Clinical and Experimental Pediatrics最新文献

Background: Childhood-onset lupus nephritis (cLN) is an aggressive disease. Although histological class has historically guided its treatment, its prognostic value remains limited. Although the National Institutes of Health (NIH)-modified activity index (AI) and chronicity index (CI) incorporate glomerular and tubulointerstitial changes and may provide better prognostic insight, their utility in cLN is not well established.

Purpose: Here we aimed to assess the utility of the NIH-modified-modified AI and CI for predicting kidney outcomes and identify histopathological features and treatment-related factors associated with the development of kidney function impairment in cLN.

Methods: We retrospectively analyzed 60 children with biopsy-proven proliferative lupus nephritis. Their baseline clinical and histological features, treatments, and outcomes were assessed. The association between AI and CI scores, along with individual histological components, and kidney function impairment, defined as an estimated glomerular filtration rate < 90 mL/min/1.73 m² sustained for ≥3 months, was evaluated.

Results: Over a median follow-up of 55.5 months, 30% of patients developed kidney function impairment. AI scores and glomerular lesions did not differ significantly between patients with and without kidney function impairment. However, the CI scores were significantly higher in patients who developed kidney function impairment, with tubular atrophy and interstitial fibrosis being the most predictive components. On a multivariate analysis, tubular atrophy was an independent predictor of kidney function impairment (hazard ratio [HR], 17.74; 95% confidence interval [CI], 1.94-162.5; P=0.01). Use of mycophenolate mofetil (MMF) as maintenance therapy was associated with a reduced risk of kidney function impairment (HR, 0.09; 95% CI, 0.02-0.47; P=0.003).

Conclusion: Chronic tubulointerstitial changes, particularly tubular atrophy, are a stronger predictor of longterm kidney function than glomerular findings or AI scores. These findings highlight the prognostic value of NIH-modified CI and the importance of MMF in maintenance therapy. The early identification of chronic lesions on biopsy may guide therapeutic decisions aimed at preserving kidney function and improving long-term outcomes in patients with cLN.

Background: Early adiposity rebound (AR) is a key predictor of later obesity and metabolic risk, yet modifiable factors related to early AR remain understudied in large populations.

Purpose: To quantify the prevalence of early AR at age 3 years and identify modifiable correlates in a population‑based cohort of Japanese preschool children.

Methods: We retrospectively analyzed health-check records for 74,466 children who attended both 1.5- and 3-year examinations (2014-2019). Body mass index (BMI) values were converted to World Health Organization z scores; early AR was defined as any increase in BMI between 1.5 and 3 years. Multivariable logistic regression adjusted for birth weight category, sex, household structure, sleep duration, and behavioral factors.

Results: Early AR occurred in 18,673 children (25%), whereas obesity (BMI z score ≥1.64) was present in 4% at 3 years. After controlling the adjustments, routine breakfast consumption (odds ratio [OR] 0.88; 95% confidence interval [CI], 0.81-0.97) and regular napping at 1.5 years (OR, 0.84; 95% CI, 0.79-0.90) were independently associated with reduced odds of early AR, while obesity at 1.5 years strongly predicted early AR (OR, 4.32; 95% CI, 4.00-4.67). Routine juice intake or fast-food consumption showed no significant associations.

Conclusion: In this population‑based cohort, one in 4 preschoolers had early AR by age 3. Simple daily routines-eating breakfast and maintaining regular sleep-may help delay AR and offer actionable targets for early obesity prevention.

Background: Although most neonatal disorders are preventable, their global burden has not been comprehensively investigated in the context of underlying epidemiological patterns. Thus, here we conducted the first comprehensive assessment of the global burden of neonatal disorders and their 5 subtypes in 1990-2021 with projections through 2050.

Purpose: To comprehensively assess the global burden of neonatal disorders in 1990-2021 and forecast trends through 2050 considering their significant contribution to infant mortality.

Methods: We estimated the global burden of neonatal disorders (preterm birth, encephalopathy due to birth asphyxia and trauma, hemolytic disease and other neonatal jaundice types, sepsis, and other neonatal infections) and their attributable risk factors, including low birthweight, short gestation, household air pollution, and ambient particulate matter, using data from the Global Burden of Disease Study (GBD) 2021. Population attributable fractions were used to calculate the rates of age-standardized incidence (ASIR), mortality (ASMR), and disability-adjusted life years (ASDR) stratified by age, sex, sociodemographic index (SDI), and region. The disease burden forecasted through 2050 was evaluated by projection modeling using the GBD framework.

