Search Results (6,912)

Cystic fibrosis (CF) is an autosomal recessive disorder caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It is increasingly understood through a genomics-informed framework linking variant architecture to phenotype, diagnosis, and therapeutic eligibility. This review summarizes current evidence on CFTR structure, variant interpretation, genotype-phenotype heterogeneity, diagnostic workflows, and modern management. We highlight how full-gene sequencing, curated disease-liability databases, functional testing, and organoid-informed theratyping refine diagnosis and treatment selection; how disrupted chloride and bicarbonate transport drives muco-obstructive airway disease and multisystem complications; and why modulator therapy must still be integrated with respiratory, nutritional, endocrine, hepatobiliary, reproductive, and psychosocial care. We also outline unresolved challenges in rare variants, residual organ damage, ancestry-related diagnostic gaps, and mutation-agnostic therapeutic development. Full article

Background: Ketogenic diets are used as a non-pharmacological treatment for drug-resistant epilepsy in childhood and adolescence. However, the potential micronutrient deficiencies associated with ketogenic diets have not been adequately investigated in vulnerable groups, such as children and adolescents, and detailed dietary analyses are lacking. Methodology: Optimized ketogenic daily meal plans were created for adolescents aged 10–18 years with different ketogenic ratios of 3:1, 2:1, and 1:1. Micronutrient supply was calculated using PRODI^® nutrition software (version 7.3, Nutri-Science GmbH, Freiburg, Germany), based on the German Nutrient Database and compared with DGE/ÖGE reference values. Nutrients below 95% of the reference values were classified as potentially critical. Results: The results showed that micronutrient density decreased with increasing dietary restriction. Vitamin D and fiber were below reference values for all ratios and age groups. The 3:1 ratio exhibited deficiencies in potassium, zinc, fluoride, and several B vitamins. Overall, the 1:1 ratio provided the most favorable nutrient coverage, though vitamin B₁ and fluoride remained insufficient. The results indicate that potentially critical micronutrients are highly sensitive to ketogenic ratios in adolescents. Conclusions: This analysis enables the identification of relevant nutrients to be more targeted, suggesting that a one-size-fits-all approach of supplementation should be replaced by options differentiated by age and dietary restrictions. Full article

Background: β-haemoglobinopathies, including sickle cell disease and transfusion-dependent β-thalassaemia, are among the most common monogenic disorders worldwide and represent a major global health burden. Conventional treatments, such as blood transfusions, iron chelation, fetal haemoglobin induction, and allogeneic haematopoietic stem cell transplantation, have improved outcomes but remain limited by treatment-related toxicity, donor availability, and incomplete curative potential. Methods: A narrative literature review was conducted using PubMed up to 2025. Search terms included “sickle cell disease,” “sickle cell anemia,” “β-thalassemia,” “transfusion-dependent beta-thalassemia,” “gene therapy,” “gene addition,” “gene editing,” “CRISPR-Cas9,” “lentiviral vector,” “children,” “paediatric,” and “pediatric.” Relevant clinical trials, reviews, consensus statements, and guidelines were selected and qualitatively analysed. Results: Gene therapy for β-haemoglobinopathies is based mainly on two strategies: gene addition and gene editing. Gene addition uses lentiviral vectors to introduce functional or modified β-globin genes into autologous haematopoietic stem cells, whereas gene editing targets regulatory pathways, particularly BCL11A, to reactivate fetal haemoglobin synthesis or correct disease-causing mutations. Clinical studies have shown encouraging outcomes, including transfusion independence in many patients with β-thalassaemia and marked reduction or elimination of vaso-occlusive crises in sickle cell disease. Paediatric and adolescent data are increasingly promising, although still limited. Conclusions: Gene therapy is reshaping the treatment landscape of β-haemoglobinopathies by offering a personalised and potentially curative approach. However, long-term safety, conditioning toxicity, fertility preservation, accessibility, costs, and implementation in high-prevalence regions remain critical challenges. Further studies are needed to optimise patient selection and expand equitable access. Full article

