Pediatric Research最新文献

{"title":"A new study provides details on COVID-19 vaccine booster efficacy among children receiving immunosuppressive medications.","authors":"Thomas A Hooven","doi":"10.1038/s41390-025-04470-7","DOIUrl":"https://doi.org/10.1038/s41390-025-04470-7","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225695","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 enteral antibiotics reduce gut inflammation and delay systemic immune development in preterm pigs.","authors":"René Liang Shen, Ziyuan Wu, Xiaoyu Pan, Shuqiang Ren, Anders Brunse, Per Torp Sangild, Duc Ninh Nguyen","doi":"10.1038/s41390-025-04436-9","DOIUrl":"https://doi.org/10.1038/s41390-025-04436-9","url":null,"abstract":"<p><strong>Background: </strong>Antibiotics are frequently administered to preterm infants after birth to prevent or treat severe infections. However, interactions between gastrointestinal health and systemic immune development following neonatal antibiotics are unclear.</p><p><strong>Methods: </strong>Using a preterm pig model, we investigated the systemic immune effects of four days of antibiotics (AB) treatment just after birth. Preterm pigs received enteral AB for 4 days and were compared with controls (water) until 9 days after birth (n = 28-32). Blood samples were collected at birth and on days 5, 7, and 9. Gut samples were collected on day 9.</p><p><strong>Results: </strong>Expression of TLR2, TLR3, S100A9, and IL10 differed by day 5, 7 and 9 in blood for controls, while AB-treated showed delay of these temporal developments. On day 9, blood transcriptomics revealed 1765 DEGs (1090 downregulated) in AB-treated pigs compared with controls, with suppression of inflammatory and energy metabolism pathways. The suppression was associated with lower intestinal permeability, bacterial adhesion and gut inflammation. The findings suggest that enteral AB exposure after preterm birth, reduces not only gut inflammation, but also delay systemic immune cell development.</p><p><strong>Conclusion: </strong>Neonatal AB treatment might reduce gut inflammation; however, it may cause subsequent reduced capacity to combat systemic infections.</p><p><strong>Impact statement: </strong>Neonatal antibiotics attenuate gut inflammation and systemic immune development. Effects persist after cessation of antibiotic treatment. Inflammatory pathways in blood are associated with gut health parameters. This study underscores the complex interplay between gastrointestinal health and systemic immune function. Neonatal antibiotics may influence risk of infectious complications even after treatment.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225762","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":"Bone age evaluation in an ethnically diverse cohort of children with premature adrenarche.","authors":"Liya Kerem, Marwa Tuffaha, Aluma Chovel Sella, Luz Elena Castellanos, Jonanlis Ramirez Alcantara, Takara Stanley","doi":"10.1038/s41390-025-04459-2","DOIUrl":"https://doi.org/10.1038/s41390-025-04459-2","url":null,"abstract":"<p><strong>Background: </strong>Bone age (BA) assessment is an essential tool in pediatric endocrinology, used to assess growth and perturbations in pubertal onset. BA advancement is common in children with premature adrenarche (PA), potentially leading to additional evaluation or intervention. The extent to which BA advancement reflects variation in metabolic and demographic factors, including body mass index (BMI), sex, race, and ethnicity, remains insufficiently characterized.</p><p><strong>Methods: </strong>We conducted a retrospective chart review of 296 children (72% female, mean age 7.3 ± 1.6 years) with isolated PA seen at a tertiary pediatric endocrinology clinic. Absolute and standardized BA advancement were analyzed in relation to BMI, sex, race, and ethnicity. Multivariate linear regression adjusted for age and covariates.</p><p><strong>Results: </strong>BA advancement was greater in children with obesity (19.2 ± 15.1 months) versus those below the 95th% (11.4 ± 13.5), and in males (19.9 ± 14.3) versus females (12.4 ± 14.3). White race was associated with lower advancement (p = 0.02). BMI (p < 0.0001), male sex (p < 0.0001), and Hispanic vs. White ethnicity (p = 0.023) significantly affected standardized BA advancement.</p><p><strong>Conclusion: </strong>BMI, sex, and race/ethnicity influence BA advancement in PA, supporting individualized interpretation and further study of clinical implications.