Clinical and Experimental Pediatrics最新文献

Background: Cerebral hypoxia-ischemia impairs brain development in extremely preterm infants and is associated with poor neurological outcomes. Near-infrared spectroscopy (NIRS) is a noninvasive continuous monitoring method for regional cerebral oxygen saturation (rcSO2).

Purpose: This study evaluated the clinical feasibility and neurological impact of a neurocritical care bundle that incorporates prolonged multidisciplinary hemodynamic monitoring and a stepwise management algorithm.

Methods: Preterm infants with a gestational age (GA) ≤28 weeks or birth weight (BW) ≤1,000 g were prospectively enrolled in a bundle group subjected to NIRS for rcSO2, electrical cardiometry for cardiac output, and daily brain and cardiac echography during the first 72 hours of life. Monitoring was repeated weekly in the first month and then monthly until discharge or the term-equivalent age (TEA) was reached. We implemented a stepwise management algorithm for treating cerebral hypoxia. The primary outcome was a composite of mortality and adverse neurological events (structural abnormalities or electroencephalogram-confirmed seizures) before discharge. The secondary outcomes were the physiological pattern of rcSO2 within the initial 72 hours and up to discharge or TEA.

Results: Thirty preterm infants (GA, 27.1±2.0 weeks; BW, 830±225 g) were enrolled in the bundle group. The mean time-averaged rcSO2 (66.8%±10.3%) was not associated with GA or BW. However, postnatal age appeared to influence physiological rcSO2 changes, given that rcSO2 values were higher during the initial 72 hours than at subsequent intervals. Seven infants (23.3%) had poor outcomes and significantly lower time-averaged rcSO2 (51.1% [50.0%-65.2%] vs. 71.8% [67.1%-73.1%], P=0.002). Multivariate regression indicated that a lower rcSO2 was an independent risk factor, and a 65% threshold showed an optimal predictive value for poor outcomes.

Conclusion: The neurocritical care bundle helped identify preterm infants at risk of cerebral hypoxia, and lower rcSO2 was an independent risk factor for composite mortality and adverse neurological outcomes.

Background: The rising prevalence of severe obesity among children and adolescents poses a major public health challenge.

Purpose: In this study, we examined the differences in body composition and physical fitness between obese and severely obese Asian youth and evaluated their responses to a customized lifestyle intervention.

Methods: A total of 136 overweight and obese participants (mean age, 11.5±3.0 years) were enrolled in an individualized lifestyle modification program. The participants were stratified by obesity severity, with severe obesity defined as a body mass index (BMI)-for-age ≥120% of the 95th percentile. Body composition and physical fitness were assessed at baseline and after 3 interventional stages. The results were compared between the severely obese group and nonseverely obese group, and the relationships between the changes were analyzed.

Results: Among the obese participants, 46% met the criteria for severe obesity. At baseline, those with severe obesity demonstrated a lower performance percentile in the 1-minute sit-up test (22.1±25.2 vs. 47.9±28.0, P=0.002) and the standing long jump (8.5±14.6 vs. 26.8±23.2, P= 0.003) than their nonseverely obese peers. Participants in both groups showed significant reductions in body fat percentage and preserved skeletal muscle mass after the intervention. Those in the severely obese group achieved greater reductions in weight, BMI, BMI z score, and fat mass, particularly during the first 2 interventional stages, indicating a stronger response to the program.

Conclusion: The severely obese youth showed poorer baseline physical fitness levels but greater improvements in key obesity-related measures following the lifestyle interventions. These findings highlight the potential benefits of early targeted interventions for this high-risk group.

Background: We aimed to investigate differences in gut microbiota between patients with Hirschsprung disease (HSCR) and healthy children; assess longitudinal changes in the microbiota of patients with HSCR from diagnosis through postoperative period; and identify microbial markers predictive of postoperative HSCR-associated enterocolitis (HAEC).

Purpose: To investigate alterations in the gut microbiota of patients with HSCR by assessing longitudinal microbiome changes after surgery and identifying microbial signatures predictive of postoperative HAEC.

Methods: A case-control study of 20 patients with HSCR and 20 controls was conducted at Maharaj Nakorn Chiang Mai Hospital. Fecal specimens were collected from patients with HSCR at initial diagnosis and from age-matched controls. Additional samples were obtained from patients intraoperatively and at 1 and 6 months postoperatively. A microbial analysis was performed using 16S rRNA gene sequencing (V3-V4 hypervariable regions).