Results: From 1990 to 2021, the ASIR, ASMR, and ASDR for neonatal disorders decreased: 466.94 (95% uncertainty interval, 461.65-473.62) to 437.43 (433.20-441.95), 46.06 (43.66-48.81) to 29.57 (25.37-34.26), and 4,343.25 (4,121.18-4,595.48) to 2,941.00 (2,547.76-3,384.20) per 100,000 population, respectively. Males (489.90 [484.15-495.69]) exhibited a higher rate of the age-standardized incidence for neonatal disorders. The burden of neonatal disorders was markedly higher in countries with lower SDI scores. Neonatal preterm birth is the leading cause of neonatal disorders in both sexes. Among 4 risk factors, a low birthweight contributed the most to the ASDR of neonatal disorders (2,227.54 [1,939.96-2,563.52]). The global ASDR for neonatal disorders is projected to decline from 2,022 (2,317.01 [1,982.04-2,700.43]) to 2,050 (1,230.57 [950.09-1,590.15]).

Conclusion: Although the overall burden of neonatal disorders has decreased, substantial disparities have persisted across SDI levels with the highest burden observed in low-SDI countries. Among the subtypes, a preterm neonatal birth accounted for the highest burden, whereas a low birthweight was the most significant risk factor. To achieve global child health targets, it is essential to address regional disparities and promote equity in access to healthcare services and health outcomes.

Background: Most children recover after an initial acute pancreatitis (AP) episode; however, some progress to recurrent AP (RAP) or chronic pancreatitis (CP).

Purpose: We aimed to quantify progression rates and identify the risk factors associated with these transitions.

Methods: 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 (OR) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic.

Results: 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.

Conclusion: Approximately one in five 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.

Sacral dimples are the most common cutaneous anomalies in newborns. While usually benign anatomical variants, some dimples are indicative of occult spinal dysraphism, such as a tethered cord, dermal sinus tract, or lipomyelomeningocele, that, if undiagnosed, may cause irreversible neurological, orthopedic, and urological deficits. Distinguishing benign from high-risk dimples is essential for timely intervention. This review summarizes the embryological origins, diagnostic criteria, imaging approaches, and management strategies for sacral dimples to help clinicians identify cases requiring further evaluation. A comprehensive literature review examines the embryology of caudal spinal development, classification of spinal dysraphism, and studies of the diagnostic accuracy of ultrasonography and magnetic resonance imaging (MRI) in infants with sacral dimples. Guidelines and high-quality studies of the surgical outcomes of tethered cords and related anomalies were also analyzed. The literature search and study selection followed the Preferred Reporting Items for Systematic Reviews and Meta- Analyses flow. Simple sacral dimples-solitary midline depressions less than 5 mm in diameter, located within 2.5 cm of the anus, and lacking associated cutaneous stigmata-are not associated with spinal dysraphism and do not require imaging. In contrast, atypical dimples (large, deep, off-midline, or associated with skin markers such as hair tufts or hemangiomas) are significantly associated with occult anomalies and warrant imaging, beginning with spinal ultrasonography in neonates and MRI in older infants or equivocal cases. Conditions such as tethered cord, dermal sinus tract, lipomyelomeningocele, and split cord malformations are best visualized using MRI. Early surgical detethering improves neurological, orthopedic, and bladder outcomes, whereas delayed intervention risks permanent deficits. Applying standardized criteria and targeted imaging avoids unnecessary investigations while ensuring a timely diagnosis of occult spinal dysraphism. Early recognition and appropriate surgical management, when indicated, are critical for preventing neurological deterioration and improving the prognosis of affected infants.

Childhood and adolescent obesity represent critical global health issues with a rising prevalence and associated cardiometabolic and psychosocial consequences. Pharmacotherapy has emerged as an adjunct treatment to lifestyle modifications in patients with severe obesity or a poor response to behavioral interventions. However, the ethnic and racial variations in drug efficacy and safety remain poorly understood. This systematic review aimed to determine whether ethnicity influences the efficacy and adverse effects of pharmacological treatments for pediatric obesity. A comprehensive literature search was conducted using PubMed, Embase, Scopus, and Cochrane Library databases for studies published between January 2000 and December 2024. Eligible randomized controlled trials included participants aged ≤18 years and reported ethnicity-specific outcomes for antiobesity pharmacotherapy. Of the 3,979 identified records, 4 randomized trials met the inclusion criteria and investigated liraglutide, metformin, phentermine/topiramate, and sibutramine. Across all studies, pharmacotherapy significantly reduced body mass index compared with placebo. This review provides a complete and clearly articulated conclusion reflecting these findings. However, consistent evidence is lacking of ethnicity-based differences in efficacy or safety. One trial suggested a possible trend of reduced responses among African American adolescents receiving sibutramine, although the findings were underpowered and exploratory. Common limitations include minority group underrepresentation, small subgroup sizes, heterogeneous outcome measures, and post hoc analyses of ethnicity. The risk of bias across trials ranged from low to some concern, primarily due to post hoc analyses, incomplete outcome data, and a lack of prespecified ethnicity-stratified outcomes, and limited confidence in the findings. Overall, the current evidence does not support major ethnicity-related differences in the pharmacological management of pediatric obesity, although the certainty of this evidence is low. Larger prospectively designed trials with prespecified ethnic subgroup analyses are urgently needed to establish equitable personalized approaches to pharmacotherapy for childhood obesity. (registration number: CRD42025117631).

