Pediatric Investigation最新文献

Pediatric epilepsy is a neurological disorder arising from various etiologies, including structural, genetic, immune, infectious, metabolic, and unknown causes. Anti-seizure medications remain the primary treatment; however, in cases of drug-resistant epilepsy, surgical interventions, ketogenic diet, and emerging therapies have become increasingly effective options. Disease-modifying treatments, such as antisense oligonucleotides and adeno-associated virus-mediated gene replacement, have shown promise in some epilepsy treatments, with early trials reporting moderate seizure reduction. Minimally invasive surgical approaches, including magnetic resonance-guided laser interstitial thermal therapy, have also demonstrated favorable outcomes, showing a 68% seizure-free rate at 2 years in the largest pediatric series. Although the ketogenic diet is effective in some patients, demonstrating superiority over conventional management for >50% seizure reduction, long-term use may be associated with metabolic risks; careful monitoring is warranted. Future treatment strategies are expected to emphasize personalized medicine through the integration of genetic, electrophysiological, and neuroimaging data to optimize therapeutic decision-making and enable targeted interventions based on the underlying etiology.

This guideline aims to standardize the prevention and management of complications related to umbilical venous catheterization (UVC). It addresses nine clinical questions, categorized into three sections: (1) questions concerning UVC-related infection, (2) catheter position, and (3) UVC maintenance. Literature screening and review were completed for all papers published up to May 31, 2025. Relevant evidence was synthesized through meta-analysis where applicable, and the GRADE methodology was applied to grade the quality of evidence and the strength of recommendations. The guideline establishes a total of nineteen recommendations and suggestions.

Importance: Acute necrotizing encephalopathy (ANE) is a rare but life-threatening pediatric neurological disorder characterized by rapid progression and high mortality. Tocilizumab, an interleukin-6 receptor antagonist, combined with high-dose methylprednisolone [MP, ≥20 mg/(kg·day)], may improve outcomes, yet the optimal MP dosing strategy remains uncertain.

Objective: To evaluate the comparative effectiveness and safety of two high-dose MP regimens [20 mg/(kg·day) vs. 30 mg/(kg·day)], each in combination with tocilizumab for ANE.

Methods: This retrospective cohort study included 23 ANE patients treated with tocilizumab and high-dose MP at Beijing Children's Hospital from January 2023 to January 2025. Patients were divided into two groups based on the initial MP dosage: 20 mg/(kg·day) (n = 11) and 30 mg/(kg·day) (n = 12). Primary outcomes included mortality and anti-inflammatory response. Secondary outcomes were the incidence of severe neurological sequelae, assessed using the pediatric overall performance category (POPC) score, and the frequency of treatment-related adverse events.

Results: Overall mortality rate was 26.1% with a lower rate observed in the 30 mg/(kg·day) group (16.7%) compared to the 20 mg/(kg·day) group (36.4%). Most patients (78.3%) had severe ANE (ANE Severity Score ≥5), and 91.3% presented with multi-organ dysfunction and brainstem involvement. Both groups demonstrated significant reductions in procalcitonin, cerebrospinal fluid protein, and cerebrospinal cytokines after 3 days of MP therapy (P < 0.05). Compared with the 20 mg/(kg·day) group, the 30 mg/(kg·day) MP group had significantly lower rates of severe neurological sequelae (POPC score 4-6) at discharge (41.7% vs. 90.9%; P = 0.027) and at 6-12 months follow-up (30.0% vs. 85.7%; P = 0.050). No statistically significant differences in adverse event rates were observed between the two groups (P > 0.05), and no tocilizumab-related adverse events were reported.

Interpretation: In pediatric ANE, tocilizumab combined with 30 mg/(kg·day) MP was associated with improved neurological outcomes compared with 20 mg/(kg·day), with comparable mortality and safety profiles. These findings suggest that a higher initial MP dose may offer neuroprotective advantages, warranting further validation in prospective, multicenter studies.

Importance: The coronavirus disease 2019 (COVID-19) pandemic and associated non-pharmaceutical interventions (NPIs) have significantly altered the epidemiology of respiratory pathogens. Understanding the interactions between non-bacterial respiratory pathogens is crucial for clinical management and surveillance.

Objective: To investigate how interactions among non-bacterial respiratory pathogens in children changed during and after the COVID-19 pandemic in two cities in eastern China.

Methods: This retrospective study reviewed the data of children hospitalized with acute respiratory tract infections in Wenzhou and Ningbo between March 1, 2021, and February 28, 2024. The SureX 13 respiratory pathogen multiplex kit was used to detect 13 pathogen types/subtypes in the respiratory tract secretion specimens. The chi-square test or Fisher's exact test, virus correlation, and vector autoregressive modelling were employed to evaluate correlations and dynamic changes in the weekly positive detection rates before and after the NPIs.

