Abstract: Background: Preterm birth, affecting more than 13 million infants worldwide each year, remains one of the leading causes of neonatal morbidity and mortality. Among its complications, respiratory distress syndrome and bronchopulmonary dysplasia are predominant contributors to prolonged hospitalization and respiratory support needs. As advances in perinatal care have improved survival, attention has increasingly turned to optimizing respiratory function and reducing complications through non-pharmacological interventions. Respiratory physiotherapy has therefore gained recognition as a valuable adjunct to medical management in this population. Purpose: To provide a comprehensive synthesis of the current clinical evidence regarding res-piratory physiotherapy techniques used in preterm neonates with respiratory distress syndrome or bonchopulmonary dysplasia. Summary of Evidence: The available liter-ature describes several physiotherapeutic modalities—including prolonged slow expi-ration, postural treatment, Vöjta therapy, and gentle mechanical techniques—aimed at improving ventilation, gas exchange, and secretion clearance. Across diverse studies, these interventions have been associated with better oxygenation, improved heart and respiratory rates, shorter mechanical ventilation time, and reduced hospital stay, while showing no relevant adverse effects. Although methodological heterogeneity persists, the consistency of beneficial trends supports their integration into multidisciplinary neonatal care. Conclusions: Respiratory physiotherapy represents a safe and promis-ing therapeutic complement for preterm neonates with respiratory distress syndrome or bronchopulmonary dysplasia. Techniques that combine postural control and con-trolled expiratory maneuvers appear particularly effective in enhancing pulmonary mechanics and recovery. Future research should focus on standardizing intervention protocols, identifying optimal timing and dosing, and evaluating the long-term respir-atory and developmental outcomes of these physiotherapeutic strategies.

Abstract: Objectives: Respiratory Syncytial Virus (RSV) is a leading cause of hospitalization for acute lower respiratory tract infections (ALRIs) in children, with bacterial coinfection complicating diagnosis and often driving antibiotic overuse. This study aimed to develop and validate a clinical prediction model using common laboratory biomarkers to enable early, accurate identification of clinically significant bacterial coinfection in children with RSV infection. Methods: A single-center, retrospective cohort study was conducted at Fujian Children’s Hospital, enrolling 518 hospitalized children with tNGS-confirmed RSV infection. Patients were randomly divided into a training set (n=363) and a test set (n=155) at a 7:3 ratio. The primary outcome, bacterial coinfection, was defined by a composite reference standard integrating etiological evidence from tNGS with clinical, inflammatory, and imaging data, and adjudicated by a blinded expert panel. LASSO regression identified independent predictors, followed by multivariable logistic regression modeling. Model performance was assessed via discrimination (AUC), calibration (Hosmer-Lemeshow test), and clinical utility (Decision Curve Analysis) in both sets. Results: Neutrophil-to-Lymphocyte Ratio (NLR), C-Reactive Protein (CRP), and Serum Amyloid A (SAA) were selected as predictors. The model achieved an AUC of 0.832 (95% CI: 0.788–0.875) in the training set and 0.811 (95% CI: 0.737–0.885) in the test set, with well-calibrated predictions (P > 0.05). Decision Curve Analysis demonstrated net clinical benefit across 10%–80% threshold probabilities. A nomogram was developed for practical application. Conclusions: This study established a model integrating NLR, CRP, and SAA. It offers a reliable tool for the early detection of bacterial coinfection in RSV-infected children, enabling targeted antibiotic stewardship and improving clinical outcomes.

