The incidence of type 1 diabetes (T1D) among the paediatric population in Latvia is gradually increasing, and ~ 50% of patients with newly diagnosed T1D present with diabetic ketoacidosis (DKA). This study aimed to initiate T1D screening for high-risk children to reduce the rate of DKA and enable early pre-symptomatic intervention. This prospective observational study was conducted at Children's Clinical University Hospital (CCUH) from March 2024 to February 2026. Siblings aged 2-17 years of patients with T1D were invited to participate. The parents completed a short questionnaire regarding participants' health status and family history. Screening was performed in two stages: (1) 3-screen ELISA and insulin autoantibody (IAA) ELISA testing; if ≥ 1 positive then (2) ELISA testing for all four autoantibodies (AAs) separately: IAA, insulinoma-associated antigen-2 (IA-2A), zinc transporter 8 (ZnT8A) and glutamic acid decarboxylase 65 (GAD-65A) antibodies, glycaemic status assessment, and screening for celiac disease and autoimmune thyroiditis. Participants with ≥ 2 AAs in the second screening underwent a 2 h-oral glucose tolerance test (OGTT). Parents of participating children were screened for anxiety and depression using GAD-7 (general anxiety disorder 7) and PHQ-9 (patient health questionnaire-9) instruments. Of the 83 participants in the first screening, 26 (31.3%) had ≥ 1 positive test results. This group more frequently had ≥ 1 family member with T1D than those with negative results (30.8 versus 5.3% respectively, p = 0.003). In the second screening stage, 13 participants (50%) tested negative for all 4 AAs, 9 (10.8%) had one positive AA (AA +), one participant had two AA + , and three children had three AA + . At the time of the second screening, all participants had normal glycaemic measurements, negative results for celiac disease and autoimmune thyroiditis screening. During observation period, two participants developed stage 3 T1D. Following the OGTT, another participant was diagnosed with stage 2 T1D, but two other participants with ≥ 2 AA + remained normoglycemic. The overall prevalence of depression and anxiety was similarly high among parents of children with both positive and negative T1D screening results; however, parents in the positive screening group more frequently exhibited severe anxiety. Positive T1D screening with ≥ 2 AAs was observed in 5 (6.02%) participants. Three participants progressed to stage 2 or stage 3 T1D during follow-up, corresponding to a positive predictive value of 60%, within a relatively short observation period of 10-24 months. These findings support the implementation of T1D screening in Latvia, particularly in high-risk populations. • Islet AA testing for several years has been used to screen for T1D in multiple international studies and national screening programs. • Timely detection of islet AA can prevent from DKA development and ensure presymptomatic insulin treatment with fewer complications. • These data are of particular significance, because no prior screening initiatives for T1D have been reported in Latvia. • There is an urgent need to improve recognition of T1D in Latvia to decrease rates of DKA and other complications, and screening could be an effective tool for that.
