World Journal of Pediatrics最新文献

Background: Williams syndrome (WS; OMIM #194,050) is a multisystem pediatric genetic disorder caused by a heterozygous microdeletion of a 1.5-1.8 Mb region at chromosome 7q11.23, encompassing 26 to 28 genes. Clinical hallmarks include cardiovascular anomalies, distinctive craniofacial morphology and neurodevelopmental deficits characterized by hypersociability, cognitive impairment and anxiety. Although causative therapies for WS still remain elusive, advances in gene editing and forebrain organoids have already greatly furthered our understanding of the underlying mechanisms.

Data sources: This narrative review was conducted by searching for papers using PubMed/MEDLINE. Relevant publications were identified using single and/or combined keywords including: Williams syndrome, 7q11.23, microdeletion, microduplication, atypical deletion, neurodevelopment, neuroanatomy, neuroimaging. cognitive impairment, mouse models, GTF2I, GTF2IRD1, CLIP2, LIMK1, NCF1, EIF4H, STX1A/B, FZD9, HIP1, CLDN3, FKBP6, organoid, induced pluripotent stem cell (iPSC) and forebrain organoids.

Results: Mouse models including multigene deletion strains recapitulating the WS critical region and single-gene knockout strains targeting Gtf2i, Gtf2ird1, Clip2 and Limk1 replicate key WS neurodevelopmental phenotypes, substantially contributing to mechanistic studies and therapeutic screening. In addition, forebrain organoids derived from patients or generated by gene editing have provided human-specific insights into progenitor dynamics, synaptic function, and ribosome biogenesis.

Conclusions: This review synthesizes recent progress in WS modeling in the context of neurodevelopmental impairments. While animal models and forebrain organoids have substantially accelerated both mechanistic understanding and translational research in WS, effective diagnostic and therapeutic approaches are still unavailable. Integration of animal models and forebrain organoids, together with the advanced technologies, will be essential for biomarker discovery and development of mechanism-based therapeutic approaches.

Background: Idiopathic short stature (ISS), a common cause of unexplained growth failure in children, remains poorly characterized at the genetic level. This study aimed to investigate the contribution of rare variant burdens in growth-related genes and pathways to the etiology of ISS using next-generation sequencing and gene-based burden testing, thereby identifying novel genetic contributors to the polygenic landscape of ISS.

Methods: We analyzed 212 pediatric patients with short stature who remained undiagnosed following trio-based whole-exome sequencing. The comparison cohort included 352 healthy adults with normal stature and 4327 internal samples from the Exome Aggregation Consortium database. Gene-based burden testing was performed using an optimized TRAPD (testing rare variants using public data) framework. Functional enrichment analyses, including Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathway analyses, were conducted to delineate the biological processes associated with the identified candidate genes.

Results: Under a dominant inheritance model, 3907 genes were significantly enriched in rare variants (P < 0.05), whereas 85 genes were significantly enriched under a recessive model (P < 0.05). The top 10 most significantly associated genes identified through primary modeling included FCGBP, FRAS1, MPDZ, and OBSCN, among which highly significant signals were identified (P < 1 × 10^-⁹). Pathway analyses revealed enrichment in steroid hormone biosynthesis, ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and porphyrin metabolism. Key genes such as OBSCN, FRAS1, and MPDZ were involved in multiple enriched pathways.

Conclusions: This study implicates rare variant burdens in growth-related genes as contributors to ISS pathogenesis, highlighting key genes (OBSCN, FCGBP, FRAS1, and MPDZ) and pathways involved. These findings suggest that the dysregulation of hormonal signaling, the extracellular matrix, and muscle-skeletal interactions impairs linear growth, suggesting potential diagnostic and therapeutic targets for ISS.

Background: Pulmonary thromboembolism is rare in children, but can be life-threatening. Timely diagnosis and treatment of pulmonary thromboembolism are crucial for reducing mortality associated with pulmonary thromboembolism in children. While guidelines for pulmonary thromboembolism in adults are available, guidelines for standardized diagnosis and management of pulmonary thromboembolism in children are not. This expert consensus aims to provide recommendations for the management of pulmonary thromboembolism in children based on the current best available evidence.

Data sources: Following the World Health Organization Handbook for Guideline Development, the expert panel consisted of 30 members from different clinical areas. The panel identified clinical questions through systematic reviews and expert discussions, systematically reviewed evidence on pulmonary thromboembolism in children, and evaluated the quality of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Using the GRADE Evidence to Decision Framework, the panel made recommendations, considering the effects of interventions, resource use, values and preferences, equity, acceptability, and feasibility.

Results: The epidemiology, classification, and pathophysiology characteristics are summarized. The expert panel developed 33 recommendations addressing 20 questions related to diagnosis steps, treatment approaches such as anticoagulant therapy, thrombolysis therapy, catheter-based interventional therapy, surgical embolectomy, multidisciplinary team, and treatment of patients with comorbidities, prognosis, education, as well as follow-up. Among these, 18 are weak recommendations based on very low quality evidence, and 15 are good practice statements.

Conclusions: The expert panel provided recommendations for pulmonary thromboembolism in children based on available evidence, which was generally low in quality and volume. The panel urges further research on early identification and diagnosis strategies, preventive and therapeutic regimens, and long-term management for pulmonary thromboembolism.

