Translational pediatrics最新文献

Background: Data on neonatal Mycoplasma pneumoniae (MP) infection in the post-coronavirus disease 2019 (post-COVID-19) era are scarce, despite MP being a common respiratory pathogen. This study explored the epidemiology and clinical features of hospitalized neonates with MP infection in Chengdu.

Methods: A retrospective study was conducted on 61 neonates with MP infections admitted to Chengdu Women's and Children's Central Hospital from January 2023 to April 2025. Demographic, clinical, laboratory, and imaging data were collected from electronic medical records (EMRs). Real-time polymerase chain reaction (PCR) and serological testing confirmed MP infection.

Results: MP infections peaked in autumn (44.3%) and winter (27.9%) and were most prevalent in neonates aged ≥22 days (49.2%). Cough (59.0%) and fever (27.9%) were the most common symptoms. Co-infections were observed in 52.5% of cases, predominantly with respiratory syncytial virus (RSV; 13.1%). Multivariate analysis identified fever [adjusted odds ratio (OR) =5.92], multiple pathogens (adjusted OR =5.33), and oxygen therapy (adjusted OR =11.84) as independent risk factors for prolonged hospital stay (>10 days). Symptomatic neonates had higher C-reactive protein (CRP) levels (P=0.01) and longer hospital stays (P=0.009) than asymptomatic ones.

Conclusions: During the post-COVID-19 era, neonatal MP infections in Chengdu show autumn-winter predominance and are associated with specific clinical factors affecting hospitalization duration, highlighting the need for targeted management in high-risk neonates.

Background: Severe pertussis usually occurs in children. The modified exchange blood transfusion (ET) has some benefits, but has not been widely used in children with severe pertussis. Therefore, the effects of ET on severe pertussis are to be illustrated. This study aimed to investigate the effects of ET on severe pertussis in children, and summarize the key points of nursing.

Methods: A case-control study of infants with severe pertussis in a tertiary hospital in south China from January 2018 to December 2019 was conducted. Severe pertussis children receiving modified ET were included in the ET group, while those without modified ET were selected into the control group. The demographics, symptoms and signs, laboratory indicators, imaging examination, and outcomes were collected and analyzed.

Results: The total mortality rate of severe pertussis children was 38.7% (12/31). The mortality rate was 16.7% (2/12) in the ET group, and 52.6% (10/19) in the control group (P<0.05). White blood cell count, absolute lymphocyte count, platelet count, and heart rate of the ET group significantly decreased (P<0.05).

Conclusions: Modified ET was effective in severe pertussis and could decrease the mortality rate. Close attention to preoperative preparations, observation, and timely intervention could reduce the occurrence of complications of modified ET.

Background: Familial hypercholesterolemia (FH) is a severe hereditary lipid metabolism disorder. Homozygous FH (HoFH) in particular was marked by rapid disease progression, with afflicted children at risk of developing coronary heart disease or even suffering from fatal myocardial infarction in their teenage years. This case report is aim to deepen understanding of HoFH's complexity and provide a scientific foundation for early diagnosis, personalized therapy to improve treatment protocols and reduce the burden on patients and families.

Case description: We report two Chinese sisters presenting with multiple xanthomas from early childhood. Laboratory results showed markedly elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. Genetic testing revealed compound homozygous variants in the low-density lipoprotein receptor (LDLR) gene: a synonymous variant (c.1216C>A, p.Arg406Arg) likely affecting mRNA (messenger RNA) splicing inherited from the mother, and a missense variant (c.1879G>A, p.Ala627Thr) from the father. Both variants were classified as potentially pathogenic based on SpliceAI prediction, clinical phenotype, and co-segregation in the family. Treatment with rosuvastatin and ezetimibe yielded limited LDL-C reduction. In the elder sister, a single dose of evolocumab reduced LDL-C by 27.1% and led to partial regression of xanthomas within 15 days.

Conclusions: This study underscores the critical importance of early diagnosis and treatment in HoFH and highlights the necessity for ongoing research into more effective therapeutic strategies. Through this report, we aim to deepen the understanding of HoFH's complexity and foster the development of improved treatment protocols. Ultimately, our in-depth analysis aspires to provide a scientific foundation for early diagnosis, risk assessment, personalized therapy, and comprehensive management of FH, thereby alleviating the health burden imposed on affected patients and their families.

