Pediatric Research最新文献

{"title":"Somewhere, high in the sky. A tribute to a longstanding commitment to neonatal air transport.","authors":"Carlo Bellini","doi":"10.1038/s41390-025-03910-8","DOIUrl":"https://doi.org/10.1038/s41390-025-03910-8","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased AGEs/sRAGE ratio and dyslipidemia risk in Down syndrome youths: a cross-sectional study.","authors":"Wendy P Gastélum Espinoza, Alma M Guadrón Llanos, Kenia K Esparza Ocampo, Jesús M Pérez Villareal, Verónica J Picos Cárdenas, Loranda Calderón Zamora, Marco A Valdés Flores, Alberto K De la Herrán Arita, Mayra Arias Gastélum, Javier A Magaña Gómez","doi":"10.1038/s41390-025-03912-6","DOIUrl":"https://doi.org/10.1038/s41390-025-03912-6","url":null,"abstract":"<p><strong>Background: </strong>Down syndrome (DS) is associated with a higher risk of diseases linked to advanced glycation end products (AGEs) accumulation.</p><p><strong>Objective: </strong>To evaluate serum AGEs and their soluble receptor (sRAGE) levels in children and adolescents with DS and explore associations with anthropometric and biochemical variables.</p><p><strong>Methods: </strong>A cross-sectional study compared 51 DS participants (ages 3-18) with an age-matched control group (n = 51). Anthropometric measurements, blood chemistry, and lipid profiles were assessed. AGEs and sRAGE concentrations were determined by fluorescence and ELISA, respectively.</p><p><strong>Results: </strong>DS individuals showed an unfavorable lipid profile, with higher triglycerides and lower HDL-C than controls. AGEs concentrations were significantly elevated in DS compared to controls (2.01 ± 0.48 vs. 1.33 ± 0.26 FAU/µg/mL; p < 0.001), while sRAGE levels were reduced (761.3 ± 433.7 vs. 1,196 ± 411.5 pg/mL; p < 0.001). The AGEs/sRAGE ratio was three times higher in the DS group than in controls (3.5 ± 1.9 vs. 1.2 ± 0.4; p < 0.001). Regression analysis identified HbA1c as a strong predictor of increased AGEs in both groups.</p><p><strong>Conclusion: </strong>Individuals with DS have an increased risk of dyslipidemia. Additionally, the elevated AGEs/sRAGE ratio associated with this genetic condition may reduce the protective effect of sRAGE against inflammatory processes.</p><p><strong>Impact statement: </strong>This is the first study to evaluate the AGEs/sRAGE ratio alongside biochemical and anthropometric markers in individuals with Down syndrome. DS individuals are at higher risk for dyslipidemia (elevated triglycerides, low HDL-C) and obesity, potentially linked to altered AGEs and sRAGE dynamics. Lower levels of sRAGE in DS may weaken its protective effects against tissue damage and inflammation caused by AGEs accumulation. HbA1c emerged as a strong predictor of AGEs, sRAGE, and the AGEs/sRAGE ratio in the DS cohort, highlighting the importance of monitoring glycemic control.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota, inflammatory cytokines, and Kawasaki disease: a Mendelian randomization study and mediation analysis.","authors":"Ji-Gan Wang, Hui-Hong Dou, Qiong-You Liang","doi":"10.1038/s41390-025-03911-7","DOIUrl":"https://doi.org/10.1038/s41390-025-03911-7","url":null,"abstract":"<p><strong>Objective: </strong>This study investigates the causal relationship between gut microbiota, inflammatory cytokines, and Kawasaki disease (KD), and whether cytokines mediate the effect of gut microbiota on KD.</p><p><strong>Methods: </strong>A Mendelian randomization analysis using the inverse-variance weighted method assessed the causal effects of gut microbiota and inflammatory cytokines on KD and explored potential mediation.</p><p><strong>Results: </strong>The study found causal links between 20 types of gut microbiota and KD. Ten types increased KD risk, notably Francisellales (OR = 27.82, P = 0.0309). Ten types provided protection, with Fusobacteriaceae showing the strongest effect (OR = 0.0424, P = 0.002). Five inflammatory cytokines were significantly associated with KD; adenosine deaminase was most protective (OR = 0.7447, P = 0.0037), while Fractalkine indicated higher risk (OR = 2.0448, P = 0.0315). Mediation analysis revealed that the Interleukin-10 receptor subunit beta mediates the effect of Bifidobacterium adolescentis on KD, with a mediation effect of -0.0237 (4.75% ratio). Interleukin-20 mediates the effect of Faecalicatena lactaris on KD, with a mediation effect of -0.1168 (15.30% ratio).</p><p><strong>Conclusion: </strong>The findings indicate a causal relationship among gut microbiota, inflammatory cytokines, and KD, suggesting that the gut microbiome influences KD through specific cytokines.