Abstract: Background: Early-onset neonatal sepsis (EONS), defined as systemic infection occurring within the first 72 hours of life, remains a major cause of morbidity and mortality in preterm infants. Increasing evidence indicates that the gut may play an active role in systemic inflammation, yet the temporal behaviour of fecal short-chain fatty acids (SCFAs) during EONS has not been characterised. SCFAs and branched-chain fatty acids (BCFAs) are key microbial metabolites involved in epithelial maturation and immune regulation and may provide a non-invasive window into early inflammatory vulnerability. Methods: This pilot prospective longitudinal cohort study enrolled preterm infants (⩽ 32 weeks’ gestation) originally identified as at high risk for necrotizing enterocolitis (NEC) and subsequently stratified into EONS and non-sepsis groups. Serial stool samples were collected at predefined timepoints (TPs; TP1 ≈ 3 days of life [DoL], TP2 ≈ 7 DoL, TP3 ≈ 14 DoL, TP4 ≈ 21 DoL, and TP5 ≈ 28 DoL). Samples were analysed using gas chromatography–mass spectrometry (GC–MS) to quantify a panel of 12 SCFAs, including BCFAs and medium-chain fatty acids (MCFAs). Both absolute concentrations and relative fractions were evaluated, with emphasis on ratio-based metrics (e.g., acetic/propionic acid ratio) and timepoint-specific group contrasts, complemented by partial least squares discriminant analysis (PLS–DA). Results: At the earliest sampling window (TP1), infants with EONS exhibited a broad redistribution of the fecal SCFA pool. The median relative fraction of acetic acid was significantly lower in EONS (86.6% vs. 94.5% in non-sepsis), while several non-acetate components—including propionic, valeric, and branched-chain acids—were relatively enriched. Acetate-to-non-acetate ratios were markedly reduced in EONS (e.g., acetic/propionic and acetic/isobutyric ratios), indicating an early shift away from acetate dominance. PLS–DA at TP1 demonstrated partial separation between groups, with acetic-acid depletion and non-acetate enrichment among the strongest contributors to discrimination. By later TPs, these early differences narrowed to a small subset of BCFA-related ratios and largely attenuated by the end of the first month. Conclusions: In this pilot cohort of preterm infants, EONS was associated with early, structured alterations in fecal SCFA profiles, characterised by reduced acetic-acid dominance and relative enrichment of non-acetate acids. Dynamic, ratio-based assessment proved more informative than absolute concentrations alone, revealing transient intestinal metabolic signatures accompanying systemic infection. These findings provide the first longitudinal evidence of gut metabolic involvement in EONS and lay the groundwork for larger, multi-centre studies integrating SCFA trajectories with microbiome and immune profiling to refine early risk stratification for systemic infection in high-risk neonatal populations.

Abstract: Effective communication in critical care units, such as the CVICU, is vital for patient safety, but clinical notes from multiple professionals are often lengthy and complex. This study evaluated the Mistral Large Language Model for summarizing progress notes from the Cardiovascular Intensive Care Unit using the I-PASS framework for structured communication. A total of 385 progress notes were combined for each patient and summarized by the model. The readability was assessed using multiple metrics, including Flesch Reading Ease, Flesch-Kincaid Grade Level, Gunning-Fog Index, SMOG Index, Automated Readability Index, and Dale-Chall Score, and cosine similarity was used to measure alignment with the original notes. The AI summaries were harder to read, with a Flesch Reading Ease score of 29.25 compared to 56.89 for the original notes, and required a higher reading level—Grade 15.24 for the summaries versus Grade 8.98 for the original notes. A cosine similarity of 0.6 showed moderate alignment, retaining key details but losing some context in the generated summaries. Mistral effectively condensed the notes, but readability suffered as a result. Future work will aim to improve clarity and preserve key clinical details through human-guided evaluation.

Abstract: Iron Deficiency Anemia (IDA) has a significant impact on the behavioral and cognitive development of children, and it is one of the most prevalent nutritional deficiencies worldwide, primarily affecting infants, young children, and adolescents. Iron plays a crucial role in brain growth, myelination, neurotransmitter metabolism, and energy metabolism, particularly during the fast neurodevelopmental period of the first two years of life. Several studies reported that children with IDA have impaired attention span, poor memory, poor academic performance, delayed language acquisition, reduced problem-solving abilities, and lower scores in intelligence tests compared to their iron-sufficient peers. Longitudinal research concluded that early untreated IDA leads to irreversible changes in brain structure and function that persist into adolescence, even after hematological recovery. Early prevention, diagnosis, and treatment of IDA are vital to safeguard optimal brain development and ensure children reach their full cognitive and behavioral potential. Addressing this issue requires a combination of nutritional interventions, supplementation programs, and caregiver education to reduce its lifelong impact. This review emphasizes the existing proof and evidence on the significant implications of IDA on the developing brain, clarifying the neurobiological mechanisms and establishing cognitive and behavioral deficits, evaluating the effectiveness of treatments, and discussing public health implications for prevention and early intervention by enhancing maternal health, providing nutritional education, and offering targeted supplementation.

