Congenital structural anomalies constitute a major source of pediatric morbidity and surgical burden. However, evidence regarding the spatial epidemiology of congenital structural anomalies and their area-level environmental context remains limited, particularly in geographically and socioeconomically heterogeneous regions. This study aimed to investigate the spatial heterogeneity of area-level environmental contextual associations with hospital-based congenital anomaly burden. We conducted a retrospective hospital-based study including pediatric inpatients with congenital structural anomalies admitted to the largest provincial pediatric referral center in Yunnan Province between 2014 and 2024. Descriptive epidemiological analyses were performed to summarize demographic characteristics, temporal trends, and system-level distributions. High-frequency congenital anomalies were selected to construct stable county-level datasets for spatial analysis. Ordinary least squares (OLS) and geographically weighted regression (GWR) models were applied to examine spatially varying, area-level contextual associations between environmental factors and anomaly burden across five congenital anomaly systems (circulatory, digestive, urogenital, musculoskeletal, and other structural anomalies). A total of 56,434 pediatric inpatients with congenital structural anomalies were identified. Among pediatric inpatients, boys accounted for the majority (67.68
Febrile infection-related epilepsy syndrome (FIRES) is a rare and severe epileptic encephalopathy characterized by refractory seizures following a febrile infection. FIRES is a subtype of new-onset refractory status epilepticus with an unknown etiology. Tocilizumab is an interleukin-6 receptor antagonist which has been recommended as an anti-inflammatory treatment for the acute phase of FIRES. However, the efficacy of tocilizumab for the chronic phase of FIRES remains unclear. This study aimed to analyze the efficacy and safety of tocilizumab in the treatment of pediatric patients with FIRES during the chronic phase. We conducted a retrospective cohort study in pediatric patients with FIRES during the chronic phase who received tocilizumab treatment. The primary outcome was the response rate at 16 weeks after tocilizumab initiation, defined as the proportion of pediatric patients who achieved a 50
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by pathogenic variants in the NF1 gene. The NF1 gene product neurofibromin, acts as a tumor suppressor primarily by negatively regulating the mitogen-activated protein kinase signaling pathway. This study aimed to characterize both the genotypic and phenotypic spectrum of pediatric NF1 patients at a single center and further explore potential genotype-phenotype correlations. Pediatric patients diagnosed with NF1 who were treated and followed up at our center from July 2013 to August 2025 were included. All patients underwent genetic testing, both phenotypic and genotypic data were collected and curated. Statistical analyses were performed using SPSS, GraphPad Prism, and Python. Growth curves and variant distribution maps were generated based on the integrated dataset. A total of 301 patients were included. They exhibited a broad multisystem phenotype with several clinical manifestations and notable sex-related differences, particularly skeletal abnormalities and developmental or intellectual impairments. Males had significantly lower height standard deviation scores (SDS) than females, and P50 growth curves were consistently below those of healthy reference values. Truncating variants were the most common (60.8
B-cell dysregulation is central to the pathogenesis of childhood-onset systemic lupus erythematosus (cSLE), yet the B-cell immunophenotypes across disease states remain incompletely defined. This study aimed to investigate the mechanistic basis and clinical relevance of B-cell–mediated immune dysregulation in cSLE. Peripheral blood samples from 64 cSLE patients and 40 age- and sex-matched healthy controls (HCs) were analyzed using flow cytometry. The subsets were compared across disease states, including lupus low disease activity state (LLDAS), active disease, and clinical flare. Diagnostic performance was evaluated using logistic regression and receiver operating characteristic analyses. Compared with HCs, patients with cSLE exhibited reduced unswitched memory B cells and expanded pathogenic subsets, including double-negative (DN) B cells, age-associated B cells (ABCs), short-lived plasma cells (SLPCs), and long-lived plasma cells (LLPCs) (all P < 0.05). LLPCs showed the strongest disease association [area under the curve (AUC) = 0.855] and a combined model further improved discrimination (AUC = 0.936). Active disease was characterized by expanded DN B cells, ABCs, SLPCs, and LLPCs (all P < 0.05). Clinical flare involved selective enrichment of ABCs, DN B cells, and plasma cells without further increase in total B cells. Of note, LLPCs remained elevated in LLDAS compared with HCs (P < 0.01). ABCs were negatively correlated with complement C3 levels (r = − 0.26, P = 0.04). cSLE is characterized by distinct peripheral B-cell immunophenotypes across different clinical states, marked by expansion of ABCs and plasma-cell populations. Persistent LLPC enrichment during clinical quiescence suggests incomplete immunological restoration and may contribute to disease heterogeneity and relapse susceptibility.
Intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) increases coronary artery risk. Early prediction is crucial for improving outcomes. This study aimed to develop and validate a machine learning (ML) model for predicting IVIG resistance in children with KD. A retrospective cohort of patients with KD was used for model development, with external validation cohorts from Fuzhou and Yangzhou, and a prospective validation cohort. Clinical and laboratory variables were extracted from electronic medical records. We evaluated 12 algorithms and support vector machine (SVM) was selected for optimal performance. SHapley Additive exPlanations (SHAP) values assessed feature importance, followed by stepwise feature elimination. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). A web-based calculator was developed. A total of 2371 patients with KD involved in the retrospective development cohort, 443 in Fuzhou cohort, 198 in Yangzhou cohort, and 253 in prospective validation cohort. The SVM model achieved AUCs of 0.782 in internal validation, 0.746 and 0.759 in the external validation cohorts from Fuzhou and Yangzhou, respectively, and 0.799 in prospective validation. The final model incorporated eight predictors, with SHAP analysis providing both global and local explanations of feature contributions. The model also demonstrated good calibration and favorable net benefit across clinically relevant thresholds in DCA. The SVM-based ML model using routine clinical data shows potential for predicting IVIG resistance in KD and may support early risk stratification.
N-methyl-D-aspartate receptors (NMDARs) play a pivotal role in neurodevelopment. While pathogenic variants in GRIN genes cause a broad spectrum of epileptic and developmental disorders, the precise molecular determinants that drive specific neurodevelopmental courses remain poorly understood. This study aims to utilize high-resolution structural modeling to identify associations between localized conformational alterations in NMDARs and distinct clinical phenotypes. We retrospectively evaluated a cohort of 31 Chinese pediatric patients with GRIN-related epilepsy (GRIN1, n = 3; GRIN2A, n = 14; GRIN2B, n = 11; GRIN2D, n = 3) using detailed electroclinical and neurodevelopmental phenotyping. Concurrently, three-dimensional structural models for 23 missense variants were generated using AlphaFold2. Domain-specific root-mean-square deviation (RMSD) and Euclidean displacements of transmembrane helices were quantified. Patients in this cohort predominantly presented with early-onset epilepsy, multiple seizure types, and significant pharmaco-resistance, with 41.9
Growth and development in children are known to be closely associated with cardiometabolic health. However, there is a lack of systematic assessments of associations between growth markers and growth patterns across different developmental stages and pediatric cardiometabolic health in prospective birth cohorts. This study aimed to identify critical developmental windows and growth characteristics that may be relevant to cardiometabolic health that could inform future prevention strategies. We utilized the Ma’anshan birth cohort and obtained repeated measurements of body length/height and weight from birth through school age at each follow-up visit to examine childhood body mass index (BMI) growth curves. During school age, additional measurements were taken for cardiometabolic risk factors (CMRFs) including waist circumference, blood pressure, blood glucose, and blood lipids. Linear mixed modeling was used to fit childhood BMI growth curves and calculate 11 growth markers: adiposity peak (AP)-age, AP-BMI, adiposity rebound (AR)-age, AR-BMI, infancy slope, toddlerhood slope, preschool/school-age slope, infancy area under the curve (AUC), toddlerhood AUC, preschool age AUC, and school-age AUC. Different growth patterns were classified using k-means clustering. Among the 1786 children included, significant differences existed between boys and girls in growth markers (t-tests) and patterns (chi-square tests) (P < 0.05). With the exception of AP-age, the remaining 10 growth markers showed significant associations with clustered CMRFs in both boys and girls (P < 0.05). Compared to low-risk patterns, children with high-risk patterns had significantly increased risks of clustered CMRFs in both boys [relative risk (RR) = 6.75, 95
