To explore the risk factors for multiple bronchoalveolar lavages in children with necrotizing pneumonia (NP) and construct a prediction model. To analyze the clinical data of patients with NP from January 2019 to June 2025, and divided into a Single- Bronchoalveolar lavage (BAL) group and Multiple-BAL group, analyze and construct the model. The single-BAL group had 139 patients, the multiple-BAL group 196. The incidence of sputum plug obstruction and bronchial erosion with necrosis was greater in the multiple-BAL group (P < 0.05). The platelet distribution width (PDW), lactate dehydrogenase (LDH) in the multiple-BAL group were greater (P < 0.05). Sputum plug obstruction, bronchial mucosal erosion and necrosis with softening, fibrinogen (FIB) < 2.84 g/L, PDW > 9.5%, and LDH > 576 U/L are risk factors for multiple alveolar lavages in pediatric patients with NP. The combined model had an AUC of 0.801, indicating good discrimination. The combined model showed good predictive performance after Bootstrap validation. The presence of sputum plug obstruction, bronchial mucosal erosion and necrosis with softening, FIB < 2.84 g/L, PDW > 9.5%, and LDH > 576 U/L are risk factors for multiple bronchoalveolar lavages in pediatric patients with NP. Identified 5 risk factors for multiple-BAL in pediatric NP, and built a quantifiable guiding model. Fills the gap of no multiple-BAL criteria in pediatric NP, integrating pathology and hematological indicators. Optimizes treatment, reduces burden, and facilitates clinical standardization.

This commentary examines emerging evidence challenging long-standing assumptions about early enteral feeding and necrotizing enterocolitis (NEC) in preterm infants. While earlier observational data led to conservative feeding practices, recent randomized trials and large registry analyses suggest that earlier, more advanced human milk-based feeding improves growth without increasing NEC risk. These findings highlight the limitations of inductive generalizations and the need to reconsider NEC as the dominant driver of nutritional decisions. Future research should focus on high-risk populations, optimize enteral nutrition strategies, and integrate mechanistic insights, while adopting broader, clinically meaningful outcomes beyond the binary outcome of NEC to guide practice and improve long-term health trajectories. IMPACT: In the modern era of human milk-based feeding, prioritizing NEC avoidance over nutritional adequacy may no longer be justified, as earlier and more complete enteral nutrition improves growth without increasing NEC risk.

Leptin communicates the body's energy utilisation and maintains a stable body weight. Preterm neonates often show rapid compensatory catch-up growth, which may increase the risk of obesity later in life. Although leptin regulates adiposity, its epigenetic role in the obesity risk of preterm neonates remains unclear. Global and LEP promoter methylation, leptin and IGF1 levels, and expression of LEP and IL6 genes were measured in umbilical cord blood from preterm and term deliveries. Genome-wide and LEP-specific methylation were decreased, while circulatory leptin, LEP, LEPR, IL6, and TNFα expression were increased in preterm cord blood (p < 0.05). Cord blood leptin levels were positively associated with birth weight in preterm (r = 0.288, p = 0.03). LEP methylation was inversely associated (r = -0.506, p = 0.03) with IGF1, while IL6 expression positively correlated with leptin (r = 0.318, p = 0.05), and LEP expression (r = 0.278, p = 0.03) in preterm cord blood. The interplay between LEP methylation and IL6 can influence each other in promoting inflammation, which may increase the risk of obesity in preterm neonates in later life. While leptin's role in adiposity is established, its epigenetic influence on the obesity risk of preterm neonates is unknown. Epigenetic dysregulation of the LEP gene, together with increased expression of IL6 and TNFα, led to a pro-inflammatory state in preterm neonates. This is the first study to report LEP-specific promoter methylation and its association with pro-inflammatory markers, exploring early-life biomarkers for predicting obesity. Predicting early biomarkers of obesity might have implications for the early identification and management of metabolic disorders in preterm neonates. Maternal factors leading to preterm birth and cord blood leptin dysregulation in predicting obesity. Elevated blood pressure, infection, and lower haemoglobin in preterm disrupted epigenetic control of leptin and activated inflammation. Leptin dysregulation may affect satiety and body fat, thereby increasing the risk of obesity. Solid arrows depict present data, and dotted lines indicate potential pathways.