Neonatal hemolytic disease is a major cause of neonatal hyperbilirubinemia and kernicterus. Intravenous immunoglobulin (IVIG) combined with phototherapy is a commonly used clinical intervention; however, the optimal dosing regimen remains controversial. This study aimed to systematically evaluate the efficacy and safety of different doses of IVIG combined with phototherapy in the treatment of neonatal hemolytic disease, and to provide evidence-based guidance for optimizing clinical dosing strategies. A comprehensive literature search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, and Scopus, as well as Chinese databases including CNKI, Wanfang Data, VIP, and the Chinese Biomedical Literature Database, from inception to February 2026. Randomized controlled trials comparing high-dose versus low-dose IVIG combined with phototherapy in neonatal hemolytic disease were included. The primary outcomes included exchange transfusion rate, duration of phototherapy, length of hospital stay, serum bilirubin levels at 24 h, hemoglobin levels at 72 h, and incidence of adverse events. Meta-analysis was performed using RevMan 5.4.1, with fixed- or random-effects models applied according to heterogeneity. A total of 10 randomized controlled trials involving 690 neonates were included. Compared with the low-dose IVIG group, the high-dose IVIG group showed a significantly lower exchange transfusion rate (Peto OR = 0.24, 95% CI: 0.12-0.50, P = 0.0001), corresponding to an approximately 76% reduction in the odds of exchange transfusion. High-dose IVIG was also associated with a shorter duration of phototherapy (MD =  - 9.11 h, P = 0.002), a shorter length of hospital stay (MD =  - 1.83 days, P = 0.0008), and lower serum bilirubin levels at 24 h (MD =  - 38.86, P < 0.00001). No statistically significant differences were observed between the two groups in hemoglobin levels at 72 h or adverse reaction rates (all P > 0.05). Compared with low-dose IVIG, high-dose IVIG combined with phototherapy was associated with lower exchange transfusion rates, shorter phototherapy duration and hospital stay, and lower serum bilirubin levels in neonates with hemolytic disease. No statistically significant differences were observed in hemoglobin levels at 72 h or adverse reaction rates between the two groups. Further large-scale, high-quality randomized controlled trials are warranted to confirm these findings and to clarify the potential impact of blood group subtype on treatment response. •Neonatal hemolytic disease remains a common cause of severe neonatal hyperbilirubinemia. •Intravenous immunoglobulin (IVIG) is frequently used as an adjunctive treatment, but the optimal dosage remains uncertain. • This meta-analysis compared different IVIG dosing regimens using randomized controlled trials only. • High-dose IVIG was associated with lower exchange transfusion rates and improved several short-term clinical outcomes.
RSV infections in children affect the entire family. Nevertheless, evidence on the overall impact is scarce. This multi-country observational study aims to investigate the association between disease severity and health-related quality of life (HRQoL) in affected families and to explore the role of factors related to mental well-being. Data were collected during the 2022-2023 RSV season in Germany, France, Italy and Sweden via an online questionnaire from parents of children (24 months) hospitalised for RSV. Parental HRQoL was assessed using the validated caregiver-reported PedsQL Family Impact Module. Exploratory analyses and multivariate linear regression models were performed focusing on potential key determinants. A total set of 138 participants was assembled. Parents of children with a severe RSV infection had on average - 12.1 [95% CI: -21.2 to - 3.03; P = 0.010] lower HRQoL Summary Score than parents of children with low severity index scores. Subsequent stratified analyses revealed a stronger association among parents who had not been offered (adequate) mental health support. Higher RSV disease severity was associated with lower parental HRQoL. These findings highlight the importance of preventing severe RSV infection and the need for further research to identify and evaluate appropriate (psychosocial) support for affected families. ClinicalTrials.gov, identifier, NCT05550545. Registered 12 September 2022.