</p><p><strong>Impact: </strong>The study confirmed a causal relationship between 20 types of gut microbiota and Kawasaki disease, finding that 10 types increase the risk of Kawasaki disease, particularly Francisellales. Five inflammatory cytokines were significantly associated with Kawasaki disease, with adenosine deaminase showing a protective effect, while Fractalkine increased the risk. Mediation analysis indicated that specific inflammatory cytokines (such as Interleukin-10 receptor subunit beta and Interleukin-20) play a significant mediating role between gut microbiota and Kawasaki disease.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle physiology and the science of tone agents.","authors":"Joshua Vova","doi":"10.1038/s41390-025-03918-0","DOIUrl":"https://doi.org/10.1038/s41390-025-03918-0","url":null,"abstract":"<p><p>Cerebral Palsy (CP) encompasses a spectrum of permanent motor disorders stemming from early insults to the developing brain, resulting in alterations in muscle tone. While spasticity and dystonia are common motor disorders in CP, non-neural factors such as changes in muscle architecture contribute to muscle stiffness. Muscle stiffness in CP involves changes in muscle morphology and structure. Current treatments, such as botulinum toxin, have limitations, leading to exploration of alternative techniques like cryoneurolysis, hyaluronidase, and extracorporeal shockwave therapy. This brief review advocates for a comprehensive approach that considers both muscular and neurologic components of hypertonia, emphasizing the need for further research on cellular-level changes contributing to muscle stiffness. IMPACT: This review highlights the gap in current literature regarding the complex interplay between neural and non-neural factors in muscle stiffness and hypertonia in children with cerebral palsy (CP). While spasticity and dystonia are well studied, the review emphasizes the need for interventions addressing muscle morphology and extracellular matrix stiffness. It introduces emerging therapies like cryoneurolysis, hyaluronidase, and extracorporeal shockwave therapy, calling for more research on their long-term efficacy and safety.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of PLASE score for patent ductus arteriosus using the PLASE study database.","authors":"Satoshi Masutani, Tetsuya Isayama, Tohru Kobayashi, Kyongsun Pak, Seiichi Tomotaki, Hiroko Iwami, Takehiko Yokoyama, Katsuaki Toyoshima","doi":"10.1038/s41390-025-03803-w","DOIUrl":"10.1038/s41390-025-03803-w","url":null,"abstract":"<p><strong>Background: </strong>No echocardiographic model, to the best of our knowledge, has been established to predict the future need for patent ductus arteriosus (PDA) surgery. This study aimed to develop a novel predictive score (PLASE score) for anticipating the need for PDA surgery using the PLASE study database.</p><p><strong>Methods: </strong>The included infants with gestational age (GA) < 30 weeks were allocated to derivation and validation groups (2:1). Logistic regression models were constructed to predict the future need for PDA surgery utilizing three clinical and three echocardiographic indices measured at 3 days of age as candidate variables. ROC-AUCs and 95% confidence intervals (CIs) were obtained by 3-fold cross-validation and the percentile method, respectively. The model with the largest ROC-AUC was tested in the validation data.</p><p><strong>Results: </strong>Derivation and validation data included 463 and 229 patients, respectively, with 55 and 22 surgical cases, respectively. The ROC-AUC was maximized in the model using GA and all three echocardiographic indices (0.846 [95% CI, 0.805-0.886]). In the validation data, the ROC-AUC for the same model was 0.827 (0.744-0.911).</p><p><strong>Conclusions: </strong>We created a surgical prediction model using simple indices at 3 days of age, and the validation data demonstrated good predictive ability.</p><p><strong>Impact: </strong>No early predictive model has been established for the future need of patent ductus arteriosus (PDA) surgery in preterm infants. A new prediction model was created with the Patent ductus arteriosus and Left Atrial Size Evaluation study in preterm infants (PLASE) database (N = 692), incorporating gestational age and three simple echocardiographic indices measured at 3 days of age. The model demonstrates high discrimination and calibration. This model provides risk stratification for preterm PDA and may contribute to early preterm management.