</p><p><strong>Impact: </strong>Bone age (BA) advancement is an important consideration in the diagnostic workup of children with premature adrenarche. In this diverse cohort, BMI status, sex, race, and ethnicity were significantly associated with BA advancement, suggesting that both metabolic and demographic factors influence skeletal maturation. While BA advancement in obesity and premature adrenarche is recognized, this study underscores their combined effects and the variability across populations. These findings point to limitations in current BA standards and support the need for individualized interpretation. Further research should explore how BA advancement in obesity and across ethnic groups affects adult height and long-term outcomes.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225727","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":"Human milk: insights on cell composition, organoids and emerging applications.","authors":"Misba Majood, Rajini Rao","doi":"10.1038/s41390-025-04458-3","DOIUrl":"https://doi.org/10.1038/s41390-025-04458-3","url":null,"abstract":"<p><p>Human milk is far more than a source of infant nutrition. It is a dynamic, living fluid packed with cells, bioactive molecules, and a complex microbiome that shapes neonatal development and lifelong health. Recent advances have illuminated the remarkable cellular diversity of human milk, including epithelial, immune, microbial and stem cells, each contributing essential biological functions. Milk contains distinct membrane-bound structures in the form of milk fat globules and extracellular vesicles that package a diverse cargo of lipids, proteins and nucleic acids for neonate nutrition, development and immune regulation. This review explores the composition of human milk, highlighting its nutrient and bioactive components and discussing growing concerns of xenobiotic and viral burden. We describe how milk-derived cells offer non-invasive windows into lactation biology and how emerging 3D mammary organoid models, particularly those generated from human milk cells, provide unprecedented tools to study breast development, lactation disorders, and regenerative therapies. We outline the potential of milk cells and extracellular vesicles in neonatal care, personalized medicine, and biobanking, while addressing current technical challenges and future research opportunities. By harnessing the unique properties of human milk, we stand at the threshold of transformative insights into maternal-infant health and novel biomedical applications. IMPACT: Up to date summary of bioactives, living cells and membrane bound compartments found in human milk. Primer on human mammary organoid technology, including advantages, recent advances and step by step methods. Highlights the unrealized potential of human milk in organoid technology, therapeutics, and regenerative medicine.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213419","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":"Identification of novel NDUFA3 variants in a patient with mitochondrial disorders.","authors":"Yu Sun, Xiujuan Wei, Bing Xiao, Yongfeng Luo, Ya Wang, Ripeng Liu, Yongkun Zhan, Xiantao Ye, Xudong Cai, Shiyi Xu, Jianxin Lyu, Hezhi Fang, Yongguo Yu","doi":"10.1038/s41390-025-04403-4","DOIUrl":"https://doi.org/10.1038/s41390-025-04403-4","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial respiratory chain (RC) dysfunction constitutes the biochemical defect underlining a group of heterogenous clinical presentations known as mitochondrial disorders. NDUFA3 is an accessory subunit of Complex I (CI) and has recently been associated with Leigh Syndrome. However, the genetic evidence is limited and no functional analysis is available on the molecular mechanism.</p><p><strong>Methods: </strong>We investigated the clinical features of the second family with biallelic NDUFA3 variants. The patient's cells and HEK293T cells with NDUFA3 knock down (KD) were assessed to study the RC dysfunction. A zebrafish model with the morpholino targeting on ndufa3 were generated to study the phenotypes caused by ndufa3 disruption.</p><p><strong>Results: </strong>The affected boy demonstrated global developmental delay, neurosensory hearing impairment, strabismus, muscle weakness, and hypertonia. He harbored a paternal exonic deletion NC_000019.9:g.54608143_54614387delinsCG and a maternally-inherited missense variant NM_004542.4:c.173G>A; p.(Arg58His). In patient's cells and HEK293T cells with NDUFA3 KD, reduced levels of NDUFA3 and CI and Complex IV (CIV) were observed, which further impaired endogenous respiration and ATP generation. Re-expression of the wild-type but not the mutant NDUFA3 restored the CI and CIV levels in NDUFA3 deficient cells. Zebrafish with ndufa3 disruption demonstrated ndufa3 KD affected locomotor development.