Pediatric Research最新文献

Background: Necrotizing enterocolitis (NEC) is a severe gastrointestinal disorder in preterm infants. The interplay between mitochondrial metabolism and immune inflammation in its development is not fully understood.

Methods: Single-cell data were analyzed using dimensionality reduction, clustering, and the high-dimensional weighted gene co-expression network analysis (hdWGCNA) algorithm to identify key gene modules in monocytes. GSE46619 was integrated with the MitoCarta3.0 to identify mitochondria-associated differentially expressed genes (MitoDEGs). Acyl-CoA synthetase long-chain family member 1 (ACSL1) was selected as a candidate. Immune infiltration was evaluated via the CIBERSORT algorithm, and a competing endogenous RNA (ceRNA) regulatory network was constructed using Cytoscape. The expression and function of ACSL1 were validated both in vivo and in vitro, using immunohistochemistry (IHC), qRT-PCR, western blot, and siRNA knockdown.

Results: A key monocyte subset was identified in NEC. Integrated analysis revealed three MitoDEGs (ACSL1, SOD2, SLC25A37) were linked to NEC, with ACSL1 showing the most significant upregulation. ACSL1 expression correlated strongly with immune cell infiltration and was confirmed to be elevated in vivo and in vitro models. Knocking down ACSL1 suppressed lipopolysaccharide (LPS)-induced inflammatory factor expression and ROS production.

Conclusion: ACSL1 plays a critical role in the pathogenesis of NEC, suggesting its potential as a novel biomarker.

Impact: Our study reveals massive monocyte infiltration and identifies the mitochondria-related gene ACSL1 as highly expressed and functionally significant in NEC. This is the first integrated analysis (single-cell, hdWGCNA, MitoCarta3.0) pinpointing ACSL1 as a novel immunometabolic hub specific to NEC pathophysiology. ACSL1 provides a crucial mechanistic link between mitochondrial function and NEC development. It significantly correlates with key immune cells (neutrophils/mast cells/macrophages/T cells), highlighting its role in NEC immune dysregulation. These findings reveal a critical role of ACSL1 in NEC pathogenesis, highlighting its potential as a novel biomarker.

Background: The NICHD Neonatal Research Network MILK Trial randomized infants born preterm to receive donor milk or preterm formula. We hypothesized that there would be no growth differences at follow-up by study diet.

Methods: We conducted a secondary analysis of the double-blind trial of infants <29 weeks' gestation or <1000 g at birth at 15 US centers (September 2012-March 2019). Infants were randomized to receive donor milk or preterm formula. The primary outcome was body mass index (BMI) Z-score at 22-26 months corrected age.

Results: Among 483 trial participants, 376 were seen at follow-up (181 donor milk, 195 formula). At 22-26 month follow-up, anthropometrics were similar for the two groups, including BMI Z-score (donor milk 0.21 ± 1.13, formula 0.23 ± 1.28, p = 0.67). There was a greater increase in weight Z-score between discharge and follow-up for children randomized to donor milk (donor milk 1.04 ± 1.28, formula 0.73 ± 1.30, p = 0.004).

Conclusions: While BMI Z-scores were similar at 22-26 months corrected age, patterns of growth between discharge and follow-up differed by study diet. Children fed donor milk in early infancy showed a greater increase in weight Z-score between discharge and follow-up than children fed preterm formula in early infancy.

Impact: At 2 years, the anthropometrics were similar for children randomized to donor milk or preterm formula in early infancy. Patterns of growth between discharge and follow-up differed by early infancy diet. There was a greater weight Z-score increase between discharge and follow-up for children randomized to donor milk than formula. Donor milk appears to be non-inferior to preterm formula with respect to growth at 2 years for children born extremely preterm. Policies and practices that facilitate parental milk provision and donor milk availability are needed for infants born extremely preterm.

Background: Fortification of human milk for very preterm infants (VPIs) with alternatives to conventional bovine milk-based fortifiers remains minimally studied. This trial tested whether fortification with protein-rich bovine colostrum (BC) improves feeding intolerance and clinical variables in VPIs receiving enteral nutrition with a relatively slow advancement.

Methods: In this unblinded, two-centre, randomised, controlled trial (FortiColos CN), VPIs (gestational age, 26 + 0 to 31 + 6 weeks) were fed human milk fortified with BC (n = 74) or a conventional fortifier (CF, FM85, Nestlé, n = 72) for at least two weeks, starting when enteral feeding volume reached 80-100 mL/kg body weight/d. Incidence of feeding intolerance, nutrition intake, body growth, morbidities and clinical biochemical parameters were compared between the two groups.

Results: No statistically significant difference was found in the incidence of feeding intolerance or in most of the nutritional or body growth parameters (p > 0.05). All recorded morbidity incidences and haematological and blood biochemical parameters were also similar between groups. Amino acids (Phe, Pro, Ser, Tyr, Val) showed higher levels in the infants receiving BC.

Conclusions: BC appeared safe when used as a fortifier to human milk for VPIs with slow feeding advancement, but did not improve feeding tolerance or clinical variables.