Emotion-induced blindness (EIB) refers to the impaired perception of a target due to attentional capture by emotional distractors. While prior research indicates that EIB can be attenuated by enhancing target priority or by regulating emotional distractors through proactive inhibition or passive habituation, it remains unclear whether the intrinsic motivational value of self-relevance can effectively counteract such emotional capture. Grounded in the self-categorization framework, three experiments investigated whether enhancing target self-relevance mitigates EIB across individual, relational, and collective levels. In a two-phase paradigm, neutral images were endowed with high or low self-relevance via associative learning and subsequently presented as targets following emotional distractors in a rapid serial visual presentation (RSVP) task. Results demonstrated that individual (Experiment 1) and relational (Experiment 2) self-relevance significantly reduced EIB, yielding higher accuracy for highly self-relevant targets following negative distractors. For the collective self (Experiment 3), modulation of EIB depended on identity concreteness. Concrete-identity self-relevance (university) effectively buffered against EIB, whereas abstract-identity self-relevance (gender) did not. These findings suggest that target self-relevance may function as a protective buffer that helps reduce emotional interference in EIB across multiple self-levels, potentially offering practical ways to enhance psychological resilience during adverse experiences in real-world settings. Full article

Objective: To characterize neurodevelopmental disorders in children and adolescents with Tuberous Sclerosis Complex (TSC) and explore associations with epilepsy onset and cortical tuber burden. Methods: This exploratory cross-sectional study included 18 children and adolescents with TSC followed at a tertiary pediatric neurology center in Brazil. Standardized neuropsychological, behavioral, and neuroimaging assessments were performed. Participants were stratified according to epilepsy onset and cortical tuber burden. Results: Epilepsy was present in 94.4% of participants, and pharmacoresistance in 52.9%. Neurodevelopmental disorders were highly prevalent, particularly autism spectrum disorder and attention-deficit/hyperactivity disorder, frequently occurring as comorbidities. Children with earlier epilepsy onset demonstrated exploratory trends toward poorer cognitive outcomes, whereas greater cortical tuber burden showed exploratory trends toward greater behavioral and emotional dysregulation, although these differences did not reach statistical significance. Conclusions: Neurodevelopmental disorders are highly prevalent in pediatric TSC. Exploratory findings suggest that epilepsy characteristics and lesion burden may be related to cognitive and behavioral outcomes. These exploratory findings support systematic multidisciplinary neurodevelopmental monitoring in children with TSC. Full article

Pediatric phlebotomy is a common invasive procedure frequently associated with pain, anxiety, and fear, which may negatively affect children’s cooperation and overall healthcare experiences. Virtual reality (VR) has emerged as a promising non-pharmacological intervention capable of providing immersive distraction and emotional engagement during painful medical procedures. The aim of this systematic review was to evaluate the effectiveness of immersive VR in reducing pain perception and anxiety-related outcomes among pediatric patients undergoing phlebotomy procedures. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research question was developed using the PICO framework. Randomized controlled trials and comparative controlled studies published between January 2020 and September 2025 were identified through systematic searches of PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL). Studies involving children and adolescents aged 4–17 years undergoing phlebotomy or venipuncture procedures were eligible for inclusion. A total of six studies comprising 557 pediatric participants were included in the review. The VR interventions involved immersive and interactive environments, including educational simulations, animated scenarios, and game-based experiences delivered through head-mounted displays. Four studies reported statistically significant reductions in pain and/or anxiety among participants exposed to VR compared with control groups, whereas two studies found no significant differences. Across the included studies, VR interventions were generally well accepted by children, parents, and healthcare professionals, with only mild and transient adverse effects reported. However, substantial heterogeneity was observed regarding clinical settings, VR technologies, intervention protocols, and outcome assessment methods. The current evidence suggests that immersive VR is a promising adjunctive strategy for reducing pain and anxiety during pediatric phlebotomy procedures. Nevertheless, the available evidence remains limited by methodological heterogeneity and relatively small sample sizes. Future research should focus on larger, well-designed randomized controlled trials using standardized intervention protocols and outcome measures to support evidence-based implementation of VR in pediatric clinical practice. Full article

