Pediatric Research最新文献

{"title":"Deleterious variants in LTBP4 are associated with severe pediatric sepsis.","authors":"Yidi Qin, Kate F Kernan, Yulong Bai, John R Shaffer, Zsolt Urban, Scott Canna, Murray M Pollack, Kathleen Meert, Christopher Newth, Tom Shanley, Rick E Harrison, Mark Hall, Joseph A Carcillo, Hyun-Jung Park","doi":"10.1038/s41390-025-04420-3","DOIUrl":"https://doi.org/10.1038/s41390-025-04420-3","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a leading global health burden in children, and its unavoidable heterogeneity has hindered providing therapies beyond antibiotics and supportive care. Recently, we identified four computable phenotypes showing distinct cytokine profiles, clinical outcomes, and therapeutic response characteristics (PedSep-A, B, C, and D) in a multicenter pediatric sepsis cohort.</p><p><strong>Methods: </strong>In the cohort data, we collected whole-exome sequencing data and identified rare variants associated with PedSep-D phenotype by conducting a gene-based analysis in an aggregated fashion.</p><p><strong>Results: </strong>As a result, one whole-exome significant gene (LTBP4) and two suggestive significant genes (PLA2G4E, CCDC157) showed association with PedSep-D, the phenotype characterized by the most severe outcomes and highest inflammation. The associated variants in LTBP4 were enriched for predicted deleterious effects based on established functional prediction metrics. All three associated genes are implicated in inflammation and immune cell activation based on existing gene function and expression data. Although the circulating cytokine profiles were overlapping between the rare variant carriers, we also identified gene-specific cytokine changes.</p><p><strong>Conclusion: </strong>Altogether, our study provides valuable insights into the genetic architecture of a pediatric sepsis phenotype with the highest inflammation level and the most severe outcomes, highlighting potential candidate genes and pathways for further biomarker and therapeutic studies.</p><p><strong>Impact: </strong>Pediatric sepsis exhibits substantial heterogeneity, with genetic variation contributing to this variability. Rare variants in LTBP4 are significantly associated with the most severe pediatric sepsis phenotype (PedSep-D), while variants in PLA2G4E and CCDC157 show associations with this phenotype in suggestive significance. Expands on the concept of sepsis phenotypes (PedSep-A, B, C, D) by incorporating genetic insights, moving beyond clinical and cytokine profiles to uncover molecular drivers. Opens new avenues for mechanistic studies to understand the genetic underpinnings of severe inflammation and immune activation in sepsis.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275409","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":"Childhood absence epilepsy and distinct dynamic functional network connectivity patterns in self-limited epilepsy with centrotemporal spikes: a resting-state fMRI study.","authors":"Linfeng Song, Guangrong Wu, Fuying Liu, Jiaren Zhang, Benqin Liu, Xu Chen, Junjun Wang, Binlin Tian, Yongzhe Li, Anjie Zhang, Xuejin Ma, Lin Jiang","doi":"10.1038/s41390-025-04460-9","DOIUrl":"https://doi.org/10.1038/s41390-025-04460-9","url":null,"abstract":"<p><strong>Background: </strong>Alterations in dynamic brain functional connectivity (dFC) have been observed in epilepsy, few studies have directly compared the dynamic functional network connectivity (dFNC) patterns between patients with self-limited epilepsy with centrotemporal spikes (SeLECTS) and those with childhood absence epilepsy (CAE). This study aimed to explore differences in dFNC between these two epilepsy types and investigate how these patterns relate to clinical features.</p><p><strong>Methods: </strong>Resting-state functional MRI data were collected from 34 SeLECTS patients, 22 CAE patients, and 32 healthy controls. Independent component analysis (ICA) was combined with a sliding-window technique to examine characteristics of dynamic FNC, including state transitions, connectivity strength, and temporal properties.</p><p><strong>Results: </strong>Three recurring dFNC states were identified. SeLECTS patients spent significantly more time in a highly flexible state characterized by strong network integration, whereas CAE patients more frequently occupied a state marked by weak inter-network connectivity. Furthermore, SeLECTS patients showed greater variability in dFNC states over time. Certain clinical factors-particularly seizure frequency-were found to correlate with specific dFNC states, most notably in the SeLECTS group.</p><p><strong>Conclusions: </strong>The study highlights distinct dynamic connectivity patterns between SeLECTS and CAE patients, suggesting that these two epilepsy types involve different network-level mechanisms. These findings contribute to a deeper understanding of epilepsy subtypes and may inform future diagnostic and treatment strategies.