Abstract: The central venous catheter (CVC) is essential in the management of pediatric patients, allowing the administration of medications, parenteral nutrition, and other treatments. However, its use carries a high risk of central line-associated bloodstream infections (CLABSI) and catheter-related bloodstream infections (CRBSI). Advanced chlorhexidine-impregnated dressings have been developed to reduce bacterial colonization, but their effectiveness in the pediatric population remains uncertain. The aim of this review is to evaluate the effectiveness of chlorhexidine-impregnated dressings compared to standard dressings in reducing CLABSI, CRBSI, and CVC colonization in pediatric patients. Randomized clinical trials published between 2005 and 2021 in PubMed, CINAHL, and Embase, in Italian or English, were selected. Methodological quality was assessed using the Joanna Briggs Institute (JBI) checklist. Relevant data were extracted and summarized in tables. Four studies, including a total of 733 pediatric patients (367 intervention, 366 control), were included. None reported a statistically significant reduction in CLABSI/CRBSI with the use of chlorhexidine-impregnated dressings. However, two studies showed a significant reduction in catheter colonization in the intervention group. Current evidence does not support a superior effect of chlorhexidine-impregnated dressings in preventing CLABSI/CRBSI in pediatric patients, although they may reduce catheter colonization. Randomized trials with larger samples and specific methodologies are needed to clarify the true clinical impact.

Abstract: Artificial Intelligence (AI) and Precision Medicine represent foundational pillars for transforming pediatric healthcare, as children exhibit age-specific pharmacokinetic variations requiring highly personalized therapeutic approaches that make AI an indispensable tool for optimizing pharmacological safety and efficacy. This review analyzes current AI applications in pediatric precision pharmacotherapy, examining clinical opportunities and implementation challenges. AI demonstrates tangible clinical impact across multiple domains: pharmacogenomics with predictive models achieving R² = 0.95 for drug exposure; adverse drug reaction prediction with 81.5% sensitivity and 79.5% specificity; clinical decision support systems with 93.4% accuracy in pediatric epilepsy diagnosis. AI implementation has reduced prescription distribution errors by 75% and improved adverse drug reaction detection by 65%. However, significant gaps persist as only 0.38% of pediatric AI models reach clinical testing level, and 77% of studies show high risk of bias. AI transforms pediatric pharmacotherapy from empirical approaches to evidence-based predictive strategies, converting pediatric vulnerability into an innovation catalyst. The technology shifts understanding from correlation to causality, enabling personalized dosing and transforming pharmacovigilance into proactive safety mechanisms. Successful implementation requires overcoming current limitations including algorithmic bias, data quality issues, ethical considerations, and validation through rigorous clinical studies specifically designed for pediatric populations. Future development of sophisticated AI models promises enhanced precision, but real-world validation through interdisciplinary collaboration remains imperative for building robust pediatric AI ecosystems that opti-mize therapeutic outcomes for this vulnerable population.