Although existing research has found that parent–child conflict significantly predicts children’s psychological adjustment, it remains unclear whether father–child and mother–child conflict exert distinct effects on psychological adjustment, the mediating processes through which they operate, and whether these processes vary across primary and secondary school stages. Using a three-wave longitudinal design, this study examined 1210 primary school students (M_age = 10.17, SD_age = 0.85) and 973 secondary school students (M_age = 12.62, SD_age = 1.36). A multiple mediation model integrating parallel and serial paths was constructed to investigate how father–child and mother–child conflict frequency respectively predicted four indicators of psychological adjustment (internalizing problems, externalizing problems, life satisfaction, and prosocial behavior) and to test the mediating roles of parental psychological control and basic psychological needs. Results showed the following: (1) parental psychological control and basic psychological needs served as significant independent mediators of the relationship between conflict frequency and psychological adjustment. In primary school, maternal psychological control emerged as the core mediator; in secondary school, the mediating role of paternal psychological control was significantly strengthened, and the basic psychological need mediated all associations between mother–child conflict and every adjustment indicator. (2) The serial mediating pathway “parental psychological control → basic psychological needs” was robust across both school stages. As a distal family stressor, parent–child conflict is indirectly transformed into maladjustment through a sequential process that first elevates psychological control and then thwarts basic psychological need. These findings illuminate a cascading mechanism underlying the impact of parent–child conflict on multifaceted adjustment and offer stage-specific guidance for targeted family interventions in primary and secondary school settings. Full article

Background/Objectives: Hypertrophic cardiomyopathy (HCM) in childhood is associated with a risk of adverse cardiovascular events despite preserved left ventricular (LV) ejection fraction (EF). The aim of this study was to evaluate echocardiographic parameters of longitudinal LV systolic function and determine their relationship with cardiac magnetic resonance (CMR) findings and major adverse cardiovascular events (MACE) in children and adolescents with HCM. Methods: This single-centre prospective observational study enrolled 31 children and adolescents with HCM and preserved LV EF. Echocardiographic assessment included mitral annular plane systolic excursion (MAPSE), tissue Doppler mitral annulus systolic velocity (s′), mitral annular displacement index (MADI), and LV global longitudinal strain (GLS). Investigated CMR parameters encompassed LV mass, maximal wall thickness, and late gadolinium enhancement (LGE). Associations between echocardiographic and CMR findings were analyzed, and the discriminative value of longitudinal function parameters for MACE was assessed. Results: Impaired longitudinal systolic function was frequently detected in our cohort. Lower MAPSE and s′ z-scores were present in 61.3% of patients, reduced MADI in 96.8%, and reduced LV GLS in all subjects. Patients with MACE showed significantly lower MADI (p < 0.001) and worse LV GLS (p = 0.003). An exploratory LV GLS cut-off value of −12.1% showed discrimination for MACE in this cohort, with 75% sensitivity and 95.7% specificity. Echocardiographic parameters significantly correlated with CMR markers of hypertrophy and fibrosis, particularly LV GLS, which demonstrated the strongest associations with LV mass and the presence and extent of LGE. Conclusions: Echocardiographic parameters of longitudinal LV systolic function could contribute to closer clinical surveillance in children and adolescents with HCM. LV GLS may identify subtle myocardial dysfunction and provide exploratory prognostic information; however, its role in risk stratification requires prospective validation in larger pediatric HCM cohorts. Full article