</p><p><strong>Impact: </strong>This study identifies distinct dFNC patterns in two common childhood epilepsies: SeLECTS and CAE. It demonstrates the value of dynamic resting-state brain network analysis in pediatric epilepsy. These findings provide new neuroimaging biomarkers for early classification of epilepsy subtypes. Results may contribute to the development of personalized diagnosis and treatment strategies in children with epilepsy.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275421","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":"Neonatal cerebral hemodynamics under elevated intracranial pressure: a near-infrared spectroscopy study in piglets.","authors":"Sule Karagulleoglu-Kunduraci, Farah Kamar, Rasa Eskandari, Saeed Samaei, Mamadou Diop","doi":"10.1038/s41390-025-04446-7","DOIUrl":"https://doi.org/10.1038/s41390-025-04446-7","url":null,"abstract":"<p><strong>Background: </strong>Elevated intracranial pressure (ICP) is a common postnatal complication in premature infants, particularly those with very low birth weight, and it is associated with hemodynamic impairments. Continuous monitoring of cerebral blood flow (CBF) and oxygenation may enable early detection and inform clinical management. We hypothesized that non-invasive, bedside optical spectroscopy measurements of CBF and oxygenation are sensitive to abrupt increases in ICP.</p><p><strong>Methods: </strong>A hybrid optical system combining broadband near-infrared spectroscopy (bNIRS) and diffuse correlation spectroscopy (DCS) was used to monitor cerebral oxygenation and blood flow in 7 newborn piglets. ICP was gradually increased through saline infusion into the ventricles, and changes in CBF, oxygen saturation (StO₂), oxyhemoglobin (HbO₂), deoxyhemoglobin (Hb), and the oxidation state of cytochrome-c-oxidase (oxCCO) were continuously monitored with the hybrid optical device.</p><p><strong>Results: </strong>Elevated ICP was associated with decreased StO₂ and CBF, while oxCCO remained stable, indicating unchanged cerebral oxygen metabolism. Across all parameters, segmented linear regression revealed a breakpoint at which ICP alterations led to steeper slopes and in turn, larger hemodynamic changes.</p><p><strong>Conclusions: </strong>This study demonstrates that bNIRS/DCS can effectively detect ICP-induced changes in cerebral hemodynamics and shows promise as a non-invasive neuromonitoring tool for neonatal critical care.</p><p><strong>Impact: </strong>Tissue optical spectroscopy can detect the hemodynamic effects of elevated ICP and could be used to guide interventions aimed at mitigating these effects. Breakpoints identified in hemodynamics highlight a compensatory mechanism, after which ICP changes lead to a larger impact on cerebral hemodynamics. Elevated ICP leads to distinct hemodynamic changes that may precede injury. This study supports the use of tissue optical spectroscopy for non-invasive neonatal neuromonitoring.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275463","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":"Umbilical cord blood platelet lysate preserves myofibroblast migration and mitigates hyperoxic lung injury.","authors":"Xueyu Chen, Bingchun Lin, Zilu Huang, Xuan Wang, Dongshan Han, Lingling Yang, Zhifeng Huang, Chuanzhong Yang","doi":"10.1038/s41390-025-04422-1","DOIUrl":"https://doi.org/10.1038/s41390-025-04422-1","url":null,"abstract":"<p><strong>Background: </strong>Traditionally, platelets were thought to originate solely in the bone marrow, but emerging evidence now indicates that the lung is a major site of platelet generation. Our previous work, along with studies by others, has revealed decreased platelet counts and enhanced platelet activation in BPD patients, linking platelets to the disease's pathogenesis.</p><p><strong>Methods: </strong>We investigated the protective effects and underlying mechanisms of umbilical cord blood (UCB) platelets in mitigating hyperoxia-induced lung injury in neonatal rats and in vitro.</p><p><strong>Results: </strong>Compared with platelet-poor plasma (PPP), UCB-derived platelets (PLT) treatment preserved lung development, as evidenced by an increased density of secondary crests and reduced small arterial wall thickness. Given that secondary crest formation depends on myofibroblast activity, we further examined the cellular function of myofibroblasts isolated from the lungs of control and hyperoxic mice. We found that hyperoxia impaired myofibroblast function, particularly their migration capacity, which can be prevented by UCB platelet lysate.