To systematically synthesise the benefits and harms of add-on oral antihistamines for managing atopic dermatitis (eczema). Systematic review and network meta-analysis of randomised trials. Medline, Embase, CENTRAL, the United States Food and Drug Administration, and the European Medicines Agency databases from database inception to 5 May 2025. Randomised trials assessing add-on oral H1 antihistamines, H2 blockers, mast cell stabilisers (nedocromil sodium and sodium cromoglycate), or their combinations. Paired reviewers independently screened records, extracted data, and assessed risk of bias using a modified Cochrane Risk of Bias tool version 2. Random effects bayesian meta-analyses synthesised atopic dermatitis severity (oSCORAD-objective scoring atopic dermatitis, 0-83; minimal important difference 8.2; lower better), itch severity (numerical rating scale, 0-10; minimal important difference 3; lower better), sleep disturbance, atopic dermatitis related quality of life, and harms. The network meta-analysis GRADE (Grading of Recommendations Assessment, Development and Evaluation) and Core GRADE approaches informed certainty of evidence ratings. 47 trials enrolled 6230 children and adults with primarily moderate to severe atopic dermatitis. With moderate certainty, compared with placebo, adding a first generation or second generation H1 antihistamine likely resulted in a small reduction in atopic dermatitis severity (mean difference -1.87, 95% credible interval -3.47 to -0.27) and itch severity (-0.89, -1.41 to -0.37). Although statistically detectable, these effects are well below established minimal important differences (smallest change in an outcome that a patient would identify as important). With low certainty, all studied interventions may not improve sleep disturbance or reduce atopic dermatitis exacerbations. First generation agents probably increase cognitive impairment and may increase treatment discontinuation because of adverse events (risk difference 66 more per 1000, 95% credible interval 0 to 231 more; moderate certainty). Second generation agents differ in their risk of cognitive impairment (range of mean effects 0 more per 1000 for loratadine, 16 more per 1000 for levocetirizine, and 17 more per 1000 for cetirizine). Among patients with atopic dermatitis, adding H1 antihistamines probably results in a clinically unimportant reduction in atopic dermatitis severity and itch severity, and may not reduce sleep disturbance or atopic dermatitis exacerbations. First generation agents increase cognitive impairment and may increase treatment discontinuation because of adverse events. Cognitive impairment risk differs among second generation agents. These findings provide evidence against routine antihistamine use in atopic dermatitis management and will inform updated clinical guidelines. PROSPERO CRD42022345643.
Sudden Unexplained Death in Youth (SUDY) requires thorough investigation to identify underlying causes and guide prevention strategies. In the Netherlands, cases are investigated using the standardized Postmortem Evaluation of Sudden Unexplained Death in Infants and Children (PESUDIC), in which autopsy is offered as a standard component. However, its invasive nature and associated time burden may limit parental acceptance. This study evaluated to what extent the cause of death can be established using a limited set of diagnostic tests compared to the standard procedure including autopsy. In this observational study, children > 2 years of age who died suddenly and unexpectedly and underwent PESUDIC, including imaging and autopsy, were included. Two expert panels, consisting of a forensic and a pediatric specialist, independently assessed early diagnostic tests available before autopsy. Cases were classified by level of diagnostic certainty and need for autopsy. Panel conclusions were compared with the reference standard: a multidisciplinary audit incorporating all available information, including autopsy findings. Sixty-six cases were included (median age 12 years (IQR 4-14.7), 63% male). Panels identified indicative information for a cause of death in 60 patients (91%). Nevertheless, autopsy was required in most cases (n = 59) to confirm the diagnosis. In 7 cases (10.6%), panels were sufficiently confident to establish the cause of death without autopsy with complete agreement with the reference standard. Causes included obstructive gastrointestinal pathology (n = 5) and diabetic ketoacidosis with dehydration (n = 2).  Only a small proportion of children > 2 years of age with sudden unexpected death have a cause of death that can be established with sufficient certainty at an early stage. In the vast majority of cases, the cause of death remains uncertain, supporting the recommendation to perform an autopsy. • Autopsy in sudden unexplained death in youth is worldwide recognized as the gold standard for postmortem examination. However, its invasive nature and associated time burden may limit parental acceptance. • In 7 of 60 sudden and unexplained deceased minors (10%), sufficient certainty regarding the cause of death can be obtained by other minimal invasive diagnostic test, so without the need of an autopsy. Causes without the need of an autopsy included obstructive gastrointestinal pathology and diabetic ketoacidosis with dehydration.
