Pediatric Research最新文献

{"title":"Association of serum inflammasome proteins and pediatric traumatic brain injury severity.","authors":"Jennifer C Munoz Pareja, Maria B Mateo Chavez, Julia Alexis Bernal, Kathryn Swaby, Natalie Machado, Charlene Pringle, Kourtney Guthrie, Jennifer Coto, Dhanashree Rajderkar, Joslyn Gober, Juan Solano, Heather J McCrea, Daniel Gonzalez Mosquera, Ayham Alkhachroum, Kristine H O'Phelan, Firas Kobeissy, Robert W Keane, Kevin K Wang, W Dalton Dietrich, Juan Pablo de Rivero Vaccari","doi":"10.1038/s41390-025-04410-5","DOIUrl":"https://doi.org/10.1038/s41390-025-04410-5","url":null,"abstract":"<p><strong>Background: </strong>Pediatric traumatic brain injury (pTBI) often leads to cognitive, behavioral, and motor impairments. NLRP3 inflammasome proteins, such as ASC and caspase-1, may serve as biomarkers for TBI severity due to their role in neuroinflammation. This study aims to assess the association between serum ASC and caspase-1 levels and TBI severity in pediatric patients.</p><p><strong>Methods: </strong>Serum samples were collected at pediatric intensive care unit (ICU) admission (first post-admission), and at 24 and 48 h post-admission, from TBI participants aged 28 days to 18 years and from demographically matched controls. TBI severity was assessed using the Glasgow Coma Scale (GCS).</p><p><strong>Results: </strong>We analyzed samples from 77 pTBI patients and 31 controls. ASC levels were significantly higher across all GCS categories, with the most pronounced differences in the severe category at first post-admission (p = 0.0005, AUROC 0.83) and 24 h post-admission (p < 0.0001, AUROC 0.83). Caspase-1 levels were significantly elevated in the severe category, particularly at first post-admission (p < 0.0001, AUROC 0.85).</p><p><strong>Discussion: </strong>Elevated ASC and caspase-1 levels, especially in severe pTBI cases, suggest their potential as biomarkers for TBI severity. These findings emphasize the role of inflammasome proteins in post-TBI neuroinflammation and support further research into targeted therapies for pediatric TBI.</p><p><strong>Impact: </strong>Increased serum levels of inflammasome proteins ASC and caspase-1 in acute-phase post-admission samples are associated with severe TBI. To our knowledge, this is the first study to examine the inflammasome pathway in pediatric TBI patients across the severity spectrum using serum samples. The study enhances our understanding of NLRP3 inflammasome activation in pediatric TBI by profiling serum levels and examining their clinical correlation with injury severity. It suggests an adjunctive approach to the Glasgow Coma Scale with biomarkers for more precise TBI diagnosis. This research lays the groundwork for future therapeutic strategies targeting inflammasomes in pediatric TBI.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177221","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":"Positive association between visceral adiposity index and asthma in US children and adolescents: an analysis of NHANES data.","authors":"Shihui Shao, Longliang Wu, Caiping Cui, Zhiyao Qin, Yinhua Liang, Jiangying Huang, Wei Li","doi":"10.1038/s41390-025-04453-8","DOIUrl":"https://doi.org/10.1038/s41390-025-04453-8","url":null,"abstract":"<p><strong>Background: </strong>Asthma represents an inflammatory condition. The exact function of VAI in asthma among children and adolescents is still not well understood.</p><p><strong>Methods: </strong>A cross-sectional investigation was carried out by utilizing data sourced from 7814 children and adolescents participating in the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020. It adjusted for covariates and employed techniques such as multivariate logistic regression, restricted cubic spline modeling, and subgroup analyses.</p><p><strong>Results: </strong>Of the 7814 participants, 1453 (18.6%) had a self-reported asthma diagnosis by a healthcare provider. After multivariate adjustment, higher visceral adiposity index (VAI) quartiles showed a dose-dependent increase in asthma risk compared to the lowest quartile (Q1): OR = 1.06 (Q2), 1.18 (Q3), and 1.26 (Q4; 95% CI: 1.05-1.51, p = 0.014). The restricted cubic spline regression demonstrated linearity. Stratified analyses showed no significant interaction between subgroups.</p><p><strong>Conclusions: </strong>Elevated VAI levels are independently linked to a higher prevalence of asthma among US children and adolescents.