Advances in genomic technologies, particularly massively parallel sequencing of cell-free fetal DNA, have transformed prenatal screening and created opportunities for fetal therapies. First-tier screening for trisomy 21 (T21) now enables early identification of affected fetuses, raising the possibility of prenatal intervention. Down syndrome (DS) is increasingly recognized not only as a neurodevelopmental condition but also as an interferon-driven disorder of immune dysregulation. Preclinical studies using human cellular models and trisomic mice demonstrated abnormalities in oxidative stress and inflammatory pathways. Connectivity Map-guided identification of apigenin, a naturally occurring flavonoid, showed partial normalization of gene expression, reduced neuroinflammation, and improved hippocampal-dependent learning in a mouse model, supporting the concept that atypical fetal brain development in T21 may be modifiable. Parallel human studies have confirmed chronic hypercytokinemia and autoimmunity in DS, and postnatal treatment with JAK inhibitors has shown early clinical benefit. A similar therapeutic paradigm is emerging for cystic fibrosis, where noninvasive prenatal testing detects CFTR variants and highly effective CFTR modulators are increasingly used during pregnancy. Early reports suggest that in utero exposure may ameliorate fetal complications such as meconium ileus. Together, these advances support a framework in which selected genetic disorders may be treatable beginning in fetal life. IMPACT: Advances in engineering and computational science, coupled with new biological and genomic knowledge, have led to novel prenatal opportunities to improve child health and treat disease.

Preterm infants have reduced nephrons at birth and are exposed to hyperoxic environments. The objective was to examine the effects of hyperoxia on renal injury. We utilized a mouse model of experimental moderate (60% O2)-severe (100% O2) bronchopulmonary dysplasia (BPD), obtaining kidney tissue on postnatal day 14. The number of glomeruli, glomerulus length, and Bowman's capsule's length were recorded. Cell death and expression of multiple biomarkers were assessed. Morphometric analyses showed a significant decrease in glomeruli in male and female mice from room air (RA) to 60% BPD. Bowman's capsule length was significantly increased from RA to 100% BPD in female kidneys. TUNEL staining, cleaved caspase 3, and 9 expression revealed significantly increased cell death in the kidneys in the moderate and severe BPD models. There was increased expression of Angiopoietin-2 in male kidneys of the moderate BPD group, whereas Angiopoietin-1 and vascular endothelial growth factor were decreased in female mice. In the moderate BPD model, there was upregulation of nuclear factor-kappa B, transforming growth factor-β1, interleukin (IL)-6, and IL-1β in male and female mice. We report here that there is significant renal injury and cell death in moderate and severe mouse models of experimental BPD. Neonatal kidneys are still developing at birth. Hyperoxia exposure to the whole mouse also impacts the developing neonatal kidney. There is significant renal injury in moderate and severe mouse models of experimental BPD. This includes morphometric changes in the kidney tissue and increased cell death. In addition, there are significant alterations in the expression of vascular and inflammatory biomarkers.

Long non-coding RNAs (lncRNAs) represent a large family of RNA transcripts that are longer than 200 nucleotides and don't code for proteins. They have recently emerged as key regulators of gene expression which modulate a wide range of biological processes from the early periods of embryonic development to disease progression. Therefore, they represent a cornerstone in pediatric neurology, possibly through orchestrating neural differentiation, synaptic plasticity, and neural circuit maturation. Furthermore, they significantly contribute to the pathogenesis of the neurodevelopmental disorders such as autism spectrum conditions, epilepsy, and delays in the neurodevelopmental milestones. The focus of this review article is on the utility of lncRNAs as biomarkers and therapies for neurological pediatric disorders, the basis for this and therapeutic strategies. In addition, this review article may represent a trial to explore how lncRNAs can establish both direct and indirect connections between the genetic, epigenetic, and environmental factors. Consequently, this may open avenues for innovative diagnostic biomarkers and the development of novel therapeutic strategies for pediatric neurological disorders. IMPACT: This article elucidates the multifaceted roles of lncRNAs in bridging the normal neural development with the disease states. This article highlights the current limitations/barriers to the clinical translation of lncRNA-based therapies in pediatrics and provides emerging solutions. Guides how lncRNAs establish connections between the genetic, epigenetic, and environmental factors. This may open avenues for innovative diagnostic biomarkers and novel therapeutic strategies for pediatric neurological disorders.

When used as early empirical antibiotics for preterm infants, ampicillin + aminoglycosides may reduce mortality more effectively than ampicillin + cefotaxime. We compared in-hospital outcomes between early-phase ampicillin + aminoglycoside and ampicillin + cefotaxime therapy. Preterm infants (<35 weeks' gestation) hospitalized between July 2010 and March 2022 were identified from a nationwide Japanese database. Patients received ampicillin + aminoglycoside (n = 33,204) or ampicillin + cefotaxime (n = 12,158) as early empirical therapy. We performed 2:1 propensity score-matched analysis to compare in-hospital mortality and major morbidities. Subgroup analyses were performed for infants <28 weeks' gestation. After 2:1 propensity score matching, mortality (2.6% vs. 2.5%; p = 0.55) and hearing impairment incidence (0.63% vs. 0.60%; p = 0.71) were similar between groups; however, among infants born at <28 weeks' gestation, hearing impairment was lower in ampicillin + aminoglycoside recipients (0.53% vs. 0.98%; p = 0.018). Ampicillin + aminoglycoside users had a lower incidence of bronchopulmonary dysplasia (21% vs. 23%, p < 0.001), retinopathy of prematurity (6.8% vs. 8.2%, p < 0.001), and hospitalization costs (USD 25,481 vs. 28,184, p < 0.001) than ampicillin + cefotaxime users. Early empirical ampicillin + aminoglycoside and ampicillin + cefotaxime therapy showed similar mortality in preterm infants. Antibiotic selection should consider resistance patterns and regimen-specific morbidities. Early-phase ampicillin + aminoglycoside administration in preterm infants possibly decreases mortality and morbidities (e.g., bacteremia) compared with ampicillin + cefotaxime administration. This large-scale, retrospective nationwide study enrolling 45,362 preterm infants revealed that early-phase antibiotic regimens (ampicillin + aminoglycosides/ampicillin + cefotaxime) did not affect in-hospital mortality. Ampicillin + aminoglycosides correlated with home assistive technology use, and ampicillin + cefotaxime with bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, and expensive hospitalization. The choice of early-phase antibiotics in preterm infants should be rooted in antimicrobial resistance patterns, considering the differences in morbidities between the two regimens.