</p><p><strong>Conclusions: </strong>Our findings confirm the association between NDUFA3 molecular defects and Leigh syndrome spectrum.</p><p><strong>Impact: </strong>NDUFA3 deficiency causes a mitochondrial respiration complex deficiency disorder. A family with biallelic NDUFA3 variants demonstrates phenotype resembling mitochondrial respiration complex defects. NDUFA3 defects reduce the amount of respiration complex I and IV; impair endogenous respiration and ATP generation. Zebrafish with ndufa3 knock down manifests delayed locomotor development. With this reported patient, the relationship between the gene and disease can be upgraded from \"limited\" to \"moderate\".</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213451","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":"Early gut microbiome composition of very preterm infants randomised to receive human milk volumes of 60 ml/kg/day or more within the first 36 hours after birth.","authors":"Ariel A Salas, Christopher J Stewart, Gregory R Young","doi":"10.1038/s41390-025-04456-5","DOIUrl":"https://doi.org/10.1038/s41390-025-04456-5","url":null,"abstract":"<p><strong>Background: </strong>Early and increased exposure to human milk combined with minimal exposure to parenteral nutrition could reduce hospitalisation costs, improve postnatal growth, and influence the diversity of the gut microbiome.</p><p><strong>Methods: </strong>Faecal samples from very preterm infants randomised to receive either 60 to 80 ml/kg/day (intervention group) or 20 to 30 ml/kg/day (control group) of human milk within the first 36 h after birth were collected at approximately postnatal day 14. After trial completion, samples were analysed by 16S rRNA gene sequencing to determine early differences in the gut microbiome between the randomisation groups using adjusted models.</p><p><strong>Results: </strong>We analysed faecal samples from 95 infants with a median gestational age of 31 weeks (mean birthweight: 1487 g). In adjusted analyses, taxonomic richness and Shannon alpha diversity were not significantly higher in the intervention group. No significant differences in microbial diversity composition between samples (i.e., beta diversity) were found. Four distinctive de novo community clusters were identified during the trial, but they did not differ according to randomisation groups.</p><p><strong>Conclusion: </strong>Early and increased exposure to human milk shortly after birth does not appear to increase the richness and diversity of the gut microbiome by postnatal day 14 in very preterm infants.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT04337710 IMPACT: In very preterm infants, early and increased exposure to human milk and its bioactive components did not alter gut microbiome richness or diversity by postnatal day 14. Randomisation strengthens microbiome analyses by limiting confounding in human milk feeding trials.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207388","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":"Brain sparing and the blood brain barrier-bridging the preclinical to clinical gap.","authors":"Tegan A White, Suzanne L Miller","doi":"10.1038/s41390-025-04479-y","DOIUrl":"https://doi.org/10.1038/s41390-025-04479-y","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213342","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":"Early postnatal echocardiographic characteristics impact survival and extracorporeal life support in congenital diaphragmatic hernia.","authors":"Caroline Y Noh, Enrico Danzer, Shazia Bhombal, Valerie Y Chock, Neil Patel, Alex Dahlen, Matthew T Harting, Kevin P Lally, Ashley H Ebanks, Krisa P Van Meurs","doi":"10.1038/s41390-025-04443-w","DOIUrl":"https://doi.org/10.1038/s41390-025-04443-w","url":null,"abstract":"<p><strong>Background: </strong>Early echocardiographic characteristics (EC) of congenital diaphragmatic hernia (CDH) neonates and their associations with outcomes, especially differences by laterality and size, are unknown.</p><p><strong>Methods: </strong>Congenital Diaphragmatic Hernia Study Group data between 2015 and 2020 were used. Early postnatal EC, including atrial and ductal shunt direction, pulmonary hypertension (PH) severity, and ventricular size and function, were assessed based on defect laterality and size. Outcomes included mortality and extracoporeal life support (ECLS) use.