Pediatric Disease Research Articles

Building Capacity for Pediatric Hematological Diseases in Sub-Saharan Africa.

The spectrum of hematological diseases in African children includes anemias, bleeding disorders, thromboses, and oncological diseases such as leukemias. While data are limited, outcomes for these diseases are poorer in Africa. The dearth of specialists, and lack of infrastructure that supports diagnosis and management, have been identified as key barriers to improving outcomes for childhood hematological disorders in sub-Saharan Africa (SSA). To address these , intentional capacity building efforts addressing education and training, diagnostic capacity and access to blood products, and medicines , are needed. This article explores some ongoing efforts in the region aimed at fostering the capacity to identify and treat childhood hematological disorders across a breadth of initiatives targeting the critical themes of education, diagnostic support and treatment. We also identify existing opportunities through international partnerships, to build sustainable programs that can support children with hematological diseases in SSA.

Chronic Pediatric Lung Diseases: Point-High-Resolution CT Is Superior to All Other Available Imaging Modalities for Detection of Early, Subtle, or Management-Altering Findings.

Chronic Pediatric Lung Diseases: Point-High-Resolution CT Is Superior to All Other Available Imaging Modalities for Detection of Early, Subtle, or Management-Altering Findings.

Status of inpatients with pediatric epilepsy in children's hospitals in China (2016-2021).

Pediatric epilepsy is the most common disease of pediatric neurological diseases in China. Current demographic characteristics and economic burdens are needed to guide public health policy. In this study, we provide the demographic characteristics and economic burden of pediatric epilepsy patients in China from 2016 to 2021, and describe the change trend and correlation of demographic characteristics and economic burden by province. Using data from the Futang Research Center of Pediatric Development, we conducted a demographic-based cross-sectional study of pediatric epilepsy patients in 29 children's hospitals in China to assess changes in the distribution and economic burden over 6 years and related factors. We obtained per capita disposable income information from the Economic Statistical Bulletin of the National Bureau of Statistics of China and the statistical bureaus of provincial administrative regions. Demographic, diagnostic classification proportion and distribution trends, and economic burden from 2016 to 2021 were verified for pediatric patients with epilepsy. From 2016 to 2021, there were 149,375 patients diagnosed with epilepsy. The proportion of patients younger than 3 years decreased significantly from 51.13% to 29.43% (P=0.00853, R2=0.9803). The root-mean-square-error between the Inter-Provincial Visits Indexes decreased from 1.70 to 0.90, decreasing significantly (R2=0.8306). The disease burden decreased from 17.26% to 12.11% with a significant upward trend (P=0.02417, R2=0.8817). A negative correlation between disease burden and the Inter-Provincial Visits Index (P=0.0383) was observed, along with a positive correlation with the proportion of patients younger than 3 years old (P<0.0001). From 2016 to 2021, the proportion of young patients, population mobility and economic burden on patients decreased, and healthcare level of pediatric epilepsy improved. In addition, based on the current observations, the healthcare level of pediatric epilepsy in Western and Central China is lower than in other regions, and the economic burden on patients is higher than in other regions. In the future, these areas require higher priority concerning policy and financial support.

Nonhuman primate models of pediatric viral diseases

Infectious diseases are the leading cause of death in infants and children under 5 years of age. In utero exposure to viruses can lead to spontaneous abortion, preterm birth, congenital abnormalities or other developmental defects, often resulting in lifelong health sequalae. The underlying biological mechanisms are difficult to study in humans due to ethical concerns and limited sample access. Nonhuman primates (NHP) are closely related to humans, and pregnancy and immune ontogeny in infants are very similar to humans. Therefore, NHP are a highly relevant model for understanding fetal and postnatal virus-host interactions and to define immune mechanisms associated with increased morbidity and mortality in infants. We will discuss NHP models of viruses causing congenital infections, respiratory diseases in early life, and HIV. Cytomegalovirus (CMV) remains the most common cause of congenital defects worldwide. Measles is a vaccine-preventable disease, yet measles cases are resurging. Zika is an example of an emerging arbovirus with devastating consequences for the developing fetus and the surviving infant. Among the respiratory viruses, we will discuss influenza and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We will finish with HIV as an example of a lifelong infection without a cure or vaccine. The review will highlight (i) the impact of viral infections on fetal and infant immune development, (ii) how differences in infant and adult immune responses to infection alter disease outcome, and emphasize the invaluable contribution of pediatric NHP infection models to the design of effective treatment and prevention strategies, including vaccines, for human infants.