This narrative review synthesizes recent technological and organizational developments in pediatric telemedicine, maps their principal clinical applications, and critically discusses implementation, safety, equity, and future priorities. This narrative review used a transparent, non-systematic literature-search approach in PubMed/MEDLINE, Scopus, and Google Scholar, considering publications available through April 2026. Searches were intended to identify and contextualize relevant literature across pediatric settings rather than to provide an exhaustive, reproducible systematic evidence synthesis. No formal risk-of-bias assessment, meta-analysis, or certainty-of-evidence grading was undertaken; therefore, findings are interpreted cautiously and according to the maturity and consistency of the available evidence. Evidence suggests that telemedicine can support follow-up, access to specialist care, and family engagement in several pediatric chronic-care pathways, particularly diabetes and asthma. However, the evidence base is heterogeneous across specialties, frequently relies on observational or implementation studies, and is less mature for acute assessment, neonatal and rehabilitation uses, wearables, and AI-enabled tools. Telemedicine should be considered a complementary component of pediatric healthcare rather than a replacement for in-person assessment. Hybrid models may support accessibility, continuity, and sustainability when embedded in structured, patient-centered, equitable, and clinically appropriate pathways. • Telemedicine expanded rapidly in pediatrics during the COVID-19 pandemic and is now used across many specialties. • It can improve access, continuity of care, remote monitoring, and family engagement, especially in chronic and complex conditions. • This review summarizes recent technological and organizational innovations, including wearables, mHealth, EHR integration, AI, and hybrid care models. • It highlights current limits and future requirements for safe, equitable, and sustainable integration into routine pediatric care.
Independent walking is more than a developmental milestone, as it reflects the integration of neuromuscular maturation, postural control, and sensorimotor coordination. In children born preterm, both the timing and the characteristics of independent walking may differ from those observed in term-born peers. This narrative review synthesizes current evidence on independent walking acquisition and gait features in preterm-born children throughout different stages of life, from toddler to school age, and discusses the clinical implications of quantitative gait assessment, with a focus on innovative wearable technologies, during neurodevelopmental follow-up. Preterm birth is consistently associated with a 1-2-month delay in independent walking onset compared with term-born peers, even after correction for gestational age (GA), with greater delays reported in infants born at lower GA or with very low birth weight (BW). Beyond milestone attainment, both qualitative and quantitative studies describe less mature gait patterns during early walking and the preschool years, including shorter step length, wider base of support, prolonged double-support phase, increased temporal variability, and reduced gait complexity. These characteristics likely reflect compensatory strategies related to immature postural control and sensorimotor organization. Although many spatiotemporal parameters improve with age and walking experience, subtle differences may persist into school age, particularly under more demanding conditions such as dual-task walking. However, currently available studies on preterm gait are quite heterogeneous in terms of GA, BW, and/or individual walking experience of included individuals and gait analysis methods employed. Furthermore, evidence regarding gait characteristics in preschool and school-aged preterm children is still relatively scarce, thus hampering a deeper understanding of preterm-born children's gait development after the toddler stage.  Instrumented gait analysis systems and wearable technologies, including inertial measurement units, enable objective and ecologically valid assessment of gait performance. Quantitative gait parameters have shown associations with standardised gross motor scores and may provide additional information beyond milestone history alone. Incorporating structured quantitative gait assessment into longitudinal follow-up programmes could support more detailed monitoring of motor development and inform individualised rehabilitation planning in children born preterm. • Children born preterm generally achieve independent walking later than term-born peers and may show immature gait features, particularly during the first years of life. • Most available evidence is heterogeneous and focuses mainly on walking onset or early gait, with limited data extending into preschool and school age. • This review integrates evidence on gait development from the fi rst independent steps to school age, identifying persistent abnormalities mainly in children born at lower gestational ages, with lower birth weight, or under demanding walking conditions. • It highlights the potential role of quantitative gait analysis and wearable inertial sensors as complementary tools for longitudinal neurodevelopmental follow-up and individualized rehabilitation planning.