Background/Objectives: Sapropterin dihydrochloride is an established treatment option for individuals with phenylketonuria (PKU) who demonstrate responsiveness, but uncertainty persists regarding dosing frequency, timing relative to meals, the influence of dietary composition, and efficacy of different formulations. Despite widespread use in the UK, real-world administration behaviours have not previously been characterised. This study aimed to characterise sapropterin administration behaviours among people with PKU in the UK. Methods: A 31-item questionnaire was developed and disseminated via the National Society for Phenylketonuria website and social media channels. The survey captured demographic information, dosing schedules, formulation use, administration techniques, co-ingestion with food, and changes in natural protein tolerance following initiation of generic sapropterin. Results: 124 current sapropterin users completed the survey. Most respondents were caregivers of children or adolescents (68.5% aged 0–18 years). Once-daily dosing was most common (66.1%, n = 82), typically administered at breakfast, followed by twice-daily (32.3%, n = 40) and three-times-daily (1.6%, n = 2). Tablets were the predominant formulation (92.7%, n = 115); 50.4% (n = 58/115) swallowed tablets whole, while the remaining (49.6%, n = 57/115) crushed or dissolved them in water or juice. Nine respondents (7.3%, n = 9/124) used powder sachets. Most participants (75%, n = 93/124) took sapropterin with food, with both low-fat (36.6%, n = 34/93) and high-fat (26.9%, n = 24/93) meals reported. Over a third of participants (33.9%, n = 42/124) tolerated a natural protein intake >30 g/day when this was measured, and a further 15.3% (n = 19) were able to maintain a fully unrestricted protein intake without protein substitute supplementation. The magnitude of protein intake improvement was significantly greater among adults (p < 0.001), those with higher baseline natural protein intake (≥30 exchanges/day) (p < 0.001), and individuals who swallowed sapropterin tablets whole (p = 0.038). Although 71.8% (n = 89/124) were pleased with their increased natural protein allowance, many expressed a desire for further improvement. Conclusions: Substantial heterogeneity in dosing schedules, formulation handling, and co-ingestion practices highlights the absence of standardised guidance. These findings emphasise the need for clearer clinical recommendations to optimise treatment effectiveness and support consistent, equitable care. Full article

Background: Avoidant/restrictive food intake disorder (ARFID) and selective eating are increasingly recognized in pediatric nutrition, but food selectivity has been predominantly studied in dedicated eating disorder settings and in underweight children, potentially underestimating its prevalence across broader clinical populations. This study aimed to characterize food selectivity as a transdiagnostic feature in children referred to a tertiary pediatric nutrition center, regardless of referral diagnosis or BMI status. Methods: This retrospective observational study included 417 consecutive children and adolescents (median age 9.3 years, IQR 4.1–12.9; 47.5% male) assessed at the General Pediatric Eating Disorders Outpatient Unit of Bambino Gesù Children’s Hospital IRCCS, Rome, Italy, between May 2024 and April 2026. Food selectivity was defined as clinician-documented avoidance of at least one of four food groups (vegetables, fruit, fish, and legumes). Patients were classified as having primary selective eating/ARFID (Group A, n = 141), unrecognized selective eating (Group B, n = 163), or no selectivity (Group C, n = 113). Results: Food selectivity was identified in 293 patients (70.3%), including 70.8% of those referred for obesity or overweight and 50.0% of those referred for eating disorders. Prevalence did not differ across BMI categories (p = 0.554), confirming that selective eating is independent of anthropometric status. Ferritin deficiency showed a significant gradient across groups (Group A 32.2%, Group B 17.9%, Group C 10.8%; p = 0.002). Screen use during meals and ultra-processed food consumption were similarly elevated in Groups A and B and significantly higher than in Group C (p = 0.002 and p < 0.001, respectively), with no difference between the two selective groups. Conclusions: Food selectivity is a transdiagnostic and BMI-independent feature affecting the majority of children referred for pediatric nutritional evaluation. Children with unrecognized selective eating share the same nutritional risks and behavioral correlates as those formally diagnosed with ARFID, supporting the integration of a brief food group avoidance screen into routine nutritional assessment regardless of the primary referral diagnosis. Full article