Evidence from repeated early-childhood BMI measurements in Chinese children remains limited. This study aimed to examine associations between body mass index (BMI) trajectories from ages 1 to 7 years and cardiometabolic risk at age 8 in this population, and to further distinguish cumulative and timing-specific effects of early BMI development. We followed 1072 mother–child pairs from Tianjin, China for 8 years. Height and weight were measured annually between ages 1 and 7 years; blood pressure, fasting glucose, and lipid concentrations were assessed at age 8. Group-based trajectory modeling was used to identify BMI trajectories. Excess BMI-years, adiposity rebound (AR) age, and interval-specific conditional BMI Z-score gain at ages 1–3, 3–5, and 5–7 years were further assessed. Generalized linear and logistic regression models were used to estimate associations with a modified continuous cardiometabolic risk score (modified cMetS) and cardiometabolic risk traits (CRTs) at age 8. Two adverse BMI trajectories were identified: late obesity growth pattern (LOGP) and persistent obesity growth pattern (POGP). Compared with control trajectory, LOGP and POGP were associated with higher modified cMetS in fully adjusted models [LOGP: regression coefficient (β) = 0.88, 95
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading chronic liver disease in children and adolescents; this parallels the global obesity epidemic. The contribution of genetic susceptibility to pediatric MASLD, and its interaction with anthropometric and biochemical indices used for non-invasive screening remains poorly understood. We aimed to evaluate waist-to-height ratio (WHtR) as a simple, equitable, and scalable tool for early identification of pediatric MASLD and relate this to genetic risk. We combined school-based data from 1010 Chinese children with analyses of the Global Burden of Disease, the 1000 Genomes Project, and the US National Health and Nutrition Examination Survey (NHANES). Thirteen MASLD-related single-nucleotide polymorphisms (SNPs) were genotyped to construct a genetic risk score (GRS). We examined global epidemiological patterns, quantified inter-population allele divergence, and assessed how GRS modifies cutoffs and performance of nine anthropometric and biochemical indices. Genetic analysis revealed minimal frequency divergence across most ancestries (mean Fixation index < 0.05), except for the African ancestry where there was moderate divergence. Higher GRS were associated with lower cutoffs across indices. When GRS Z-score increased from −3 to 3, visceral adiposity index showed the sharpest changes (Z-score decreased from 1.5 to −1.8), while BFP (1.2 to 0.1) and WHtR (1.5 to 0.1) showed gradual change. Furthermore, incorporating GRS into the base anthropometric models yielded only marginal improvements in overall screening performance [area under the receiver operating characteristic curve (AUC) and Youden Index]. Validation in NHANES showed WHtR ≥ 0.48 retained high discrimination (AUC > 0.87) across most genetic variants. This study suggests that WHtR is a consistent and practical tool for screening pediatric patients with MASLD across diverse populations. While genetic variation may influence optimal thresholds, WHtR ≥ 0.48 appears broadly applicable, supporting its potential use as a frontline screening metric in diverse settings.
As a consequence of hypertension, left ventricular (LV) structural alterations are associated with cognitive decline in the elderly. However, its role in early childhood remains unclear. We examined the relationship between blood pressure (BP), LV structure, and cognitive function in preschool-aged children. This population is free from aging-related comorbidities. We recruited 1279 4-year-old children from the Shanghai Birth Cohort (2018–2021), excluding those with birth defects or developmental delays. BP and echocardiographic assessment were conducted at follow-up. Cognitive function was evaluated using the Wechsler preschool and primary scales of intelligence-fourth edition. Elevated BP (107.4 ± 6.2 mmHg) compared to normal BP (96.0 ± 5.9 mmHg) tended towards lower full scale intelligence quotient (IQ) [adjusted mean difference (β) = − 2.95, 95