The purpose of this study is to provide institution-specific, contemporary long-term outcome data to improve counselling at the limit of viability after previable preterm prelabour rupture of membranes (pPROM). This is a retrospective cohort study (2009-2022) of infants with pPROM < 23 + 0 weeks' gestation who received active neonatal care. Primary outcome was neurodevelopmental outcome at 24-36 months' corrected age. Among 109 infants, 33 (30.3%) died before discharge. Of 76 survivors, 13 (17.1%) were lost to follow-up and outcome data were available for 63/76 (82.9% follow-up). The mean gestational age was 21.6 weeks at pPROM and 25.7 weeks at delivery. Median Bayley-III scores were 90 (IQR 73-100) for cognition, 81 (IQR 63-97) for language, and 89 (IQR 65-100) for motor function. Cerebral palsy occurred in 11.1%. Survival without moderate or severe neurodevelopmental impairment (NDI) was 72.6%; moderate NDI occurred in 11.0% and severe NDI in 16.4%. Latency duration and gestational age at rupture were not significantly associated with outcome. Severe neonatal morbidity was associated with lower survival without moderate or severe NDI (57.6% vs. 89.7%). In multivariable analysis, gestational age at birth and female sex were associated with favourable outcomes in a perinatal model; after inclusion of major neonatal morbidities, only morbidity burden remained independently associated with outcome (OR 0.39, 95% CI 0.17-0.89).  A substantial proportion of survivors after pPROM < 23 weeks achieved favourable neurodevelopment at 2-3 years. In this cohort, latency duration and gestational age at membrane rupture were not independently associated with long-term neurodevelopmental outcome. However, any influence of antenatal factors may be mediated through neonatal morbidity. These findings support individualized counselling that considers both antenatal factors and the subsequent postnatal clinical course when discussing long-term prognosis. • Previable preterm prelabour rupture of membranes (pPROM) before 23 weeks' gestation is associated with high perinatal mortality and substantial risk of long-term neurodevelopmental impairment, but available follow-up data remain limited. • Previous studies have suggested that gestational age at membrane rupture and latency duration may influence survival, yet their association with long-term neurodevelopment among survivors remains unclear. • In this single-centre cohort with standardized Bayley-III follow-up, 72.6% of survivors survived without moderate or severe neurodevelopmental impairment, and 83.6% survived without severe impairment at 2-3 years' corrected age. • Neonatal morbidity burden, rather than gestational age at rupture or latency duration, was more closely associated with later neurodevelopmental outcome, highlighting the importance of the postnatal clinical course for prognostication and counselling.
High-dose caffeine may improve respiratory outcomes in preterm neonates, but evidence remains uncertain in the era of routine early caffeine use and non-invasive ventilation. We compared high-dose (HDC) versus standard-dose caffeine (SDC) in preterm neonates at risk of or having apnea of prematurity. This single-center, assessor-blinded, randomized controlled trial enrolled preterm neonates born at < 32 weeks' gestation. Neonates were randomized to receive either HDC (loading dose 40 mg/kg, maintenance 10 mg/kg/day) or SDC (loading dose 20 mg/kg, maintenance 5 mg/kg/day). The primary outcome was the need for escalation to non-invasive positive pressure ventilation (NIPPV) for apnea. Secondary outcomes included duration of respiratory support before successful weaning, extubation failure, duration and utilization of respiratory support, feeding outcomes, adverse effects, neonatal morbidities and mortality. A total of 140 neonates were randomized, with 70 assigned to each group. Baseline maternal and neonatal characteristics were comparable. Requiring escalation to NIPPV for apnea in HDC was 30 (42.9%), and in SDC, 38 (54.3%) (RR 0.79; 95% confidence interval (CI) 0.56, 1.11; p = 0.176). The median (IQR) duration of respiratory support before successful weaning was 11.5 (5.0-25.0) days in the HDC and 8.5 (5.0-17.3) days in the SDC group (median difference 1 day; 95% CI - 2.0, 5.0; p = 0.385). Competing-risk analysis accounting for death before successful weaning showed no difference between groups (sub-distribution hazard ratio: 0.89; 95% CI 0.61, 1.30; p = 0.570). Extubation failure, respiratory support utilization, neonatal morbidities, adverse effects, and mortality were similar between groups. Among preterm neonates born at < 32 weeks' gestation, high-dose caffeine did not demonstrate a statistically significant difference in escalation to NIPPV for apnea. Adequately powered multicentre trials are required to evaluate the additional benefit of HDC alongside the use of NIPPV. CTRI/2024/03/063926. Registration date: 11/03/2024. • Caffeine, at standard pharmacological doses, facilitates extubation in preterm infants and reduces the rates of bronchopulmonary dysplasia. • Previous studies have suggested that higher caffeine doses may reduce extubation failure and bronchopulmonary dysplasia. • In preterm neonates born at < 32 weeks' gestation, high-dose caffeine did not significantly reduce the need for escalation to non-invasive positive pressure ventilation for apnea compared with standard-dose caffeine. • High-dose caffeine did not improve duration of respiratory support, extubation failure, neonatal morbidities, or mortality.