Background/Objectives: Health literacy (HL) is recognized as an important social determinant of health. It supports healthy behaviors and effective health management throughout one’s life. For children and adolescents, developing HL influences their well-being, development, and ability to make informed health decisions. Nurses are strategically positioned to promote HL from an early age. To our knowledge, no prior synthesis has specifically examined nurse-led HL interventions targeting pediatric populations, highlighting the originality and relevance of this scoping review. The purpose of this review was to map and characterize nursing interventions aimed at improving HL outcomes in children and adolescents. Methods: A scoping review was conducted according to the Joanna Briggs Institute methodology, using a three-step search strategy, and reported in accordance with the PRISMA-ScR guidelines. Searches were conducted in MEDLINE, CINAHL, Scopus, Web of Science, and ProQuest with no date restriction, including studies published in Portuguese, English, or Spanish. Studies involving children and adolescents (ages 0–18) in any healthcare or community setting were eligible. Data on intervention characteristics and HL outcomes were extracted and analyzed descriptively, and no critical appraisal of the included sources was conducted. Results: A total of 44 studies were included. Interventions were predominantly school-based and focused on adolescents (n = 26), with a clear gap in early childhood (n = 2). Studies of early childhood primarily used storytelling and reading activities, whereas interventions targeting older children and adolescents more often employed participatory educational strategies, group-based approaches and digital platforms. The most frequently addressed topics were chronic disease management (n = 12), mental health (n = 7), and nutrition (n = 5). HL domains mainly focused on healthcare and health promotion, with fewer studies addressing disease prevention. Most interventions were conducted in school settings (n = 24), highlighting this context over those in primary care, community, and hospital settings. Conclusions: The results revealed nursing interventions used to promote HL, particularly in the management of chronic diseases, mental health and nutrition. However, the existing body of research is still limited. Key gaps include the absence of standardized measurement tools and the scarcity of longitudinal studies evaluating long-term outcomes. These limitations constrain the comparability and generalizability of findings, highlighting the necessity of more rigorous, methodologically robust research to support evidence-based practices. This scoping review comprehensively maps nurse-led interventions that promote HL among children and adolescents, identifying key priorities to guide future research in this area. Full article

Background: Eye-closure sensitivity (ECS) is a rare reflex epilepsy phenomenon characterized by epileptiform discharges on electroencephalogram (EEG), triggered by eye closure. It has been reported in all genetic generalized epilepsies (GGEs), particularly in adolescents and adults. However, pediatric cases remain uncommon in the literature. Case Presentation: We report a 10-year-old previously healthy girl who presented with recurrent generalized tonic–clonic seizures beginning at age nine. Seizures occurred every few months without identifiable triggers, lasting 1–2 min with complete loss of consciousness, limb stiffening, rhythmic jerking, and upward eye deviation. Her developmental history was unremarkable, with no family history of epilepsy or febrile seizures. Neurological examination was normal. Initial EEG revealed intermittent generalized spike-and-wave and polyspike-and-wave discharges at 3 Hz (range 2–4 Hz), triggered by eye closure, consistent with ECS. These discharges occurred immediately following both spontaneous and instructed eye closure, were more prominent during drowsiness, and resolved upon eye opening. The patient remained alert during these subclinical events. No photosensitivity or hyperventilation response was observed. Brain magnetic resonance imaging was normal. The patient’s electroclinical findings were most consistent with a GGE phenotype with prominent ECS. She was treated with levetiracetam and has remained seizure-free for approximately 1.5 years to date. Conclusions: This case demonstrates that ECS can present in pediatric patients with GGE primarily manifested as generalized tonic–clonic seizures. EEG evaluation should include repeated eye-open/close maneuvers to unmask ECS, particularly in children with suspected generalized seizures. Full article

Objective: This study examined the disparities in the prevalence of obesity among children and adolescents from 1990 to 2022. Methods: Crude prevalence estimates were obtained from the World Health Organization’s (WHO) Global Health Observatory, accessible through the WHO Health Equity Assessment Toolkit (WHO HEAT). The study population comprised children and adolescents aged 5 to 19 years. Obesity was defined as a body mass index (BMI) exceeding two standard deviations above the mean, in accordance with the WHO Growth Reference. Descriptive analysis was employed to examine longitudinal trends and disparities in crude obesity prevalence. The dimensions of age (5–9 and 10–19 years) and sex (female and male) were utilised to assess disparities related to obesity. Absolute and relative inequalities were evaluated using difference (D) and ratio (R) summary measures, respectively. Results: In 1990, the crude prevalence of obesity was higher among female children and adolescents (1.45%; confidence interval [CI] 0.38–3.41) compared to their male counterparts (1.07%; CI 0.14–3.40). However, by 2022, the prevalence was higher among males (8.20%; CI 5.15–12.01) compared to females (5.78%; CI 3.57–8.48). Regarding age, the prevalence of obesity in 1990 was 2.24% among 5–9-year-olds, compared with 0.59% among 10–19-year-olds. Both age groups saw an increase in crude obesity prevalence over time, and by 2022, the prevalence of obesity was 12.10% among 5–9-year-olds, compared with 4.04% among 10–19-year-olds. In 1990, the difference and ratio estimates were 0.38 and 1.36, respectively, indicating a higher prevalence among females than males. Concurrently, the ratio decreased from 1.36 in 1990 to 0.71 in 2022, further confirming the shift towards a higher prevalence of male obesity in later years. The difference in obesity prevalence (5–9 years minus 10–19 years) stayed positive throughout the study period. In 2022, the age difference in crude obesity prevalence was +8.07 percentage points, and the ratio was 3.00, indicating that the younger group had a prevalence three times that of the older group. Conclusions: The prevalence of childhood and adolescent obesity increased significantly from 1990 to 2022, with a shift from females to males and a disproportionate impact on younger children. These trends underscore the necessity for targeted public health interventions that address age- and sex-specific disparities. Full article