Abstract: Objectives: To assess risk factors for post-extubation stridor in children and its impact on clinical outcomes. Methods: Prospective cohort study with children aged from 0 to 13 years who were intubated or underwent orotracheal intubation in the pediatric intensive care units (PICU) of two tertiary public hospitals. The outcome of interest was the occurrence of post-extubation stridor. The information collected included patient characteristics, comorbidities, history of airway manipulation, and factors related to orotracheal intubation. A logistic regression was used to identify potential risk factors for post-extubation stridor; data were analyzed until hospital discharge, death, or referral to another facility. Results: A total of 239 children were included, with a median age of 1.3 years and a duration of intubation of three days. Post-extubation stridor was observed in 57.3% of children. A multivariate analysis included prehospital or non-specialized hospital intubation, trauma or complications during intubation, and orotracheal intubation longer than seven days as risk factors for stridor. Children with stridor had a longer PICU length of stay, longer duration of invasive mechanical ventilation, and were often managed with non-invasive ventilation (p < 0.05). Most children with extubation failure (p = 0.001) and cardiorespiratory arrest (p = 0.03) presented stridor. Conclusions: Risk factors for post-extubation stridor included intubation performed in prehospital or non-specialized hospitals, orotracheal intubation longer than seven days, and trauma or complications during intubation. Children with stridor had a worse prognosis, with longer stays in the PICU and on mechanical ventilation and higher rates of extubation failure.

Abstract: Background: Childhood obesity demonstrates substantial metabolic heterogeneity. We determined insulin resistance prevalence in Slovak children with obesity using multiple validated markers and identified high-risk phenotypes. Methods: Cross-sectional study of 54 obese children (BMI 29.5±4.7 kg/m²) and 33 controls (BMI 20.6±1.9 kg/m²). All underwent bioelectrical impedance analysis and fasting metabolic profiling including HOMA-IR and triglyceride-to-HDL cholesterol (TG/HDL-C) ratio. Insulin resistance was defined as HOMA-IR >3.42 (obese) or >1.68 (controls), and TG/HDL-C >0.99 mmol/L. Age-matched sensitivity analysis was performed on 30 pairs. Results: Among obese children, 44.4% demonstrated HOMA-IR-defined insulin resistance versus 51.7% of controls using respective cut-offs, with significantly higher mean HOMA-IR (3.66±2.07 vs 2.53±2.55, p40%) characterized 24.1% of obese children, demonstrating 85.7% insulin resistance prevalence versus 30.0% without low muscle mass (p< 0.01), with HOMA-IR 1.52 points higher (95% CI: 0.31-2.73). Remarkably, 42.9% of children with low muscle mass showed concordant elevation of both metabolic markers versus 15.0% without (OR 4.25). Conclusions: Low skeletal muscle mass in obese Slovak children represents an ultra-high-risk phenotype with 85.7% insulin resistance prevalence and 4.25-fold increased odds of severe metabolic dysfunction. Age-matched analysis confirmed that metabolic differences are independent of age effects. Body composition-based risk stratification enables personalized interventions targeting the highest-risk children.

Abstract: Background/Objectives: Drug-resistant epilepsy (DRE) is a significant health problem leading to cognitive impairment and reduced quality of life. This study aimed to in-vestigate the incidence and etiology of DRE in children in Estonia. Methods: A retrospective, population-based study of childhood DRE was conducted in Estonia from January 1, 2013, to December 31, 2017. All cases were identified through the only two pediatric neurology departments in the country, both located at tertiary care hospitals (Tartu University Hospital and Tallinn Children’s Hospital), ensuring complete nationwide coverage. Epidemiological, magnetic resonance imaging (MRI), and genetic data (chromosomal microarray, single-gene tests, gene panels, and exome/genome se-quencing) were collected. Results: The incidence rate of childhood epilepsy was 84.1 per 100,000. DRE developed in 10% of children with new-onset epilepsy, corresponding to an incidence rate of 8.5 per 100,000. Etiologically relevant MRI abnormalities were identified in 43% of patients with DRE, most commonly congenital brain malformations (19%). Pathogenic single-gene sequence variants were detected in 27% of patients who underwent genetic testing. Copy number variants were identified in 4% of tested patients, and chromosomal aberrations in 1%. Four patients carried novel candidate disease genes, although their pathogenicity remains uncertain. The most frequent etiology of DRE was structural (29%), followed by genetic (19%), with combined etiologies (13%) also contributing significantly. Conclusions: Our study is the first epidemiological study of DRE in children in Estonia and the Baltic region. The relatively low incidence observed may reflect the comprehensive national ascertainment and centralized management of pediatric epilepsy in tertiary care centers.