Background: Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease causing right heart failure. Idiopathic PAH (IPAH), a type of PAH with unknown causes, has a particularly poor prognosis. Current targeted therapies are insufficient, highlighting the need for new therapeutic targets and biomarkers. This study aims to identify potential metabolic biomarkers and dysregulated pathways for the diagnosis and treatment of IPAH through integrated metabolomic and transcriptomic analyses.

Methods: This study enrolled PAH patients [2023-2024] and collected pretreatment blood samples, using healthy children as controls. RNA sequencing analyzed gene expression in peripheral blood mononuclear cells (PBMCs), and liquid chromatography-mass spectrometry (LC-MS) detected blood metabolites. Metabolites were identified via multiple databases, and bioinformatics analyses [principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA)] explored PAH's molecular mechanisms.

Results: In PAH patients, 1,629 differentially expressed genes (DEGs) were found, with 802 upregulated and 827 downregulated genes, enriched in cell cycle regulation, stress response, and mitochondrial dysfunction. Metabolomics showed 30 upregulated and 29 downregulated metabolites, mainly in amino acid and energy metabolism. Key genes like LDHB and IRS2, and metabolites such as glucose and L-glutamine, are closely linked to PAH's pathology, especially in glycolysis pathways.

Conclusions: The study underscores the intimate connection between transcription factor (e.g., JUNB, ZNF281)-regulated gene expression (e.g., LDHB, IRS2) and metabolite (e.g., glucose, L-glutamine) alterations in PAH, revealing that key genes and metabolites closely tied to the disease's pathology.

Background: Sudden infant death syndrome (SIDS) remains a critical global public health threat. This study comprehensively assessed the global burden, inequalities, frontier progress, and risk factors of SIDS from 1990 to 2021.

Methods: Using data from the Global Burden of Disease (GBD) 2021 study, we performed a cross-sectional study to analyze the mortality and disability-adjusted life years (DALYs) of SIDS across 204 countries and regions, stratified by sex, age, and sociodemographic index (SDI). Advanced methodologies included inequality analysis, frontier analysis to identify unfulfilled improvement potential, and risk factor quantification via meta-regression.

Results: From 1990 to 2021, the global burden of SIDS demonstrated a substantial decline, with deaths decreasing from 75,719 to 30,608 and the mortality rate declining from 59.3 to 24.2 per 100,000 population. Males had higher mortality and DALYs rates compared to females, peaking at 51.9% in those aged 1 to 5 months. While absolute inequalities narrowed, relative disparities worsened. Frontier analysis revealed 15 high-priority countries (e.g., USA, Nigeria, India) with unfulfilled improvement potential despite socioeconomic advancement. Low birth weight and short gestation were identified as major risk factors, with the burden of SIDS attributable to these factors increasing after 2019.

Conclusions: Despite an overall reduction in the global burden of SIDS, it remains a significant public health challenge with pronounced gender, age, and socioeconomic inequalities. However, significant heterogeneity in diagnostic practices and a well-documented shift in death certification from SIDS to broader classifications mean our results may underestimate the true decline in sudden unexpected infant deaths. To further reduce the burden of SIDS, targeted interventions are needed, focusing on perinatal health, addressing gender and age disparities, tackling region-specific air pollution issues, and prioritizing efforts in high-burden countries.

Background: Glycogen storage disease type IV (GSD IV), Andersen disease, is a rare autosomal recessive disorder of glycogen metabolism typically associated with liver failure and cardiomyopathy. Isolated non-infectious cardiac valvular disease as a sequela of GSD IV has not been previously reported in this population. We aim to describe the first reported case of non-infectious endocarditis as a novel cardiac manifestation in a patient with GSD IV.

Case description: We report the case of a 16-year-old male with GSD IV, status post liver transplant in infancy, who presented with fever, fatigue, and cough. He was found to have new-onset mitral valve disease and, over 6 weeks, developed progressive polyvalvular pathology affecting the mitral, aortic, tricuspid, and pulmonary valves. Despite broad-spectrum antibiotics, his condition worsened and necessitated surgical mitral valve replacement, aortic valve reconstruction, and tricuspid valve repair. An extensive infectious and rheumatologic work-up-including serial blood cultures, cell-free deoxyribonucleic acid (DNA) testing (Karius^©), and broad-range polymerase chain reaction (PCR) on excised tissue-was negative. Histopathologic analysis of the mitral valve revealed sheets of glycogenated histiocytes and inflammatory infiltrates, consistent with noninfectious endocarditis as a sequela of GSD IV.