</p><p><strong>Impact: </strong>Key message: Elevated visceral adiposity index (VAI) is independently associated with increased asthma prevalence in US children and adolescents, revealing a dose-dependent relationship. Novelty to literature: This study establishes a nationally representative, large-scale epidemiological link between VAI (a validated biomarker of visceral fat dysfunction) and pediatric asthma using NHANES data (N = 7814). It advances prior obesity-asthma research by quantifying how visceral adiposity-rather than general obesity-drives risk. Clinical/public health impact: Our findings propose VAI as a potential screening tool for asthma risk stratification. This could inform targeted interventions (e.g., metabolic health optimization) to mitigate asthma burden in pediatric populations.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177319","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":"Clinical research study: cerebral autoregulation in neonates and infants undergoing open heart surgery: global patterns and derived cerebral hemodynamic metrics.","authors":"Pierre Bourgoin, Erta Beqiri, Peter Smielewski, Ariane De Windt, Remi Bernardon, Guillaume Emeriaud, Ugo Gouedard, Alban Baruteau, Alexis Chenouard, Nicolas Joram, Pascal Amedro","doi":"10.1038/s41390-025-04401-6","DOIUrl":"https://doi.org/10.1038/s41390-025-04401-6","url":null,"abstract":"<p><strong>Background: </strong>Optimal perfusion pressure targets during cardiopulmonary bypass in children are debated. Monitoring of CAR allow determination of optimal perfusion pressures, but its feasibility within a large cohort of children warrants further investigations.</p><p><strong>Methods: </strong>Prospective, single center, observational study. Cerebral Oxygenation Index (COx) was calculated as a moving linear correlation coefficient between slow waves of mean arterial pressure (MAP) and cerebral oxygenation saturation. Postoperative outcomes were recorded and associations with CAR derived metrics were explored.</p><p><strong>Results: </strong>Mean COx values demonstrated CAR disruption during CPB (0.17 ± 0.17 before vs. 0.36 ± 0.13 during, p < 0.001). Post-CPB, CAR restored partially (mean Cox 0.32 ± 0.16, p < 0.05). Factors associated with CAR Disruption were age at surgery and average hematocrit during CPB. MAPopt determination was feasible in 83.3%, 75.4%, and 67.5% of patients before, during, and after surgery, respectively. LLA was determined in 78.1%, 53.5%, and 56.1%, and ULA in 71%, 50%, and 57% during the same time frames. Dose of MAP below LLA during CPB was independently associated with pre-postoperative serum creatinine ratio and 24 h postoperative serum lactate levels.</p><p><strong>Conclusions: </strong>The findings highlight the clinical significance of CAR monitoring, with implications for optimizing cerebral and systemic perfusion in this vulnerable population.</p><p><strong>Impact: </strong>In most cases, cardiopulmonary bypass is associated with CAR disruption, highlighting the need for rigorous perfusion pressure management. Individualized determination of optimal MAP target is feasible in neonates and infants undergoing cardiopulmonary bypass using CAR-derived metrics. The time spent within a range of optimal pressure is associated with better body perfusion. Live determination of optimal MAP may be used to develop individualized PAM management interventions, and ultimately improve body perfusion including the brain.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177253","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":"Downregulation of insulin receptor isoform A in the forebrain of fetal growth-restricted rats.","authors":"Yutaro Tomobe, Seiichi Tomotaki, Yukinori Yoshimura, Kouji Motokura, Ryosuke Araki, Junko Takita, Masahiko Kawai","doi":"10.1038/s41390-025-04372-8","DOIUrl":"https://doi.org/10.1038/s41390-025-04372-8","url":null,"abstract":"<p><strong>Background: </strong>Children with asymmetrical fetal growth restriction (FGR), whose head size is relatively preserved, often have a poor neurodevelopmental prognosis. Insulin receptor isoform A (IR-A) is predominantly expressed in neurons and is important in neurodevelopment. This study investigated changes in brain IR-A expression in neonatal FGR model rats.</p><p><strong>Methods: </strong>FGR model rats were generated by maternal caloric restriction (CR). Glucose uptake and the expression of glucose transporter (GLUT) genes in the brain and liver, and of the IR-A gene in the brain were compared between CR and control group neonates. Gene expression in the brain was examined by RNA sequencing. Brain IR-A localization was analyzed using immunohistochemistry.