Ileana Ioniuc

Pediatric obstructive sleep apnea syndrome (OSAS) is a common sleep-related breathing disorder increasingly recognized as a multisystem disease rather than an isolated disorder of the upper airway. Recurrent episodes of upper airway obstruction generate intermittent hypoxia, reoxygenation, and sleep fragmentation, promoting excessive production of reactive oxygen and nitrogen species and disruption of antioxidant defenses. This narrative review summarizes current evidence regarding the mechanisms, biomarkers, and clinical consequences of oxidative stress in pediatric OSAS. Intermittent hypoxia activates several redox-sensitive pathways, including NADPH oxidases, hypoxia-inducible factor-1α, nuclear factor-κB, mitochondrial dysfunction, and endoplasmic reticulum stress, thereby creating a bidirectional relationship between oxidative stress and systemic inflammation. Pediatric studies have demonstrated alterations in lipid peroxidation products, glutathione redox balance, urinary 8-hydroxy-2′-deoxyguanosine, isoprostanes, NOX2-related markers, and inflammatory mediators. These abnormalities are associated with endothelial dysfunction and cardiovascular, neurocognitive, metabolic, hepatic, renal, and immune consequences, and several may improve following effective treatment. Importantly, the magnitude of oxidative and end-organ injury does not consistently parallel the apnea-hypopnea index, suggesting that hypoxic burden, obesity, genetic susceptibility, antioxidant capacity, and disease duration influence individual biological vulnerability. Although several oxidative biomarkers show potential for disease characterization and treatment monitoring, methodological heterogeneity and the absence of standardized pediatric reference values currently limit their clinical application. Future integration of polysomnographic hypoxic-burden metrics with oxidative, inflammatory, metabolomic, and genomic biomarkers may improve risk stratification and facilitate more personalized management of pediatric OSAS.

Background: The deep-intronic variant 3849+10kbC>T preserves residual CFTR function and is recurrently associated with pancreatic sufficiency, normal or borderline sweat chloride and diagnosis beyond early childhood. A co-occurring poly-T 5T allele adds a second layer of uncertainty: its penetrance depends on the TG repeat carried in cis, and its contribution to the phenotype can be weighed only once its phase relative to the second variant has been established. Case Presentation: A boy with recurrent respiratory infections from the age of three was diagnosed with cystic fibrosis at 12 years, in 2018—four years before newborn screening became national policy in Romania. Two sweat conductivity measurements, 125 and 80 mmol/L NaCl-equivalent, together with targeted CFTR analysis identifying 3849+10kbC>T and a 5T allele, established the diagnosis. Phase was not determined—parental samples were not obtained and no allele-specific or long-range analysis was performed—so the two findings are reported as co-occurring rather than as demonstrably in trans. His elder brother, who had recurrent spontaneous pneumothorax and two negative sweat tests, was never genotyped because the test was not reimbursed. Bilateral bronchiectasis and chronic airway infection followed; inhaled colistimethate eradicated Pseudomonas aeruginosa, whereas Staphylococcus aureus persisted despite successive antibiogram-guided regimens. Access to elexacaftor/tezacaftor/ivacaftor was granted in January 2026 on the basis of the genotype. Conclusions: Molecular characterisation contributed to a diagnosis that rested on the combination of clinical phenotype, abnormal sweat conductivity, and CFTR analysis, and was, eight years later, the sole criterion for access to modulator therapy; phase and TG-repeat length remain undetermined. No follow-up data are available, therapy having been authorised but not yet started at the time of writing.

Childhood obesity now affects more than 160 million children and adolescents worldwide, and over the same period ultra-processed foods have come to dominate the early-life diet. This review sets out a single argument: that the effect of ultra-processed foods on childhood obesity is better read developmentally, and that the digestive tract is the organ through which much of that effect is transmitted. Exposure begins before birth and continues through the first 1000 days and complementary feeding, the period in which the gut microbiota assembles and the intestinal barrier matures. We show how ultra-processed foods perturb these two systems in particular: a low-fibre, additive-rich, energy-dense diet reshapes microbial community structure and depletes short-chain fatty acid production, while emulsifiers and other additives thin the mucus layer and raise intestinal permeability, admitting microbial products that sustain low-grade inflammation. We trace how these gut-level changes feed forward into altered appetite regulation, adipocyte biology and, ultimately, excess adiposity, and we situate the other proposed mechanisms (matrix disruption, hyperpalatability, accelerated eating rate, endocrine-disrupting additives and central reward signalling) around this digestive core, marking at each step where the evidence is paediatric and where it rests on adult or animal data. The epidemiological literature is appraised by study design, and the constraints on causal inference are stated plainly: NOVA misclassification, residual confounding, reverse causation, dietary misreporting and the scarcity of paediatric trials. The practical implication is that prevention framed around early-life gut health, rather than around cumulative adult-style exposure, is where intervention is most plausibly effective. We are explicit throughout that most of the mechanistic evidence derives from animal or adult studies and that a causal role for ultra-processed foods in childhood adiposity, though biologically plausible, is not yet established in paediatric populations; the developmental reading we advance is the most coherent interpretation of an associational evidence base, not a demonstrated causal chain.