Hospital-wide access to genomic data advanced pediatric rare disease research and clinical outcomes

Boston Children’s Hospital has established a genomic sequencing and analysis research initiative to improve clinical care for pediatric rare disease patients. Through the Children’s Rare Disease Collaborative (CRDC), the hospital offers CLIA-grade exome and genome sequencing, along with other sequencing types, to patients enrolled in specialized rare disease research studies. The data, consented for broad research use, are harmonized and analyzed with CRDC-supported variant interpretation tools. Since its launch, 66 investigators representing 26 divisions and 45 phenotype-based cohorts have joined the CRDC. These studies enrolled 4653 families, with 35% of analyzed cases having a finding either confirmed or under further investigation. This accessible and harmonized genomics platform also supports additional institutional data collections, research and clinical, and now encompasses 13,800+ patients and their families. This has fostered new research projects and collaborations, increased genetic diagnoses and accelerated innovative research via integration of genomics research with clinical care.

Cross-cultural adaptation and validation of Work Productivity and Activity Impairment questionnaires for caregivers of patients with pediatric inflammatory bowel disease in Spain. A multicenter study.

Introduction. The WPAI-UC/CD-Caregiver questionnaires assess the impact of ulcerative colitis (UC) or Crohn's disease (CD) on parents'/caregivers' work life and daily activities. Our objective was to adapt and validate these questionnaires in the Spanish population. Methods. A translation and back-translation were done. The document was assessed by an expert committee and a pilot group of families of patients with pediatric inflammatory bowel disease (p-IBD). For validation, the parents/caregivers of patients with p-IBD (10-18 years old) were recruited. The expert committee and the pilot group conducted a subjective assessment of the format and time necessary to complete the questionnaires. Cronbach's alpha coefficient was estimated and a factor analysis with varimax rotation was done. Kaiser- Meyer-Olkin (KMO) coefficients and Bartlett's sphericity test were estimated to test the adequacy of the factor analysis. Results. A total of 370 patients (median age: 14.1 years) and 263 parents/caregivers of patients with UC or unclassified IBD and 261 parents/caregivers of patients with CD were included. The KMO coefficients (0.6947 and 0.7179) and Bartlett's sphericity test (p < 0.001) confirmed the adequacy of the factor analysis. The 6 items targeted the same domain. The factor model accounted for 99.99% and 94.68% of variance, and Cronbach's alpha coefficients (0.6581 and 0.6968) showed an adequate consistency. The format and the median time of 2 minutes to complete the questionnaires were considered optimal. Conclusions. The versions of the WPAI-Caregiver questionnaires validated in the Spanish population may be used in families whose children have IBD.

The Effect of Metabolic Disease on Language and Swallowing Skills in Children: A Case Report

Objectives: The present research aims to highlight the impact of hyperammonemia, a common pediatric metabolic disease, on children’s language and feeding skills. This research was conducted through a literature review and the presentation of a 2.5-year-old girl diagnosed with hyperammonemia. Case Presentation: The research was conducted on a 2.5-year-old girl who had been diagnosed with a sudden-onset metabolic disorder that resulted in swallowing, speech, and language problems. The child’s receptive and productive language and feeding history were obtained through interviews with her mother. Formal and informal tests were used to assess the child’s language and feeding skills at two different times after the onset of symptoms. Discussion: This study presents a new and unique case of a child with very high levels of ammonia and severe clinical manifestations of cognitive, language, and motor dysfunctions. Although the child did not receive any direct interventions during the study, a secondary assessment revealed slight improvements in some language and oral motor skills, possibly due to maturation and advice provided by rehabilitation team members.

Education and employment outcomes in pediatric chronic kidney disease.

