistic regression, restricted cubic spline, subgroup, interaction, and sensitivity analyses were performed. In fully adjusted models, higher levels of NLPR, NLR, NMLR, PNI, and SIRI remained associated with an increased risk of cholestasis, whereas PLR was inversely associated with cholestasis risk. Specifically, each unit increase in NLR, NMLR, and SIRI was associated with a 28
Accurate early risk stratification in patients with congenital diaphragmatic hernia (CDH) remains challenging, as existing pediatric mortality prediction scores may not adequately reflect CDH-related pathophysiology. The main objective was to develop an early risk stratification model by adaptation of the Simplified Acute Physiology Score II (SAPS II) for mortality and extracorporeal membrane oxygenation (ECMO) requirement prediction in patients with CDH. This retrospective single-center study included pediatric patients with CDH treated at a tertiary neonatal and pediatric intensive care unit between January 2000 and December 2025. An expanded CDH-SAPS was developed by age adaptation and CDH-specific modification of SAPS II variables, followed by simplification for bedside applicability, resulting in CDH-SAPS. Both scores integrate early clinical and laboratory parameters during the first 4 h after admission complemented by 3 variables reflecting the need for major therapeutic interventions during the first 24 h. Predictive performance was compared with the Pediatric Index of Mortality 3 (PIM3) and the Score for Neonatal Acute Physiology II (SNAP-II), with the ICU mortality as primary, and ECMO requirement as secondary outcome. Among 95 included patients, the ICU mortality was 12
This systematic review and meta-analysis evaluated the immediate effects of acute exercise on state anxiety in children and adolescents. It also examined whether exercise modality, developmental stage, and setting influenced the effects. Five databases were searched up to March 2026 for studies on acute exercise and state anxiety in individuals aged 6–18 years. Meta-analysis was conducted using Stata 17.0, with effect sizes pooled as standardized mean differences (SMDs). Sensitivity analysis and GRADE were used to assess heterogeneity and evidence certainty. Twelve studies involving 739 participants were included. Acute exercise significantly reduced state anxiety (SMD = − 0.77, 95
Infective Endocarditis (IE) continues to pose significant risks for children and adolescents, particularly those with Congenital Heart Disease (CHD). Improved survival among pediatric CHD patients has expanded the population susceptible to IE, especially involving prosthetic materials. This study aims to characterize the clinical features, diagnostic challenges, outcomes and complications of IE in relation to valve type and underlying heart defects in a pediatric population. We conducted a retrospective review of pediatric IE cases diagnosed using modified Duke criteria from 2013 to 2024 across a specialized cardiac center. Patients were categorized as having Native Valve Endocarditis (NVE) or Prosthetic Valve Endocarditis (PVE). Data included demographics, microbiology, imaging modalities, and complications and outcomes. 95 patients were identified for the analysis. Of the cohort, 62.2
Fever is one of the most common symptoms in childhood and a frequent reason for medical consultation. Current guidelines recommend treating fever only when discomfort is present. However, the concept of fever-related discomfort remains poorly defined and inconsistently applied in clinical practice and research studies. We aimed to develop an expert-based definition and a pragmatic clinical framework for the assessment and management of discomfort in febrile children. An international modified Delphi consensus was conducted to develop an operational definition and pragmatic clinical framework for fever-related discomfort in children. A steering international committee developed initial statements, which were evaluated across three iterative online Delphi rounds by seven international experts from high-income countries. Agreement was assessed using a 5-point Likert scale, with consensus predefined as ≥ 75
This study was conducted to identify factors associated with phubbing and to investigate the mediating role of mindfulness in the relationship between digital game addiction and phubbing. A cross-sectional design with mediation analysis was adopted. The study was completed with 2013 voluntary adolescents. The data were collected via paper questionnaires that included validated Turkish versions of the Digital Game Addiction Scale, General Phubbing Scale in Adolescents, and Mindful Attention Awareness Scale Adolescent Form. Associations were analyzed using multiple linear regression. Process Macro Model 4 was conducted to verify the mediating role. The study found an indirect mediating role of mindfulness in the relationship between digital game addiction and phubbing. Sex, academic achievement, daily smartphone use, following social media, surfing on the internet, watching videos, taking photographs, doing homework, participation in social activities, digital game addiction, and mindfulness score were significantly related to phubbing. The study found that higher levels of digital game addiction were associated with a higher level of phubbing among adolescents. In contrast, higher levels of mindfulness were associated with a lower level of phubbing. Mindfulness had a partial mediating role in the relationship between digital game addiction and phubbing. This study highlights the importance of addressing factors associated with youth services to reduce phubbing and digital game addiction. Health professionals could consider mindfulness-focused interventions for at-risk adolescents for addressing these behaviors.