Results: Compared to controls, patients with HSCR exhibited gut dysbiosis characterized by reduced microbial diversity and altered community composition as determined by Analysis of Compositions of Microbiomes with Bias Correction. Increased relative abundances of Robinsoniella, Fusobacterium, Cutibacterium, Citrobacter, and Eubacterium fissicatena were observed in patients with HSCR, whereas NK4A214, Lachnospiraceae XPB1014 groups, Acinetobacter and Acetitomaculum were decreased (q< 0.05). Alpha diversity in patients with HSCR was significantly increased at 6 months postoperatively versus at theinitial diagnosis (P<0.05). Longitudinal changes in Eubacterium and Eubacteriales suggest their potential use as markers of treatment efficacy. In patients who developed postoperative HAEC, Olsenella was enriched in the proximal intestine, whereas Holdemanella, Corynebacterium, Collinsella, and CAG-352 were elevated in the distal intestine (q<0.05).

Conclusion: Patients with HSCR exhibited distinct alterations in the gut microbiota, with significant shifts observed between the pretreatment period and 6 months postoperatively. Specific bacterial taxa were identified as potential markers for HAEC development. Future microbiome- targeted.

Most children recover after an initial acute pancreatitis (AP) episode; however, some progress to recurrent AP (RAP) or chronic pancreatitis (CP). We aimed to quantify progression rates and identify the risk factors associated with these transitions. PubMed/MEDLINE, Embase, and Cochrane databases were searched on December 21, 2024, for pediatric studies reporting progression to RAP or CP (PROSPERO number: CRD420251086520). All observational studies were included, while case reports and case series were excluded. To evaluate the differences in RAP rates, we conducted subgroup analyses of etiology and severity. We also assessed clinical, structural, and genetic risk factors for disease progression. A random-effects model was used to pool proportions and odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic. A total of 68 studies met the inclusion criteria. After the first AP attack, RAP developed in 18% (95% CI, 16%-22%; I²=76%; k=39 studies) and CP developed in 10% (95% CI, 6%-16%; I²=67%; k=5 studies) of patients. Among children with RAP, 35% (95% CI, 24%-49%; I²=78%; k=7 studies) progressed to CP. The RAP rates varied according to etiology and severity: hypertriglyceridemia, 33%; idiopathic, 28%; biliary, 19%; traumatic, 16%; drug-induced, 14%; virus-induced, 3%; severe, 39%; moderate, 24%; and mild, 21%. Structural abnormalities were associated with a higher risk of RAP (OR, 3.15; 95% CI, 1.51-6.56; I²=0%; k=5 studies). Pancreas divisum (OR, 2.64; 95% CI, 1.51-4.63; I²=17%; k=7 studies) and PRSS1 mutation (OR, 4.56; 95% CI, 3.06-6.80; I²=0%; k=7 studies) were associated with CP. Approximately 1 in 5 pediatric AP episodes recurred, and over one-third of the RAP cases progressed to CP. The risk of RAP is influenced by the underlying etiology and severity of the initial episode, whereas structural and genetic factors are associated with later progression.

Background: Iron overload is a hallmark complication in patients with transfusion-dependent β-thalassemia major, primarily resulting from ineffective erythropoiesis, repeated blood transfusions, and increased gastrointestinal iron absorption. This iron accumulation, reflected in elevated serum ferritin levels, has been implicated in immune dysregulation. Natural killer (NK) cells are a pivotal component of the innate immune system, known for their cytotoxic activity and cytokine secretion, particularly interferon-gamma (IFN-γ). Disruption in NK cell subsets may compromise immune surveillance and defense against infections in these patients.

Purpose: To evaluate the distribution and function of NK cell subpopulations in pediatric patients with transfusion-dependent β-thalassemia major and explore their association with iron overload and immune dysfunction.

Methods: Seventy-eight children were enrolled and divided into 2 groups: 43 pediatric patients with transfusion-dependent β-thalassemia major and 35 apparently healthy controls. NK cells and their subsets (CD56bright, CD56dim, CD56neg) were quantified using multicolor flow cytometry. Serum IFN-γ levels were measured to assess NK cell cytokine activity. Ferritin levels were used as a marker of iron overload.