Elevated blood pressure (BP) in childhood is a predictor of adult hypertension. We characterized existing blood pressure (BP) percentile trajectories in children aged 3-9 years and examined factors associated with BP trajectory and elevated BP among 1040 participants in a prospective birth cohort study in Durham, North Carolina (2005-2011). We obtained BP measurements from medical records and demographic, social, and behavioral characteristics from questionnaires. We identified systolic blood pressure (SBP) percentile trajectories using group-based trajectory modeling as well as diastolic blood pressure (DBP) percentiles as a secondary outcome. We then calculated associations between trajectory group and covariates of interest using multinomial logistic regression. We also estimated the association of these covariates with elevated BP using generalized estimating equations. We identified four distinct SBP percentile trajectories (lower stable, lower increasing, higher stable, and higher decreasing) and three distinct DBP percentile trajectories (lower increasing, higher decreasing, and higher stable). Birthing parent race and ethnicity, pre-pregnancy BMI, relationship status, educational attainment, and gestational diabetes status were significantly associated with offspring SBP percentile trajectory group assignment. Offspring sex assigned at birth, birthing parent race and ethnicity, pre-pregnancy BMI, smoking, relationship status, educational attainment, and chronic hypertension status were significantly associated with offspring DBP percentile trajectory group assignment. Infant sex, preterm birth, birthing parent race and ethnicity, pre-pregnancy BMI, and chronic hypertension status were significantly associated with offspring elevated BP. Our results enhance understanding of pediatric SBP and DBP patterns and assist in identifying factors that contribute to elevated BP in children. Our research contributes to understanding of pediatric BP patterns leveraging percentiles which account for age, sex, and height. We identified four distinct SBP and three distinct DBP trajectories in children aged 3-9 years. We identified associations of several social, demographic, and clinical characteristics with childhood BP trajectories and elevated BP. Elevated blood pressure in childhood is a leading precursor for adverse cardiovascular outcomes in adults. Our research may assist in targeted interventions for high-risk groups.

Early detection of kidney allograft injury is essential to preserve long-term graft function. Current diagnostics, particularly biopsy, are invasive and may be inconclusive. Extracellular-vesicles (EVs) carry molecular cargo that reflects renal cellular states. Although EV proteomics has shown promise for detecting acute rejection (AR) in adults, its value in pediatrics(PKT) is not well defined. In this pilot study, urine samples from 29 PKT recipients and 3 healthy controls were analyzed, including 7 with biopsy-confirmed AR, 9 with chronic rejection (CR), and 13 with stable graft function (ST). Classification was based on urine findings, creatinine trends, and biopsy results. EVs were isolated from fresh-second-void urine by ultracentrifugation and analyzed using LC/MS. Longitudinal samples from three AR patients assessed temporal proteomic changes. Overall, 192 proteins were differentially abundant across groups (FDR p < 0.05). AR showed enrichment of immune-related pathways and increased free hemoglobin proteins compared with ST, while CR closely resembled ST. EV concentration and size distribution were similar across groups, indicating proteomic differences were independent of EV abundance. Longitudinal analyses revealed dynamic proteomic changes corresponding to rejection and recovery. EV proteomics is a promising approach for detecting and monitoring AR in PKT recipients and warrants larger multicenter studies. This pilot study demonstrates urinary extracellular vesicle (EV) proteomics as a promising non-invasive approach to detect and monitor acute rejection (AR) in pediatric kidney-transplant (PKT) recipients. EVs carry molecular cargo reflecting kidney cell states, providing a dynamic readout of graft health and injury. Early identification of rejection may reduce reliance on invasive biopsies, enable timely intervention, and support precision-based, personalized management. As the first study to characterize EV proteomic profiles in PKT, it lays important groundwork. Larger multicenter studies are warranted to validate these findings.