Pediatric Research最新文献

Background: Moyamoya arteriopathy confers a high stroke risk. We hypothesized that elevated cerebral blood flow velocities (CBFV), as measured by transcranial Doppler (TCD) ultrasound, are associated with future ischemic events in individuals with moyamoya.

Methods: In this prospective observational study, participants ≤ 26-years-old with moyamoya or moyamoya-like arteriopathy who had not undergone surgical revascularization underwent TCD. Receiver operating characteristic curve analysis was performed using ischemic event (clinical stroke, silent cerebral infarct, or transient ischemic attack) following TCD acquisition as the dependent variable and middle cerebral artery (MCA) CBFV as the independent variable. Optimal cutoff velocity was determined using the Youden index.

Results: Nineteen participants with moyamoya, median age 7.4 years, were enrolled. Over median follow-up of 2.4 years, four participants (21%) experienced a total of six ischemic events and seven participants (37%) underwent surgical revascularization. Median MCA velocity at enrollment was higher in participants with subsequent side-congruent ischemic events (179 cm/s vs 127 cm/s, p = 0.021). MCA velocity had excellent discernment of risk for future side-congruent strokes (AUC 0.819, 95% CI, 0.60-1.0). The optimal cutoff velocity was 164 cm/s (sensitivity 0.80, specificity 0.87).

Conclusions: TCD may have a role in stroke risk stratification and surgical decision-making in moyamoya arteriopathy.

Impact: Middle cerebral artery blood flow velocities, as measured by transcranial Doppler (TCD) ultrasound, are high in patients with moyamoya. Middle cerebral artery velocity has excellent discernment of risk for future side-congruent strokes. Optimal cutoff velocity of the receiver operating characteristic curve analysis was 164 cm/s, which yielded a sensitivity of 0.80 and specificity of 0.87. If validated in future studies, TCD parameters may help to determine optimal imaging frequency, and incorporation of these parameters into precision-medicine risk stratification models may improve surgical decision-making.

Perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT) cause significant neurological morbidity, including cerebral palsy, in preterm infants. Compared to term infants, the epidemiology, risk factors, and outcomes of PAIS and CSVT in preterm infants are less well understood. This systematic review aimed to summarize the literature on incidence, risk factors, clinical presentation, neuroimaging, and neurodevelopmental outcomes of PAIS and CSVT in infants born before 37 weeks' gestation. A comprehensive search of PubMed, Embase, and Web of Science for studies from 2004 to 2025 identified 14 eligible studies including 132 infants with PAIS and 57 with CSVT. Incidence rates were higher in infants of lower gestational age. Identified PAIS risk factors included twin-to-twin transfusion syndrome, fetal heart rate abnormalities, and hypoglycemia. Perforator artery strokes were most common, while CSVT frequently involved the transverse sinus. Many risk factors overlapped with term infants but preterm infants showed more prematurity-related complications, longer ventilation, and postoperative states. Neurodevelopmental outcomes were poor, with high rates of impairment and mortality, especially in CSVT. The review highlights urgent needs for larger, controlled studies to improve prevention, early diagnosis, and management in this vulnerable population. IMPACT: This review systematically summarizes incidence, risk factors, neuroimaging patterns, treatment, and outcomes of perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT) specifically in preterm infants-a group often excluded from previous studies. The findings reveal that preterm infants with PAIS and CSVT have unique and overlapping risk factors (such as twin-to-twin transfusion syndrome and hypoglycemia), often present asymptomatically, and are at high risk for poor neurodevelopmental outcomes and mortality. The review highlights urgent knowledge gaps, especially regarding the safety and effectiveness of anticoagulation therapy in preterm CSVT, and stresses the need for larger studies and targeted strategies to improve recognition, management, and long-term outcomes for this vulnerable group.

Background: Packed red blood cell transfusion (PRBCT) is a common intervention for neonatal anemia, primarily guided by hemoglobin thresholds. Electrical velocimetry (EV) portable, non-invasive impedance cardiography tool, provides continuous systemic hemodynamics (SH) parameter measurements, offering valuable insights into the physiological effects of transfusions.

Methods: This prospective, observational cohort study, conducted between May 2021 and October 2023, included 30 extremely low gestational age neonates requiring elective PRBCT during their neonatal intensive care unit stay. Using EV, 11 SH parameters were continuously recorded over 31 hours: 4 hours before, 3 hours during, and 24 hours after transfusion. The effect of transfusion on these parameters was assessed using ARIMA, paired t-tests and mixed linear models.

Results: Of the 30 infants, 20 were <26 weeks gestation, and 10 were 26 + 0 to 27 + 6 weeks gestation. Index of cardiac contractility, stroke volume, and cardiac output decreased significantly post-transfusion (p < 0.01). Systemic vascular resistance increased significantly after transfusion compared to before transfusion (p < 0.01).

Conclusion: This pilot study detected significant hemodynamic changes in response to PRBCT, which, while notable, remained within normal physiological range. These findings underscore the need to better understand the physiological impact of PRBCT and the highlight role of non-invasive SH monitoring in optimizing neonatal care.

Impact: This study is the first to apply Electrical Velocimetry (EV) for continuous, high-resolution monitoring of systemic hemodynamic (SH) parameters before, during, and after packed red blood cell transfusion (PRBCT) in extremely low-gestational-age neonates (ELGANs). The findings demonstrate measurable minute-by-minute fluctuations in cardiac contractility, stroke volume, cardiac output and vascular resistance temporally associated with transfusion. These fluctuations occurred even in infants who were hemodynamically stable at baseline, suggesting that EV may detect transfusion-related physiological variability not captured by routine monitoring, without implying a direct causal effect. Advanced monitoring technologies, such as EV, may enable more accurate and individualized neonatal care. To optimize outcomes for this vulnerable population and refine transfusion guidelines, further research including larger prospective studies and randomized controlled trials are needed.

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.