Min Kyung Shin, Yejun Son, Dong Keon Yon, Jinseok Lee
{"title":"Potential gut-brain axis-targeted therapies for autism spectrum disorder in children: opportunities and challenges.","authors":"Min Kyung Shin, Yejun Son, Dong Keon Yon, Jinseok Lee","doi":"10.1007/s12519-025-00924-4","DOIUrl":"10.1007/s12519-025-00924-4","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) lacks definitive treatment, but recent research has highlighted the potential of gut‒brain axis-targeted therapies for managing ASD symptoms in children. This review evaluated the effects of microbiota transplantation (MT), probiotics, dietary interventions, and nutritional supplements on ASD symptoms in children.</p><p><strong>Data sources: </strong>A systematic review was conducted via PubMed/MEDLINE, Scopus, and Web of Science to identify studies published up to June 2024. The inclusion criteria consisted of peer-reviewed articles encompassing both observational studies and interventional trials, and studies specifically targeted symptoms of ASD and included patients under the age of 18, with a minimum sample size of 20 participants.</p><p><strong>Results: </strong>Of the 3424 identified studies, 31 met the inclusion criteria. MT emerged as the most consistently effective intervention, showing improvements across multiple symptom domains, including behavior and social interaction, particularly for individuals with severe gastrointestinal (GI) issues. Probiotics have reported strain-specific efficacy, with some studies reporting behavioral improvements, but the results have been inconsistent. Dietary interventions, such as gluten-free casein-free and modified Atkins diets, have shown partial efficacy, particularly for individuals with cooccurring GI symptoms, with adherence challenges and variability in outcomes. Nutritional supplements yielded mixed outcomes, highlighting the need for personalized approaches. Despite promising findings, significant heterogeneity in study protocols and outcome measures underscores the need for standardized methodologies. Future research should prioritize standardization of these protocols. Long-term studies and longitudinal designs can help increase the reliability and practicality. Precision strategies based on individual microbiota compositions and genomics could optimize outcomes. Combined therapies should undergo rigorous evaluation. Reliable markers could improve cost-effectiveness by targeting therapies to responders. Broader research populations, economic evaluations, new technologies and interdisciplinary research will contribute to achieving a broader application and better outcomes.</p><p><strong>Conclusions: </strong>This review emphasizes the potential of gut‒brain axis-targeted therapies to improve the quality of life of children with ASD and their families. MT showed the most consistent improvements in managing pediatric ASD symptoms, with probiotics, dietary interventions, and nutritional supplements offering additional, albeit variable benefits. Efforts should be made to standardize the protocols, to conduct long-term studies, and to explore cost-effective solutions to ensure accessibility, particularly in resource-limited settings.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"447-467"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bereket Kefale, Jonine Jancey, Amanuel T Gebremedhin, Gavin Pereira, Gizachew A Tessema
{"title":"Changes in the contributions of risk factors to under-five mortality in low- and lower-middle-income countries (1997-2022): an analysis of Demographic and Health Survey data.","authors":"Bereket Kefale, Jonine Jancey, Amanuel T Gebremedhin, Gavin Pereira, Gizachew A Tessema","doi":"10.1007/s12519-025-00912-8","DOIUrl":"10.1007/s12519-025-00912-8","url":null,"abstract":"<p><strong>Background: </strong>Under-five mortality (U5M) is a critical public health challenge in low- and lower-middle-income countries (LLMICs), where over 90% of global deaths occur. Despite progress, the changing contributions of risk factors to U5M in LLMICs remain unexplored.</p><p><strong>Methods: </strong>We analysed Demographic and Health Survey (DHS) data from 24 LLMICs across two periods: 1997-2005 and 2016-2022. We included 139,890 live births in 1997-2005 and 319,034 in 2016-2022. A mixed-effects robust Poisson regression model with a log link function was employed to identify risk factors of U5M in each period. Population-attributable fractions (PAFs) were calculated and compared to investigate changes in the contributions of risk factors over time.</p><p><strong>Results: </strong>U5M attributable to never having been breastfed increased by 15.5 percentage points (95% CI 8.6, 22.9), early maternal age at birth (< 20 years) by 5.4 percentage points (95% CI 3.1, 5.7), and plural births by 1.2 percentage points (95% CI 0.4, 1.8). U5M reductions attributable to maternal secondary education were increased by 5.5 percentage points (95% CI 0.4, 11.0) and tertiary education increased by 2.6 percentage points (95% CI 1.6, 4.2). However, U5M reductions associated with 1-3 antenatal care (ANC) visits decreased by 7.2 percentage points (95% CI 2.4, 11.7).