Pediatric Research最新文献

Critically ill preterm and term neonates are uniquely vulnerable to and constantly confront potential harmful and unintended exposures in every aspect of their care, including diagnostic imaging, sensory environments, medications, nutrition, blood products, and device exposures. The rapidly changing pathology, physiology, and metabolism of these infants, along with a lack of treatments tailored to the needs of neonates, lead to unintended negative consequences with impacts reaching far out into adulthood. Families, nurses, clinicians, and researchers provide the best care for neonates with the resources and knowledge available, but more needs to be done from the healthcare policy and societal levels. More research is needed to understand the negative impacts of environmental exposures on neonates and children in general. Concerted efforts should focus on eliminating known toxic and harmful substances from commercial products used in neonatal care, and alternatives should be made available. Resource allocation is needed by community leaders and health policy makers, through regulations and incentives, to ensure that neonates and children can have healthy, happy, and productive lives. Our society should be judged by how we care for and treat this most vulnerable population, who deserve environments and treatments free from unintended, unnecessary harmful exposures. IMPACT: Technological advances have significantly improved survival of critically ill term and pre-term infants, but pose a unique challenge of exposure to multiple environmental toxins. In this review, we have summarized these exposures and the pathways through which they may negatively impact the neurodevelopmental outcomes in this highly vulnerable population. Ongoing environmental exposures in the NICU are a global healthcare problem and need policies and resources in place to mitigate their negative impact on infant and child health outcomes.

Background: Umbilical cord blood (UCB) is increasingly studied for regenerative therapies, yet the impact of different collection techniques on cell yield and quality remains unclear. This study compared standard needle-and-bag UCB collection with manual cord milking, performed both in utero (placenta attached) and ex utero (placenta delivered), using samples from healthy term infants ( > 37 weeks gestation).

Method: Forty-two samples (n = 10 standard in utero, n = 10 standard ex utero, n = 10 milking in utero, n = 12 milking ex utero) were analyzed for blood volume, mononuclear cell count, and cellular composition via flow cytometry. Key cell populations included hematopoietic stem cells (CD34 + CD45 + ), endothelial progenitor cells (CD45 + CD34 + CD31 - CD133 + ), and mature endothelial cells (CD34 - CD45 - CD31 + ). Plasma cytokines, including inflammatory and angiogenic markers, were also assessed.

Results: No significant differences were found in total blood volume or mononuclear cell counts across groups. However, endothelial progenitor cell viability was significantly reduced in cord milking ex utero compared to standard in utero collection (p < 0.0001). Cytokine analysis showed elevated IL-1RA and reduced VEGF-A in cord milking ex utero samples (p < 0.0001 and p = 0.0004, respectively).

Conclusion: These findings suggest that in utero cord milking may be a viable alternative to standard UCB collection, preserving cell viability and cytokine integrity.

Impact: The standard method for collecting umbilical cord blood (UCB) has limitations, especially in cases like premature birth, where low volumes yield insufficient mononuclear and hematopoietic stem cells for therapeutic use. This study evaluated an alternative technique-umbilical cord milking-against the standard approach. As the first study to assess its efficacy for UCB collection, the findings offer insights into a viable alternative method.

Background: Perinatal disruption of sodium homeostasis, which is critical for organ and cell function, may impact growth, metabolism, and pulmonary function.

Methods: Two murine models were studied. First, maternal mice were supplied with a standard (0.15%) or low sodium (0.04% Na) diet from embryonic day 18 until postnatal day 21 (E18-P21). Second, offspring of mothers on standard Na were administered daily furosemide (30 mg/kg ip) on P10-P13 or sham injection. All pups received 0.15% Na diet at weaning. In male offspring, weight and body composition were serially measured while total energy expenditure was determined at 8-9 weeks of age. Ventilatory function was assessed at 3-5 weeks and again at 6-8 weeks of age in males and females. Lung structure was assessed at 9-10 weeks.