As outcomes and survival for children with chronic kidney disease (CKD) have improved over the last 30years, there is an emerging need to characterize and understand later educational and employment outcomes across the spectrum of pediatric CKD severity-ranging from mild CKD to requirement for dialysis and kidney transplantation. Although large-scale research on the topic of long-term educational and employment outcomes in the pediatric CKD population is relatively scarce, the existing literature does support that children across the spectrum of CKD severity are at risk for education-related difficulties including chronic school absenteeism. These education-related difficulties are compounded by well-described neurocognitive deficits-particularly in the domain of executive functioning-that may potentially perpetuate the risk for academic underachievement. This is particularly concerning given that data from the general pediatric population suggest that childhood academic underachievement is associated with higher likelihood of un-/underemployment in adulthood. This review highlights what is known about educational and employment outcomes among persons with a history of childhood CKD, as well as suggestions for interventions to improve educational outcomes for this population.

Current practice in the management of paediatric autoimmune liver disease in Europe

AbstractObjectivePaediatric autoimmune liver disease (pAILD) is a rare condition with serious health implications. Notwithstanding treatment advancements, areas of uncertainty and knowledge gaps still exist. We here investigated the real‐life approach to pAILD management in Europe.MethodsA survey was distributed to members of the RARE‐LIVER ERN and the ESPGHAN Hepatology Interest Group. Information was gathered regarding clinical activity, medications used, and access to paediatric drug formulations at each site.ResultsThirty‐six centres from 22 European countries responded to the survey. The majority are exclusively paediatric units (86%). Among participants, 80% follow &lt;50 children with pAILD, of which 25%–50% are &lt;10 years old in 44% of centres. All centres use predniso(lo)ne as first‐line therapy, alone (15/36) or with azathioprine (21/36). Azathioprine and mycophenolate are the preferred second‐line options in centres using first‐line steroid monotherapy (11/15) or combined steroid‐azathioprine (19/21), respectively. Tacrolimus is used as third‐line agent in 15/36 centres. Proactive measurement of drug metabolites and target levels vary widely among centres. Paediatric predniso(lo)ne formulations are commercially available in 7/22 European countries, azathioprine in 3, mycophenolate in 14, tacrolimus in 15 and ursodeoxycholic acid in 14. When paediatric formulations are unavailable, children are treated with magisterial preparations or ‘solid’ formulations (crushed or intact).ConclusionsTreatment of pAILD in Europe varies widely in terms of medications used and treatment monitoring. Availability of paediatric drug formulations across Europe is limited. Collaborative initiatives are needed to define evidence‐based strategies for management of pAILD and to promote an equal, age‐appropriate treatment for affected children.

Prognostic Factors Associated With Increased Mortality in Pediatric Veno-Occlusive Disease Following Hematopoietic Cell Transplantation.

Hepatic veno-occlusive disease (VOD) is a life-threatening complication of hematopoietic cell transplantation (HCT) and is categorized as a transplant-related, systemic endothelial disease. Severe VOD can lead to multi-organ dysfunction (MOF) and is associated with a high mortality rate. To evaluate the incidence of VOD in children after HCT and analyze the outcomes and risk factors associated with increased mortality. A retrospective cohort study of 1243 children with malignant and non-malignant diseases who underwent HCT at two large pediatric centers over 20 years. One hundred one patients (8%) developed VOD post HCT. Most patients developed VOD post allogeneic HCT (76%) versus autologous (24%). The incidence of VOD was twice as high in children with malignant diseases compared to non-malignant (68%vs. 32%). A much higher incidence of VOD occurred in patients after a busulfan-based regimen versus total body irradiation-based and treosulfan-based, 73%, 18%, and 1%, respectively. The 100-day survival rate of HCT patients with VOD was 69%. The overall survival rate of the entire group was 50%, showing improvement over the span of the study years, from 40% between 2000 and 2009 to 63% between 2010 and 2021 (p = 0.022). Factors associated with increased mortality included infections before transplant (p = 0.013), conditioning regimen (p = 0.01), abnormal liver function (p = 0.019), presence of ascites (p = 0.008), MOF (p < 0.001), and the need for admission to a pediatric intensive care unit (p < 0.001). There was no significant difference in survival rates between children treated with defibrotide alone or with those treated with defibrotide and steroids (61% and 65%, respectively; p = 0.685). Severe VOD in pediatric patients following HCT remains a life-threatening complication with a high mortality rate. Early diagnosis and treatment with defibrotide are critical for managing this condition. In our cohort, the addition of steroids to defibrotide was not associated with improved outcomes.