Background/Objectives: Childhood obesity represents a major global health challenge. Sugar-sweetened beverages (SSBs) remain an important modifiable dietary exposure; however, adolescent beverage behavior is often examined independently of dietary patterns established earlier in life. This narrative review examines SSB consumption and adiposity across the life course, particularly during the first 1000 days as a sensitive period for developing dietary habits. Methods: Targeted literature searches were conducted in PubMed, Scopus, and Web of Science (January 2021–13 August 2026). We prioritized systematic reviews, meta-analyses, prospective cohort studies, randomized trials, and mechanistically informative studies. Study selection was purposive, and causal language was reserved for rigorous designs. Results: SSB intake is associated with higher body mass index, waist circumference, body fat percentage, and pediatric obesity. Potential mechanistic pathways include incomplete energy compensation for liquid calories, fructose-related hepatic de novo lipogenesis under conditions of high exposure, and insulin resistance; however, the independent contribution of fructose remains difficult to disentangle from excess energy intake, beverage form, and the broader dietary matrix. SSB consumption patterns may emerge early and track through childhood, influenced by family, socioeconomic, and commercial determinants. Evidence does not consistently support the hypothesis that repeated sweetness exposure increases subsequent sweetness liking. Metabolic consequences include dyslipidemia, hypertension, and metabolic dysfunction-associated steatotic liver disease (MASLD). Prevention approaches include family- and school-based interventions, beverage reformulation, and fiscal policies. Conclusions: A life-course perspective supports shaping beverage environments early, strengthening healthy home food environments, and implementing structural public-health interventions rather than addressing unhealthy patterns only after they become established. However, policy effects may vary across pediatric subgroups.

Neonatal sepsis remains a leading cause of morbidity and mortality in the first month of life, yet its presentation is nonspecific, and its microbiological confirmation is uniquely difficult. Low-circulating bacterial loads, small obtainable blood volumes, frequent intrapartum antibiotic exposure, and the ambiguity of skin-commensal isolates erode the sensitivity and specificity of blood culture, the long-standing reference standard, so that most evaluated infants are treated empirically despite sterile cultures. This review synthesizes current evidence on the integrated microbiological evaluation of the newborn: the host- and specimen-related diagnostic challenge; the etiologic spectrum and its antimicrobial-resistance burden; conventional culture; rapid and molecular methods, including mass spectrometry and syndromic and broad-range PCR; metagenomic and cell-free-DNA sequencing; host-response biomarkers; and antimicrobial-susceptibility determination. The evidence indicates that newer methods accelerate or supplement culture but do not yet replace it, each addressing one limitation while introducing caveats of its own. Notably, much of the evidence for direct-from-blood molecular testing, microbial cell-free DNA, and metagenomic sequencing is extrapolated from adults, whereas neonatal data are stronger for several biomarkers. The greatest benefit arises from integrating complementary modalities within diagnostic- and antimicrobial-stewardship frameworks. Neonatal-specific validation, standardized thresholds, and outcome-driven trials remain the principal priorities.

Asthma prevalence in school-age children varies widely by geography, from below 5% in some regions to above 20% in others, averaging 10–12% across industrialized countries, but genetic factors account for less than 40% of disease liability. Gut microbiota is increasingly recognized as a critical intermediary between early-life dietary exposure and immunological trajectories that determine asthma susceptibility. Through the production of short-chain fatty acids (SCFAs), particularly butyrate, propionate, and acetate, commensal bacteria regulate dendritic cell function, promote T-regulatory (Treg) cell differentiation, and attenuate Th2-polarized airway inflammation via the gut–lung axis. Epidemiological cohorts including CHILD, WHEALS, and PASTURE associate early-life dysbiosis and reduced Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii with increased asthma risk, while dietary patterns rich in fermentable fibre, omega-3 polyunsaturated fatty acids, and diverse plant-based foods are associated with preserved microbial diversity and, in preclinical models, attenuated type-2 inflammatory signalling. This narrative review synthesizes mechanistic and epidemiological evidence on how nutritional exposures shape gut microbiota composition and influences asthma onset and severity in paediatric populations, including the distinct obesity-related asthma phenotype. Critical gaps, insufficient dietary intervention trials with microbiome endpoints, methodological heterogeneity across cohorts, and the paucity of data from non-Western populations are discussed, with implications for preventive nutritional counselling in paediatric allergology practice.

