Pediatric Research最新文献

{"title":"Is cardiomyopathy intrinsic to Marfan syndrome?","authors":"Alexis M Wolf, Carolyn M Wilhelm, James Strainic, Timothy J Mead","doi":"10.1038/s41390-025-03899-0","DOIUrl":"https://doi.org/10.1038/s41390-025-03899-0","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123393","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":"Opportunities in the translational pipeline for pediatric brain cancer therapies.","authors":"Lindsay Rumberger Rivera, Nora L Springer, Katherine Bailey, Jenny Patel, Christopher Brett, Elizabeth Barker","doi":"10.1038/s41390-025-03847-y","DOIUrl":"https://doi.org/10.1038/s41390-025-03847-y","url":null,"abstract":"<p><p>Primary malignant central nervous system (CNS) tumors are the leading cause of cancer-related mortality in the pediatric population. Moreover, survivors often experience significant long-term treatment-related morbidity. Challenges unique to drug delivery to the central nervous system have hampered therapeutic progress. In the past decade, significant advancements in our understanding of molecular biology, genetic alterations, and the tumor microenvironment have allowed us to improve our in vitro and laboratory animal models to better replicate diseases seen in the pediatric population. Recently, a comparative approach using naturally-occurring CNS malignancies in dogs with similar disease progression, histologic presentation, and treatment response has been proposed as an enticing model system. Given these improvements in the translational pipeline, there is an opportunity to identify and implement effective therapies more efficiently to pediatric CNS malignancy populations. IMPACT: Relevant and translational pre-clinical studies are needed to find chemotherapeutics and targeted agents that can reach therapeutic doses within tumors in children without causing systemic adverse effects. A discussion of comparative oncology is provided with the intent to foster veterinary/human oncology collaboration. While the traditional pipeline for translating medications from bench to bedside has been evolving and improving over the last decade, the advances and remaining roadblocks of this pipeline are reviewed and discussed in this article.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075025","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 intermittent hypoxemia events are associated with later systemic hypertension.","authors":"Stephanie Martinez, Zhengyi Chen, Juliann M Di Fiore, Christina Nguyen, Nori M Minich, Anna Maria Hibbs","doi":"10.1038/s41390-025-03881-w","DOIUrl":"https://doi.org/10.1038/s41390-025-03881-w","url":null,"abstract":"<p><strong>Background: </strong>Approximately 5% of very premature infants delivered at less than 30 weeks' gestation have systemic hypertension. In adult human and animal models, intermittent hypoxemia events are associated with systemic hypertension. In neonates, intermittent hypoxemia events are associated with adverse outcomes, but it is unknown if they are a risk factor for hypertension. We hypothesize that early intermittent hypoxemia events in very preterm neonates are associated with systemic hypertension at 34-36 weeks' postmenstrual age.</p><p><strong>Methods: </strong>Secondary analysis of a single-center cohort study of 164 infants, <31 weeks' gestational age. Intermittent hypoxemia events were continuously recorded during the first 21 days of age.</p><p><strong>Results: </strong>There was a significant association between the number of intermittent hypoxemia events (per 100) and systemic hypertension (OR (95% CI) = 1.08 (1.01-1.15)), and both the number of intermittent hypoxemia events (per 100 β (95% CI) = 0.22 (0.10-0.34)) and percent of time with hypoxemia (β (95% CI) = 0.10 (0.01-0.19)) and systolic blood pressure at 34-36 weeks' postmenstrual age.</p><p><strong>Conclusion: </strong>This study demonstrated a higher incidence of early intermittent hypoxemia events in preterm infants with hypertension. Decreasing intermittent hypoxemia during this critical period may reduce incidence of later vascular stress in this population.</p><p><strong>Impact: </strong>Intermittent hypoxemia events are very common in premature infants and increased frequency of intermittent hypoxemia events is associated with morbidity. Intermittent hypoxemia events in adult human as well as adult and neonatal animal models are associated with systemic hypertension. This study demonstrated an association between early intermittent hypoxemia events and systemic hypertension in very preterm neonates, adding to the body of literature of possible morbidities caused by intermittent hypoxemia events. This study addresses the common, though under-recognized, issue of neonatal hypertension, and suggests increased intermittent hypoxemia events may be contributory.