Impact: Fortifying human milk with bovine colostrum (BC) in very preterm infants (VPIs) is safe but did not improve feeding tolerance, growth or clinical outcomes, compared with a conventional fortifier (CF), when used during slow enteral feeding advancement. This study adds to the limited clinical evidence on the use of BC as a human milk fortifier in VPIs receiving enteral feeding with different feeding protocols. The findings support the safety of BC as a human milk fortifier in VPIs but suggest limited short-term clinical benefits over currently used fortifiers.

Background: Each year, over half a million children worldwide are born extremely prematurely (EPI), often requiring potentially harmful ventilatory support. An artificial placenta with gas exchange provided by an oxygenator offers an alternative. However, current oxygenators are not designed for long-term applications in patients experiencing growth. Thus, a new type of "growing" oxygenator is needed.

Methods: We developed the A-Maze-Ox, a novel maze-inspired membrane oxygenator featuring two concentric compartments that can be opened sequentially to address patient growth. Each compartment has a priming volume of 5 mL and a gas exchange area of 0.065 m². The prototype was tested for feasibility, gas transfer performance and pressure loss according to ISO 7199.

Results: Adding the second compartment increased O₂ and CO₂ transfer performance by 57.06% and 35.59%, respectively. While CO₂ transfer was mostly sufficient, O₂ transfer remained below the target. The targeted maximum pressure drop of 20 mmHg was exceeded at 90 mL/min.

Conclusions: The A-Maze-Ox demonstrates the ability to adapt to increasing demands with good results in CO₂ elimination but requires improvement in terms of O₂ transfer and pressure drop. However, it shows the potential for a growing oxygenator in future artificial placenta applications.

Impact: Current oxygenators cannot adapt to the dynamic patient growth of extremely premature infants. A-Maze-Ox-a novel membrane oxygenator with two compartments can adapt to growth. Each compartment has a volume of 5 mL and a gas exchange area of 0.065 m². Oxygen transfer increased by 57.06% and carbon dioxide transfer by 35.59% when adding the second compartment. A-Maze-Ox could improve health of extremely premature infants in the future.

Impact: Call for action to implement special interest groups regarding planetary health within pediatric research societies Pointing out the role and responsibility of pediatricians and pediatric researchers in times of climate crisis Raising awareness about research gaps, e.g., regarding mitigation strategies Focusing on the carbon footprint of conferences, hospitals and, laboratories Recommendations for sustainable medical and research practice.

Background: Bronchopulmonary dysplasia (BPD) and significant hemodynamic patent ductus arteriosus (hsPDA) are both common and important clinical issues in extremely preterm infants. The potential impact on prognosis when these conditions coexist is a major focus of clinical concern. This study examined the relationship between hsPDA and adverse outcomes in BPD infants.

Methods: A retrospective analysis of 781 preterm infants (<32 weeks) from three hospitals (2018-2023). Based on echocardiographic assessment, infants were categorized as the non-PDA group, the non-hsPDA group, or the hsPDA group. Further subgroups were formed according to treatment and ductus arteriosus size (<1.5 mm, 1.5-3 mm, ≥3 mm). The effects of hsPDA on short-term outcomes in infants with BPD were assessed using logistic regression and linear regression.

Results: The study included 781 infants (548 non-BPD, 233 BPD). The hsPDA subgroup had lower gestational age, higher birth asphyxia rates, and required more invasive respiratory support. In BPD infants, hsPDA was linked to longer respiratory support, higher pneumonia and feeding intolerance risks, prolonged oxygen therapy, and PH. Infants with hsPDA had longer hospital stays and oxygen therapy. Intervention therapy in infants with hsPDA was associated with prolonged oxygen therapy duration, reduced feeding intolerance, and increased risk of pulmonary hypertension（PH）. Meanwhile, ductus arteriosus diameter >3 mm was linked to elevated risks of feeding intolerance, pulmonary hypertension, and extrauterine growth restriction. After adjusting for gestational age and birth weight, results from multivariate logistic regression and multiple linear regression analyses indicated that hsPDA was independently associated with increased risk of neonatal PH (aOR = 7.502, 95% CI: 4.046-13.911, P < 0.001) and significantly prolonged invasive respiratory support duration (β = 6.530 days, 95% CI: 1.691-11.368, P = 0.008).

Conclusion: In BPD infants, hsPDA is associated with the occurrence of PH and longer duration of invasive respiratory support.

Impact: This study highlights the significant correlation between hemodynamically significant patent ductus arteriosus (hsPDA) and adverse outcomes in infants diagnosed with bronchopulmonary dysplasia (BPD), providing valuable clinical evidence for better management strategies. This study adds to the literature by showing that in very preterm infants with BPD, the presence of hsPDA was independently correlated with both an increased risk of pulmonary hypertension and a longer duration of invasive respiratory support.

Background: Very early onset inflammatory bowel disease presents a rare condition with an enrichment of monogenic disorders. This cohort study aims to investigate the prevalence of IBD-like monogenic disorders as well as genotypic and phenotypic characteristics in an Iranian cohort of VEO-IBD patients.

