Frontiers in Pediatrics最新文献

Objective: Over the previous decade, fibroblast growth factor 23 (FGF23) has been identified as a key biomarker in the context of cardiovascular diseases(CVD). The primary goal of this investigation was to determine the association between FGF23 and the susceptibility to CVD among children and adolescents.

Methods: We performed an electronic search of the Cochrane Library, PubMed, Web of Science, and Embase databases, covering the period from their inception until August 4, 2022. The random effects model was applied. Additionally, we conducted stratified analyses and performed a sensitivity analysis as part of our further investigation.

Results: A total of 11 studies involving 1,428 participants, including 366 individuals with cardiovascular disease and 1,062 control subjects, were included in the analysis. Children and adolescents with cardiovascular disease exhibited significantly higher serum FGF-23 levels compared to the control group [standardized mean difference [SMD] = 1.28, 95% confidence interval [CI] 0.53-2.03; I ² = 93.0%], as determined using a random-effects model. In categorical analyses across six studies, the pooled odds ratio did not demonstrate a statistically significant association with disease risk [odds ratio (OR) = 1.64, 95% CI 0.86-3.12; I ² = 100.0%]. Meta-regression analysis, accounting for variables such as type of cardiovascular disease, assay type, chronic kidney disease (CKD) status, and CKD stage, yielded a restricted maximum likelihood (REML) estimate of (τ ² = 0.2321) for the SMD outcome, indicating residual heterogeneity (I ²_res ≈ 70.3%) and an adjusted R² of 83.6%. The joint test for covariates was not statistically significant (Knapp-Hartung corrected Prob > F = 0.3165). For the categorical outcome, the meta-regression analysis produced a boundary estimate (τ ² = 0) with I ²_res = 0% and a non-significant joint test (Prob > F = 0.3479); however, these findings are likely influenced by the limited number of studies and restricted degrees of freedom.

Conclusion: Serum FGF-23 levels are elevated in pediatric populations with cardiovascular disease, but study-specific thresholds have not shown a clear independent association with risk. The variability in findings, reliance on observational study designs, and differences in assay methods contribute to the uncertainty about its prognostic value. Therefore, standardized prospective studies reporting on renal function and mineral metabolism markers are needed.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023480899, PROSPERO CRD42023480899.

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening disease characterized by uncontrolled complement activation and is associated with various genetic factors, including multiple variants at the gene locus encoding the complement component 3 (C3). However, only a few functional amino acid substitutions have been identified in C3. We report a pediatric case of aHUS presenting with refractory hypertension and massive gastrointestinal bleeding. Comprehensive histopathological, immunohistochemical, genetic, and molecular structural analyses were performed. Biopsy specimens were stained for renin and the membrane-attack complex of the complement system (C5b-9). Plasma levels of the Ba fragment of complement factor B were measured to evaluate the alternative pathway activation. Genomic DNA was obtained with consent and analyzed by targeted next-generation sequencing using a custom gene panel, followed by Sanger sequencing for variant confirmation. The possible effects of the identified amino acid substitution on the molecular structure of C3 were analyzed using computer-aided simulation with MODELLER and DoGSiteScorer. As a result, the juxtaglomerular apparatus was hyperplastic and intensely stained for renin. Endothelial cells of renal and intestinal blood vessels were positive for C5b-9. The plasma Ba level was elevated compared to the control level. The ileal and colonic mucosae were denuded and highly edematous, with epithelial cells undergoing regenerative and metaplastic changes in the active phase. Mucosal blood vessels contained intraluminal red cell fragments and neutrophils attached to swollen endothelial cells. However, the colonic mucosa showed near-normal histology after disease convalescence. Genetic analyses identified a single nucleotide C3 variant NM_000064.4(C3):c.4811T>C (p.Met1604Thr), resulting in an M₁₆₀₄T substitution in the functional C345C domain. Molecular structural analyses indicated that this amino acid substitution can cause the formation of a large cavity within the hydrophobic core of the C-terminal domain, possibly destabilizing the spherical structure of C3. Our study highlights that the M₁₆₀₄T substitution in the C3 C345C domain may drive the observed excessive complement activation, C5b-9 deposition on endothelial cells, and severe circulatory disturbances in the intestinal mucosa.

Background: The prognosis for pediatric patients with relapsed or refractory sarcoma remains poor, and standard salvage therapies are lacking. This study evaluated the efficacy and toxicity of the gemcitabine and docetaxel (GEMDOX) combination in this patient population.

Methods: We retrospectively analyzed 36 pediatric patients treated with GEMDOX at our institution between 2015 and 2025. Patients received gemcitabine (1,000 mg/m² on days 1 and 8) and docetaxel (100 mg/m² on day 8) in 21-day cycles.

