Pediatric Research最新文献

Backgrounds: This research aims to characterize the metabolic profiles of prepubertal patients with TS to elucidate the potential impact of X chromosome haploinsufficiency on glycolipid metabolism.

Methods: Fouty-nine prepuberty TS and 50 age-, sex- and BMI standard deviations scores (SDS)-matched healthy children (HC) were enrolled. Untargeted ultra-performance liquid chromatography-coupled mass spectroscopy was performed in all participants. Differentially expressed metabolites (DEMs) were identified and annotated using the KEGG and HMDB databases. Correlation analyses were conducted to explore associations between DEMs and relevant clinical parameters. Logistic regression models were performed to evaluate the potential impact of the interaction between X-chromosome haploinsufficiency and metabolite abnormalities on metabolic status.

Results: Metabolomics analyses indicated separation between TS and HC groups with 70 DEMs enriched in caffeine metabolism, purine metabolism, and insulin resistance pathways. Among TS, 34 DEMs were found to be correlated with height, weight, glucose and lipid metabolism, and sex hormone levels. Three DEMs-sodium cholate, N-arachidonoyl-L-serine, and N1-pyrazin-2-yl-4-chlorobenzamide--were identified to interact with X chromosome haploinsufficiency in influencing metabolic status.

Conclusions: Prepubertal children with TS exhibit distinct metabolic profiles, with DEMs enriched in caffeine metabolism, purine metabolism, and insulin resistance pathways. These metabolites show correlations with clinical parameters and demonstrate interactions with X chromosome haploinsufficiency affecting metabolic health.

Impact: This study described the distinctive metabolic profiles of TS children for the first time. The impact of X chromosome haploinsufficiency on glycolipid metabolism was elucidated through a study of prepubertal TS children. Three novel metabolites were identified with significant interaction effects with X chromosome haploinsufficiency on glycolipid metabolic status.

Background: Therapeutic benefits of intravenous immunoglobulin (IVIG) and steroids remain inconclusive in optimizing treatment strategies for acute myocarditis.

Methods: PubMed, EMBASE, Cochrane databases, and Web of Science were searched for studies evaluating the effectiveness of adjunctive IVIG, steroids, or both with standard heart failure treatment in pediatric acute myocarditis. A random-effects network meta-analysis was conducted using frequentist and Bayesian approaches. Effect sizes were calculated as risk ratio (RR) and mean difference (MD). P-scores provided a ranking of treatments.

Results: Thirteen studies comprising 2850 participants were involved. Compared with standard treatment, IVIG reduced in-hospital mortality (RR, 0.52; 95% CI, 0.35-0.76), long-term mortality (RR, 0.5; 95% CI, 0.27-0.98), overall mortality (RR, 0.52; 95% CI, 0.34-0.76), and better composite outcome (RR, 0.61; 95% CI, 0.43-0.88). IVIG was optimal for reducing in-hospital and overall mortality and improving the composite outcome (P-scores = 0.993, 0.999, 0.986). Steroids or their combination with IVIG showed no significant benefit. IVIG improved cardiac function by increasing left ventricular ejection fraction (MD, 6.00%; 95% CI, 0.94-11.06) and reducing left ventricular end-diastolic diameter (MD, -3.77; 95% CI, -7.02 to -0.52).

Conclusions: Integrating IVIG into standard treatment may significantly enhance outcomes in children with complicated acute myocarditis.

Impact: This systematic review and network meta-analysis addresses the gap between clinical trial efficacy and real-world effectiveness in pediatric clinical practice. This study suggests that adding IVIG to standard heart failure therapy may improve survival and cardiac function in children with acute complicated myocarditis. The routine use of steroids requires the cautious clinical application. High-quality randomized controlled trials are needed to inform guidelines and optimize therapy.

Background: Executive functioning (EF) deficits are frequently observed in preterms. EF development is linked to the prefrontal cortex and sleep-regulating homeostatic processes. As sleep is an essential driver of early brain maturation, curtailment of sleep in the NICU may be unfavorable. This study examined whether neonatal sleep behavior influences EF at 2 years corrected age in preterm children.