</p><p><strong>Results: </strong>The brain-to-liver ratios for organ weight and glucose uptake were significantly higher in CR rats. GLUT gene expression was maintained in the CR brain. Whole brain IR-A expression was reduced in CR rats. Furthermore, IR-A expression was decreased in the forebrain of CR rats, but not changed in the hindbrain.</p><p><strong>Conclusion: </strong>The regional differences in IR-A in the FGR rat brain indicate that an endocrinological mechanism regulates brain IR-A to maintain brain function under nutrient deficiency. However, a decrease in IR-A in the fetal period may cause postnatal brain impairment.</p><p><strong>Impact: </strong>Insulin receptor isoform A (IR-A) expression is reduced in the neonatal brain of asymmetrical fetal growth restriction (FGR) model rats generated by maternal caloric restriction. IR-A expression is decreased in the forebrain, which is important for cognitive brain functions, whereas IR-A expression is maintained in the hindbrain, which is important for basic vital activities. The expression of genes related to forebrain development is significantly decreased, while the expression of genes related to hindbrain development is increased in neonatal FGR model rats. These results can explain why FGR infants have a poor neurodevelopmental prognosis despite their brain size being relatively protected.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177267","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":"Causal relationship between gut microbiota and blood metabolites with childhood Obesity: a Mendelian randomization study.","authors":"Ji-Gan Wang, Xiu-Hua Pan, Yan Li","doi":"10.1038/s41390-025-04414-1","DOIUrl":"https://doi.org/10.1038/s41390-025-04414-1","url":null,"abstract":"<p><strong>Background: </strong>This study aims to explore the causal relationship between gut microbiota and childhood obesity and to assess the potential mediating role of blood metabolites in this relationship.</p><p><strong>Methods: </strong>This study covering 473 gut microbiota and 1400 metabolites. The bidirectional two-sample Mendelian Randomization method is employed, with Inverse Variance Weighted as the main statistical approach, to assess the causal relationships between gut microbiota, metabolites and Childhood Obesity.</p><p><strong>Results: </strong>The study found significant causal associations between 12 types of gut microbiota and childhood obesity, with 7 microbiota showing a negative correlation and 5 acting as risk factors for obesity. Bacillaceae A showed the strongest association with childhood obesity (OR = 0.0481, P = 0.0126), while Eubacterium Q was identified as a major risk bacterium for obesity (OR = 5.4330, P = 0.0452). Additionally, 18 metabolites were found to be associated with childhood obesity, with 6-bromotryptophan being the strongest negatively correlated metabolite (OR = 0.5680, P = 0.00023) and methylsuccinate being the strongest positively correlated risk metabolite (OR = 1.6987, P = 0.0383). Mediation analysis identified 10 significant pathways, highlighting Adrenate (22:4n6) as a mediator for the gut microbiota UBA2922 sp900313925 in promoting childhood obesity (mediation effect: 0.106, mediation proportion: 10.94%), and X-12830 as a mediator for K10 sp001941205 in inhibiting childhood obesity (mediation effect: -0.0772, mediation proportion: 13.68%).</p><p><strong>Conclusion: </strong>This study provides novel evidence of the causal roles of gut microbiota and blood metabolites in childhood obesity. The identification of key metabolites mediating the effects of gut microbiota on obesity risk offers potential targets for future interventions and therapeutic strategies.</p><p><strong>Impact: </strong>Analysis revealed 12 gut microbiota causally related to childhood obesity, with seven negatively correlated and five identified as risk factors. Bacillaceae A (protective) and Eubacterium Q (risk) were notably associated. Among 1400 metabolites studied, 18 showed causal relationships with obesity, notably 6-bromotryptophan (protective) and methylsuccinate (risk factor). Mediation analysis identified 10 significant causal pairings between gut microbiota and blood metabolites, with Adrenate (22:4n6) mediating the promotion of childhood obesity by UBA2922 sp900313925, and X-12830 mediating the inhibition of childhood obesity by K10 sp001941205.