Nonspecific increase of αβTCR+ double-negative T cells in pediatric rheumatic diseases.

An increased number of double-negative T (DNT) cells expressing the αβ T cell receptor (αβ+DNT cells) is one of the diagnostic criteria for autoimmune lymphoproliferative syndrome (ALPS). Moreover, these cells are expanded in a widely used murine model for lupus. However, the homeostasis of αβ+DNT cells remains inadequately investigated in rheumatic disorders, especially in pediatric patients. In this cross-sectional, prospective, and observational study, children with rheumatic disorders and healthy controls were recruited to analyze the quantity and characteristics of circulating DNT cells using flow cytometry. Overall, the two study groups did not differ in their total DNT cell pool in the bloodstream. However, the number of αβ+DNT cells was significantly higher in rheumatic children than that in the controls, whereas the γδ+DNT cells remained similar. This expansion in the circulating pool of αβ+DNT cells was comparable across different rheumatic diseases, all showing significant differences from the controls in this regard. Moreover, no significant correlation was found between αβ+DNT cell numbers and disease activity. These preliminary results indicate that circulating αβ+DNT cells are significantly expanded in children with rheumatic disorders; however, this finding appears to be a nonspecific (disease-unrelated) marker of autoimmunity. Further and larger studies are necessary to better investigate and define the role of DNT cells in pediatric rheumatic diseases.

Cerebral organoid research for pediatric patients with neurological disorders.

Cerebral organoids derived from human induced pluripotent stem cells offer a groundbreaking foundation for the analysis of pediatric neurological diseases. Unlike organoids from other somatic systems, cerebral organoids present unique challenges, such as the high sensitivity of neuronal cells to environmental conditions and the complexity of replicating brain-specific architectures. Cerebral organoids replicate the human brain development and pathology, enabling research on conditions such as microcephaly, Rett syndrome, autism spectrum disorders, and brain tumors. This review explores the utility of cerebral organoids for modeling diseases and testing therapeutic interventions. Despite current limitations such as variability and lack of vascularization, recent technological advancements have improved the reliability and application of such interventions. Cerebral organoids provide valuable insight into the mechanisms underlying complex neural disorders and hold promise as novel treatment strategies for pediatric neurological diseases.

Donor cytomegalovirus serology impacts overall survival in children receiving first unrelated hematopoietic stem cell transplant for acute leukemia: European Society of Bone Marrow Transplantation Pediatric Diseases Working Party Study.

Not available.

Association between hyponatremia and disease severity in pediatric urinary tract infections

BackgroundAcute urinary tract infection (UTI) is a common disease in pediatrics, with around 8% of girls and 2% of boys experiencing a UTI by age 7y/o. UTIs can range from asymptomatic bacteriuria to acute pyelonephritis (APN) in severe cases involving renal parenchymal infection. UTI patients admitted to the pediatric ward usually have more severe clinical presentation, compared to those treated in the outpatient settings. Therefore, it will be helpful to have markers that predict the severity of the disease and the likelihood of having APN.MethodsWe performed a retrospective review on all pediatric UTI/APN patients treated in the inpatient setting at a Medical Center from October 2012 to September 2022. Patients were assigned to the “hyponatremia” or “eunatremia” group according to their serum sodium concentrations. Detailed information, including renal echo, blood, and urine test results, were collected for the analysis of multivariable logistic regression model.ResultsThe study included 344 patients, of which 99 (28.8%) had hyponatremia, and 245 (71.2%) had normal serum sodium levels. The hyponatremia group had higher APN frequency, renal echo abnormality, and higher CRP level. In multivariable analysis, hyponatremia was independently associated with increased serum glucose (OR: 1.01, 95% CI: 1.00-1.03, p = 0.0365) and CRP levels (OR: 1.00, 95% CI: 1.00-1.01, p = 0.0417), without a significant increase in APN frequency as the final diagnosis.ConclusionsOur findings suggest that hyponatremia in pediatric UTI patients may indicate a more severe disease, such as APNs, higher CRP levels, or renal echo abnormalities. The complex mechanisms underlying hyponatremia and its predictive value for disease severity warrant further investigation.