This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to compare honey with pharmacological treatment in pediatric patients with acute cough. Studies were searched across 5 databases. Analyzed outcomes were cough frequency, severity, and bothersomeness, alongside its impact on the sleep of both children and caregivers. A random-effects meta-analysis was performed using the Review Manager Web tool. A post-hoc subgroup and leave-one-out sensitivity analysis were conducted to evaluate the influence of individual studies and medication class on heterogeneity. 7 studies were included in the systematic review and 6 in the meta-analysis, totaling 576 patients. Among them, 305 (53
Voiding dysfunction (VD) is a common condition in childhood that is associated with lower urinary tract symptoms and bowel dysfunction. It may also adversely affect patients' emotional, behavioral, and social functioning. This cross-sectional case–control study evaluated emotional and behavioral problems, attention-related symptoms, and cognitive disengagement syndrome (CDS) in children with VD and examined their relationship with lower urinary symptoms severity and constipation. VD was diagnosed according to International Children’s Continence Society criteria using voiding diaries, imaging findings, and Dysfunctional Voiding Symptom Score (DVSS ≥ 9). Emotional and behavioral symptoms were assessed using the Strengths and Difficulties Questionnaire, and attention-related and CDS symptoms were evaluated with the Barkley Child Attention Scale (BCAS). The study population included 72 children aged 6–12 years with VD and 46 age- and sex-matched healthy controls. Children with VD showed significantly more severe attention-deficit/hyperactivity disorder (ADHD) symptoms, emotional problems, behavioral difficulties, and peer problems, as well as higher total difficulty scores compared with controls. Increasing DVSS were positively associated with greater emotional–behavioral difficulties and poorer quality of life. Children with both daytime and nighttime urinary incontinence and those with concomitant constipation exhibited the highest psychosocial burden. In contrast, CDS-related symptoms did not differ significantly between children with VD and healthy controls. Conclusion: These findings indicate that VD is associated with a substantial emotional and behavioral burden, particularly attention-related difficulties, whereas CDS does not appear to be specifically linked to VD. Routine psychological screening and a multidisciplinary, biopsychosocial approach may improve symptom management and quality of life in affected children.
Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, highly aggressive World Health Organization grade 4 brain tumors associated with early cerebrospinal fluid dissemination (CSF). AT/RTs typically occur in children under 4 years of age however, can also occur in adults and often carry a poor prognosis. These tumors are exceptionally uncommon, with evidence limited to isolated case reports. We illustrate a case of hemorrhagic left lateral ventricular AT/RT in a 5-year-old boy and systematically synthesize global literature evaluating clinical presentations, therapeutic interventions, and survival outcomes of primary supratentorial intraventricular AT/RT. Systematic searches were executed across PubMed, Embase, and Scopus databases up to 31 May 2026. Studies tracking histologically or immunohistochemically confirmed pediatric intraventricular AT/RT were included. Study quality was evaluated qualitatively via Joanna Briggs Institute tools; qualitative descriptive analysis synthesized outcomes, supplemented by post hoc stratified subgroup analysis. Twenty-four descriptive, uncontrolled studies comprising 28 pediatric patients (mean age: 3.9 years) were synthesized. The lateral ventricle was the primary epicenter (53.5
This study aimed to analyze the evolving etiology, clinical features, surgical outcomes, and long-term prognosis of pediatric necrotizing pneumonia (NP). Data were collected from 398 children diagnosed with NP between January 2017 and June 2025, among whom 42 (10.55
Children with Down syndrome (DS) are at increased risk for recurrent and severe respiratory infections. Pneumococcal IgG measurements are used in clinical practice to evaluate humoral immunity, yet their clinical relevance in DS remains unclear. We examined potential associations between pneumococcal IgG concentrations and clinical characteristics in children with DS, including recurrent infections and respiratory hospital admission. We conducted a retrospective study in a paediatric DS cohort with repeated pneumococcal IgG measurements obtained from left-over plasma samples using ELISA and multiplex bead-based (Luminex) assays. Potential associations with selected clinical variables, including respiratory hospital admission, the presence of autoimmune comorbidity, and infections, were assessed using mixed-effects modelling. A cross-sectional analysis using only the last available measurement per participant was performed to address the temporal uncertainty between the static information on the clinical variables and the repeated antibody measurements. Across both assays, a history of hospital admission for respiratory problems was associated with lower pneumococcal IgG concentrations in linear mixed-effect regression analyses; a history of autoimmune comorbidity was associated with higher concentrations. A history of recurrent ear infection was associated with lower ELISA-measured IgG concentrations in the last-timepoint analysis. Conclusion: Our exploratory analysis suggests a potential association between lower pneumococcal IgG concentration and selected clinical characteristics in children with DS. These findings support further investigation into the clinical relevance of pneumococcal antibody measurements in children with DS in larger, prospective studies.
Noonan syndrome (NS) is a multisystem disorder caused by mutations affecting the RAS–MAPK signaling pathway and is associated with an increased risk of proliferative disorders. This study aimed to evaluate the frequency and spectrum of cranial pathologies in patients with NS and to assess their clinical significance. This cross-sectional study included patients with NS followed between January 2000 and January 2025. Clinical, anthropometric, laboratory, and cranial MRI data obtained at diagnosis and during follow-up were retrospectively reviewed. Statistical analyses were performed using SPSS version 29.0. Cranial abnormalities were identified in 54.1
Appropriate analgosedation and mobilization are essential elements of care in critically ill children. On extracorporeal membrane oxygenation (ECMO), analgosedation and mobilization are tailored to individual pharmacokinetics and mobilization risks. We aimed to investigate analgosedation and mobilization practices in pediatric ECMO across Europe. We performed a multicenter cross-sectional survey-based study. We surveyed one experienced physician per pediatric ECMO center in Europe (March–July 2025). Additionally, we investigated differences in practices based on ECMO volume (≤ 10 vs > 10 cases/year) and ICU type (exclusively pediatric ICU vs other ICUs). Among 123 ECMO centers, 96 (77
Children with chronic kidney disease (CKD) exhibit progressive body composition alterations. While dual-energy X-ray absorptiometry (DXA) is the reference standard, its routine use is limited by cost, radiation, and availability. Bioelectrical impedance analysis (BIA) offers a portable, radiation-free alternative, but its accuracy relative to DXA in paediatric CKD remains insufficiently evaluated. This cross-sectional study enrolled 102 children aged 5–14 years with CKD stages 3–5. Same-day BIA and DXA measurements were performed. Agreement between methods was assessed using Pearson’s correlation coefficient, Lin’s concordance correlation coefficient (CCC), and Bland–Altman analysis. Associations with CKD stage and sex were examined. BIA showed strong to very strong correlations with DXA for fat mass (FM; r = 0.93), fat-free mass (FFM; r = 0.91), and total bone mineral content (BMC; r = 0.84). Lin's CCC indicated poor concordance for all parameters (all < 0.90): FFM 0.87, total BMC 0.81, total bone mineral density (BMD) 0.74, FM 0.66 and body fat percentage (BF