Abstract:

Background/Objectives: The hospitalization of a child in the Pediatric Intensive Care Unit (PICU) is one of the most stressful life events a family can experience. The critical nature of the illness, the complexity of the hospital environment, and the uncertainty of the prognosis place parents under considerable emotional strain. This study aimed to identify the most influential factors associated with parental stress and psychological distress in the PICU. Methods: A quantitative, cross-sectional analytical design was employed. Anonymous surveys were administered to assess parental stress and anxiety, along with sociodemographic and clinical variables. Data were collected using the Parental Stressor Scale: Infant Hospitalization (PSSIH) and the Depression Anxiety Stress Scale-42 (DASS-42), both validated in Spanish. Results: The highest-scoring stressor dimension was Images and/or Sounds (M = 2.03, SD = 0.97). Within the DASS-42, the Stress subscale yielded the highest mean score (M = 10.06, SD = 9.34). Significant positive correlations were found between emotional distress and perceived stressors. Inferential analyses indicated that fathers reported higher emotional stress (p = .040); parents without prior PICU experience reported greater clinical stress (p = .049); and participants with low income and limited family support showed significantly higher distress (p < .05). Conclusions: Parental stress in the PICU is a multifactorial phenomenon influenced primarily by sociodemographic characteristics and the clinical dimension of stressors. Identifying vulnerable subgroups—such as fathers, parents with low income, limited social support, or no prior PICU experience—can guide the implementation of targeted psychosocial interventions, thereby reducing the risk of adverse outcomes such as PTSD and improving family coping during the hospitalization process.

Abstract: The vaccination has a lot of measures that concerns overall population, but none at individual scale concerning the burden of vaccines in infants. Looking at Early Immunization of infants, a theoretical framework for the measurement of the early life vaccine load in infants having less than 1 year -vaccinometrics-is developed. This study introduces the Age-adjusted Vaccine Burden Index (BIV) to quantify vaccine load in infants up to 12 months. The BIV accounts for the number, intensity, and timing of vaccine doses, offering a measure of Early-Life Vaccine Load. A lower BIV reflects reduced neonatal exposure to vaccines, while a higher BIV indicates increased burden in vaccination and potential risks. The index ranges from 0 (no vaccination) upward, correlating with vaccine intensity. BIV serves as a surveillance tool to guide developmentally sensitive immunization strategies, aiming to balance disease prevention with long-term neurological health. Although there is a hot and contradictory debate about a possible relationship between vaccines and autism spectrum disorder (ASD), this study tests the BIV by using national immunization schedules from a sample of countries with varying autism rates. Results suggest that countries with a higher rate of autism tend to have a high magnitude of BIV, associated with lower average age of infants during vaccinations and a higher average number of vaccines and doses, including vaccination at birth, varicella and hepatitis B vaccines, that generate a higher early-life vaccine load both a 6 and 12 months, and can be also a proxy of possible risks of adverse effects in infants having less than or equal to 1 year. These findings align with broader epidemiological patterns and support the hypothesis that vaccine timing and concentration may be relevant factors in neurodevelopmental outcomes. The larger significance of this research lies in its potential to inform international vaccination policy. By introducing a standardized index, the study enables cross-country comparisons and supports evidence-based adjustments to vaccine schedules. It suggest a health policy for delaying non-critical vaccines after the 3 months and reducing dose intensity in the first year of infants. These recommendations are consistent with best practices observed in Nordic countries, which maintain high immunization coverage while minimizing early-life exposure. The BIV provides a tool for such surveillance, offering a framework for monitoring and mitigating potential risks. This study advances the theoretical and practical understanding of vaccine scheduling and its implications for possible neurodevelopment. It also encourages a shift toward developmentally sensitive immunization strategies, balancing disease prevention with long-term neurological health, and lays the groundwork for future studies and policy reforms worldwide.