Results: Maternal low Na diet programmed significantly decreased weight gain in offspring associated with increased total energy expenditure. No significant effects on lung structure or breathing were seen. Furosemide resulted in increased weight, fat and fat-free mass in males. Furosemide was also associated with significantly decreased minute ventilation and tidal volume in males without changes to lung structure.

Conclusion: Perinatal Na homeostasis is crucial for long-term growth, metabolism, and pulmonary function.

Impact: Maintenance of early life sodium homeostasis is essential for growth and organ development Using different mouse models, we demonstrated a crucial role of early Na balance in long term growth, body composition, and metabolic and respiratory functions. Optimized intervention to maintain sodium homeostasis may improve long-term outcomes of preterm infants.

Background: The DLK1-MEG3 gene locus on human chromosome 14q32.2 contributes significantly to glucose metabolism and is linked to SGA development, but the role of its methylation in glucose regulation and SGA remains unclear.

Methods: A nested case-control study of 330 participants (165 SGA, 165 AGA) measured methylation levels of IG-DMR (5 CpGs) and MEG3-DMR (7 CpGs) in umbilical cord blood using bisulfite pyrosequencing. Blood glucose and insulin levels were assessed. Logistic regression and mediation analysis were used.

Results: Higher IG-DMR (Pos. 3) methylation level was associated with elevated SGA risk (OR = 1.068, 95% CI [1.002-1.142]) and lower blood glucose (Percentage change = -2.69%, 95% CI [-4.75% to -0.58%]). The average methylation level of MEG3-DMR was negatively correlated with SGA risk (OR = 0.931, 95% CI [0.876 to 0.987]) and positively with insulin (Percentage change = 3.38%, 95% CI [0.23% to 0.63%]). Mediation analysis suggested insulin mediated the effect between the average methylation level of MEG3-DMR and SGA (explaining 11.7%). After excluding preterm infants, the association between the average methylation level of MEG3-DMR and insulin was not significant, while other results remained similar.

Conclusion: These results offer new insights into how DNA methylation influences pregnancy outcomes and provide a foundation for SGA management and prevention research.

Impact: Epigenetic changes, such as DNA methylation, are believed to play a significant role in regulating intrauterine growth. The DLK1-MEG3 locus, which includes two differentially methylated regions (IG-DMR and MEG3-DMR) is involved in glucose metabolism regulation, a key factor in fetal growth. We identified a marked association of the mean methylation levels of MEG3-DMR and SGA, and insulin may mediate this association. The findings offer novel insights into the epigenetic mechanisms linking DNA methylation patterns with adverse gestational consequences. This research has potential implications for improving the management of SGA risk.

Background: Cobalamin C (cblC) deficiency, caused by MMACHC mutations, is a rare metabolic disorder with multisystem involvement. Pulmonary hypertension (PH) is an underrecognized but potentially life-threatening complication. This study aimed to characterize the clinical features and treatment outcomes of PH in children with cblC deficiency, particularly those carrying the MMACHC c.80 A > G variant.

Methods: We retrospectively analyzed 17 pediatric patients with genetically confirmed cblC deficiency who presented with PH as the initial manifestation. Clinical, biochemical, imaging, genetic, and therapeutic data were reviewed.

Results: All patients had PH at diagnosis, with 64.7% (11/17) exhibiting moderate-to-severe pulmonary artery systolic pressure (PASP) elevation. Macrocytic anemia and renal dysfunction were common. HRCT revealed centrilobular ground-glass nodules, interlobular septal thickening, and pulmonary hemorrhage. B-type natriuretic peptide (BNP) levels were significantly higher in the moderate-severe group. All patients received metabolic therapy, and 11 received PH-targeted drugs. Glucocorticoids led to rapid clinical improvement in two patients presenting with pulmonary hemorrhage or hypoxemia. PASP normalized in all cases within 18 months. No recurrence occurred during follow-up.

