Clinical and Experimental Pediatrics最新文献

Background: Impaired renal function (IRF), defined as the rate of decline in serum creatinine levels during the week after birth, frequently affects neonates with moderate or severe hypoxic-ischemic encephalopathy (HIE). However, its clinical relevance in this vulnerable population requires further investigation.

Purpose: This study aimed to evaluate the association between IRF and brain injury severity in neonates with HIE.

Methods: This retrospective single-center study included neonates treated with therapeutic hypothermia for moderate or severe HIE. A multivariable logistic regression analysis evaluated the association between IRF and the combined outcomes of early death or severe brain injury (ED/SevereBI).

Results: Of the 147 included neonates, 67 (45.6%) had IRF and 32 (22%) had ED/SevereBI. Those with ED/SevereBI were more likely to have a lower 5-min Apgar score (median [interquartile range]: 4 [2-5] vs. 2 [1-3], P<0.01), have a higher initial blood lactate level (mean cord blood lactate level, +34%, P<0.05), be intubated in the delivery room (50% vs. 75%, P=0.01), and have IRF (39% vs. 69%, P<0.01). After the adjustment for neonatal characteristics and perinatal asphyxia parameters, neonates with IRF had a 2- to 3-fold higher odds of ED/SevereBI than those without IRF (adjusted odds ratio [95% confidence interval]: 2.66 [1.09-6.84], P=0.03).

Conclusion: In neonates treated with therapeutic hypothermia for HIE, IRF can be used as a marker of adverse outcomes. Further studies are required to evaluate its long-term prognostic value.

Background: Infantile epileptic spasms syndrome (IESS) is a severe form of infantile epilepsy with a high lifetime morbidity burden.

Purpose: We aimed to assess the long-term epilepsy and neurodevelopmental outcomes based on how children with IESS have been managed over the past few decades.

Methods: This retrospective multicenter study included children diagnosed with IESS between 1994 and 2021 with a minimum follow-up period of 2 years. Data on demographics, clinical features, medical history, diagnostic evaluations, and treatments used to control spasms were collected. Epilepsy and neurodevelopmental outcomes were assessed at final follow-up.

Results: A total of 378 infants with IESS were included. The mean age at onset of spasms was 7.3 (range, 1-24) months and mean follow-up duration was 7.9 (range, 2-28) years. Etiologies were identified in 65.1% of cases, with acquired structural etiologies being the most prevalent (29.9%). Among the genetic and genetic-structural etiologies, tuberous sclerosis complex (n=35), Down syndrome (n=8), Miller-Dieker syndrome (n=3), and 15q duplication syndrome (n=3) were the most common. Vigabatrin was prescribed to 93.9% of the patients, suggesting that it was the mainstay of treatment. At the last follow-up, 77.8% of the children remained on antiseizure medications and 29.1% had drug-resistant epilepsy. Approximately 90% had intellectual disabilities, and half of the eligible individuals had received special education.

Conclusion: The IESS imposes a substantial burden on affected children and their families and often leads to chronic epilepsy and impaired cognitive function. Consensus diagnostic and treatment guidelines tailored to the Korean clinical practice are necessary to ensure early diagnosis and timely treatment.

Background: Neurodevelopmental disorders (NDDs) are frequently encountered in pediatric neurology clinics. However, their extensive genetic heterogeneity often limits the diagnostic yield of standard diagnostic tests, highlighting the need for comprehensive genomic approaches.

Purpose: This study aimed to evaluate the diagnostic utility of whole exome sequencing (WES) and whole genome sequencing (WGS) in children with unexplained NDDs and assess the clinical relevance of the genomic findings.

Methods: We retrospectively reviewed the medical records of 64 pediatric patients with NDDs who underwent WES or WGS between March 2018 and November 2024. Clinical data, neuroimaging and electroencephalography findings, and the results of previous genetic tests were analyzed. The diagnostic yield was calculated, and clinical characteristics were compared between patients with and without a genetically confirmed diagnosis. Patients were categorized as genetically confirmed (positive) when a definitive molecular diagnosis was identified through WES or WGS and as not genetically confirmed (negative) when no causative variant was detected.

Results: A definitive molecular diagnosis was achieved in 25 of 64 patients (39.1%). Diagnostic yields were 37.5% and 33.3% for WES and WGS, respectively. Most variants showed autosomal dominant (n=13) inheritance, followed by X-linked (n=9) and autosomal recessive (n=3) patterns. Novel variants accounted for 57.7% of the pathogenic or likely pathogenic variants. A positive family history was significantly associated with a higher diagnostic yield (20.0% vs. 2.6%, P=0.030), while prematurity was more common in the negative group (33.3% vs. 8.0%, P=0.032). Three WES-negative patients were later diagnosed using chromosomal microarray analysis (CMA) or repeat expansion testing.