Results: Among the 73 096 children tested, 65.18% had at least one non-bacterial respiratory pathogen, and 11.97% had multiple pathogens. Detection rates declined significantly by 56.65% during NPIs but rebounded by 75.46% afterward, particularly for Mycoplasma pneumoniae, which increased from 5.29% to 34.78%. Post-pandemic, the co-detection of non-bacterial respiratory pathogens increased, with interaction patterns varying by phase. Notably, after the pandemic, the positive and negative correlations among pathogens intensified, with a significant increase in negative associations. Furthermore, a persistent negative correlation existed between the influenza B virus and Mycoplasma pneumoniae (-0.36 to -0.25), suggesting the potential presence of pathogen interference.

Interpretation: The interactions between non-bacterial respiratory pathogens markedly changed after COVID-19, showing strengthened correlations, which were primarily negative in nature. These observations underscore the importance of the ongoing surveillance of respiratory pathogens in evolving NPIs and epidemiological patterns.

Importance: The production of tetrahydroxylated bile acids (THBAs) is associated with better prognosis in some cholestatic patients as well as in multidrug resistance protein 2 knockout (Mdr2^-/- ) mice. However, it remains unclear whether this protective effect is specific to Mdr2^-/- mice.

Objective: To evaluate the effects of THBA (3α,6α,7α,12α-Tetrahydroxy-10β,13β-pentanoic acid) in Zfyve19^-/- mice, a newly developed mouse model characterized by cholestatic liver injury.

Methods: THBA was administered to Zfyve19^-/- mice challenged with alpha-naphthyl isothiocyanate (ANIT). Serum biochemistry, liver histology and immunostaining, and quantitative PCR for hepatic expression of pro-fibrotic, pro-inflammatory, and bile acid metabolism-related genes were performed and compared against ANIT-treated wild-type and Zfyve19^-/- mice fed normal chow.

Results: THBA administration reduced serum alanine aminotransferase (P < 0.001) and total bile acid levels (P < 0.001), decreased necrosis (P = 0.046), portal inflammation (P < 0.001), bile duct hyperplasia (P = 0.007), and portal fibrosis (P = 0.002) in liver histology, along with a significant reduction in hepatic expression of pro-fibrotic genes (Acta2, Col1a1, Tgfb1, Tgfb2, and Timp1), as well as the pro-inflammatory cytokines Tnf and macrophage chemokines (Ccl2, Cxcl1, Cxcl9, Cxcl10, and Nos2). Additionally, the mRNA expression of Nr1h4 was profoundly upregulated, while key enzymes involved in bile acid synthesis were downregulated.

Interpretation: THBA effectively alleviated cholestatic liver injury and fibrosis, and may represent a potential agent for the medical management of such diseases.

Newborn screening (NBS) is a key public health intervention that improves children's health outcomes by enabling precise intervention through the early detection of hereditary and metabolic diseases. With advances in genomic technology, genomic NBS (gNBS) is gradually overcoming the limitations of conventional biochemical NBS and emerging as an innovative approach. This review systematically summarizes the developmental trajectory of NBS, highlighting the transformative transition from conventional biochemical methods to genetic approaches. It also presents global initiatives and preliminary findings from gNBS practices. Although gNBS offers broad potential applications, several critical challenges must be addressed to optimize its clinical implementation. Comprehensive international collaboration is essential for advancing gNBS and enhancing newborn health worldwide.

Importance: Understanding the dynamic interplay between gut microbiota development and bilirubin metabolism may provide new insights into the pathophysiology of neonatal jaundice. Identifying microbial taxa associated with bilirubin fluctuations could help inform early prediction and microbiota-targeted interventions for hyperbilirubinemia.

Objective: To investigate the correlation between dynamic changes in the gut microbiota and bilirubin concentrations during the neonatal period.

Methods: Bilirubin concentrations were monitored daily throughout the neonatal period. Fecal samples were collected from neonates on days 1, 3, 7, 14, 21, and 28 after birth. The composition of the gut microbiome was assessed by 16S rRNA gene amplicon sequencing of the fecal samples. Within-subject, same-day associations between transcutaneous bilirubin (TcB) and genus-level abundance were quantified using a repeated-measures correlation.