</p><p><strong>Conclusion: </strong>These findings suggest that UCB PLT preserve lung development by protecting myofibroblast migratory capacity, offering new insights into BPD pathogenesis and potential therapeutic strategies.</p><p><strong>Impact: </strong>Hyperoxia impairs myofibroblast function, particularly their migratory capacity, which can be prevented by umbilical cord blood platelet lysate. Umbilical cord blood platelets preserve lung development in hyperoxia-exposed newborn rats by increasing the density of secondary crests and mitigating vascular remodeling in small arteries. These findings underscore the promising therapeutic potential of umbilical cord blood-derived platelets for the management of BPD.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275475","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":"COVID-19 infection during pregnancy and infant neurodevelopment.","authors":"Moriah E Thomason, Denise M Werchan, Lanxin Ji, Iris Menu, Cassandra L Hendrix, Bradley Susskind, Mark Duffy, Natalie H Brito, Clare McCormack","doi":"10.1038/s41390-025-04409-y","DOIUrl":"https://doi.org/10.1038/s41390-025-04409-y","url":null,"abstract":"<p><strong>Introduction: </strong>The impact of maternal SARS-CoV-2 infection on fetal brain development during pregnancy remains unclear. Prior research has associated other antenatal infections with adverse neurodevelopmental outcomes in offspring.</p><p><strong>Objective: </strong>To compare neurodevelopmental outcomes in infants born to mothers infected with SARS-CoV-2 during pregnancy (COVID+) to infants without congenital exposure (COVID-).</p><p><strong>Methods: </strong>This study included 77 COVID+ infants and 157 COVID- infants assessed at 6 and/or 12 months. Outcomes were based on maternal self-report, observed infant behavior and brain fMRI.</p><p><strong>Results: </strong>Overall, COVID+ and COVID- infant groups showed no significant differences across a range of neurobehavioral measures. However, analyses not adjusted for multiple comparisons revealed differences: fewer night awakenings at 6 (t(154) = 2.24, p < 0.03) and 12 months (t(107) = 1.94, p < 0.05), and reduced duration of orienting at 12 months (t(55.38) = 2.15, p < 0.04) in COVID+ infants. Neural differences were noted in posterior-anterior midline, insular-frontal, insular-posterior cingulate, and frontal-cingulate regions at an uncorrected threshold of p < 0.01.</p><p><strong>Conclusion: </strong>This study of multi-level infant development suggests that infants born to mothers infected with COVID during pregnancy are not experiencing harmful effects of that exposure.</p><p><strong>Impact: </strong>This study contributes comprehensive data on infant neurodevelopmental outcomes following prenatal SARS-CoV-2 exposure, evaluating a wide range of behavioral and neural measures to address gaps in previous research. Findings suggest that congenital exposure to SARS-CoV-2 does not result in significant neurodevelopmental impairments in infants, offering reassurance amidst concerns about potential long-term effects of maternal prenatal COVID-19 infection. Results indicate that any observed differences, such as fewer night awakenings and functional neural connectivity patterns, may reflect a more mature developmental profile in the exposed group. Continued longitudinal research is necessary to understand behaviorally relevant and lasting neurodevelopmental effects of prenatal SARS-CoV-2 exposure.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275403","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":"The Science of Health: Pediatric Research that should have been in the MAHA report.","authors":"David Keller","doi":"10.1038/s41390-025-04511-1","DOIUrl":"https://doi.org/10.1038/s41390-025-04511-1","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275466","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":"Science for kids: unveiling the association between 24-h movement guidelines and academic engagement in adolescents.","authors":"Celia Hayward, Amira Naoom, Amelie Rudy, Sheila Gilligan","doi":"10.1038/s41390-025-04337-x","DOIUrl":"https://doi.org/10.1038/s41390-025-04337-x","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275426","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":"Outcomes of preterm infants stabilized with flow-inflating bag or T-piece resuscitator at birth-a Canadian neonatal network cohort study.","authors":"Melanie Shaker, Jennifer Toye, Eugene Ng, Ruben Alvaro, Ayman Sheta, Deepak Louis, Joseph Y Ting, Marc Beltempo, Georg M Schmölzer","doi":"10.1038/s41390-025-04467-2","DOIUrl":"https://doi.org/10.1038/s41390-025-04467-2","url":null,"abstract":"<p><strong>Background: </strong>To compare the outcomes of premature infants stabilized in the delivery room using either the T-piece resuscitator (TPR) or flow-inflating bag (FIB).