Background: Advances in neonatal care have improved survival rates in preterm neonates. However, concerns persist regarding the long-term kidney implications of prematurity. Nephrogenesis is disrupted, particularly in those born very preterm (≤ 32 weeks of gestation), increasing the risk of early kidney dysfunction and hypertension later in life. Objectives: This systematic review and meta-analysis aimed to evaluate kidney health outcomes in former very preterm children and adolescents compared to full-term peers. Data sources: A systematic literature search was conducted in MEDLINE/PubMed, Scopus, and Web of Science from their earliest available records to October 9, 2024. Study eligibility criteria: We included observational studies comparing kidney health parameters between children/adolescents born very preterm (gestational age – GA ≤ 32 weeks) and their full-term counterparts (gestational age > 36 weeks or birth weight > 2000 g) within the age range of 6 to 18 years. Participants and interventions: Children and adolescents aged 6–18 years born very preterm were compared to their full-term counterparts. The analyzed kidney function markers included serum Cystatin C, serum creatinine (sCr), estimated glomerular filtration rate (eGFR) based on sCr (Cr-eGFR), and blood pressure (systolic and diastolic, SBP/DBP). Study appraisal and synthesis methods: The Newcastle–Ottawa Scale was used to assess study quality. The mean difference with 95% confidence intervals was used for continuous outcomes. Statistical significance was set at p < 0.05. Sensitivity, subgroup and meta-regression analyses were conducted for further exploration of the outcomes. Statistical analyses were performed using R software (Version 4.3.2). Results: Thirteen studies (16 reports; 2,112 participants) were included. Very preterm children and adolescents had higher serum Cystatin C (0.05 mg/L; 95%CI: 0.02–0.08), lower Cr-eGFR (-11.87 mL/min/1.73 m ² ; 95%CI: -22.44 to -1.31), and higher SBP (1.96 mmHg; 95%CI: 0.21–3.71). Sensitivity analysis confirmed Cystatin C findings but rendered Cr-eGFR and SBP differences non-significant. Subgroup analysis showed a significant GA effect on sCr ( p < 0.0001), though the ≥ 28 weeks subgroup included only two studies. Limitations: Considerable heterogeneity across studies persisted despite sensitivity and subgroup analyses. The lack of randomized controlled trials and longitudinal studies limits result interpretation, while non-significant meta-regression findings hinder full explanation of heterogeneity. Insufficient data prevented the assessment of additional kidney function parameters. Conclusions and implications of key findings: Cystatin C was elevated in very preterm individuals compared to full-term peers, reinforcing its role as an early marker of kidney dysfunction. While differences in Cr-eGFR and SBP lost significance after sensitivity analysis, these markers remain relevant for long-term follow-up in this vulnerable population. Systematic review registration number: PROSPERO (CRD42024554702). Graphical

Background: Neutrophil extracellular traps (NETs) are granule- and nucleus-derived structures that support innate immunity. While the contribution of NETs to adult infections and autoimmune diseases is well studied, evidence in children is still inconsistent. This review aimed to summarize current findings on NETs in pediatric infections. Methods: This study followed the Cochrane Handbook for Systematic Reviews of Interventions and adhered to the PRISMA guidelines. A search was conducted in major databases (MEDLINE/PubMed and Scopus) from inception until 5 September 2025. The study quality was evaluated using the modified Newcastle–Ottawa Scale. Results: Eleven studies were included in the systematic review. In respiratory disease, the role of NETs was well described and their formation correlated with severity. Patients with febrile urinary tract infections showed elevated urinary NET-associated markers. In COVID-19 infection, NET levels were unchanged in uncomplicated cases but elevated in multisystem inflammatory syndrome in children. Findings in sepsis were inconsistent. Conclusions: This systematic review presents the published evidence on NET formation in the pediatric population, assessing the current knowledge and identifying the gaps to guide research. Future studies should aim to standardize NET detection methods, evaluate their prognostic value in large prospective cohorts, and explore the various NET-associated mechanisms in children.

Background: Children with febrile urinary tract infections (fUTI), especially those with acute pyelonephritis (APN) and vesicoureteral reflux (VUR), may face several complications, especially kidney scarring. Different biomarkers, such as urinary neutrophil gelatinase-associated lipocalin (uNGAL) and procalcitonin (PCT), have been studied for predicting kidney scarring without the need for a DMSA scan. Objectives: This systematic review and meta-analysis examines the role of biomarkers in pediatric patients with a history of fUTI and their prognostic value in the diagnosis of APN and prediction of kidney scarring. Data sources: A search through major databases (MEDLINE/PubMed and Scopus) was conducted from inception until January 2, 2025. The mean difference (95% CI) was applied. A p < 0.05 was considered statistically significant. Results: The systematic review included 2300 participants from 28 studies. Procalcitonin and uNGAL were higher in individuals with scarring after a fUTI episode compared to those without scarring ( p = 0.035 and p < 0.0001, respectively). In addition, PCT was higher in patients with APN compared to those with lower UTI ( p < 0.0001). Finally, the good and moderate overall diagnostic accuracy (I ² = 29.8%) of PCT in predicting APN (AUC: 0.861) and uNGAL (I ² = 16.8%) in predicting kidney scarring after an episode of fUTI (AUC: 0.74), respectively, should be considered. Conclusions: This study showed that PCT and uNGAL can detect APN and kidney scarring after fUTI. More studies should be conducted exploring the role of other biomarkers in scarring after an episode of fUTI in pediatric patients with or without VUR. Graphical