Methods: 76 preterm infants ( < 34 weeks gestation and/or 1500 g) underwent overnight polysomnography before discharge. Sleep stages-Total Sleep Time, Active Sleep (AS), Quiet Sleep (QS) and Transitional Sleep-were quantified using an automated sleep algorithm. EF was assessed at 2 years corrected age, focusing on spatial working memory, cognitive flexibility, and inhibitory control. General linear models were used, adjusting for confounders.

Results: More Total Sleep Time was significantly associated with higher overall EF scores, and the subtest for spatial working memory. AS and QS durations were influenced by postmenstrual age. Longer AS bouts were linked to increased Total Sleep Time. However, individual AS or QS percentages were not directly associated with EF. Higher levels of Transitional Sleep were related to lower EF performance.

Conclusions: Neonatal sleep duration is positively associated with better EF outcomes at 2 years. Protecting sleep in the NICU may support early brain development and executive functioning.

Impact: This study links objective neonatal sleep measurements-using polysomnography and automated sleep staging-with later executive functioning development in preterm children. Neonatal sleep duration, particularly Total Sleep Time, is positively associated with executive functioning at 2 years in children born preterm. This study highlights neonatal sleep as a potential early marker of altered brain development. The findings support the importance of protecting and improving sleep in the NICU as a possible modifiable factor that could enhance early brain maturation and neurodevelopment.

Background: The severe, degenerative muscle condition known as Duchenne Muscular Dystrophy (DMD) typically manifests in early childhood.

Objective: This study aims to investigate how DMD cases express the genes for Ewing's Tumor-associated Antigen 1 (ETAA1), Topoisomerase IIβ-binding protein 1 (TOPBP1), and ATR (Ataxia Telangiectasia and Rad3-related).

Subjects and methods: A total of 50 ambulatory male patients with DMD attending pediatric neurology clinic at Menoufia University Hospital were included and compared to 25 healthy control males matched for age. General clinical information, neurological information, and laboratory tests were performed. This included measuring serum levels of creatine phosphokinase CPK, human creatine kinase, muscle (CK-mm), human lactate dehydrogenase (LDH), total antioxidant status (TAS), total oxidant status (TOS), and quantitative expression of the genes ETAA1, TOPBP1, and ATR.

Results: In contrast to those in good health, the expression levels of the ETAA1, TOPBP1, and ATR genes were significantly greater in DMD cases. Additionally blood levels of CPK, CK-mm, LDH, and TOS were significantly higher in DMD than those of healthy individuals.

Conclusion: The gene expression of ETAA1, TOPBP1, and ATR is substantially elevated in cases with severe DMD, making them potentially significant indicators of the severity of DMD cases.

Impact: This study evaluates the expression of DNA damage response genes-ETAA1, TOPBP1, and ATR-in patients with Duchenne Muscular Dystrophy (DMD). The results demonstrate that DMD patients have much greater gene expression levels and oxidative stress indicators than healthy controls. These genes show a favorable correlation with clinical severity indicators such as CKMM, CPK, and LDH. Combining the three markers improves diagnostic sensitivity and specificity, indicating their potential as a multi-gene biomarker panel. The findings shed fresh light on DMD etiology by correlating genomic instability to disease progression and identifying possible molecular targets for early detection and future treatment approaches.

Background: CFTR modulators such as lumacaftor/ivacaftor (LUM/IVA) may reshape microbiota-mycobiota composition in the lungs and gut. While the gut-lung axis is established in other settings, little is known about its role following modulator therapy, particularly in the 2-11 age group.

Methods: In a prospective national multicentre study, 116 children with cystic fibrosis (2-11 years) starting LUM/IVA were followed for 12 months. Stool and sputum were collected at baseline, 3, 6 and 12 months. Bacterial and fungal communities were profiled by 16S rRNA and ITS2 sequencing; diversity, dysbiosis indices, faecal and sputum calprotectin, and gut-lung microbial networks were analysed.

Results: LUM/IVA was associated with increased bacterial diversity and compositional shifts in gut and lung microbiota, alongside a significant reduction in faecal calprotectin. Airway mycobiota diversity remained stable. Two lung microbiome response profiles emerged: "responders" (greater bacterial diversity gain) and "non-responders" (minimal change). Baseline gut and lung composition predicted these profiles with 81% accuracy in a random-forest model. Inter-organ microbial interactions peaked at 3 months after initiation and then diverged between profiles, indicating distinct gut-lung axis remodelling.