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150319","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":"Safe use of human milk for preterms in the context of maternal polypharmacy: a framework to improve practices.","authors":"Dotan Shaniv, Anne Smits, Karel Allegaert","doi":"10.1038/s41390-025-04416-z","DOIUrl":"https://doi.org/10.1038/s41390-025-04416-z","url":null,"abstract":"<p><p>Maternal pharmacotherapy during lactation is an ongoing research field, which relies on scientific evidence, pharmacological reasoning and extrapolation to support risk-to-benefit assessment. Typically, drugs are studied individually for potential effects on a nursing infant, with limited information on the preterm infant. Polypharmacy during lactation is still poorly studied, leaving healthcare professionals without any scientific guidance when consulting on human milk safety in this scenario. When focusing on a dyad of a postpartum mother on polypharmacy and a preterm infant, the benefits of mother's own milk (MOM) should be weighed against the unknown potential risks of polypharmacy during lactation. Within this setting of limited evidence, a framework to improve clinical and research practices is provided. Possible measures to minimize the risk of maternal (poly)pharmacy to the newborn include: multi-disciplinary prenatal counseling; preferring medications with low passage rate into human milk; relative rating of medications according to safety profile; and 'mixed feeding' (alternating between MOM and other types of feed, preferably donor human milk). These measures can be used to support shared informed decisions on the risk-to-benefit assessment. As the topic of polypharmacy during lactation is still poorly explored, a research agenda is suggested. IMPACT: Polypharmacy during lactation is poorly studied, and practical, evidence-based guidelines for healthcare professionals are lacking. Various methods can be employed to reduce exposure to medications through human milk, even more so when applied concomitantly: preference of medications with low passage into human milk, relative rating of medications according to known safety profile, or 'mixed feeding' where mother's own milk is alternated with other types of feed, preferably donor human milk. A framework to improve clinical and research practices on provision of human milk in the setting of maternal polypharmacy and prematurity as an added challenge is provided.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150287","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":"Age specific clinical manifestations and vascular involvements in childhood-onset Takayasu arteritis.","authors":"Yingjie Xu, Congying Wang, Wenquan Niu, Min Kang, Jia Zhu, Fan Liu, Baoping He, Weihong Chu, Lian Wang, Xue Zhao, Gaixiu Su, Dan Zhang, Tong Yue, Ming Li, Jianming Lai, Xiaohui Li","doi":"10.1038/s41390-025-04424-z","DOIUrl":"https://doi.org/10.1038/s41390-025-04424-z","url":null,"abstract":"<p><strong>Background: </strong>Limited studies focused on characteristics of childhood-onset Takayasu arteritis (cTAK) throughout growth and development.</p><p><strong>Methods: </strong>111 cTAK patients were recruited from six tertiary hospitals across China from January 2009 to December 2021. Patients were classified into infant group (<12 months), toddler and preschool group (≥12 months, <72 months), school-age group (≥72 months, <144 months) and adolescent group (≥144 months).</p><p><strong>Results: </strong>Infantile cTAK patients tended to had a significantly higher proportion presenting with fever (91.7%, P-trend <0.001), and had significantly higher levels of C-reactive protein (CRP), white blood cells (WBC), platelet (PLT), and lower hemoglobin (HGB) compared to the other three groups (all P < 0.0125). Adolescent patients were more likely to present with headache (33.3%), dizziness (24.2%) and fatigue (51.5%; all P-trend < 0.001). Infantile patients were more likely to have coronary artery involvement (75.0%, P trend < 0.001). Adolescent patients were more likely to have superior mesenteric artery (36.4%, P trend = 0.005), carotid artery (30.3%, P trend = 0.003), and celiac trunk artery stenosis (27.3%, P trend = 0.005).Younger patients, especially infants, had a lower proportion of glucocorticoids use (P trend = 0.001). 73.0% (81/111) of patients were in remission, with a median follow-up time of 2.00 [2.00, 5.00] years.