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067162","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":"European training requirements in Neonatology 2021-towards a unified training standard for Neonatologists.","authors":"Charles C Roehr, Sven Wellmann, Tomasz Szczapa, Pascal Fentsch, Petra Hüppi, Olivier Baud, Ana Alarcon, Willem P de Boode, Michael Hall, Olivier Danhaive, Maximo Vento","doi":"10.1038/s41390-025-03840-5","DOIUrl":"https://doi.org/10.1038/s41390-025-03840-5","url":null,"abstract":"<p><p>The European Society for Paediatric Research (ESPR) first developed recommendations for a Neonatology specific European training curriculum in 1998, with updates in 2007 and 2021. The aim of these recommendations was to define a common, European standard of training for national educational programmes for Neonatologists. Following the Union of European Medical Specialists' (UEMS) framework of European Training Requirements (ETR), and similar to the American Board of Pediatrics (ABP) recommendations, graduates of training programmes conforming to the ETR will be eligible throughout Europe for recognition of equality of training, and with that should be enabled to freedom-of-movement. This concept also accounts for neonatal specialists. We therefore present the pan-European work on the ETR Neonatology in its third iteration (ETR III), summarising the basic requirements for contemporary training programmes, trainers, and training centres in neonatology. We highlight the European School of Neonatology (ESN) as a comprehensive online educational platform which provides the theoretical and practical background to satisfy the ETR-III. Lastly, we introduce the European Board of Neonatal & Child Health Research (EBNCHR) as a committee dedicated to gaining acceptance for the concept of harmonising education and training in Neonatology and recognising Neonatology as a Paediatric subspecialty in every European Union member state. IMPACT: Neonatology currently is not uniformly recognised as a Paediatric subspecialty throughout the 27 European countries. Hence, training in Neonatology formerly followed no commonly agreed standard throughout the European Union (EU). To ensure a minimum standard of care, an agreed minimum standard of training is required. The European Society for Paediatric Research (ESPR) has led on generating an EU-accredited, pan-European Syllabus for Neonatal training in Europe, the European Training Requirements (ETR) in Neonatology (2021). This article presents the ETR Neonatology from commissioning to accreditation and discusses means of how high-grade post-graduate education, aligned with the ETR can be achieved by practitioners.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074970","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":"Obesity is a growing problem and a modifiable factor affecting lung health.","authors":"Matthew J Hegewald","doi":"10.1038/s41390-025-03887-4","DOIUrl":"https://doi.org/10.1038/s41390-025-03887-4","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074972","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 resuscitation video review - has the time for wider adoption come?","authors":"Anne Lee Solevåg, Maxi Kaufmann, Ruben Witlox, Charles Christoph Roehr","doi":"10.1038/s41390-025-03857-w","DOIUrl":"https://doi.org/10.1038/s41390-025-03857-w","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067166","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":"Repetitive neonatal pain increases spinal cord DNA methylation of the µ-opioid receptor.","authors":"Mathilde Baudat, Elbert A J Joosten, Sinno H P Simons, Daniël L A van den Hove, Renzo J M Riemens","doi":"10.1038/s41390-025-03892-7","DOIUrl":"https://doi.org/10.1038/s41390-025-03892-7","url":null,"abstract":"<p><strong>Background: </strong>Repetitive neonatal painful procedures experienced in the neonatal intensive care unit (NICU) are known to alter the development of the nociceptive system and have long-lasting consequences. Recent evidence indicates that NICU stay affects the methylation of the opioid receptor mu 1 encoding gene (Mor-1). Additionally, a preclinical model of neonatal procedural pain established lower adult post-operative MOR-1 levels in the spinal cord. Thus, we hypothesized that neonatal procedural pain increases the DNA methylation status of Mor-1 in the spinal cord and dorsal root ganglia (DRGs).</p><p><strong>Methods: </strong>To this end, repetitive neonatal procedural pain was induced in animals, during the first postnatal week, a period equivalent to preterm human brain development. On postnatal day 10 methylation of Mor-1 promotor was assessed in the spinal cord and the DRG using bisulfite pyrosequencing.</p><p><strong>Results: </strong>Our findings demonstrated that neonatal procedural pain increased spinal cord Mor-1 promotor DNA methylation in the ipsilateral side as compared to the contralateral side, an effect that was not observed in the control animals, nor in the DRG.</p><p><strong>Conclusion: </strong>This study is the first to highlight a localized and noxious-stimuli-dependent effect of repetitive neonatal procedural pain on Mor-1 promotor methylation and emphasizes the need to explore the effects of repetitive neonatal procedural pain on the epigenome.</p><p><strong>Impact: </strong>This study reveals that repetitive neonatal procedural pain is associated with increased DNA methylation of the Mor-1 promoter in the spinal cord of neonatal rats. This is the first study to identify an effect of neonatal procedural pain on DNA methylation, emphasizing the critical need for further investigation into the epigenetic consequences of neonatal procedural pain. These insights could lead to better management and treatment strategies to mitigate the long-term impacts of early pain exposure on neurodevelopment and behavior.