Conclusion: LUM/IVA influences gut-lung microbiota-mycobiota dynamics, with heterogeneous responses between paediatric patients. Identifying factors predictive of response is a key future challenge.

Impact: In 116 children aged 2-11, lumacaftor/ivacaftor reshaped gut and lung microbiota and reduced fecal calprotectin over 12 months. First pediatric multicenter study integrating bacterial and fungal profiling of stool and sputum with gut-lung network analyses; identifies two distinct lung microbiome response profiles. Baseline gut and lung composition predicted the response profile with approximately 81% accuracy. Highlights a 3-month interaction peak and baseline profiling as practical markers to guide monitoring and microbiome-informed precision care.

Background: Cardiorespiratory coupling (cardiovascular-respiratory interactions) is a marker of autonomic nervous system function and maturation. We hypothesize that differences in autonomic maturation are associated with disparate outcomes of premature infants.

Methods: We collected continuous bedside cardiorespiratory data from birth to 40 weeks post-menstrual age (PMA) for 191 preterm infants born between 23-0/7 weeks to 28-6/7 weeks of gestation. Using the respiratory and ECG wave forms, we calculated cardiorespiratory phase synchronization (CRPS) as a measure of cardiorespiratory coupling. Using linear mixed effects modeling, we studied the trajectory of CRPS as a function of PMA and chronological age (CA) and any difference between groups separated by discharge status, respiratory outcome and neurological outcomes at the 40th week PMA, and different gestational ages.

Results: CRPS showed a decline reaching a nadir at approximately 3 weeks of age followed by a gradual increase toward term. The infants born at later GA showed higher values and steeper increases than infants of lower GA. Contrary to our hypothesis, the trajectory of the increase was similar regardless of outcome assessed.

Conclusion: Autonomic maturation following preterm birth shows a fixed predictable pattern that appears to be independent of respiratory or neurologic outcomes or clinicians' assessment of readiness for discharge.

Impact: Cardiorespiratory phase synchronization (CRPS) trajectories, a marker of autonomic nervous system functio is provided for 175 extremely preterm infants across post-menstrual age (PMA) and chronological age (CA). CRPS initially declines but subsequently increases with advancing PMA and CA, irrespective of discharge status and respiratory and neurological outcomes at 40 weeks PMA. At all CAs after the initial decrease, CRPS was higher for infants born at 27-28 weeks compared to those born earlier.

Background: A previous study reported that among patients with complete Kawasaki Disease (KD), those exhibiting all six principal clinical features were more likely to develop coronary artery (CA) sequelae than those exhibiting only five features. We aimed to determine which specific features are associated with CA sequelae.

Methods: This retrospective cohort study analyzed 14,732 patients diagnosed with complete KD across Japan from January 2019 to March 2020. Separate multivariable conditional logistic regression analyses were performed to evaluate relative risk for CA sequelae in patients with all six principal clinical features, compared individually to those lacking each specific feature.

Results: 7234 (49.1%) exhibited all six principal clinical features, while 7498 (50.9%) presented with five features. CA sequelae occurred in 2.1% of those with six features versus 1.7% with five. Multivariable conditional logistic regression analysis determined that patients with conjunctival injection were significantly more likely to develop CA sequelae compared with those lacking it (adjusted odds ratio [95% confidence interval], 3.6 [1.3-10.1]).

Conclusions: Among patients with complete KD, the absence of conjunctival injection-a relatively rare presentation-was associated with a lower cumulative incidence of CA sequelae. This finding may help identify distinct low-risk phenotypes of KD and support risk stratification.

Impact: This study emphasizes the importance of feature-specific risk for coronary artery (CA) sequelae among patients with complete Kawasaki Disease (KD). We found that among patients with complete KD, those with conjunctival injection were more likely to develop CA sequelae than were those lacking it. The absence of conjunctival injection-a relatively rare presentation in KD-is associated with a markedly lower cumulative incidence of CA sequelae. This finding may help identify a distinct low-risk phenotype of KD and aid risk stratification.