Intravenous maintenance fluid therapy is one of the most common therapies for hospitalized children, yet the field lacks standardized outcomes to evaluate its effectiveness. Although intravenous maintenance fluid therapy has been used for nearly two centuries, existing studies show wide heterogeneity in reported endpoints, limiting the ability to perform meta-analyses and generate robust evidence. No core outcome set specific to pediatric intravenous maintenance fluid therapy currently exists, and previous initiatives have focused narrowly on fluid accumulation rather than the five components of intravenous maintenance fluid therapy prescription. This study aimed to create a comprehensive core outcome set—COSMIC—to standardize outcome reporting across research involving indications, tonicity, balanced solutions, composition, and volume of intravenous maintenance fluid therapy in children. The study followed the core outcome measures in effectiveness trials and core outcome set–standards for development guidelines and was prospectively registered. Four phases were undertaken: a systematic literature review (1960–2023), the extraction and classification of all reported intravenous maintenance fluid therapy-related outcomes, a two-round modified Delphi process involving international experts and non-experts, and two online consensus meetings to finalize the cost. Eligible participants included authors of intravenous maintenance fluid therapy publications and healthcare professionals. Outcomes were rated on a 9-point Likert scale, and predefined consensus thresholds determined inclusion or exclusion. Items without consensus were discussed and voted on during the final meetings. The literature review identified 259 outcomes, of which 104 unique items entered Delphi round 1. Ninety participants completed round 1 and 82 round 2. Participants represented all continents. Four outcomes were deemed essential for all five PICO-based intravenous maintenance fluid therapy questions: 28-day mortality, survival free of organ dysfunction, hospital length of stay, and natremia. Additional outcomes were defined specifically for each of the five intravenous maintenance fluid therapy components, resulting in a structured and globally applicable core outcome set. COSMIC is the first comprehensive core outcome set to address all core questions related to pediatric intravenous maintenance fluid therapy. It covers the full spectrum of prescription components and includes outcomes feasible across diverse healthcare settings. COSMIC adheres to the standards and provides a practical, internationally relevant framework. Its adoption will harmonize reporting, strengthen future trials, and support meta-analyses, ultimately improving evidence-based intravenous maintenance fluid therapy in children.
Both influenza A infection (IAV) and type I hypersensitivity mechanisms have been independently linked to acute appendicitis. Particularly the expression of type I hypersensitivity associated with cytokine interleukin (IL) 13 has been shown to be of significance in both, appendicitis and influenza infection. The aim of the current study was to analyze possible associations of respective gene expressions at the level of mathematical correlations. We analyzed messenger RNA (mRNA) gene expressions of IAV-associated markers, hypersensitivity type I-related cytokines and inflammatory markers IL-17A and c-reactive protein (CRP) in peripheral blood mononuclear cells from 29 children aged 7–17 years, who were operated for histologically confirmed appendicitis at Charité–Universitätsmedizin Berlin between April and August 2019. Statistical relationships between gene expressions were investigated using Spearman’s correlation analysis, with a correlation coefficient r ≥ 0.5 or r ≤ − 0.5 representing high, and r ≥ 0.7 or r ≤ − 0.7 very high correlations. Statistical significance was assumed at P < 0.01. A total of 29 patients were involved in this study. Particularly the expression of IL-13 showed highly significant negative correlations with that of IAV-specific antiviral response genes, ranging from – 0.89 (P < 0.0001) to – 0.49 (P = 0.006). A strong inflammatory background was demonstrated by very high correlations of IL-13 with CRP (r = 0.91, P < 0.0001) and IL-17A (r = 0.82, P < 0.0001). These findings suggest a connection between IAV infection and acute appendicitis in children, implicating sequential immune responses, including hypersensitivity type I mechanisms, in appendicitis pathophysiology.
Introduction The diagnosis of congenital hip dislocation is historically included in the first clinical examination of the newborn baby[1].Later,the term developmental dysplasia of the hip was defined,with congenital hip dislocation being the most severe form of developmental dysplasia of the hip[2-4].