Methods: Patients with VEO-IBD diagnosed between September 2019 and May 2023 were evaluated retrospectively. Clinical data were collected, and whole exome sequencing (WES) was performed on patients. Biological therapy was given to 10 patients (52%), and three underwent intestinal surgery.

Results: Among the 19 patients, 7 (36%) had Crohn's disease, 3 (15%) had ulcerative colitis, and 9 (47%) had unclassified IBD. Monogenic disorders were identified in 8 patients (42%), including variants in IL10RB, DKC1, FERMT1, GUCY2C, NLRC4, and a susceptibility gene variant in the MEFV gene. We identified a novel heterozygous duplication on chromosome 6 by karyotype and SNP-array analysis but the relevance of the genetic findings remains elusive and further functional testing is required. Four patients were considered for HSCT, and the patient with the MEFV variant responded well to colchicine.

Conclusions: The study revealed that 42% of VEO-IBD patients had underlying monogenic disorders. Early identification of causative mutations is crucial for improving prognosis and treatment strategies.

Impact: VEO-IBD is a rare condition with a high prevalence of monogenic disorders. Early detection of causal mutations is crucial for improving prognosis and selecting optimal treatment strategies. In our cohort study, eight patients were found to have five known and three novel pathogenic variants in five different genes. We also identified a de novo duplication of the 6q22 region. Allogeneic HSCT provides a curative treatment for IL-10R-deficient patients, while colchicine treatment resulted in sustained remission in a patient with an MEFV mutation. Our study indicates that early genetic diagnosis of immune-related IBD-like monogenic disorders is essential for effective patient management.

Background: Acute pancreatitis (AP) is one of the serious complications among patients with hematopoietic stem cell transplantation (HSCT). We aimed to evaluate the impact of AP on hospitalization outcomes in pediatric HSCT recipients.

Methods: We retrospectively queried the PHIS database to include all pediatric patients who underwent HSCT between 2005-2024. The study population was divided into those with and without AP, and compared for various demographic and clinical variables. The primary outcome was in-hospital mortality, and secondary outcomes included healthcare resource utilization.

Results: A total of 33,439 HSCT recipients were identified, and the prevalence rate of AP was 1.1%. The AP group had a significantly higher in-hospital mortality rate (22.7% vs. 4.6%), higher median hospitalization costs (USD 698,372 vs. 187,583), and higher median length of stay (138.5 vs. 60 days) (all p < 0.001). Our risk stratification model predicted a 2.7 (95% CI: 2.2 to 3.4) increased risk of AP for a score of >10, with an AUC of 0.85 (95% CI: 0.84 to 0.88).

Conclusion: AP in HSCT prognosticates adverse outcomes with increased in-hospital mortality, prolonged length of stay, and higher hospitalization costs. Clinicians need to be vigilant in preventing and aggressively managing AP in HSCT.

Category of study: Population study IMPACT: Acute pancreatitis (AP) in pediatric hemopoietic stem cell transplant (HSCT) recipients prognosticates adverse outcomes with increased mortality, prolonged length of stay, and higher hospitalization costs. The risk stratification model predicted a 2.7 (95% CI: 2.2 to 3.4) times increased risk of AP for a score of >10, with an AUC of 0.85 (95% CI: 0.84 to 0.88). Multivariable analysis showed AP was associated with 1.5 (CI:1.2 to 2, p = 0.001) times increased risk of mortality in pediatric population.

Background: Autism spectrum disorder (autism) describes a heterogeneous neurodevelopmental phenotype arising from the interplay of environmental and genetic factors in early life.

Methods: In a general population birth cohort, we employed a scoping approach to identify prospective associations between prenatal and birth factors and a subsequent autism diagnosis.

Results: Factors associated with increased likelihood of autism included those related to i) maternal health (maternal pre-pregnancy body mass index, pre-existing maternal mental health conditions, maternal use of selective serotonin reuptake inhibitors) ii) environmental exposures (maternal passive tobacco smoke exposure, and exposure to vinyl floors) iii) demographic factors (socioeconomic disadvantage). Factors associated with a decreased likelihood of autism included maternal dietary nutrition and supplementation (higher folic acid, magnesium, and iron, as well as adherence to the Australian Dietary Guidelines).

Conclusion: Our findings extend the evidence that autism may have a multifactorial origin in early life. Further studies should explore the composite effects of these prenatal and birth factors on autism outcomes via shared biological pathways, such as inflammation, and oxidative stress, in concert with genetic predisposition.

Impact: Autism spectrum disorder (autism) is a multifactorial condition. Here we report on multiple prenatal environmental, demographic, maternal and pregnancy factors that are associated with an increased likelihood of an autism diagnosis. For example, adherence to the Australian Dietary Guidelines during pregnancy is linked to a reduced likelihood of autism in the offspring, consistent with mounting evidence that prenatal nutrition impacts brain development. We examine how the multiple risk factors, identified by our comprehensive approach, may be linked to shared biological mechanisms. Future work should examine composite exposure measures acting through shared mechanisms as a more productive approach to understanding aetiology than focusing solely on individual exposures.