Results: Patients showed a significant reduction in CD56bright and CD56dim NK cells compared to controls (P<0.001), indicating impaired NK-mediated immunity. Conversely, the CD56neg subset, associated with dysfunctional or altered NK cell phenotypes, was significantly elevated in patients (P<0.002). A strong negative correlation was observed between serum ferritin levels and CD56dim NK cells (P=0.003), suggesting that iron overload suppresses cytotoxic NK activity. Moreover, IFN-γ levels inversely correlated with CD56bright (P<0.001) and CD56dim (P=0.019) cells, but positively correlated with CD56neg cells, implicating this altered subset as a potential compensatory source of cytokine production.

Conclusion: Hyperferritinemia in pediatric β-thalassemia major is linked to a dysregulated NK cell profile, marked by suppression of functional CD56bright and CD56dim subsets and expansion of the atypical CD56neg subset. These alterations may compromise innate immunity and contribute to increased infection risk. Our findings highlight the immunomodulatory impact of iron overload and underscore the clinical importance of monitoring NK cell dynamics in thalassemia management.

Background: Influenza and coronavirus disease 2019 (COVID-19) are major causes of pediatric respiratory illness with overlapping clinical features but potentially differing impacts on healthcare utilization and outcomes.

Purpose: To compare the clinical presentations, healthcare resource utilization, and outcomes of children hospitalized with influenza and COVID-19 and address the gaps in pediatric data from Southeast Asia.

Methods: This retrospective observational study included children aged ≤12 years hospitalized with laboratory-confirmed influenza or COVID-19 at a tertiary hospital in Malaysia between May 1, 2022, and May 1, 2023. Patients with viral or bacterial coinfections were excluded. Influenza A and B cases were collectively analyzed. The patients' demographic data, clinical presentation, resource utilization, and outcomes were also evaluated. Propensity score matching (PSM) was performed to balance the cohorts for age, sex, ethnicity, and comorbidities. Outcomes were compared using standardized mean differences (SMDs).

Results: A total of 299 patients were included (influenza, n=177; COVID-19, n=122). Patients with influenza were older (median, 3.6 years vs. 1.8 years; P<0.001) and more likely to have fever, cough, and rhinorrhea. COVID-19 patients presented earlier in the illness (median, 2 days vs. 4 days; P<0.001). After PSM, 102 patients were included in each group. Patients with influenza required greater healthcare resource use, including intravenous fluids (60.8% vs. 43.1%; SMD=0.36), empirical antibiotics (40.2% vs. 12.7%; SMD=0.66), respiratory support (40.2% vs. 26.5%, SMD=0.29), pediatric intensive care unit admission (10.8% vs. 2.9%; SMD=0.32), and longer duration of oxygen therapy (SMD=0.93).

Conclusion: Children hospitalized for influenza demonstrated higher clinical severity and greater healthcare resource utilization than those hospitalized for COVID-19. These findings highlight the burden of influenza and inform hospital resource planning during periods of viral circulation.

Background: Allopurinol is widely used to prevent hyperuricemia in patients with tumor lysis syndrome. However, its use can trigger severe cutaneous adverse reactions (SCARs) with a mortality rate of approximately 11.39%. The human leukocyte antigen (HLA)-B*58:01 genotype is a major risk factor for SCARs. Although most studies to date have examined HLA-B*58:01 in Thai adults, data on pediatric patients are limited.

Purpose: Here we aimed to evaluate the association between HLA-B*58:01 and skin reactions in children with hematological or oncological diagnoses receiving allopurinol and determine its prevalence in this population.

Methods: Pediatric patients (age≤18 years) with hematological or oncological diseases who received allopurinol were enrolled in this cross-sectional study of previously exposed and newly prescribed cases. HLA-B*58:01 genotyping was performed to assess its association with skin reactions.

Results: A total of 108 patients (mean age, 9.3 years) were included. Most patients (n=93, 86.1%) received allopurinol as prophylaxis for tumor lysis syndrome. Of them, 75 (69.4%) received allopurinol concomitantly with chemotherapy for malignancies, whereas the remaining patients received allopurinol during conditioning for hematopoietic stem cell transplantation. The prevalence of HLA-B*58:01 positivity was 17.6% (n=19 of 108 patients). The median exposure duration was 5 days (range, 1-19 days). No HLA-B*58:01-positive patients experienced a skin reaction. However, one patient who tested negative for HLA-B*58:01 developed a maculopapular rash on day 2 of the allopurinol therapy and required intravenous antihistamines.

Conclusion: Short-duration allopurinol exposure likely mitigates the risk of SCARs regardless of HLA-B*58:01 status. Routine HLA-B*58:01 testing may not be warranted in pediatric patients receiving brief allopurinol courses. However, larger studies are required to confirm these findings.