Conclusion: WES and WGS are effective diagnostic tools for pediatric NDDs. Phenotype re-evaluation and the selective use of genetic tests such as CMA and repeat expansion analysis enhance diagnostic yield.

Background: Diverse factors including seizure onset age, seizure frequency, epilepsy duration, total number of antiseizure medications trialed are considered as seizures-related neurocognitive loads in children with drug-resistant focal epilepsy (DRE). However, their associations with the structural integrity of neurocognitive networks remain largely unknown.

Purpose: This study investigates a novel diffusion-weighted imaging (DWI) connectome methodology that can extract seizure-associated structural abnormality biomarkers from clinical DWI tractography, use them to classify neurocognitive impairments prior to surgery, and unveil the relationship between epilepsy-related factors and neurocognitive impairments.

Methods: Thirty-three DRE children (age: 11.8±3.3 years, 17 boys) and 29 age-matched healthy controls were enrolled to create seizure-affected networks whose edges connect epileptogenic regions to key brain regions of 6 neurocognitive networks. The deviations of local efficiency values were averaged across the seizure-affected brain regions and used as new imaging-based biomarkers quantifying the degrees of seizure-associated structural abnormalities accumulated on individual neurocognitive networks and classifying the neurocognitive impairments along with the epilepsy-related factors.

Results: Effect sizes of the proposed biomarkers for differentiating DRE from healthy controls were consistently very large across various subgroups defined by lesion types, lobar locations of epileptogenic foci, seizure frequency categories, and seizure types (i.e., Cohen d value >1.8). Compared with the epilepsy-related factors, the proposed biomarkers demonstrated superior classification accuracy for identifying neurocognitive impairments in general, verbal, and nonverbal domains. When combined with the epilepsy-related factors, the classification performance further improved, achieving an accuracy range of 90%-98% in the independent test patients. The subsequent association analysis using the proposed biomarkers as seizure-associated structural abnormality indicators demonstrated that the inclusion of such imaging indicators significantly enhances the strength of associations between epilepsy factors and neurocognitive impairments.

Conclusion: These findings offer strong potential for objectively identifying neurocognitive impairments in DRE children, supporting early, data-driven decisions for personalized interventions to mitigate long-term effects.

Background: Individualized targeted fortification based on human milk (HM) analysis reportedly achieves optimal outcomes in preterm infants. Therefore, understanding the effects of macronutrients in HM on preterm infant growth is essential.

Purpose: This study aimed to determine the association between HM macronutrients and the growth of preterm infants. We also compared macronutrient intake data obtained from an HM analyzer (HMA)-based calculation with those derived from a reference-based calculation.

Methods: This prospective-retrospective cohort study included infants born at 34 weeks' gestation or less. HM samples were collected weekly for up to 4 weeks or until discharge, whichever occurred first. Clinical outcomes were recorded. The macronutrient composition was analyzed using midinfrared HMA. Associations were determined using a linear regression model.

Results: Of 121 preterm infants, 65 (51.2%) were male. A total of 200 HM samples were analyzed. Fat composition showed a significant positive association with weight gain velocity, with an adjusted unstandardized coefficient (aB) of 3.07 (95% confidence interval [CI], 0.22-5.93). Total protein and fat intakes were positively associated with weight gain (aB, 3.41; 95% CI, 0.83-5.98; and aB, 7.07; 95% CI, 1.73-12.42, respectively). When using the HMA-based calculation, protein intake was lower and carbohydrate intake was higher throughout the 4-week period compared with those obtained based on the reference-based calculation.

Conclusion: Higher protein and fat intakes could potentially enhance weight gain in preterm infants. These findings provide further evidence to support the concept of individualized HM fortification. Our findings underscore the importance of using HMA-based methods to calculate macronutrient intakes among preterm infants.

Sarcopenia-the pathologic loss of skeletal muscle mass and strength-is increasingly recognized in pediatric gastroenterology and hepatology as an important determinant of clinical outcomes. Although historically linked to aging, secondary sarcopenia in children arises from chronic inflammation, malnutrition, physical inactivity, corticosteroid exposure, endocrine disturbances, and anabolic resistance. Unlike adult medicine, where diagnostic frameworks are more established, pediatric definitions remain heterogeneous because growth and puberty substantially influence body composition and muscle function. Diagnosis therefore relies on size-adjusted muscle indices, usually normalized to height squared, interpreted against age- and sex-specific reference curves. Body mass index alone is insufficient because muscle depletion and abnormal fat distribution may be present despite normal or elevated body weight, particularly in children with sarcopenic obesity and metabolic dysfunction-associated steatotic liver disease. Accumulating evidence suggests that pediatric sarcopenia is not simply a marker of frailty but a clinically meaningful predictor of adverse outcomes. In pediatric liver transplantation and cirrhosis, sarcopenia is associated with higher waitlist mortality, longer intensive care stays, and more posttransplant infections. In pediatric inflammatory bowel disease, reduced muscle mass correlates with aggressive disease, earlier biologic escalation, and increased surgical risk. This review summarizes current evidence on the epidemiology, pathophysiology, diagnosis, and management of pediatric sarcopenia in gastrointestinal and liver diseases. We discuss available diagnostic tools, including computed tomography/magnetic resonance imaging, dual-energy x-ray absorptiometry, bioelectrical impedance analysis, and grip strength, highlighting their practical advantages and limitations. We also propose a pragmatic diagnostic algoririthm and outline management strategies that extend beyond caloric supplementation, emphasizing adequate protein intake, resistance exercise, and optimization of underlying disease. Early recognition of sarcopenia may improve risk stratification, functional outcomes, and long-term prognosis in children with chronic gastrointestinal and liver diseases.