</p><p><strong>Conclusions: </strong>The main contributors of U5M in LLMICs were never breastfeeding, short birth intervals (<33 months), ANC uptake, higher maternal education (secondary and tertiary), advanced maternal age at birth (≥35 years), early maternal age at birth (<20 years), very small infants at birth, male sex, plurality, and single motherhood. The contributions of risk factors to U5M have changed over time. Interventions need to prioritise promoting breastfeeding, enhancing maternal education and increasing ANC uptake, and addressing other significant contributors to U5M.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"502-514"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessment of the respiratory chain enzyme activity in peripheral blood monocytes for the noninvasive diagnostics of mitochondrial disease.","authors":"Jing-Jing Liu, Si-Min Wang, Zi-Han Zhang, Xue-Qian Wang, Xiao-Hui Zhang, Hong-Ying Wang, Ting Chen","doi":"10.1007/s12519-025-00918-2","DOIUrl":"10.1007/s12519-025-00918-2","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial diseases are among the most common metabolic disorders caused by mitochondrial dysfunction. Analyzing mitochondrial respiratory chain enzyme activity is essential for diagnosis. However, clinical laboratories often rely on mitochondria isolated from muscle biopsies or cultured skin fibroblasts, which may be unacceptable for some pediatric patients. This highlights the need for improved blood-based diagnostic methods.</p><p><strong>Methods: </strong>This paper describes spectrophotometric assays to evaluate mitochondrial respiratory chain enzyme activity in peripheral blood monocytes. Sample preparation methods and assays for respiratory complexes I-IV and the mitochondrial matrix enzyme citrate synthase are detailed. The assays were validated via samples from a panel of 28 healthy children and validated in patients with combined and isolated mitochondrial oxidative phosphorylation system (OXPHOS) deficiency.</p><p><strong>Results: </strong>The citrate synthase-normalized activities were 0.23 ± 0.08 for complex I, 0.22 ± 0.081 for complex II, 0.16 ± 0.07 for complex III, and 0.22 ± 0.07 for complex IV. All patients with mitochondrial disease exhibited the expected reductions in respiratory complex activity.</p><p><strong>Conclusions: </strong>We established a method to analyze the respiratory complex activities via blood samples. The normal enzymatic activity ranges were established from healthy Chinese pediatric populations. We also validated the assay via samples from patients with mitochondrial disease. By establishing the first pediatric-specific reference ranges for mitochondrial respiratory chain complex activities in a Chinese population and validating this minimally invasive blood-based assay in patients with mitochondrial disease, our study enabled earlier detection, precise monitoring, and personalized management of mitochondrial disorders while avoiding the need for invasive tissue biopsies.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"515-524"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing toward a curative frontier: an updated narrative review on stem-cell therapy in pediatric type 1 diabetes.","authors":"Samia Sulaiman, Abdallah Alaarag, Nadin Rayyan, Yousof Tuffaha, Nada Al-Awamleh, Khalid Adel Al Dojan","doi":"10.1007/s12519-025-00908-4","DOIUrl":"10.1007/s12519-025-00908-4","url":null,"abstract":"<p><strong>Background: </strong>Type 1 diabetes (T1D) is a chronic autoimmune disease primarily diagnosed in childhood, characterized by pancreatic β-cell destruction, severe insulin deficiency, and hyperglycemia. Current treatments, including insulin therapy and glucose-lowering medications, manage the condition but fall short of offering a cure. In this review we explore the potential of stem-cell therapy as a transformative and curative approach for T1D, focusing on its promise in regenerating β-cells and addressing challenges specific to the pediatric population.</p><p><strong>Data sources: </strong>A comprehensive review of the literature was conducted to evaluate stem-cell types: embryonic, perinatal, adult, induced pluripotent and cancer stem cells, and their role in T1D treatment. Particular emphasis was placed on methods for β-cell differentiation, advancements in autologous and allogeneic stem-cell transplantation and emerging strategies to overcome safety, efficacy, and economic barriers. Challenges such as immune rejection, tumorigenicity, and cost-effectiveness were analyzed, alongside novel solutions like immune-shielding and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 (Cas9) technology.</p><p><strong>Results: </strong>Stem-cell therapy presents a promising avenue for curing T1D, offering potential for β-cell regeneration and reduced dependence on exogenous insulin. However, challenges such as delayed β-cell functionality, immune responses, tumor risks, and high costs hinder widespread application.