The rising prevalence of neurodevelopmental, emotional, and behavioral disorders in children has prompted interest in dietary strategies that target neuroinflammation, oxidative stress, and gut dysbiosis. Blueberries (Vaccinium spp.) contain substantial amounts of anthocyanins and other neuroactive polyphenols that may confer neuroprotective effects. We summarize the literature published between 2016 and 2025 to examine how the bioactives in blueberries affect symptoms relevant to children with diagnosed neurodevelopmental or emotional–behavioral disorders, including ADHD, mood problems, and cognitive difficulties. Mechanistically, anthocyanins appear to modulate gut microbial composition, modulate neuroinflammation and alleviate oxidative stress via the Nrf2 pathway, and support synaptic plasticity and neurogenesis. Clinical trials, although limited in number and sample size, have reported modest improvements in mood and verbal memory in typically developing children and adolescents, with some gains in attention and executive function. However, direct trials in children with diagnosed neurodevelopmental or emotional–behavioral conditions remain scarce. There are substantial hurdles to translating these findings. Anthocyanins have poor physicochemical stability and low bioavailability, and routine food processing degrades their activity. Emerging solutions such as green extraction from agricultural by-products, colon-targeted microencapsulation, and zero-waste engineering could address these limitations. Rigorous randomized controlled trials in children with diagnosed neurodevelopmental or emotional–behavioral disorders are essential, as are advances in food engineering. Both are needed to move blueberry-based interventions from the laboratory to application. Full article

Background and Objectives: Pulmonary sequestration (PS) is a rare congenital lung anomaly with anomalous systemic arterial supply. Surgical resection is the standard treatment, but some children have contraindications. Endovascular embolization (EE) is an established alternative; published pediatric experience is limited, particularly in neonates. We report a two-centre experience with extended follow-up and quantitative hemodynamic data. Methods: Six pediatric patients (five male; median age 6 months, range 11 days to 4 years and 8 months) underwent EE for PS at two centres in Gdańsk, Poland, between 2020 and 2025. Contraindications to surgery were severe pulmonary arterial hypertension, high-output cardiac failure, low body weight with comorbidity, complex extralobar anatomy or refused parental consent. Procedures were performed under general anesthesia via right common femoral arterial access; device strategy was tailored to vessel anatomy. Results: Technical success was 100% with no procedural complications. Median feeding-artery diameter was 3.4 mm (range 2.1 to 5.3 mm). An Amplatzer-family vascular plug was used in five patients (83.3%), pushable platinum coils in two (33.3%) and Onyx-18 in one (16.7%); two had hybrid combinations and one underwent planned staged two-step embolization. Median procedural duration was 51 min. At median follow-up of 50 months (range 11 to 68), all patients showed sequester regression on imaging. Reverse cardiac remodelling occurred within five weeks in the patient with pre-procedural left ventricular dilation (Z-score +2.45 returning to normal); systolic pulmonary artery pressure fell from 35 to 40 to 17 mmHg within six weeks in the neonate treated at 11 days of life for high-output cardiac failure. No patient required surgical resection. Conclusions: Endovascular embolization is safe and effective in pediatric patients with pulmonary sequestration and contraindications to surgery, including neonates with comorbidity. Documented reverse cardiac remodelling and rapid hemodynamic improvement support its use in selected cases. Full article