Background: Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. While physical exercise is a promising non-pharmacological intervention, the efficacy of integrating cognitive demands with physical activity remains underexplored. This trial compared the effects of integrated cognitive-motor exercise, aerobic exercise, and a minimal intervention on core symptoms and executive functions (EFs) in children with ADHD.

Methods: In this randomized, controlled, multicenter trial, 107 children with ADHD (aged 6-10 years) were allocated to one of three groups for 12 weeks: (1) integrated cognitive-motor exercise (EG1, n = 36); (2) aerobic exercise (EG2, n = 35); or (3) wait-list control (CG, n = 36). Both EG1 and EG2 performed their respective interventions three times per week in 45-minute sessions. The primary outcomes were inattention and hyperactivity-impulsivity symptoms and EFs (inhibitory control, working memory, and cognitive flexibility). The analysis followed the intention-to-treat principle with linear mixed models.

Results: Compared with the CG, both exercise groups presented significant, comparable reductions in inattention and hyperactivity-impulsivity symptoms (all P ≤ 0.01). However, EG1 demonstrated superior improvements in specific EFs. For inhibitory control (Stroop color-word interference), EG1 resulted in a significantly greater reduction in color-word interference time than both EG2 [β = - 6.24, 95% confidence interval (CI) = - 12.28 to - 0.20, P = 0.045] and CG (β = - 13.97, 95% CI = - 19.97 to - 7.97, P < 0.001). For immediate working memory, the improvement in EG1 was greater than that in both EG2 (β = 2.09, 95% CI = 0.33-3.85, P = 0.032) and CG (β = 3.57, 95% CI = 1.83-5.31, P < 0.001). Both exercise groups improved similarly in cognitive flexibility compared with the CG. Parental satisfaction was significantly greater in EG1 than in EG2 (P < 0.001). No adverse events were reported.

Conclusions: A structured integrated cognitive-motor exercise intervention is an effective and safe non-pharmacological treatment for children with ADHD. Compared with aerobic exercise alone, it not only alleviates core symptoms but also yields superior benefits for key EFs, specifically inhibitory control and immediate working memory.

Background: Pediatric inflammatory bowel disease (pIBD) often begins early in life, progresses rapidly, and is associated with impaired growth and delayed development. These challenges demand treatment strategies that address both intestinal inflammation and the broader developmental needs of children.

Data sources: This review summarizes current advances in small-molecule therapies for pIBD based on published clinical trials, real-world studies, and mechanistic investigations retrieved from PubMed and clinical trial registries. Special emphasis is placed on Janus kinase (JAK) inhibitors and sphingosine-1-phosphate (S1P) modulators, which represent the main translational research focus in pediatric IBD.

Results: JAK inhibitors such as tofacitinib and upadacitinib have demonstrated promising efficacy in pediatric patients with refractory disease, although their use remains off-label worldwide. Long-term safety concerns persist, including infection risk, developmental effects, and potential risks of malignancy or major adverse cardiovascular events. S1P modulators such as ozanimod are under clinical evaluation in children, but robust long-term data are still lacking. Emerging technologies such as single-cell and spatial profiling have begun to reveal age-dependent remodeling of gut immune architecture, emphasizing the importance of developmentally informed therapeutic approaches.

Conclusions: Small-molecule therapies offer a promising and mechanistically precise direction for the management of pIBD. Future progress will depend on age-specific clinical trials, physiologically based pharmacokinetic modeling, and biomarker discovery through integrated multiomics. Collaborative multicenter research is essential to optimize the safety and efficacy of these agents in children.

Background: While international evidence suggests seasonal variations may influence outcomes of interventions for pediatric obesity, data for Aotearoa New Zealand are limited. We examined seasonal variations in changes in body mass index standard deviation score (BMI SDS) in young people with obesity enrolled in an intervention programme.

Methods: We studied 397 children and adolescents (median = 10.1 years; range 3.7-16.8 years) from Whānau Pakari, a multidisciplinary community-based healthy lifestyle programme (initially a randomised clinical trial that subsequently transitioned into the regional childhood obesity service). Participants were stratified by season at entry and 6-month BMI SDS changes (Δ) were evaluated. Lifestyle factors were also assessed. Data were analysed using traditional linear models and machine learning (random forest).

Results: 68% of participants had BMI SDS reductions at 6 months (mean = - 0.16 SDS; P < 0.0001). Linear models showed seasonal variations in programme effectiveness, with BMI SDS reductions among summer (- 0.17 SDS), autumn (- 0.19 SDS) and winter (- 0.18 SDS) but not among spring entrants. Random forest modelling identified higher baseline BMI SDS and younger age as the most influential predictors of greater 6-month reductions in BMI SDS. Season of entry was more important than any single lifestyle factor; spring entrants exhibited attenuated reductions relative to other seasons.

Conclusions: The season at programme entry was an important factor associated with intervention effectiveness. Spring entry was associated with attenuated BMI SDS reductions, likely due to the inclusion of the summer holidays within the 6-month intervention. These findings highlight the need for targeted support during such unstructured periods to improve participant outcomes.