The many faces of pediatric hydatid disease: a pictorial review.

Hydatid disease, caused by the larval stages of Echinococcus species, poses a significant public health challenge, especially in resource-limited cattle-producing areas of South America. The number of cases in children under the age of 15 is nearly 16% of the total cases in South America according to the latest report of the Pan American Health Organization (PAHO). The presentation of the disease depends on the anatomic location and correlates with the parasitic life stage. The liver is the most commonly affected organ in children, followed by the lungs, kidney, bone, and brain. The classification of hydatid cysts varies based on the parasite's stage, from purely cystic lesions to solid masses. The radiological approach varies by cyst location. Clinically, hydatid disease symptoms are nonspecific and organ-dependent, with imaging playing a crucial role in diagnosis. Complications include cyst rupture and superinfection, with potential severe consequences. This pictorial essay aims to illustrate the manifestations of hydatid cysts in an endemic population and highlight atypical signs for radiologists evaluating pediatric cysts in endemic regions.

Dihydroxyacetone phosphate is a novel predictor of hepatic fibrosis in Latino adolescents with obesity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common pediatric liver disease and can progress to liver fibrosis. Latino adolescents have increased MASLD and fibrosis risk. While fibrosis is diagnosed by biopsy or imaging, more accessible, noninvasive, and economical screening methods are needed. We aimed to use plasma metabolomics/lipidomics to identify potential fibrosis biomarkers in Latino adolescents with obesity. Liver stiffness (LS) was measured in 93 Latino adolescents with obesity using magnetic resonance elastography. Metabolites and lipids were extracted from plasma and identified on Compound Discoverer. Associations between metabolites/lipids and fibrosis (LS > 2.73 kPa) were determined using linear regression models after covariate adjustment. False discovery rate (FDR) adjusted Pearson's correlations were performed. Analytes yielding significant FDR-adjusted correlations were examined further by receiver operator curve analysis. Mean (±standard deviation) alanine transaminase (ALT) was 45.7(±65.2) IU/L, hepatic fat fraction was 12.7(±9.1)%, and LS was 2.4(±0.3) kPa. We identified 795 metabolites and 413 lipids in plasma, but only one single metabolite, dihydroxyacetone phosphate (DHAP), a marker of triglyceride synthesis, was significantly associated with fibrosis after FDR adjustment (p < 0.05). In terms of predicting fibrosis, ALT had an area under the curve (AUC) of 0.79, and DHAP had an AUC of 0.79. When combined, ALT + DHAP had an AUC of 0.89. The combination of ALT + DHAP may have the potential as an accurate, noninvasive test for liver fibrosis. Our data is limited to Latino children with obesity, and a larger cohort should be examined to further validate this novel biomarker.

Evaluating the Effectiveness and Coverage of Vaccination Programs in Reducing the Incidence of Paediatric Infectious Diseases

Background: Pediatric infectious diseases pose a significant risk to child health worldwide. Vaccination programs have greatly reduced the incidence and severity of these diseases, though coverage and efficacy differ across regions. This mini-review examines how effectively these programs reduce pediatric infectious diseases by analyzing existing literature on vaccine impact in various countries. Methodology: A literature search across PubMed, MEDLINE, ScienceDirect, and CINAHL (Dec 2017 - May 2022) used specific MeSH terms, including ‘pediatric vaccination,’ ‘disease incidence,’ and ‘vaccine efficacy.’ Out of 928 articles initially retrieved, 48 underwent full-text screening, and seven met the final criteria. Results: The review highlights significant reductions in pediatric infectious diseases, particularly in regions with high vaccination coverage for diseases such as pneumococcal pneumonia, measles, and Hib (Haemophilus influenzae type b). Studies report over 90% reductions in incidence rates for certain diseases in countries with comprehensive immunization programs, showcasing the importance of sustained, widespread coverage. Conversely, in regions with lower coverage, diseases remain prevalent, indicating the need for strengthened immunization strategies. Conclusion: Effective vaccination programs are crucial for reducing pediatric disease rates, improving public health, and fostering herd immunity. Increased vaccine accessibility, education, and coverage are necessary, especially in low-coverage regions, to advance global health goals for pediatric control.