</p><p><strong>Conclusion: </strong>The age-specific patterns identified in this study offered valuable insights for a comprehensive understanding of cTAK.</p><p><strong>Impact: </strong>Infantile Takayasu arteritis patients tended to present with fever, elevated inflammatory biomarkers and coronary artery involvement. Adolescent patients were more likely to present with headache, dizziness and fatigue, with superior mesenteric artery, carotid artery involvement and celiac trunk artery stenosis. Clinical manifestations and vascular involvement of childhood-onset Takayasu arteritis differ across age groups. The clinical manifestations of childhood-onset Takayasu arteritis lack specificity. The age-specific patterns identified in this study may provide clues for early diagnosis.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138256","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":"Sex differences in preterm cytokine and inflammasome responses and modulation by exogenous sex steroids.","authors":"Matthew McGovern, Lynne A Kelly, Rebecca Finnegan, John F Murphy, John Kelleher, Ashanty M Melo, Catherine M Greene, Eleanor J Molloy","doi":"10.1038/s41390-025-04350-0","DOIUrl":"https://doi.org/10.1038/s41390-025-04350-0","url":null,"abstract":"<p><strong>Background: </strong>Preterm infants are at increased risk of sepsis compared to adults and older children. Preterm immune cells have altered cytokine responses compared to term neonates and adults and all have sex-related differences in immunity. We examined inflammasome activation and cytokines with endotoxin and sex steroid hormones between preterm and term neonates.</p><p><strong>Methods: </strong>Preterm (n = 40) and term (n = 32) peripheral blood samples were incubated with Lipopolysaccharide (LPS), Estradiol (E2), Progesterone (Pg) or Pam3CSK4 and biomarkers were analysed by ELISA. Inflammasome genes, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), Interleukin-1 beta (IL1-β) and Absent In Melanoma 2 (AIM 2) were analysed with Taqman RT-PCR.</p><p><strong>Results: </strong>IL-1β cytokine expression was reduced by female sex hormones and notably the effect of estradiol was greatest in the preterm population. Female preterm neonates were more responsive to the anti-inflammatory effect of progesterone than male preterm infants. Term neonates had higher IL-1β, IL-18 and IL-1RA expression than preterm infants. Overall, in preterms, E2 and Pg lowered cytokine expression levels. Inflammasome gene expression profiles did not differ between preterm male and female neonates.</p><p><strong>Conclusion: </strong>Sex hormones altered the expression of multiple cytokines, and cytokine responses differ by sex. Gestation plays an important role in the inflammatory response, and we note term infants have a more robust profile while preterm infants are more responsive to hormonal stimulus. Female sex hormones have an important role in modulating neonatal immune response and may contribute to the female immune advantage.</p><p><strong>Impact: </strong>Female sex hormones play an important role in modulating the neonatal immune response. This is reflected clinically by better bacterial clearance and improved sepsis outcome in females. This study aims to test the hypothesis that male and female neonates differ in their cytokine and inflammasome response and in response to endotoxin and sex steroid hormones. In preterm infants there is a sex difference in IL-1b responses which is observed rapidly following endotoxin stimulation. Differing immune responses according to sex has implications for future clinical application. Further work to characterise these sex differences may help in guiding therapy during sepsis.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138226","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":"Automated detection of neonatal pulmonary hypertension in echocardiograms with a deep learning model.","authors":"Holger Michel, Ece Ozkan, Kieran Chin-Cheong, Anna Badura, Verena Lehnerer, Stephan Gerling, Julia E Vogt, Sven Wellmann","doi":"10.1038/s41390-025-04404-3","DOIUrl":"https://doi.org/10.1038/s41390-025-04404-3","url":null,"abstract":"<p><strong>Background: </strong>In infants, pulmonary hypertension (PH) increases morbidity and mortality. Echocardiography, though standard, is time- and expertise-demanding. We propose a deep learning approach for automated PH detection using standard echocardiography videos, validated by the systolic eccentricity index (EIs).