Abstract: Background: The use of oral home antibiotics (OHA) after discharge in children undergoing surgery for complicated acute appendicitis (CAA) remains controversial. This systematic review and meta-analysis aimed to evaluate whether OHA reduces the risk of infectious complications or readmissions compared to patients discharged without antibiotics (NHA).Methods: This systematic review was prospectively registered in PROSPERO (CRD420251049919). We searched PubMed, Web of Science, Scopus, Ovid, and Cochrane CENTRAL from inception to March 2025. Two independent reviewers screened the studies, extracted the data, and assessed the methodological quality using the ROBINS-I tool. Eight random-effects meta-analyses and four leave-one-out meta-analyses were conducted for intra-abdominal abscesses (IAA), surgical site infections (SSI), organ/space infections (OSI), and hospital readmissions (RA). Two exploratory random-effects meta-regression models were performed for RA. Certainty of evidence for all outcomes was formally graded using GRADE.Results: Fourteen studies comprising 26,174 pediatric patients with CAA were included. Meta-analyses showed no significant differences between intervention (IG) and comparator (CG) groups for IAA (RR 0.97; 95% CI: 0.38–2.47), OSI (RR 1.19; 95% CI: 0.73–1.93), or RA (RR 1.02; 95% CI: 0.73–1.41). In exposure-restricted analyses, OHA was associated with a borderline statistically significant increased risk of RA (RR 0.78; 95% CI 0.61–1.01; p = 0.05). The risk of SSI was significantly higher among patients in the CG (RR 0.77; 95% CI, 0.61–0.96; p = 0.02). However, this apparent association was not robust and was lost in sensitivity analyses restricted to studies with crude patient-level exposure data, where the effect reversed direction (RR > 1), consistent with protocol-based confounding. Meta-regression exploring differences in predischarge total leukocyte counts showed a non-significant trend toward increased RA in patients receiving OHA. Across all outcomes, certainty of evidence was rated very low, primarily driven by potential confounding by indication and non-randomized designs.Conclusions: OHA after discharge does not appear to reduce the risk of postoperative complications in children treated surgically for CAA. Given the lack of consistent benefit and potential for unnecessary harm, routine use of post-discharge OHA is not supported. The exposure-restricted analysis also raises a plausible signal of harm in terms of RA. Because the certainty of evidence is very low, further high-quality prospective research is needed to clarify the true effect of OHA in this context.

Abstract:

Background: Sleep disorders are common in childhood and adolescence and can negatively affect cognitive development, mood regulation, behaviour and quality of life. Parents frequently seek complementary therapies such as homoeopathy, yet the scientific evidence for homoeopathic treatments in paediatric sleep disorders remains uncertain. This systematic review examines the effectiveness of homoeopathic interventions for sleep disorders in children and adolescents according to evidence-based medicine principles. Objectives: To systematically review and evaluate the effectiveness of homoeopathic treatments for sleep disorders in children and adolescents, following evidence-based principles. We aimed to summarize current clinical evidence from 2015–2025 on whether homoeopathy improves paediatric insomnia and other sleep-related disorders, and to assess the quality of that evidence. Methods: PubMed, Scopus, and allied databases were searched for RCTs and observational studies involving participants <18 years with sleep disorders (insomnia, bruxism, enuresis) treated with homoeopathy. English-language studies were screened manually, and bias was assessed qualitatively. Results: Five studies (three RCTs, two observational; ~400 participants) met inclusion criteria: A multicenter RCT found a complex homoeopathic remedy superior to glycine for insomnia symptom reduction. A crossover RCT reported significant bruxism improvement with Melissa officinalis 12C versus placebo (ΔVAS –2.36 vs –1.72, p≈0.05). A double-blind RCT in enuretic children showed individualized homoeopathy reduced weekly bedwetting episodes (median –2.4 nights, p<0.04). Observational studies also noted symptom improvement. No serious adverse effects were reported. Bias risk varied: one open-label trial showed high risk; others were adequately blinded. Conclusions: Homoeopathic treatments may provide modest benefits for paediatric insomnia, bruxism, and enuresis, with good safety. However, evidence remains limited and heterogeneous. Larger, high-quality trials are warranted before firm recommendations can be made.