Background: Vitamin D deficiency affects an estimated 40–60% of pregnant women worldwide and is associated with adverse obstetric and neonatal outcomes. Childhood asthma, the most prevalent chronic paediatric disease, has emerged as a plausible programming target, since vitamin D regulates foetal lung branching morphogenesis, calibrates the developing immune system, and modulates decidual and placental function in early gestation. Two landmark randomised trials, VDAART (intervention from weeks 10–18) and COPSAC2010 (from week 24), each reported a 20–25% reduction in offspring asthma or recurrent wheeze at age 3, yet neither reached significance in primary analysis, and the protective signal attenuated by school age. Post hoc stratification by baseline maternal 25-hydroxyvitamin D [25(OH)D] and 17q21 genotype recovered significant effects, raising the possibility that population-average nulls conceal a real but modifier-conditional benefit. Aim: This narrative review re-examines the evidence through a developmental-timing lens, arguing that the periconceptional and first-trimester window, rather than mid-gestation, is the biologically relevant interval for any protective effect. Methods: The review utilises a narrative synthesis of randomised trials, birth-cohort studies, mechanistic investigations, and recent meta-analyses (PubMed, Embase, Cochrane Library to April 2026) relevant to maternal vitamin D, placental biology, and offspring asthma. Findings: The periconceptional weeks coincide with implantation, decidualisation, the embryonic and pseudoglandular phases of airway morphogenesis, and the onset of epigenetic programming, while decidual CYP27B1 expression is prominent in the first trimester. Both trials initiated supplementation after branching morphogenesis was largely complete. Effect modifiers, including baseline 25(OH)D, vitamin D-binding protein, and maternal 17q21 genotype, indicate substantial inter-individual heterogeneity masked in unselected populations. Conclusions: Repositioning preventive supplementation toward the preconceptional and first-trimester window, stratified by baseline status, offers a biologically coherent strategy that existing mid-pregnancy trials have not tested. Adequately powered preconceptional trials with serial biomarker measurement and objective respiratory phenotyping are the priority.

Background: Early-onset neonatal listeriosis is a rare, life-threatening infection of vertical origin caused by Listeria monocytogenes. First-line therapy is intravenous ampicillin combined with an aminoglycoside; acquired β-lactam resistance is exceptionally uncommon. Case Presentation: A 34-week preterm female neonate (birth weight 1990 g, appropriate for gestational age) was born to a febrile primigravida with fetid greenish amniotic fluid at a regional secondary maternity and transferred at 30 h of life to our tertiary NICU with respiratory failure requiring mechanical ventilation. L. monocytogenes was recovered from blood, gastric aspirate, pharyngeal exudate, ocular secretion, and skin swab. Gradient strip susceptibility testing reported ampicillin and trimethoprim–sulfamethoxazole non-susceptibility, although confirmatory broth microdilution was unavailable. Broad-spectrum empirical therapy was revised on Day 5 to include ampicillin–sulbactam, with piperacillin–tazobactam and gentamicin continued. A follow-up blood culture on Day 9 remained sterile through 7 days. The hospital course was complicated by thrombocytopenia, transiently elevated aminotransferases, and a Grade I subependymal hemorrhage; tertiary NICU length of stay was 25 days. Conclusions: Recovery under a multi-agent regimen precludes attribution of effect to any single component. Discordant gradient strip susceptibility results in L. monocytogenes should be confirmed by broth microdilution before any therapeutic change; survivors of severe early-onset listeriosis require structured multidisciplinary follow-up.

Background and Clinical Significance: Childhood-onset Sjögren’s disease (cSjD) is a rare autoimmune disorder that remains challenging to diagnose because of its heterogeneous clinical presentation and the frequent absence of classic sicca symptoms at disease onset. Recurrent parotitis and systemic manifestations often predominate in pediatric patients, contributing to diagnostic delay and potential irreversible glandular damage. Early recognition is essential to prevent complications and improve long-term outcomes. Case Presentation: We report the case of a 17-year-old female diagnosed with primary Sjögren’s disease following a prolonged history of recurrent parotid involvement and progressive glandular dysfunction. Comprehensive evaluation revealed positive anti-SSA antibodies, hypergammaglobulinemia, characteristic salivary gland ultrasonography abnormalities, and a positive minor salivary gland biopsy, resulting in fulfillment of all domains of the 2016 ACR/EULAR classification criteria. The patient also exhibited unusual vascular findings, including carotid atheromatous calcifications in the absence of traditional cardiovascular risk factors. Conclusion: This case highlights the diagnostic complexity of cSjD and underscores the value of a multimodal diagnostic approach integrating clinical assessment, serology, imaging, and histopathology. The presence of early vascular abnormalities broadens the spectrum of potential extraglandular manifestations and emphasizes the need for comprehensive evaluation and long-term monitoring in affected patients.

Type 1 Diabetes (T1D) is a complex autoimmune disorder characterized by immune-mediated destruction of pancreatic β cells, driven by genetic susceptibility and modulated by environmental factors, notably the gut microbiome. Dysbiosis, manifested as reduced microbial diversity, perturbations in the Firmicutes/Bacteroidetes ratio, and compromised short-chain fatty acid production, contributes to T1D pathogenesis through mechanisms involving immune system dysregulation and heightened intestinal permeability. Emerging evidence indicates a relationship between the gut and oral microbiomes, as well as the potential influence of the virome and mycobiome. This narrative review synthesizes the current literature on the intricate interplay between the gut microbial ecosystem, the host immune response, and the development of T1D, highlighting the potential for targeted microbiome-based interventions to ameliorate disease progression. A more nuanced understanding of these multi-kingdom interactions is essential for developing precise therapeutic strategies to prevent or delay T1D onset and to improve patient outcomes through restoration of immune tolerance and gut homeostasis.