</p><p><strong>Methods: </strong>The training and validation set comprised 975 videos and the held-out set 378 videos, including five echocardiographic standard views from infants aged 3-90 days, taken between 2018-2021 and 2021-2022, respectively. Echocardiograms were labeled as PH (EIs < 0.82) and healthy (EIs ≥ 0.87). After preprocessing and random segmentation of all videos into 13.530 frames, spatial and spatio-temporal convolutional neural network architectures were used for training of a PH prediction model and gradient-weighted class activation mapping for explainability.</p><p><strong>Results: </strong>The best single-view performance was achieved using parasternal short axis view (AUROC spatial and spatio-temporal: 0.91 and 0.94 in validation set, 0.93 and 0.88 in held-out set, respectively). Combination of three standard views improved accuracy with AUROC 0.96 and 0.90 in validation (spatio-temporal) and held-out set (spatial), respectively. Saliency maps revealed model focus on clinically relevant regions, including interventricular septum and left atrial filling.</p><p><strong>Conclusions: </strong>The presented deep learning model for automated detection of PH in neonates shows high accuracy, explainability, and reproducibility.</p><p><strong>Impact: </strong>This study presents a deep learning model that enables accurate, automated detection of pulmonary hypertension in infants using standard echocardiography videos, enhanced and evaluated with eccentricity index, an established and prognostically relevant echocardiographic parameter. The parasternal short-axis view showed the best single-view performance, combined views further improved accuracy. Explainability through saliency maps supports clinical acceptance, highlighting physiologically relevant regions in the decision process. It adds novel evidence to the literature, demonstrating the utility of spatio-temporal convolutional neural networks for early, non-invasive diagnosis. The model provides a scalable and reproducible tool for routine PH screening, potentially improving early detection and outcomes.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138250","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 utility of CNV analysis in identifying the molecular etiology of pediatric epilepsy patients.","authors":"Shuyue Zhang, Xuetao Wang, Jing Meng, Jiaci Li, Yan Dong, Dong Li, Jianbo Shu, Chunquan Cai","doi":"10.1038/s41390-025-04427-w","DOIUrl":"https://doi.org/10.1038/s41390-025-04427-w","url":null,"abstract":"<p><strong>Background: </strong>Copy number variations (CNVs) are considered to be associated with various neurocognitive disorders, particularly severe pediatric conditions such as intellectual disability and epilepsy. In this study, our aim is to determine the distribution and pathogenicity of CNVs in pediatric epilepsy patients, thereby expanding the spectrum of related syndromes or gene phenotypes, explore potential new epilepsy genes within CNVs.</p><p><strong>Methods: </strong>We collected clinical data from 425 pediatric epilepsy patients and performed WES, including both pathogenic variant analysis and CNV analysis. Variants were classified per ACMG guidelines. Analyzed the phenotypic characteristics associated with genetic diagnostic results and performed further research and analysis on diagnostic CNVs.</p><p><strong>Results: </strong>Among the 425 pediatric epilepsy patients, diagnostic SNVs/indels were detected in 104 cases (24.5%). CNV testing revealed 49 cases with diagnostic CNVs (11.5%). For patients with epilepsy phenotypes unexplained by CNVs, two potential epilepsy genes were suggested through analysis.</p><p><strong>Conclusion: </strong>CNV analysis significantly improves the genetic diagnostic yield in pediatric epilepsy patients, achieving a rate of 11.5%. Patients with developmental delay or cardiopathy are more likely to harbor diagnostic CNVs. In-depth analysis of diagnostic CNVs can identify the genetic etiology in epilepsy patients, guide follow-up strategies, and facilitate the discovery of promising candidate epilepsy genes.</p><p><strong>Impact: </strong>CNV analysis can enhance the molecular diagnostic capability of epilepsy. Patients with developmental delay or cardiac disease are more likely to have diagnostic CNVs. In-depth analysis of CNVs can help uncover potential candidate epilepsy genes.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138300","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}