Background: Acute necrotizing encephalopathy (ANE) is a rare but devastating neurological disorder in children that is typically triggered by viral infections such as influenza, sudden acute respiratory syndrome coronavirus 2, and human herpesvirus-6. ANE is characterized by cytokine storm and associated with high mortality; however, optimal immunomodulatory strategies remain undefined.

Purpose: To evaluate the effectiveness of multiple immunomodulatory strategies, including high-dose methylprednisolone (MP), plasma exchange (PLEX), and tocilizumab, at reducing short-term mortality among pediatric patients with ANE stratified by disease severity using the ANE severity score (ANE-SS).

Methods: We retrospectively reviewed 65 pediatric patients (median age, 4.8 years; interquartile range, 2.8-7.7 years) diagnosed with ANE at Beijing Children's Hospital from 2016 to 2024. Patients were stratified by ANE-SS at admission into low- to medium-risk (ANE-SS<5) and high-risk (ANE-SS≥5) groups. Immunomodulatory treatments included different doses of MP, intravenous immunoglobulin, PLEX, and tocilizumab. The primary outcome was the 28-day postdischarge mortality. Multivariate logistic regression was used to identify the treatment strategies that were independently associated with improved survival.

Results: The overall 28-day postdischarge mortality rate was 45.9%, significantly higher in patients with ANE-SS ≥5 (65.7%) than in those with ANE-SS<5 (16.7%; P<0.001). A notable decline in mortality has been observed since 2022, coinciding with the increased use of high-dose MP (20 and 30 mg/kg/day) and tocilizumab. The annual mortality rate will drop to 38.9% in 2022, 36.8% in 2023, and 16.7% in 2024. In low- to medium-risk patients (ANE-SS<5), both 20-mg/kg/day and 30-mg/kg/day MP were associated with improved outcomes. In high-risk patients (ANE-SS≥5), the combination of 30-mg/kg/day MP and tocilizumab provided the greatest survival benefit. Multivariable logistic regression analysis identified that this combined therapy was independently associated with reduced mortality (odds ratio, 0.04; 95% confidence interval, 0.01-0.18; P<0.001). No significant survival benefit was observed following PLEX treatment.

Conclusion: In low- to moderate-risk patients, the 20- and 30-mg/kg/day MP regimens were effective. In high-risk patients with ANE, high-dose MP (30 mg/kg/day), particularly when combined with tocilizumab, may improve survival and possibly long-term neurological recovery. These findings support the use of a severity-based immunotherapy strategy for pediatric patients with ANE.

Pneumococcal disease remains the leading cause of morbidity in young children worldwide. Recent advances have expanded pneumococcal conjugate vaccines (PCVs) beyond 13-valent (PCV13) to 15-valent (PCV15) and 20- valent (PCV20) vaccines, which add 2 and 7 serotypes, respectively, thereby broadening their potential protective effects against invasive pneumococcal disease (IPD). Although policies vary among countries, Korea incorporated PCV15 and PCV20 into its National Immunization Program for children in April 2024 and October 2025, respectively, an implementation that is considered within the context of global epidemiology and policy trends. This review discusses evidence of the immunogenicity and safety of PCV15 and PCV20 from clinical trials and early postlicensure data, examines the serotype distribution and IPD burden in Korea alongside data from other regions, and summarizes vaccination recommendations for healthy and high-risk pediatric populations, including considerations for catch-up, interchangeability, and their coadministration. By integrating national updates and global evidence, this review aims to support clinicians and policymakers worldwide optimizing pneumococcal vaccination strategies for children.

The ingestion of foreign bodies and caustic substances represents a significant clinical concern in pediatric populations, particularly among children aged 1-5 years. These events can result in a wide spectrum of complications ranging from acute, life-threatening emergencies to delayed sequelae with long-term morbidities. The severity and clinical course are influenced by multiple factors, including ingested material's nature, size, shape, and chemical composition, as well as its anatomical location, particularly when esophageal impaction occurs. High-risk foreign bodies- such as button batteries, high-powered magnets, sharp objects, superabsorbent polymers, and items containing toxic substances-pose an elevated risk of rapid tissue injury or perforation. Similarly, the ingestion of caustic agents, whether acidic or alkaline, carries the potential for extensive mucosal damage, with the degree of injury dictated by the pH, volume ingested, and inherent toxicity. Clinical management requires a highly individualized, case-by-case approach guided by the clinical presentation, imaging findings, and endoscopic evaluation findings. Endoscopy plays a pivotal role in the diagnostic assessment of mucosal injury and is a therapeutic modality for foreign body retrieval. Timely endoscopic interventions are strongly associated with improved outcomes and reduced complication rates. A high index of clinical suspicion remains critical to ensuring early diagnosis, prompt intervention, and the prevention of both acute and long-term complications, including strictures, perforations, and impaired quality of life. Comprehensive, multidisciplinary management is essential for optimizing patient outcomes in these potentially complex clinical scenarios.