Abstract: Decision Curve Analysis (DCA) bridges the gap between statistical accuracy and clinical usefulness—a distinction frequently overlooked in diagnostic research. Using a simulated cohort representing a real-world diagnostic scenario, this tutorial demonstrates how predictors with similar ROC-based performance can yield markedly different net benefit profiles when evaluated through DCA. Three tools were compared: a strong predictor (composite clinical score), a moderate biomarker (leukocytes), and a weak marker with modest AUC but limited practical value (serum sodium). Whereas ROC curves portray discrimination alone, decision curves situate performance within real clinical trade-offs, making explicit when a model adds value beyond default strategies such as treating all or none. The tutorial provides a step-by-step framework for interpretation, clarifies frequent misconceptions (thresholds, prevalence effects, calibration), and illustrates how DCA incorporates the consequences of decisions rather than just their statistical accuracy. Rather than adding ‘just another metric’, DCA reframes evaluation around a practical question: does using this model improve decisions across clinically reasonable thresholds?

Abstract: Two large observational studies examining the association between aluminum adjuvant exposure from childhood vaccines and subsequent asthma diagnosis yielded conflicting results: Daley et al. (2023) reported a positive hazard ratio (HR) of 1.19 per mg (95% CI: 1.14-1.25), while Andersson et al. (2025) found a negative HR of 0.96 per mg (95% CI: 0.94-0.98). This discrepancy potentially arises from a failure to test linearity assumptions in the dose-response relationship. This paper reanalyzes the Daley et al. dataset using the same population and Cox proportional hazards methodology, but incorporates tests for nonlinearity by dividing the 0-24 month exposure window into six age-based sub-windows (0-1m, 1-3m, 3-5m, 5-7m, 7-15m, 15-23m) and assessing hazard ratios per sub-window. Results revealed significant nonlinearity as a function of age at exposure, with sub-window HRs ranging from 0.83 (0-1m) to 1.94 (1-3m), all statistically differing from the overall HR of 1.27 via two-sample t-tests (adjusted t-statistics: -9.27 to 5.98). No nonlinearity by dose was observed. These findings indicate that differing vaccine schedules in the U.S. and Denmark may have sampled distinct domains of a nonlinear function, confounding the results. Uncorrected dose-response nonlinearities can cause arbitrarily large errors and future research protocols should include explicit tests for these possible nonlinearities.

Abstract: The connection between acetaminophen use in the pediatric population and the etiology of autism spectrum disorder (ASD) have been a subject of misunderstanding, miscalculation, and misinformation for more than a decade. This narrative review summarizes 29 lines of evidence pointing with no reasonable doubt to the conclusion that exposure of susceptible babies and children to acetaminophen is responsible for many if not most cases of ASD. Susceptibility to acetaminophen-induced injury is imposed by a range of environmental, genetic, and epigenetic factors associated with oxidative stress, and is apparently the greatest immediately after birth. Susceptibility then decreases until about six years of age, which is likely outside of the developmental window in which regression into ASD can occur. Exposure to acetaminophen very early in life can occur for a variety of reasons, including treatment of pain during administration to the mother during labor and delivery, during vaccination, and during circumcision. Although acetaminophen use during vaccination is generally not recommended, the vaccine against meningococcal serogroup B (MenB), administered at 2, 4, and 12 months of life, is now recommended with 3 accompanying doses of acetaminophen in some countries with dramatically rising levels of ASD. Unfortunately, based on current knowledge, it is expected that such exposures to acetaminophen will induce ASD in some susceptible individuals. Evidence therefore strongly and unequivocally indicates that medical recommendations should mandate the MenB vaccine be given separately from other vaccines and without acetaminophen, which some national healthcare services (e.g., Australian and Canadian) have already identified as an acceptable clinical approach.