Conclusions: This is the first report of non-infectious endocarditis, also known as Libman-Sacks endocarditis, in a patient with GSD IV as a primary manifestation of their underlying metabolic disorder, representing a novel cardiac manifestation of the disease. In patients with GSD IV who develop valvular lesions and have a negative infectious work-up, clinicians should consider noninfectious endocarditis as a progression of their genetic disease. Regular cardiac surveillance may be warranted in this population to identify valvular involvement early.

Background: Necrotizing enterocolitis (NEC) is a life-threatening neonatal gastrointestinal emergency, characterized by a high surgical mortality rate, and growth retardation and adverse neurodevelopmental outcomes among survivors. Given these challenges, this study aimed to evaluate and analyze factors that affect the rate of postoperative weight gain in children undergoing NEC surgery, and the rate of postoperative weight gain influence on short-term clinical outcomes.

Methods: A retrospective study was conducted of infants with NEC who underwent intestinal surgery between January 1, 2014, and December 31, 2022. The patients were stratified into the low rate of weight gain (LRWG) group and high rate of weight gain (HRWG) group, with the threshold defined as an average postoperative weight gain of ≥10 g/(kg·d). Univariate and multivariate logistic regression analyses were employed to identify the risk factors associated with a LRWG. Both groups underwent comprehensive physical and neurodevelopmental assessments. Statistical analyses were performed using SPSS 26.0; a two-sided P value <0.05 was considered statistically significant.

Results: In total, 80 patients were included in the final analysis, of whom, 45 were assigned to the LRWG group, and 35 to the HRWG group. The proximal remaining bowel length, duration of postoperative antibiotics, and time to full enteral feeding (EF) were identified as risk factors for a LRWG in the preterm infants with NEC postoperatively. The LRWG group had worse neurodevelopmental outcomes [i.e., lower Neonatal Behavioral Neurological Assessment (NBNA) scores] than the HRWG group. At 1-3 months of corrected age, the patients in the LRWG group had lower scores in terms of their fine motor skills, language proficiency, length-for-age Z-score (LAZ), weight-for-age Z-score (WAZ), head circumference-for-age Z-score (HcAZ), and ability to respond to materials and people than those in the HRWG group. A similar trend was observed at corrected ages of 4-6 and 7-12 months; that is, the patients in the LRWG group exhibited lower scores in terms of their fine motor skills, ability to respond to materials and people, WAZ, LAZ, and HcAZ than those in the HRWG group. At 13-24 months of corrected age, the patients in the LRWG group had lower scores in terms of their ability to respond to materials and people, WAZ, and HcAZ than those in the HRWG group.

Conclusions: A LRWG may affect the subsequent physical and central nervous system (CNS) development of infants. Therefore, optimizing intestinal length preservation and refining nutritional management are essential strategies for improving the surgical outcomes and long-term prognosis of NEC patients.

Background: Idiopathic central precocious puberty (ICPP) and early puberty (EP) in boys affect growth and development. While brain magnetic resonance imaging (MRI) is routinely used to exclude organic causes, the diagnostic value of quantitative pituitary morphometry remains largely unexplored in male populations. This study aimed to investigate the associations between pituitary morphometry (including length, width, height, and volume) and ICPP or EP in boys, and to evaluate their potential as imaging biomarkers for diagnostic purposes.

Methods: In this retrospective case-control study, boys who underwent evaluation for precocious puberty at the Department of Endocrinology, Children's Hospital, Capital Institute of Pediatrics, Beijing, China between January 2015 and December 2024 and were subsequently diagnosed with ICPP or EP were enrolled. Age-matched healthy boys served as controls. Pituitary dimensions (length, width, height) and volume were measured by contrast-enhanced MRI. Spearman correlation analyzed their relationships with sex hormones and gonadal development. Multivariable logistic regression evaluated associations with ICPP/EP, with restricted cubic spline (RCS) regression exploring nonlinear trends.

Results: A total of 354 boys were enrolled: 118 in the case group (ICPP/EP) and 236 in the healthy control group. The median age of the case group was 9.86 years, among whom 24.6% (29/118) were obese and 11.9% (14/118) were overweight. The case group exhibited significantly greater pituitary width and volume compared with the control group (width: 11.80 vs. 10.90 mm, P<0.001; volume: 201.50 vs. 165.58 mm³, P<0.001). In the case group, pituitary width and volume were significantly correlated with serum levels of luteinizing hormone and testicular volume (P<0.05). For boys with ICPP/EP, a pituitary width >13 mm or a volume >240 mm³ was associated with an increased risk of ICPP/EP.