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067167","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":"Improving UK data on avoidable perinatal brain injury: review of data dictionaries and consultation.","authors":"Jan W van der Scheer, Victoria Komolafe, Kirstin Webster, Stamatina Iliodriomiti, Charles C Roehr, Asma Khalil, Tim Draycott, Louise Dewick, George Dunn, Rachel Walsh, Philip Steer, Alessandra Giusti, Mark L Cabling, Nick Fahy, Mary Dixon-Woods","doi":"10.1038/s41390-025-03842-3","DOIUrl":"https://doi.org/10.1038/s41390-025-03842-3","url":null,"abstract":"<p><strong>Background: </strong>High quality data is important to understanding epidemiology and supporting improvement efforts in perinatal brain injury. It is not clear which data items relevant to brain injury are captured across UK sources of routinely collected data, nor what needs to be done to ensure that those sources are fit for purpose in improving care.</p><p><strong>Methods: </strong>We reviewed data dictionaries of four main UK perinatal data sources and consulted a multi-professional group (N = 27) with expertise in neonatal/maternity care, statistics, and clinical negligence.</p><p><strong>Results: </strong>None of the data sources we reviewed currently captures, on its own, the range of items relevant to brain injury. Data items lack common definitions and ongoing linkage across the different sources. Our consultation identified the need for standardising the definition of avoidable perinatal brain injury, resolving inconsistencies in capturing data, improving linkage of data across existing data sources, and co-designing a strategy for meaningful use of data.</p><p><strong>Conclusions: </strong>Limited standardisation and linkage across UK data sources are key problems in using data to guide improvement efforts aimed at reducing risk of avoidable perinatal brain injury. A programme involving co-design with healthcare professionals and families to improve capture and use of data is now needed.</p><p><strong>Impact: </strong>Limited standardisation and linkage across UK data sources currently challenge the use of data as the basis of efforts to reduce risk of avoidable perinatal brain injury. A harmonisation programme involving consultation and co-design with healthcare professionals, families, and other specialists is needed to enable better capture and use of data in this key area. There is need to standardise the definition of avoidable perinatal brain injury, resolve inconsistencies in capturing data, improve linkage of data collected across existing data sources, and co-design a strategy for meaningful use of data.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067152","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":"Different effects of vitamins on hypoxic and normal fetal lungs.","authors":"Fuat Emre Canpolat, Hayriye Gözde Kanmaz Kutman","doi":"10.1038/s41390-025-03903-7","DOIUrl":"https://doi.org/10.1038/s41390-025-03903-7","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067132","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 serum GM-CSF at diagnosis of biliary atresia is associated with improved biliary drainage.","authors":"Sarah A Taylor, Sanjiv Harpavat, Kyle D Gromer, Victor Andreev, Kathleen M Loomes, Jorge A Bezerra, Chaowapong Jarasvaraparn, Kasper Wang, Simon Horslen, Philip Rosenthal, Jeffrey Teckman, Pamela L Valentino, Vicky L Ng, Saul J Karpen, Ronald J Sokol, Estella M Alonso, Cara L Mack","doi":"10.1038/s41390-025-03804-9","DOIUrl":"https://doi.org/10.1038/s41390-025-03804-9","url":null,"abstract":"<p><strong>Background: </strong>The immune heterogeneity of biliary atresia (BA) presents a challenge for development of prognostic biomarkers. This study aimed to identify early immune signatures associated with biliary drainage after Kasai Portoenterostomy (KPE).</p><p><strong>Methods: </strong>Serum samples, liver slides, and clinical data were obtained from patients enrolled in the NIDDK-supported Childhood Liver Disease Research Network. Serum cytokines and hepatic immune cell subsets were measured at diagnosis and compared among 3 groups: 38 infants with BA (20 with evidence of bile flow after KPE; 18 without) and 17 non-BA cholestatic infants.</p><p><strong>Results: </strong>BA participants had lower numbers of lipid associated macrophages (LAM), and increased serum levels of Eotaxin-3, interleukin (IL) 12p70, and IL-8 versus non-BA groups (p < 0.05 for all). Among BA participants, monocyte like macrophages and serum levels of granulocyte-macrophage colony stimulating factor (GM-CSF) were increased in BA participants with good biliary drainage (p = 0.004 and p < 0.001 respectively). Levels of GM-CSF, IL-16, c-reactive protein, TNF-β predicted successful biliary drainage with an area under the receiver operating curve of 0.84 (p < 0.001).</p><p><strong>Conclusion: </strong>These findings suggest that distinct macrophage-associated immune networks at diagnosis may impact biliary drainage after KPE. Identification of early prognostic immune-modulatory markers has potential to improve patient stratification for medical and surgical therapies.</p><p><strong>Impact statement: </strong>We identify serum cytokines, particularly GM-CSF, that are associated with future biliary drainage in patients with biliary atresia. Characterization of macrophage-associated immune networks provides novel insight into early disease mechanism that may impact patient outcomes. Early prognostic biomarkers markers in biliary atresia can help in patient stratification for medical and surgical therapies.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067160","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}