Early-life growth trajectories, especially during the first two years, are important for future health. However, in the context of rapidly rising childhood obesity, it is essential to characterize BMI-for-age Z-score (BAZ) trajectories in early childhood, compare optimal modeling approaches, and identify associated risk factors. This prospective birth cohort study enrolled participants in Jinan, Shandong from 2019 to 2022. World Health Organization (WHO)-standardized BAZ scores were calculated for children at eight timepoints (0–24 months). Sex-specific BAZ trajectories were derived using growth mixture modeling (GMM) and k-means for longitudinal data (KML). The possible risk of being overweight (BAZ > 1) at age three years was predicted using logistic regression with five folds cross-validation, comparing model performance via the area under the curve (AUC). Associations between trajectory classification and antenatal and postnatal factors were examined. A total of 4629 mother-infant dyads were enrolled in this study. The KML-derived four-class trajectory model demonstrated optimal predictive performance for possible risk of being overweight at age three years, achieving an AUC of 0.749 and significantly outperforming the GMM model (AUC = 0.571). Male sex [odds ratio (OR) = 1.314; 95
The developmental trajectory for children with spinal muscular atrophy (SMA) has been significantly altered following the availability of survival motor neuron (SMN) augmenting therapies. In the treatment era, a holistic patient-centred approach that looks beyond outcomes of survival and motor function is critical and must incorporate everyday functioning (“adaptive functioning”) and participation. A literature review was conducted using PubMed, drawing on articles published until 2025. Keywords included: “spinal muscular atrophy”, “adaptive function”, “adaptive behaviour”, “the International Classification of Functioning, Disability and Health”, “function”, “participation” and “patient-reported outcome measures”. Articles were screened and included on the basis of their contextual relevance to the current SMA care paradigm, with preference given to studies providing insights into the application of the International Classification of Functioning, Disability and Health (ICF), and adaptive functioning. This review highlights the growing importance of everyday functioning and participation within the contemporary SMA treatment paradigm. Current evidence suggests that adaptive functioning is affected across mobility, self-care, social, and neurodevelopmental domains. The ICF provides a practical and multidimensional framework that supports a holistic assessment approach, extending beyond traditional performance-based and motor-focused outcomes to better capture capabilities in everyday functioning, including outcomes that directly influence independence, participation, and quality of life for children with SMA and their families. Furthermore, the ICF may assist in identifying treatment goals, guiding personalised management, and facilitating multidisciplinary collaboration. A limitation of current evidence is that thus far studies have predominately been completed prior to the advent of SMN augmenting therapies, emphasising the necessity of assessing adaptive functioning, especially in the domain of patient-reported outcome measures, to support personalised care and meaningful long-term outcome assessment. The ICF is highly applicable for applying a holistic management approach for SMA in the treatment era, enabling SMA to be conceptualised through a multidimensional lens. Developing a minimum set of core SMA outcomes which incorporate the ICF framework and aim to understand and improve outcomes is a priority and of practical relevance to people with SMA, families and clinicians. This approach promotes an essential paradigm shift by emphasising functioning and participation as key focuses within clinical care and research.
Childhood obesity is associated with cardiometabolic and musculoskeletal health risks. Because fat reduction may be accompanied by loss of skeletal muscle, this trial aims to evaluate whether a plyometric-based high-intensity interval training (Plyo-HIIT) program improves muscle-to-fat ratio (MFR) in children aged 9–12 years. This pragmatic, assessor-blinded, three-arm randomized controlled trial will recruit 210 children aged 9–12 years from primary schools in Hong Kong, China. Participants will be randomly assigned to Plyo-HIIT, structured fitness (SF) program, or the health education (HE) control group in a 1:1:1 ratio. Each group will engage in two 45-minute weekly sessions for 16 weeks. The Plyo-HIIT program involved developmentally appropriate plyometric exercise (e.g., jumping, skipping). The SF program includes moderate- to high-intensity activities maintaining 60
Oral propranolol, with or without corticosteroids, has been shown to benefit diffuse infantile hepatic haemangioma (IHH); randomized trial evidence is lacking. We aimed to evaluate the efficacy and safety of propranolol monotherapy versus propranolol plus prednisone for the treatment of problematic IHHs to determine whether oral prednisone provided an added benefit to propranolol. We conducted an open-label, multicenter, randomized controlled trial across six referral centers in China from July 2019 to November 2023 (clinicaltrials.gov registration: NCT03331744). Infants with problematic diffuse IHH were assigned (1:1) to oral propranolol alone or propranolol plus a short course of prednisone. The primary endpoint was the proportion of patients who achieved a lesion response at week 4 on serial ultrasound. Analyses followed the intention-to-treat principle. Forty-five patients were included in this study (propranolol, n = 22; propranolol plus prednisone, n = 23). Four weeks following treatment, lesion response rates were higher with propranolol plus prednisone than with propranolol alone [21/23 (91.3
We read with great interest the editorial by Siren,recently published in World Journal of Pediatrics[1].The article deserves commendation for redirecting attention toward an often-overlooked respiratory structure in the pathophysiol-ogy of sudden infant death syndrome(SIDS):the diaphragm.By emphasizing respiratory muscle failure rather than focus-ing on central autonomic dysregulation,the author broad-ens the current framework for understanding this tragic and multifactorial event.