Abstract: Background: Severe lower urinary tract dysfunction (LUTD) in neurologically and anatomically normal children is uncommon but clinically important, often presenting with recurrent urinary tract infections (rUTIs), incontinence, or urinary retention. We report three illustrative cases and integrate a structured narrative review to contextualize diagnostic and therapeutic strategies. Methods: Retrospective review of three children (aged 3–10 years) evaluated at a tertiary pediatric urology center (2018–2024) for severe LUTD with rUTIs and no neuroanatomical or structural abnormalities. Assessment included ultrasound, voiding cystourethrography (VCUG), urodynamics, and cystoscopy. Management combined urotherapy, pelvic floor biofeedback, targeted pharmacotherapy, and, when indicated, continuous antibiotic prophylaxis (CAP) or clean intermittent catheterization (CIC). A structured narrative literature search (1970–2024) was undertaken to compare phenotypes and outcomes. Results: Case 1 (7-year-old male) had detrusor overactivity with reduced capacity and cystoscopic remodeling (deep trabeculations, pseudopolypoid mucosa); symptoms resolved on urotherapy + trospium + biofeedback, with relapse after treatment withdrawal. Case 2 (3-year-old female) exhibited poor compliance, detrusor–sphincter dyssynergia, high post-void residuals, and secondary high-grade VUR, consistent with Hinman syndrome; CAP + trospium + CIC + biofeedback led to durable control of rUTIs. Case 3 (10-year-old male) had hypocontractile detrusor with recurrent retention; α-blockade (tamsulosin) plus biofeedback achieved symptom resolution. Across cases, endoscopic findings correlated with urodynamic phenotypes, and a function-first multimodal approach was effective. Conclusions: Severe functional LUTD can occur in otherwise healthy children and may mimic structural disease. Early phenotyping with noninvasive testing, urodynamics, and selective cystoscopy, followed by structured conservative therapy, can control infections, restore function, and prevent unnecessary surgery and upper tract damage.

Abstract: Risperidone is widely used in treating pediatric neuropsychiatric disorders but concerns about its metabolic side effects—especially weight gain—remain significant. This prospective observational study was conducted in a tertiary-care hospital to evaluate short-term metabolic changes and behavioral outcomes in children aged 7 to 12 years who were newly initiated on risperidone. A total of 27 antipsychotic-naïve children were followed for an average of 9.5 weeks. Baseline and follow-up assessments included anthropometric measurements, fasting laboratory tests, and behavioral evaluation using the Child Behavior Checklist (CBCL). Over the study period, children showed a significant mean weight increase of 3.59 kg, and a BMI increase of 2.21 kg/m²—reflecting more than a 12% rise in both parameters. The degree of weight and BMI gain showed moderate correlation with risperidone dosage per body weight, while no link was found between these changes and either age or treatment duration. On the positive side, notable behavioral improvements were observed, with total CBCL scores dropping by 25.9 points, marking a 34% improvement, particularly in externalizing behaviors. These results highlight a concerning but measurable trade-off: while risperidone offers clear benefits in managing behavioral issues in children, it is also associated with significant and rapid weight gain that appears to be dose dependent. The findings reinforce the importance of cautious prescribing, with emphasis on using the lowest effective dose, regular metabolic monitoring, and integrating lifestyle counselling from the start of therapy. This study contributes to the growing body of evidence urging careful risk–benefit assessment in pediatric psychopharmacology.

Abstract: Background: Kawasaki disease (KD) is an acute vasculitis of childhood that usually affects children under five but can also present in adolescence. Although less common, ado-lescent cases pose unique diagnostic and therapeutic challenges due to atypical features and increased cardiovascular risk. Methods: A targeted PubMed search was conducted for studies on KD in adolescents published between 2000 and 2024. Nine studies were included in the synthesis, along with one national surveillance study. Results: Adolescents with KD often do not meet full diagnostic criteria, leading to delays or missed diagnoses. Presentations frequently involve symptoms that mimic those of mucocutaneous, gastrointestinal, musculoskeletal, and neurological conditions. These delays are linked with higher rates of coronary artery abnormalities compared with younger children. Intravenous immunoglobulin (IVIG) remains the primary treatment, though resistance occurs more frequently in this group. Beyond the acute illness, ado-lescent KD impacts school participation, physical activity, and independence, under-scoring the importance of addressing developmental and psychosocial outcomes. Conclusions: While KD is primarily a disease of younger children, adolescent cases require greater clinical awareness, prompt intervention, and developmentally informed follow-up to reduce complications and support effective transition to adult care.