Conclusion: PH is a serious but reversible complication of cblC deficiency. Early diagnosis and combined metabolic and PH-targeted therapy can reverse vascular remodeling. Screening for cblC should be considered in children with unexplained PH and macrocytic anemia or renal involvement.

Impact: This study presents the largest cohort to date of pediatric patients with cblC deficiency presenting with pulmonary hypertension (PH) as the initial manifestation. It identifies a potential genotype-phenotype association between the MMACHC c.80 A > G variant and reversible pulmonary vascular disease. The findings highlight the importance of early metabolic and PH-targeted therapy, and support screening for cblC deficiency in children with unexplained PH and macrocytic anemia or renal involvement.

Background: Multiple studies demonstrated increased risk for psychological symptoms among childhood cancer survivors (CCS) and their parents. We aimed to assess the prevalence and severity of post-traumatic stress symptoms (PTSS), depression, and anxiety among CCS and their parents, examine associations between these measures, and identify potential risk factors.

Methods: A cross-sectional study comprising 118 CCS aged 7-21 years and their parents, at least one year post-treatment. PTSS, depression and anxiety were assessed using validated questionnaires. Medical and sociodemographic data were collected from the medical charts.

Results: PTSD criteria were met by 8.7% of CCS and 18.3% of parents, about a third reporting post-traumatic stress symptoms. Moderate-to-severe depression occurred in 22% of CCS and 7.6% of parents, and anxiety in 12.7% of CCS and 22% of parents. There were robust positive correlations between depression, anxiety, and PTSS within both CCS and parental self-reports. Parents' proxy- reports correlated more strongly with their self-report than with CCS self-reports. Predictors of PTSS included time since diagnosis, parent's education, parent's sex, type of cancer, and depression and anxiety level.

Conclusions: The study highlights the importance of screening both children and parents, prioritizing child self-report, and providing tailored, ongoing psychosocial support for CCS and their families.

Impact: Our study revealed high rates of psychological symptoms among CCS and their parents during the survivorship phase. The dual-informant design using pediatric self-report, parent self-report, and parent-proxy report enabled exploration of interconnections between psychological symptoms of CCS and their parents. Parents' perceptions of children's distress correlated more with their own emotional state than with children's self-reports, suggesting parental projection. Predictors of post-traumatic stress symptoms, including time since diagnosis, parental education and biological-sex, depression and anxiety. Our results emphasize the need for screening both children and parents, prioritizing child self-report, and providing tailored, ongoing psychosocial support for CCS and their families.

Background: Iatrogenic preterm premature rupture of fetal membranes (iPPROM) following fetoscopic interventions remains a major barrier to the advancement of fetal therapies. The mechanisms underlying iPPROM are poorly understood, but the inability of fetal membrane (FM) defects to heal spontaneously likely plays a key role, contrasting with the regenerative potential of amniotic membranes in other contexts.

Methods: To assess the impact of fetoscopic procedures on FMs, tissue samples from patients who underwent laser surgery for twin-to-twin transfusion syndrome (16-27 weeks gestation, n = 8) were collected after cesarean delivery at 29-35 weeks. Samples were categorized by proximity to the trocar site and analyzed using proteomic and histological methods.

Results: While differential expression analysis in the amnion revealed no significant changes, pathway enrichment indicated increased collagen deposition at defect sites. In the chorion, seven differentially expressed proteins were identified, largely linked to enhanced intercellular contact stability. These findings suggest the amnion may respond to mechanical stress by reinforcing structural integrity through collagen deposition, while the chorion may attempt to stabilize cell junctions. However, no other signs of tissue regeneration were observed.

Conclusion: This study provides molecular and cellular evidence that FMs lack a substantial healing response post-surgery, underscoring the need for biologically informed repair strategies.

Impact: By combining untargeted proteomics with histological and qPCR evaluations, this study demonstrates subtle molecular and cellular changes in fetoscopy-induced fetal membrane defects at the time of delivery. This indicates minimal molecular and cellular healing mechanisms in the fetal membranes. This underscores the potential for sealing FM defects after fetoscopy to prevent amniotic fluid leakage, thereby reducing the incidence of intra-amniotic preterm rupture of membranes.