Conclusions: Increased pituitary width and volume in boys with ICPP/EP are associated with elevated serum LH levels and testicular volume, suggesting their potential as imaging biomarkers for the clinical diagnosis of ICPP/EP. Further research is needed to validate these findings.

Background: Persistent sporadic congenital non-autoimmune hyperthyroidism (PSNAH), a rare autosomal dominant disorder caused by gain-of-function thyroid-stimulating hormone receptor (TSHR) pathogenic variants, manifests with protean clinical features that frequently elude timely detection. We present a pediatric case of genetically confirmed PSNAH harboring a de novo TSHR mutation, in which diagnostic delays triggered life-threatening multiorgan complications.

Case description: We report a 34-month-old boy presenting with acute-onset dyspnea, severe mitral regurgitation, ventriculomegaly, and cerebellar tonsillar herniation. Biochemical profiling demonstrated severe hyperthyroidism: extremely low levels of thyrotropin (TSH 0.01 µIU/mL), elevated free triiodothyronine (fT3 >30.8 pmol/L; normal 3.5-6.5), free thyroxine (fT4 73.39 pmol/L; normal 11.5-22.7), total T3 (9.78 nmo/L; normal 1.6-4.1), and total T4 (288.7 nmol/L; normal 94-193.1). Genetic testing identified a de novo heterozygous TSHR mutation (c.1868C>T, p.Ala623Val). Multidisciplinary management included methimazole, metoprolol, diuretics, and staged procedures: emergent ventriculoperitoneal shunting preceding mitral valvuloplasty with chordal reconstruction under cardiopulmonary bypass. Postoperative echocardiography confirmed normalization of left ventricular end-diastolic dimension (LVEDD) at 30-day follow-up, though biochemical euthyroidism remained elusive post-9-month antithyroid therapy.

Conclusions: PSNAH may manifest as a multisystem disorder with thyrotoxicosis-associated valvular heart disease as a sentinel presentation. Prenatal thyrotropin receptor hyperactivity and delayed treatment initiation induce structural valvulopathy and cerebellar tonsillar herniation. Early pharmacologic intervention coupled with valve-sparing surgery can restore valvular integrity. The necessity for further neurosurgical intervention in the subsequent management of cerebellar tonsillar herniation requires further longitudinal follow-up.

Background: Respiratory syncytial virus (RSV) poses a significant global health burden, particularly among neonates and preterm infants due to their immunologic immaturity, with limited regional epidemiological data. We aimed to explore the epidemiology of acute lower respiratory tract infections (ALRTI) related to RSV infections in hospitalized neonates and the risk factors associated with severe infections.

Methods: A total of 7,420 hospitalized ALRTI neonates admitted to the Children's Hospital of Soochow University from January 2013 to December 2023 were included in this retrospective study. Their epidemiological and clinical data were collected and analyzed. The general data and laboratory test data between the two groups were compared. Severe RSV infection was defined as requiring oxygen therapy, ICU admission, or mechanical ventilation.

Results: There were 875 (11.79%) neonates with positive RSV infection, with 459 males (52.46%) and 416 females (47.54%) and a median age of 19 days. The detection rate of RSV was the highest in winter [24.83% (583/2,299)]. Moreover, 191 RSV cases (21.83%) were severe cases. Logistic regression analysis showed that preterm birth [odds ratio (OR) =2.325, 95% confidence interval (95% CI): 1.112-4.859], high-sensitivity C-reactive protein (hsCRP) ≥8 mg/L (OR =2.580, 95% CI: 1.527-4.359), mixed infection (OR =1.493, 95% CI: 1.038-2.146), and combined underlying disease (OR =3.679, 95% CI: 2.247-6.023) were the independent risk factors for hospitalized neonatal RSV infection among ALRTI neonates.

Conclusions: RSV is one of the most common causes of ALRTI in hospitalized neonates. RSV affects neonates and carries the greatest impact in late preterm neonates with seasonal peaks in the autumn and winter months. Early identification of risk factors (as prematurity or elevated levels of hsCRP, mixed infections, or preexisting conditions or risk factors) can help make timely interventions and enable targeted preventive approaches to alleviate the burden.