</p><p><strong>Results: </strong>The study population included 1777 infants. Severe PH, right-to-left shunt, left ventricular (LV) hypoplasia, right ventricular dilation, and ventricular dysfunction were more prevalent in larger defects. Independent of defect size, neonates with R-CDH had more severe PH, more bidirectional and right-to-left atrial shunt, and more biventricular (BV) dysfunction. In contrast, L-CDH neonates had more LV hypoplasia and left-to-right atrial shunt. After adjusting for defect side, larger defects were associated with LV hypoplasia and right-to-left and bidirectional atrial shunt. In multivariate analysis, right-to-left atrial shunt and BV dysfunction were associated with increased mortality, whereas bidirectional atrial shunt and BV dysfunction were associated with ECLS use.</p><p><strong>Conclusions: </strong>CDH neonates are at increased risk for early cardiac dysfunction. EC differ by laterality and size. Management of cardiac dysfunction in CDH may improve outcomes.</p><p><strong>Impact: </strong>Cardiac dysfunction has emerged as a factor contributing to adverse outcomes in congenital diaphragmatic hernia (CDH). However, there are limited data on the impact of defect size, laterality, and severity of postnatal cardiac dysfunction on outcomes. Echocardiographic characteristics in the first two days of life differ by defect laterality and size. Right-to-left atrial shunt and biventricular dysfunction are associated with increased mortality. Bidirectional atrial shunt and biventricular dysfunction were associated with extracorporeal life support use. Our results support the need for standardized cardiac function assessment in critically ill neonates with CDH. Future strategies to identify and manage these diverse hemodynamic profiles are needed to improve outcomes.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207378","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 morbidity in early-onset fetal growth restriction with and without anticoagulant therapy.","authors":"Alba González, Anna Peguero, Eva Meler, Marta Camprubi, Carlota Rovira, Maria Dolores Gomez-Roig, Daniel Oros, Patricia Ibáñez, Jon Schoorlemmer, Narcís Masoller, Judit Hidalgo, Dolores Tàssies, Francesc Figueras, Edurne Mazarico","doi":"10.1038/s41390-025-04347-9","DOIUrl":"https://doi.org/10.1038/s41390-025-04347-9","url":null,"abstract":"<p><strong>Background: </strong>The study aims to evaluate the effectiveness of low molecular weight heparin (LMWH) in reducing neonatal morbidity in pregnancies with early-onset fetal growth restriction (FGR).</p><p><strong>Methods: </strong>A phase III, multicenter, triple-blind, parallel-arm randomized clinical trial conducted in two university hospitals in Spain. Singleton pregnancies with early-onset placental FGR (20 + 0-31 + 6 weeks at diagnosis) were randomized to receive bemiparin (3500 IU/0.2 mL/day) or placebo from diagnosis to delivery. The primary neonatal outcome was morbidity up to hospital discharge, assessed using the Morbidity Assessment Index for Newborns (MAIN) score. Analyses followed an intention-to-treat approach.</p><p><strong>Results: </strong>Fifty patients were randomized (25 per arm), with 49 included in the final analysis (23 LMWH, 26 placebo). Median gestational ages at inclusion were 28.7 weeks (LMWH) and 28.4 weeks (placebo). No significant differences were observed in MAIN scores between groups (171.5 vs. 290; p = 0.887; adjusted median difference 139.1 [95% CI -88.4 to 319.8]). NICU stay lengths were also similar (9 vs. 6.5 days; p = 0.738; adjusted median difference 1.08 [95% CI -0.74 to 13.4]).</p><p><strong>Conclusion: </strong>Prophylactic LMWH started at diagnosis of early-onset FGR does not decrease neonatal morbidity or NICU stay duration.</p><p><strong>Impact: </strong>Prophylactic LMWH started at the diagnosis of early-onset FGR does not decrease neonatal morbidity or NICU stay duration. Its design is a randomized, triple-blind clinical trial, which provides high-quality evidence. LMWH is often prescribed during pregnancy for various indications, and in the absence of effective alternatives, it is increasingly used empirically in such cases. Our findings do not support its use for reducing perinatal morbidity or NICU admission duration.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207353","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":"Re-discovering white cell parameters in the diagnosis of sepsis and necrotising enterocolitis.","authors":"Eleanor J Molloy, Dearbhla Byrne, Eoghan Dunlea, Melanie Cotter","doi":"10.1038/s41390-025-04480-5","DOIUrl":"https://doi.org/10.1038/s41390-025-04480-5","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207332","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}