Results: Thirty neonates were included in the final analysis. Among the top-30 genera, six exhibited false discovery rate significant, same-day within-subject associations with TcB under the repeated-measures correlation framework (|r_rm| ≥0.30). Changes in the abundances of the genera Streptococcus (r _rm = +0.416, 95% confidence interval [CI] 0.272-0.543, P = 2.084 × 10^-7; P-adj = 3.126 × 10^-6) and Rothia (r _rm = +0.340, 95% CI 0.187-0.476; P = 3.134 × 10^-5; P-adj = 1.567 × 10^-4) were positively correlated with bilirubin concentrations throughout the neonatal period. In complementary cross-sectional analyses centered on meconium, additional genus-bilirubin correlations were identified for TcB measured on postnatal days 3-7 and for the neonatal TcB peak, with multiplicity controlled separately for each endpoint.

Interpretation: A correlation was found between dynamic changes in the gut microbiome and bilirubin concentrations during the neonatal period. The identified genera might be potential markers or targets for intervention for neonatal jaundice.

Importance: Dystroglycanopathies (DGPs) are a group of muscular dystrophies with abnormal glycosylation of dystroglycan. CRPPA is a gene associated with DGPs. Understanding the genetic basis, genotype-phenotype correlations, and population-specific mutations is crucial for accurate diagnosis and genetic counseling.

Objective: To investigate CRPPA mutations in Chinese pediatric patients with DGPs, analyze genotype-phenotype correlations, and determine whether specific deletions represent founder mutations in this population.

Methods: Clinical and genetic data of pediatric patients with CRPPA-related DGPs between June 2006 and December 2023 from Peking University First Hospital were collected and analyzed. Muscle biopsy specimens from four patients were examined using immunohistochemistry, immunofluorescence, and electron microscopy. Haplotype analysis was performed to investigate the potential founder mutation.

Results: Among the 16 patients studied, phenotypes ranged from severe muscle-eye-brain disease to milder limb-girdle muscular dystrophy. Twenty-one pathogenic variants were identified, including five novel variants. A recurrent exon 6-9 deletion emerged as the second most frequent variant (25.0%, 4/16), with haplotype analysis supporting a founder mutation in Chinese patients. At follow-up, most patients remained non-ambulatory, and one patient died of respiratory failure.

Interpretation: This study broadens the CRPPA mutational spectrum and identifies a founder mutation of exon 6-9 deletion in Chinese patients. These findings have important implications for population-specific screening, diagnosis, and genetic counseling.

Importance: The ketogenic diet (KD) is effective in managing epilepsy, particularly West syndrome (WS); however, the role of gut microbiome (GM) and metabolome in its efficacy remains unclear. Understanding these mechanisms could optimize the KD for WS treatment.

Objective: To identify microbiome-metabolome signatures associated with KD efficacy in WS by analyzing changes in GM composition and metabolic pathways.

Methods: Fecal samples were collected from WS patients (n = 16) and healthy children (n = 24). Metagenome and metabolome analyses were performed to assess GM composition and metabolic profiles.

Results: WS patients showed GM imbalances compared to healthy children. Disease status contributed sufficiently to the GM. The abundance of Bacteroides, Parabacteroides, and Faecalibacterium was lower in WS (3.30% vs. 39.86%, P-adj = 0.140; 0.14% vs. 0.73%, P-adj = 0.023; 0.04% vs. 1.35%, P-adj = 0.018), whereas Bifidobacterium and Escherichia were higher (6.08% vs. 2.23%, P-adj = 0.140; 7.57% vs. 0.15%, P-adj < 0.001). After KD, Parabacteroides (particularly P. distasonis) and Bacteroides (particularly B. fragilis) increased (0.14% vs. 0.35%, P-adj = 0.034; 3.30% vs. 21.18%, P-adj = 0.380); Bifidobacterium (particularly B. breve) and Escherichia (particularly E. coli) decreased from 6.08% and 7.57% to 1.24% and 2.52%, respectively. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that ATP-binding cassette (ABC) transporters, fatty acid biosynthesis, tyrosine metabolism, and other pathways were significantly altered in patients with WS, and these alterations were reversed following ketogenic diet (KD) consumption. The KD also altered intestinal metabolites. Integrative analysis of microbial features, gene functions, and metabolites revealed that Bacteroides species and P. distasonis were significantly associated with ABC transporters, alanine aspartate and glutamate metabolism, and negatively correlated with 3-sulfinoalanine, suggesting potential regulatory roles in metabolic pathways.

Interpretation: KD induces significant shifts in GM composition and metabolic pathways, which may contribute to its therapeutic efficacy in WS. The restoration of Bacteroides and Parabacteroides dominance, alongside alterations in gene functions and neurotransmitter-related metabolites, suggests a potential mechanism for the antiepileptic effects of KD.