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomics of pediatric cardiomyopathy.","authors":"Teresa M Lee, Stephanie M Ware, Alicia M Kamsheh, Surbhi Bhatnagar, Mohammed Absi, Elyse Miller, Enkhsaikhan Purevjav, Kaitlin A Ryan, Jeffrey A Towbin, Steven E Lipshultz","doi":"10.1038/s41390-025-03819-2","DOIUrl":"https://doi.org/10.1038/s41390-025-03819-2","url":null,"abstract":"<p><p>Cardiomyopathy in children is a leading cause of heart failure and cardiac transplantation. Disease-associated genetic variants play a significant role in the development of the different subtypes of disease. Genetic testing is increasingly being recognized as the standard of care for diagnosing this heterogeneous group of disorders, guiding management, providing prognostic information, and facilitating family-based risk stratification. The increase in clinical and research genetic testing within the field has led to new insights into this group of disorders. Mutations in genes encoding sarcomere, cytoskeletal, Z-disk, and sarcolemma proteins appear to play a major role in causing the overlapping clinical phenotypes called cardioskeletal myopathies through \"final common pathway\" links. For myocarditis, the high frequency of infectious exposures and wide spectrum of presentation suggest that genetic factors mediate the development and course of the disease, including genetic risk alleles, an association with cardiomyopathy, and undiagnosed arrhythmogenic cardiomyopathy. Finally, while we have made strides in elucidating the genetic architecture of pediatric cardiomyopathy, understanding the clinical implications of variants of uncertain significance remains a major issue. The need for continued genetic innovation in this field remains great, particularly as a basis to drive forward targeted precision medicine and gene therapy efforts. IMPACT: Cardiomyopathy and skeletal myopathy can occur in the same patient secondary to gene mutations that encode for sarcomeric or cytoskeletal proteins, which are expressed in both muscle groups, highlighting that there are common final pathways of disease. The heterogeneous presentation of myocarditis is likely secondary to a complex interaction of multiple environmental and genetic factors, suggesting a utility to genetic testing in pediatric patients with myocarditis, particularly those in higher risk groups. Given the high prevalence of variants of uncertain significance in genetic testing, better bioinformatic tools and pipelines are needed to resolve their clinical meaning.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking the silence: challenges and opportunities in pediatric drug development.","authors":"Kanwaljit Singh, Tim Franson, Susan McCune, Daniel Jorgensen, Kenneth Getz, Cynthia Bearer, Jonathan M Davis","doi":"10.1038/s41390-025-03923-3","DOIUrl":"10.1038/s41390-025-03923-3","url":null,"abstract":"<p><p>Pediatric drug development faces significant challenges, including underfunding, ethical concerns, and complex regulatory frameworks. Despite significant advances in adult drug development, children remain underserved due to their unique physiological needs and difficulties conducting clinical trials. Current pediatric therapeutic options are limited, off-label, and lack evidence from well-controlled trials. Incorporating global regulatory frameworks can provide valuable insights when addressing these challenges. The disparity in investment is evident as several pharmaceutical companies have recently closed their pediatric drug centers with plans to focus on more profitable adult markets, leaving pediatric research underprioritized. This article discusses the root causes of this imbalance and potential solutions including: 1) the use of emerging technologies - artificial intelligence, modeling, and simulation; 2) leveraging innovative trial designs, 3) the use of real-world data, 4) the need for public-private partnerships to drive progress in pediatric drug development; and 5) advocacy groups to shape policies and investments. By focusing on enhancing regulatory incentives, encouraging long-term industry commitment, and engaging patient advocacy groups, a more sustainable pipeline can be established. This call to action underscores the moral imperative of prioritizing pediatric health and fostering innovation to improve outcomes for vulnerable pediatric populations and shape a healthier future for all children. IMPACT: Pediatric drug development faces significant challenges, including underfunding, ethical concerns, and complex regulatory frameworks. The most important causes include the absence of robust advocacy, regulatory hurdles, and economic disincentives. Potential solutions involve leveraging innovative trial designs, the use of real-world data, and public-private partnerships.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visuospatial outcomes of a prospective national cohort of young adults with very low birthweight.","authors":"Sarah L Harris, Lianne J Woodward, L John Horwood, Tracy R Melzer, Samudragupta Bora, Maddie Pascoe, Brian A Darlow","doi":"10.1038/s41390-025-03890-9","DOIUrl":"https://doi.org/10.1038/s41390-025-03890-9","url":null,"abstract":"<p><strong>Background: </strong>Visuospatial processing is reportedly impaired in children born very preterm (VP) compared with full term (FT) controls but there are few data for VP adults.