Sarcopenia is a muscle disorder characterized by the progressive loss of muscle mass and strength, leading to diminished physical performance. Although primarily associated with aging and chronic diseases, it is increasingly recognized in younger populations, particularly among those with chronic illnesses. Recent evidence suggests that muscle mass and strength deficits can manifest as early as childhood and adolescence, affecting three out of ten adolescents. Pediatric sarcopenia, while challenging to define due to the lack of standardized diagnostic criteria, presents significant health risks, including increased susceptibility to metabolic syndrome and chronic non-communicable diseases. Recent studies have attempted to establish normative values for muscle health in pediatric populations, yet many rely only on assessment of either muscle mass or strength, thus limiting the understanding of overall muscle health. In this context, the interaction between muscle mass, strength, and functionality, herein referred to as the muscle mass-strength-functionality triad (MSFt), is crucial for understanding the onset and progression of pediatric sarcopenia. The present review provides a perspective on concepts and operators defining pediatric sarcopenia and advocates for incorporating novel diagnostic criteria encompassing the MSFt. Furthermore, the importance of physical literacy and the acquisition of fundamental movement skills during childhood is highlighted, as these factors significantly influence long-term muscle health and physical activity levels. IMPACT: This perspective review provides an insightful view of muscle health in children and adolescents centered around the definition of pediatric sarcopenia. We discussed how to understand and describe sarcopenic-like deficits in pediatric populations. We propose the muscle mass-strength-functionality triad as an attribute that describes physical competence and is key to defining pediatric sarcopenia. We suggest the addition of physical literacy and movement competence assessment to the current diagnostic criteria of pediatric sarcopenia.

Background: Gastrointestinal graft-versus-host disease (GI-GVHD) is diagnosed via histological examination of endoscopic mucosal biopsy specimens; however, the optimal endoscopic diagnostic strategy remains unclear. This study aimed to identify key clinical symptoms, gastrointestinal sites, and endoscopic approaches for diagnosing pediatric GI-GVHD.

Methods: A retrospective analysis of post-bone marrow stem cell transplant patients with gastrointestinal symptoms at Shanghai Children's Medical Center (2018-2023) was conducted. A nomogram prediction model was developed using univariate and multivariate logistic regression analyses based on clinical, endoscopic, and histopathological characteristics.

Results: Among 63 patients (29 GI-GVHD, 34 non-GI-GVHD), GI-GVHD was associated with skin rejection (P = 0.002), diarrhea (P = 0.07), and bloody stools (P = 0.009). C-reactive protein (CRP) > 30 mg/L and mucosal ulcers were more common in the non-GI-GVHD group than the GI-GVHD group (P = 0.016, P = 0.029). Independent GI-GVHD indicators included skin rejection (P = 0.035), apoptotic corpuscles (P = 0.030), mucosal edema (P = 0.007), and tortoise shell-like mucosa (P = 0.020). Transverse colonic mucosal edema (76.2%) and tortoise shell-like mucosa (74.6%) demonstrated the highest diagnostic accuracy in the nomogram.

Conclusions: Gastroscopy combined with colonoscopy is recommended for diagnosing GI-GVHD. The key diagnostic indicators include skin rejection, mucosal edema, tortoise shell-like mucosa, and apoptotic corpuscles. Our nomogram aids in GI-GVHD diagnosis.

Impact: Our study identified key clinical, endoscopic, and histopathological markers for pediatric gastrointestinal graft-versus-host disease (GI-GVHD), emphasizing colonic mucosal edema and tortoise shell-like mucosa as GI-GVHD indicators. Our results underscore the value of combining gastroscopy and colonoscopy while introducing a predictive nomogram for risk assessment. These findings can enhance early and accurate diagnosis, enabling timely, targeted interventions to improve patient outcomes.