Malnutrition is common among hospitalized children, especially those who are critically ill. Routine measures, such as anthropometric measurements, body composition, and nutritional assessment, comprise the basics of monitoring. This review discusses the adequacy of nutritional screening tools (NSTs) such as the SGNA (Subjective Global Nutritional Assessment), PYMS (Pediatric Yorkhill Malnutrition Score), STAMP (Screening Tool for the Assessment of Malnutrition in Paediatrics), and STRONGkids (Screening Tool for Risk of Nutritional Status and Growth). This review included recently published reports supporting the validation and implementation of NSTs in pediatric populations. A child's nutritional status during hospitalization is of great importance for their recovery, while the implementation of screening tools enhances their clinical outcomes. Current tools have varying sensitivities and specificities, and no single tool can be recommended for all groups of hospitalized children. A combination of tools or adaptation of existing tools with validation in different contexts might be ideal. Further studies are required to develop more robust and comprehensive screening tools.

Background: The effects of genetic background on the biological effects of vitamin D on coronavirus disease 2019 (COVID-19) in children remain unclear.

Purpose: This study aimed to explore the association between vitamin D-related genetic background and 25-hydroxyvitamin D status and COVID-19 occurrence and severity in children. Here we explored key genetic variants within the vitamin D pathway in pediatric COVID-19 patients in relation to circulating vitamin D binding protein (VDBP).

Methods: Sixty children aged 0-14 years with severe acute respiratory syndrome coronavirus 2 infection and 60 matched controls were genotyped for the vitamin D receptor (VDR) gene (FokI, BsmI, TaqI, ApaI), Gc gene of VDBP (rs7041, rs4588), and CYP27B1 promoter (rs10877012) single nucleotide polymorphisms by polymerase chain reaction and restriction fragment length polymorphism assay.

Results: The FokI FF genotype was more frequently identified among COVID-19 patients than controls, among whom the TaqI TT genotype was prevalent (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.08-4.73; P=0.02; and OR, 0.29; 95% CI, 0.13-0.63; P=0.001, respectively). The Gc1F haplotype was significantly more represented in controls versus COVID-19 patients (OR, 0.39; 95% CI, 0.19-0.81; P=0.01). A 2.04-fold increased risk of COVID-19 was observed in the presence of the VDR FokI F allele (OR, 2.04; 95% CI, 1.14-3.64; P=0.01). A multivariate analysis revealed a significant association between the FokI FF genotype and disease severity (OR, 0.20; 95% CI, 0.04-0.83; P=0.02). Serum VDBP levels were similar between groups.

Conclusion: The FF genotype of the VDR FokI polymorphism may be associated with COVID-19 and have a significant clinical impact on disease severity in children.

Background: Open cardiac surgery involving cardiopulmonary bypass (CPB) triggers a systemic inflammatory response that significantly affects clinical outcomes. However, the dynamics and specific roles of cytokine release after CPB in the pediatric population remain unclear.

Purpose: To evaluate the dynamics of cytokine levels and their association with low cardiac output syndrome (LCOS)-related outcomes.

Methods: A prospective observational cohort study was conducted of 32 children who underwent elective open cardiac surgery with CPB at Songklanagarind Hospital, Thailand. Levels of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α were analyzed preoperatively and immediately (T0), 6, 12, and 24 hours after intensive care unit admission. LCOS-related outcomes were defined with at least two of the following criteria being met within 24 hours postoperative: clinical and laboratory parameters, vasopressor-inotropic score ≥20, ejection fraction <50% on echocardiography; and requirement for a serious postoperative intervention. Statistical analyses utilized linear mixed models and multivariate logistic regression to identify the independent predictors of LCOS.

Results: The mean patient age was 34.8±34.4 months; 56.2 % were male. Roughly one-third (37.5%) had a history of previous cardiac surgery, while one-quarter (28.3%) had a Risk Adjustment for Congenital Heart Surgery score ≥3. LCOS-related outcomes occurred in 37.5% of patients. IL-6, IL-8, and TNF-α levels differed significantly between patients with and without LCOS outcomes. An increase in IL-8 of >56 pg/mL from baseline to T0 showed the strongest association with LCOS (odds ratio, 37.34; 95% confidence interval, 4.53-836.53).

Conclusion: An elevated postoperative IL-8 level is a robust predictor of LCOS-related outcomes in pediatric patients undergoing cardiac surgery. These findings emphasize the importance of monitoring cytokine dynamics to guide interventions and improve patient outcomes.