</p><p><strong>Design/methods: </strong>Data from five participating level III NICUs within the Canadian Neonatal Network were reviewed. Infants born between 24⁺⁰ and 29⁺⁶ weeks' gestational age (GA) from January 1, 2018, to December 31, 2022, receiving mask ventilation in the delivery room were included. Infants who were outborn or had major congenital abnormalities were excluded. The primary composite outcome was death or bronchopulmonary dysplasia (BPD) or severe neurologic injury (intraventricular hemorrhage grade III-IV or periventricular leukomalacia). Logistic regression models adjusted for potential confounders were used to estimate odds ratios with 95% CI for the association with exposure.</p><p><strong>Results: </strong>Of the 2007 infants admitted to participating sites, 426 were excluded, leaving 1581 who met the inclusion criteria. The primary outcome occurred in 367/745 (49%) infants with the FIB and in 438/836 (52%) infants with the TPR (adjusted OR = 0.87; 95% CI 0.44 to 1.71). There was no association between TPR or FIB with the individual components of the composite outcome (death, BPD, and severe neurological injury).</p><p><strong>Conclusions: </strong>There were no significant differences in the outcomes of preterm infants stabilized in the delivery room with TPR compared to FIB.</p><p><strong>Impact: </strong>No significant difference in the composite outcome (death, bronchopulmonary dysplasia (BPD), and severe neurological injury) between a flow-inflating bag (FIB) or a T-piece resuscitator (TPR) for respiratory support at birth. Large real-world analyses comparing TPR and FIB in clinical settings. Respiratory support with either device resulted in no statistically different key clinical outcomes. There was no impact on mechanical ventilation or major morbidities with either device. This emphasizes the importance of provider experience and consistent device use over the choice of resuscitation device.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275477","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":"Prediction of motor developmental outcomes based on MRI radiomics in premature infants.","authors":"Han Meng, Fang He, Fei Li, Haiping Zu, Feng Wang, Hao Xie, Ying Liu, Mengyi Wang, Qiaozhi Ma, Siqing Dong, Junnan Dai, Bing Wu, Xuetao Mu","doi":"10.1038/s41390-025-04377-3","DOIUrl":"https://doi.org/10.1038/s41390-025-04377-3","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to combine radiomics and clinical variables to predict motor developmental outcomes in preterm infants.</p><p><strong>Methods: </strong>Brain MRI images at term-equivalent age (TEA), perinatal clinical variables, and Bayley Scales of Infant and Toddler Development assessment results at 12-24 months corrected age were retrospectively collected for each preterm infant. Radiomic analysis was conducted on conventional MRI sequences, and a binary classification model for predicting motor neurodevelopmental outcomes was developed. A clinical prediction model was established on the basis of perinatal data, and a combined prediction model was created by integrating selected radiomic features. The predictive performance of each model was evaluated via the AUC.</p><p><strong>Results: </strong>Preterm infants (n = 218) were included in the study, with 90 (41.3%) diagnosed with motor developmental delays. The AUCs of the prediction models were 0.75 (sensitivity 0.69, specificity 0.69) for multisequence radiomics, 0.87 (sensitivity 0.83, specificity 0.77) for clinical variables, and 0.94 (sensitivity 0.91, specificity 0.87) for the combined multisequence radiomics and clinical variables model.</p><p><strong>Conclusion: </strong>A prediction model combining MRI-based radiomic biomarkers with clinical variables increases the accuracy of predicting motor developmental outcomes in preterm infants.</p><p><strong>Impact: </strong>Our results showed that birth weight and maternal hypertensive disorders are important risk factors for motor nerve development abnormalities in preterm infants with no significant abnormalities on magnetic resonance imaging. The combination of multisequence radiomic Rad-scores and clinical variable models can improve the prediction efficiency of adverse prognoses. These findings contribute to the early detection of motor nerve abnormalities in related preterm infants and timely interventions for the benefit of families with preterm infants.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258858","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":"Weighing up the options: childhood intervention to tackle obesity.","authors":"Owen R Vaughan, Dino A Giussani","doi":"10.1038/s41390-025-04483-2","DOIUrl":"https://doi.org/10.1038/s41390-025-04483-2","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258808","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}