</p><p><strong>Methods: </strong>At 26-30 years, 225 very low birthweight (VLBW) adults (70% national cohort survivors) and 100 FT controls were assessed on motor-dependent visuospatial skills using the Block Design subtest of the Wechsler Adult Intelligence Scale, and nonmotor-dependent skills by the Benton Judgment of Line Orientation and Brixton Spatial Anticipation tests. A composite score was created by summing standardized scores for the three tests. MRI measures of cortical volume, thickness and surface area were obtained for 150 VLBW participants.</p><p><strong>Results: </strong>VLBW born adults performed less well than controls across all visuospatial measures and their composite score (P < 0.001), with moderate to large effect sizes (Cohen's ds = 0.41-0.82). Between group differences were not explained by current vision impairment, cerebral palsy, sex, ethnicity or socio-demographic factors. The unadjusted visuospatial composite score was significantly correlated with reduced cortical surface area and cortical volume, but few correlations remained significant after adjustment for age, sex and intracranial volume.</p><p><strong>Conclusion: </strong>The visuospatial functioning of adults born VLBW is significantly poorer than their FT peers with only modest associations with cortical brain structure.</p><p><strong>Impact: </strong>Previous reports have shown very preterm children have impaired visuospatial processing compared with term-born peers but only limited data address whether these impairments persist into adulthood. Visuospatial functioning, assessed by both motor and non-motor dependent tests, of adults born very low birthweight is significantly poorer than that of term-born peers. Poorer visuospatial functioning in this very low birthweight cohort is not explained by vision impairment and had only modest associations with cranial MRI brain structure. Persisting visuospatial impairment in very preterm adults may significantly impact quality of life. Early recognition of these difficulties could facilitate support strategies to improve outcomes.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Authentic collaboration in research: partnering with people with lived experience.","authors":"Natasha Garrity, Kylie Facer, Rod Hunt, Shannon Olivey, Sophie Marmont, Nadia Badawi, Melinda Cruz, Sarah McIntyre","doi":"10.1038/s41390-025-03824-5","DOIUrl":"https://doi.org/10.1038/s41390-025-03824-5","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing bedside measures of autonomic nervous system dysregulation in the PICU.","authors":"Colleen M Badke, Michael S Carroll, Tricia R Pendergrast, Debra E Weese-Mayer, L Nelson Sanchez-Pinto","doi":"10.1038/s41390-024-03778-0","DOIUrl":"https://doi.org/10.1038/s41390-024-03778-0","url":null,"abstract":"<p><strong>Background: </strong>Autonomic nervous system (ANS) dysregulation is common during critical illness and is often measured using heart rate variability (HRV). It is unknown if other forms of ANS function, such as pupillary light reflex and thermoregulation, are altered in critically ill children. We aimed to determine whether automated pupillometry and delta (central-to-peripheral) skin temperatures were associated with HRV.</p><p><strong>Methods: </strong>In this prospective observational pilot, inclusion criteria were admission to the pediatric intensive care unit (ICU) and mechanical ventilation. HRV was calculated using age-adjusted integer HRV (HRVi). Automated pupillometry and skin temperatures were recorded during the first 72 h of admission. The primary outcomes were: (1) correlation between HRVi and Neurological Pupil index (NPi), and (2) correlation between HRVi and delta skin temperature.</p><p><strong>Results: </strong>Of 29 patients enrolled, 18 had pupillometer data and 20 had temperature data. There were significant, small correlations between left and right NPi values and HRVi (r = 0.13, r = 0.12; p < 0.001), and delta skin temperatures and HRVi (r = 0.15, p < 0.001), which persisted after adjusting for confounders.</p><p><strong>Conclusions: </strong>Abnormal pupillary light response and decreased delta skin temperatures are associated with lower HRVi. If validated, pupillometry and skin temperature could be considered physiologic biomarkers of ANS dysregulation in critically ill children.</p><p><strong>Impact: </strong>While heart rate variability has strong associations with outcomes in critically ill children, there are limited data on other bedside tools of autonomic function in critically ill children. In this study, we found that pupillometry and skin temperature sensors correlate with heart rate variability in critically ill children. These physiological biomarkers may have a role in early detection of autonomic nervous system dysregulation.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}