Results: The median age was 13.5 years, with osteosarcoma being the most common diagnosis (58.3%). GEMDOX was administered predominantly as a third-line regimen (58.3%). The objective response rate (ORR) at the final assessment was 5.8%, and the disease control rate (DCR) was 14.6%. The median progression-free survival (PFS) and overall survival (OS) were 5.72 months (95% CI, 3.95-7.48) and 12.33 months (95% CI, 8.97-15.66), respectively. The most common Grade 3-4 toxicities were neutropenia (22.2%) and febrile neutropenia (19.4%), both of which were manageable with G-CSF support. No treatment-related mortality occurred.

Conclusions: Although the objective response rate was modest in this heavily pretreated cohort, GEMDOX demonstrated a manageable safety profile. It represents a viable palliative option with a manageable toxicity profile for pediatric patients with relapsed/refractory sarcoma when curative options are limited. However, given its intensive nature, optimal efficacy may be better achieved when utilized earlier in the relapse setting rather than as a late-line rescue therapy.

Invasive aspergillosis is a severe opportunistic infection in immunocompromised children, particularly those receiving chemotherapy for hematologic malignancies. We report the case of a 2-year-old girl with acute lymphoblastic leukemia who developed massive hemoptysis during consolidation chemotherapy. Thoracic computed tomography revealed a saccular pseudoaneurysm of the proximal left subclavian artery. Surgical resection and autologous vein graft replacement were performed, and Aspergillus flavus DNA was detected in the resected tissue using Aspergillus-specific polymerase chain reaction. The patient received dual antifungal therapy with liposomal amphotericin B and voriconazole, followed by long-term voriconazole prophylaxis. She made a full recovery. This case highlights the importance of considering angioinvasive aspergillosis in immunocompromised children presenting with hemoptysis and lung lesions. Early recognition and multidisciplinary management are critical to preventing fatal vascular complications.

Introduction: Some individuals with spinal muscular atrophy (SMA) transition from nusinersen to risdiplam during disease-modifying therapy (DMT) due to factors such as treatment convenience, economic considerations, and adverse events (AEs). This study evaluates the safety and effectiveness of switching DMTs by analyzing real-world clinical data from multiple centers in China.

Methods: Patients with 5q-SMA who switched from nusinersen to risdiplam were enrolled from four medical institutions in Jiangsu Province. The reasons for switch, as well as any adverse events experienced, were documented. Assessments of motor function were conducted prior to treatment, following the switch, and at four-month intervals subsequently.

Results: A total of eleven patients were included in this retrospective analysis. RULM scores showed maintains improvement following the switch compared to baseline measurements prior to treatment initiation. No significant adverse events were reported after the switch.

Conclusion: Despite the small sample size and lack of a control group, these findings suggest that switching from nusinersen to risdiplam in real-world clinical settings is safe and allows for continued improvement of motor function in SMA patients.

Introduction: Juvenile idiopathic arthritis (JIA) is the commonest rheumatologic disease in children and frequently affects the knee joint. Synovial inflammation and tenosynovitis are key pathological features, and ultrasound plays an increasingly important role in their assessment. Superb Microvascular Imaging (SMI) is a novel Doppler technique with enhanced sensitivity to low-velocity microvascular flow, but evidence on its repeatability in JIA remains limited. This study aimed to evaluate intra- and inter-observer repeatability of knee SMI in children with JIA.

Methods: In this prospective multicenter study (June 2023-October 2024), 76 children with JIA were examined (Hannover Medical School and St. Josef-Stift Sendenhorst). Each underwent three standardized SMI scans: two by the same and one by a different examiner. Synovial vascularity was graded using the Pediatric OMERACT scoring system. Intra- and inter-observer reliability measures were calculated using intra-class correlation coefficients (ICC). Agreement between longitudinal and transverse suprapatellar planes was assessed using weighted kappa statistics, and correlations with clinical disease activity were analyzed via logistic regression.

Results: Intra-observer reliability was excellent (ICC = 0.972, 95% CI: 0.956-0.982). Inter-observer reliability was strong (ICC = 0.828-0.928), regardless of examiner experience. Agreement between imaging planes was substantial (κ = 0.72, p = 0.32). Synovial vascularity scores correlated significantly with clinical measures of active arthritis (OR = 1.182, p = 0.0004), particularly with swelling (OR = 1.249, p < 0.0001).

Discussion: SMI demonstrates excellent repeatability for assessing synovial vascularity in JIA. Its reliability, examiner independence, and non-invasive nature support its use for routine monitoring and longitudinal disease evaluation in pediatric rheumatology.