</p><p><strong>Conclusions: </strong>Advancements in personalized medicine, immune-shielding strategies, and cost reduction may pave the way for clinical success, especially in pediatric populations. Further research addressing these barriers is essential to establish stem-cell therapy as a viable and equitable treatment option.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"436-446"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Maternal inflammation during the second trimester of pregnancy with adverse birth outcomes: a prospective cohort study.","authors":"Wan-Qing Xiao, Si-Chi Zhu, Zhu-Gu Huang, Qi-Wen He, Zi-Yin Lyu, Xu-Tao Li, Qing-Qun Lyu, Ya-Shu Kuang, Xue-Ling Wei, Dong-Mei Wei, Jin-Hua Lu, Jian-Rong He, Xiu Qiu","doi":"10.1007/s12519-025-00909-3","DOIUrl":"10.1007/s12519-025-00909-3","url":null,"abstract":"<p><strong>Background: </strong>Distinct characteristics of maternal inflammation at midgestation related to fetal and neonatal health are not clear. This study aims to explore the associations between the maternal circulating inflammatory profile during the second trimester of pregnancy and a series of adverse birth outcomes.</p><p><strong>Methods: </strong>The present study was a prospective cohort study based on the Born in Guangzhou Cohort Study conducted in Guangzhou, China. Peripheral blood samples from women were obtained during the second trimester. Adverse newborn outcomes were collected through electronic medical records at birth and within the first week after birth. We used logistic, Poisson and generalized linear regressions to assess the impact of inflammatory indicators during pregnancy on different outcomes.</p><p><strong>Results: </strong>A total of 1567 singleton pregnant women were included. The proportions of preterm birth, small for gestational age (SGA), low birth weight (LBW), neonatal asphyxia and hyperbilirubinemia cases were 4.3%, 6.6%, 3.9%, 1.1% and 12.6%, respectively. The maternal circulating level of log2-transformed interleukin (IL)-7 was positively associated with preterm birth [adjusted odds ratio (OR) = 1.58, 95% confidence interval (CI) = 1.03-2.41]. A higher level of log2-transformed IL-2 was correlated with increased LBW risk (adjusted OR = 1.48, 95% CI = 1.09-2.02) and a decreased birth weight Z-score (adjusted β = - 0.06, 95% CI = - 0.11, - 0.01). IL-7 was associated with an increased risk of LBW (adjusted OR = 1.80, 95% CI = 1.14-2.86), whereas log2-transformed IL-15 was positively related to SGA (adjusted OR = 1.39, 95% CI = 1.02-1.91). There were no significant associations of maternal inflammatory indicators with neonatal asphyxia or hyperbilirubinemia.</p><p><strong>Conclusion: </strong>Maternal circulating IL-2, IL-7 and IL-15 levels during the second trimester of pregnancy were associated with preterm birth or birth weight.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"468-477"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Melatonin use in the pediatric population: an evolving global concern.","authors":"Judith Owens","doi":"10.1007/s12519-025-00896-5","DOIUrl":"https://doi.org/10.1007/s12519-025-00896-5","url":null,"abstract":"<p><strong>Background: </strong>The impact of melatonin on pediatric populations has not yet been widely researched. This narrative review is intended to summarize the current literature regarding the efficacy and safety of melatonin for children and potential pitfalls in its clinical use, in order to assist pediatric practitioners in making evidence-based recommendations that serve the best interests of their patients and families.</p><p><strong>Data sources: </strong>A literature review of melatonin in the pediatric population was conducted using PubMed search terms: melatonin, pediatrics, child/adolescent.</p><p><strong>Results: </strong>Melatonin use in the pediatric population world-wide has increased significantly over the past several decades. While a number of studies, largely in children with neurodevelopmental disorders with insomnia, have suggested that melatonin is generally safe and well-tolerated, a similar body of evidence is overall lacking for typically developing children and prospective studies regarding long-term adverse events are lacking. In addition, recent studies have raised concerns regarding the variable content of melatonin in over-the-counter products, as well as safety issues relating to accidental ingestions.</p><p><strong>Conclusions: </strong>Due to a number of concerns regarding inappropriate use, lack of efficacy and safety data across pediatric populations and variability in actual content, melatonin should be used with caution in children and only under medical supervision.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhao-Yu Chen, Tian-Nan Zhang, Ji Li, Zhen-Jie Zhang, Hong-Mei Song
{"title":"Tofacitinib: a promising agent for the treatment of persistent rashes in juvenile dermatomyositis.","authors":"Zhao-Yu Chen, Tian-Nan Zhang, Ji Li, Zhen-Jie Zhang, Hong-Mei Song","doi":"10.1007/s12519-025-00901-x","DOIUrl":"10.1007/s12519-025-00901-x","url":null,"abstract":"","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"419-422"},"PeriodicalIF":6.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}