Development of Time-Aggregated Machine Learning Model for Relapse Prediction in Pediatric Crohn's Disease.

Pediatric Crohn's disease (CD) easily progresses to an active disease compared to adult CD, making it important to predict and minimize CD relapses. However, prediction of relapse at various time points (TPs) during pediatric CD remains understudied. We aimed to develop a real-time aggregated model to predict pediatric CD relapse in different TPs and time windows (TWs). This retrospective study was conducted on children diagnosed with CD between 2015 and 2022 at Severance Hospital. Laboratory test results and demographic data were collected starting at 3 months after diagnosis, and cohorts were formed using data from six different TPs at 1-month intervals. Relapse-defined as a pediatric CD activity index ≥30 points-was predicted, and TWs were 3-7 months with 1-month intervals. The feature importance of the variables in each setting was determined. Data from 180 patients were used to construct cohorts corresponding to the TPs. We identified the optimal TP and TW to reliably predict pediatric CD relapse with an area under the receiver operating characteristic curve score of 0.89 when predicting with a 3-month TW at a 3-month TP. Variables such as C-reactive protein levels and lymphocyte fraction were found to be important factors. We developed a time-aggregated model to predict pediatric CD relapse in multiple TPs and TWs. This model identified important variables that predicted relapse in pediatric CD to support real-time clinical decision making.

A Review of Fecal Microbiota Transplantation in Children-Exploring Its Role in the Treatment of Inflammatory Bowel Diseases.

Background and Objectives: There is an increasing use of fecal matter transplantation (FMT) worldwide as research into the impact of the gut microbiome in various disease states is growing. FMT is the transfer of stool from a healthy human donor to a patient for the purpose of restoring intestinal dysbiosis. This review will assess the efficacy and safety of FMT in the treatment of pediatric inflammatory bowel diseases (IBDs) and explore the future directions of the use of FMT in children. Materials and Methods: A systematic review was performed where a literature search of publications published prior to 15 September 2023 was performed. Efficacy outcomes and safety data as well as microbiome analysis were reviewed from the studies where applicable. Results: Nine studies on UC and two studies on CD satisfied eligibility criteria and individually analysed. Most of the studies provided microbiome analyses. Conclusions: FMT is a safe treatment for paediatric IBD, and is shown to be effective in inducing clinical response by some studies. However the lack of randomized controlled trials limited the results of our study.

Quantified small bowel motility assessment on magnetic resonance enterography in paediatric inflammatory bowel disease - does it reflect clinical response?

Quantified small bowel motility assessment using cine magnetic resonance enterography (MRE) has shown promise as a biomarker in adult inflammatory bowel disease. Whether quantified motility corresponds to treatment response in paediatric inflammatory bowel disease is unknown. To test whether changes in motility reflect response. Local ethics approval was granted for this single-institution, retrospective study. All children < 18years with confirmed inflammatory bowel disease, who had more than one MRE between Jan 2011-Jan 2022, were included. Simplified MaRIA (sMaRIA) and motility index (quantified motility) at all terminal ileum and diseased non-terminal ileum segments were independently assessed by two radiologists each with ≥ 9years' experience. Change in (Δ) motility index was compared to clinical (gastroenterologist physician's global assessment) and consensus radiological reference standard (response = decrease in sMaRIA of more than or equal to 2 points) in responders versus non-responders using the Mann-Whitney test. Sensitivity and specificity of Δ motility index more than zero were compared to decrease in sMaRIA of 2 or more points for identifying clinical response. Of 64 children aged 5-16, 21 out of 64 (33%) were responders, 37 out of 64 (58%) were non-responders and 6 out of 64 (9%) had inactive disease according to clinical reference standard. Δ Motility index by both radiologists was higher in responders (+ 16, + 39) than non-responders (-43, -44), P = 0.04, P = 0.01 each radiologist, respectively. Motility index was more sensitive (57% versus 24%), but less specific (67% versus 93%) than sMaRIA in identifying clinical response. Motility index on cine MRE corresponds to clinical response, and is more sensitive at detecting response compared to sMaRIA in paediatric inflammatory bowel disease.