Background: Intraventricular Hemorrhage (IVH) is one of the common and serious complications of Very Low Birth Weight Infant (VLBW) that may lead to long-term neurodevelopmental deficits. Although several studies have been conducted to explore its risk factors, the results have been inconsistent. The aim of this study was to identify the major risk factors for intraventricular Hemorrhage in VLBW by systematic evaluation and Meta-analysis of the available evidence.

Methods: PubMed, Web of Science, Embase, Cochrane Library were systematically searched, and observational studies (case-control and cohort studies) were included from the time of library construction to 20 January 2025, and the literature that met the criteria were screened and relevant data were extracted. Meta-analysis was performed using Stata 15.0 software to assess the combined odds ratio (OR) and 95% confidence interval (CI) for each risk factor.

Results: A total of 21 studies included 6 case-control studies, 15 cohort studies, involving a total of 13,800 patients, The results of the meta-analysis showed that hypotension [OR = 3.64, 95%CI (1.87, 7.08)], patent ductus arteriosus (PDA) [OR = 1.86, 95%CI (1.46, 2.36)], vaginal delivery [OR = .10, 95%CI (1.61, 2.72)], neonatal thrombocytopenia[OR = 2.43, 95%CI (1.79, 3.30)], pulmonary hemorrhage [OR = 2.45, 95%CI (1.43, 4.20)], mechanical [OR = 2.09, 95%CI (1.40, 3.10)], sepsis[OR = 2.28, 95%CI (1.77, 2.95)] were a risk factor for the development of IVH in VLBW. While antenatal corticosteroids [OR = 0.68, 95%CI (0.55, 0.84)] was a protective factor for the development of IVH in VLBW.

Conclusion: This study indicates that hypotension, patent ductus arteriosus (PDA), antenatal corticosteroid use, vaginal delivery, neonatal thrombocytopenia, pulmonary hemorrhage, mechanical ventilation, and sepsis constitute the primary risk factors for IVH in VLBW infants. Although these factors exhibit strong clinical associations, current understanding of IVH pathogenesis remains largely dependent on preclinical studies. Integrating clinical and preclinical evidence facilitates a more comprehensive understanding of IVH etiology and informs early intervention strategies.

Systematic review registration: identifier CRD42025633474.

Background: This multicenter study investigated the association between birthweight discordance (BWD) and extrauterine growth restriction (EUGR) in preterm twins, and evaluated the modifying role of small for gestational age (SGA).

Methods: Data from 2,496 infants (1,248 twin pairs) admitted to 22 Chinese NICUs (2018-2020) were analyzed. BWD was calculated as the percentage difference in birthweight between larger and smaller twins, categorized into four groups (≤15%, 15%-20%, 20%-25%, >25%). EUGR was defined as discharge weight below the 10th percentile for corrected gestational age and sex (Fenton's chart). A generalized linear mixed model was employed to analyze the association between BWD and EUGR. Modification analysis was performed to assess the effect of SGA on this association.

Results: BWD of >25% was associated with a significantly increased risk of EUGR compared to BWD ≤15% (adjusted OR = 1.59, 95% CI: 1.05-2.41). Stratified analysis revealed a consistent association in SGA infants (OR = 1.38, 95% CI: 1.30-1.47).

Conclusion: Findings highlight BWD as a critical risk factor for EUGR, particularly in SGA twins. This association suggests that future research should investigate whether tailored monitoring and nutritional interventions in NICUs could help mitigate these growth disparities.

Objective: The current diagnostic and prognostic assessment of congenital diaphragmatic hernia (CDH) in neonates remains challenging. This study aimed to evaluate the utility of neonatal ultrasonography in the diagnosis and prognostic prediction of CDH in infants.

Materials and methods: A retrospective analysis was conducted on clinical data from 152 infants diagnosed with CDH and admitted to the Department of Neonatal Surgery at Children's Hospital between 2017 and 2023. The cohort included 86 (56.6%) males and 66 (43.4%) females. Multivariate logistic regression was employed to identify factors associated with CDH prognosis. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of significant ultrasonographic indicators.

Results: Multivariate logistic regression identified four factors as significant predictors of mortality: diaphragmatic defect length >4 cm [odds ratio [OR] = 2.41, 95% confidence interval [CI]: 1.08-10.58], the presence of hepatic herniation (OR = 2.61, 95% CI: 1.16-5.87), absence of a hernial sac (OR = 4.86, 95% CI: 2.00-11.76), and concomitant lung ultrasound abnormalities (OR = 10.86, 95% CI: 1.28-21.85). The combination of these four parameters demonstrated strong predictive performance for mortality, with an area under the ROC curve of 0.860 (95% CI: 0.786-0.935).

Conclusion: Diaphragmatic defect length, hepatic herniation, hernial sac status, and lung ultrasound findings serve as valuable prognostic indicators in infants with CDH. Integrating these four parameters enhances prognostic accuracy and may support clinical decision-making.