Background: Preeclampsia (PE) is a serious complication of pregnancy that affects the offspring and mothers. Those with a history of PE are at higher risk of future cardiometabolic diseases, the etiology of which remains uncertain.

Purpose: To investigate the transcriptomic profiles of mothers and neonates to determine whether certain genes are commonly affected after shared exposure to PE.

Methods: In this observational study, pregnant mother-neonate dyads with PE and healthy normotensive mothers were prospectively recruited. We used RNA sequencing and bioinformatics analysis to characterize the transcriptomic profiles of maternal blood leukocytes (MBLs), cord blood leukocytes (CBLs), and umbilical arterial and venous endothelial cells (UAECs and UVECs, respectively). These results were further validated using real-time reverse transcription polymerase chain reaction.

Results: Gene expression during the perinatal/peripartum period was context-dependent in patients with PE and involved various signaling pathways. Inflammation- and immune-related signaling pathways in maternal blood and coagulation-related signaling pathways in cord blood were upregulated in the PE group compared to those in the control group. Ten differentially expressed genes were commonly affected in MBLs and CBLs. Maternal LMNA and CBL levels of MAST4 differentiated those with PE from those with normotension in a gestational-age-adjusted model. Maternal levels of ADAMTS2 and CBL levels of ADAMTS2, GABRE, and MMP8 independently determined neonatal gestational age and birth weight. CBL MMP8 levels independently determined maternal blood pressure. However, the transcriptomic profiles of endothelial cells differ from those of blood leukocytes. Heart morphogenesis-related signaling pathways in UAECs and leukocyte cell-cell adhesion-related signaling pathways in UVECs were more involved in PE. The messenger RNA levels of FAT3 and SLC25A18 in the UAECs were higher in the PE group than in the control group.

Conclusion: Perinatal and peripartum genes in PE are expressed in a context-dependent manner via diverse signaling pathways, with little overlap between mothers and neonates.

Background: The survival rate of pediatric acute lymphoblastic leukemia (ALL) currently exceeds 90% in high-income settings, shifting the focus to its long-term effects. Kidney injury, acute kidney injury (AKI), and chronic kidney disease (CKD) are increasingly recognized associated conditions; however, the determinants of CKD in pediatric ALL remain poorly defined.

Purpose: To quantify the burden of AKI during induction and CKD in children with ALL, estimate CKD-free survival, and identify clinical predictors of CKD.

Methods: This retrospective cohort at a single university-affiliated tertiary center included patients aged 2-18 years with ALL who completed ≥3 months of follow-up. AKI was classified by Kidney Disease: Improving Global Outcomes serum-creatinine criteria, while CKD was defined as a glomerular filtration rate <90 mL/min/1.73 m2 for ≥3 months. CKD-free survival was estimated using the Kaplan-Meier method. Associations with time to CKD were assessed using the Cox proportional hazards model.

Results: Of 113 children (median age, 5.6; interquartile range [IQR], 3.8-9.4 years), AKI occurred during induction in 49 (43.4%). Leukemic kidney infiltration (LKI) was more frequently noted in patients with versus without AKI (P=0.01). Over 644 patient-years of follow-up (median, 5.1; IQR, 2.9-8.3 years), 15 (13.3%) developed CKD (stage 2 [n=12], stage 3 [n=3]). The 1-, 3-, and 5-year CKD-free survival rates were 99.1%, 95.3%, and 94.1%, respectively. In multivariate models, age was independently associated with CKD (adjusted hazard ratio [aHR], 1.28 per year; 95% confidence interval [CI], 1.04-1.57; P=0.02), whereas the incidence of LKI did not reach significance (aHR, 2.93; 95% CI, 0.87-9.89; P=0.08).

Conclusion: AKI commonly developed during induction. An older age at diagnosis was the principal independent predictor of CKD development. The age effect demonstrated a linear risk gradient rather than a conventional dichotomous ≥10-year threshold. A LKI was associated with AKI and suggestive of subsequent CKD. These results suggest that older children may benefit from intensive kidney surveillance and supportive care. Multicenter prospective studies are warranted to refine the prevention strategies.