Especially, the coxsackievirus B group of enteroviruses has been linked to the development of islet autoimmunity and type 1 diabetes in genetically susceptible individuals. Our aim was to study the possible associations of 10 different microbial infections with islet autoimmunity in a large international prospective study. In a nested case-control study within the TRIGR study, follow-up serum samples from 240 islet autoantibody-positive case children and 436 age- and country-matched control children were analysed for IgG class antibodies against 10 different respiratory and gastrointestinal microbes using an enzyme immunoassay, and for neutralising antibodies against all six coxsackievirus B types. The samples were obtained at several time points prior to and at the time of seroconversion for multiple islet autoantibodies. All children had a first-degree relative with type 1 diabetes, and they carried risk-associated HLA-DQ alleles. Coxsackievirus B5 was associated with an increased risk of islet autoimmunity (OR 2.22, 95% CI 1.29-3.80, p = 0.004, corrected p = 0.024), which remained after adjustment for HLA, sex, and maternal type 1 diabetes. This association was particularly seen for infections occurring more than 12 months (OR 2.02, 95% CI 1.06-3.84, p = 0.032) and 0-6 months (OR 2.66, 95% CI 1.11-6.35, p = 0.028) before the first detection of multiple islet autoantibodies. After correction for multiple comparisons, none of the other viruses showed an association with islet autoimmunity. This study supports previous evidence of the risk association of coxsackievirus B infections. These results support the role of certain virus infections as possible modulating factors in the pathogenesis of type 1 diabetes.
Around one-third of patients with monosymptomatic nocturnal enuresis (MNE) do not respond to conventional first-line treatments. Although international guidelines outline second- and third-line treatment options, these recommendations may not fully address the needs of every case encountered in daily practice. Therefore, the question of which treatment strategy should be used for refractory cases remains unanswered. We conducted a scoping review (PROSPERO CRD420251171197) following PRISMA Extension for Scoping Reviews (PRISMA-ScR), searching the PubMed, Embase, Ovid MEDLINE, Scopus, Web of Science, Google Scholar, CINAHL and the Cochrane Library databases to identify all published reports of treatment for refractory MNE in paediatric patients up to March 2026. Eligible studies included randomized controlled trials and prospective or retrospective observational cohort studies written in English. The primary outcome was the number of wet nights (classified as complete, partial or no response according to the ICCS criteria). Secondary outcomes included a comparison of the efficacy of second- and third-line treatment options if enough data could be found. The Cochrane RoB 2 tool was used to assess the risk of bias in randomized clinical trials, and the Methodological Index for Non-Randomized Studies (MINORS) was used for non-randomized cohort studies. Following screening and eligibility assessment, 17 out of 2578 articles met the PICO inclusion criteria. The included studies enrolled a total of 1348 children and adolescents with mean ages ranging from approximately 8 to 17 years. Many of the second- or third-line treatments described in the literature were excluded due to incorrect methodology, study design or patient population. The results showed that, following first-line treatment, a combination of biofeedback, electrical nerve stimulations, anticholinergics (e.g. oxybutynin, tolterodine, solifenacin), β3-adrenoceptor agonists (e.g. vibegron), tricyclic antidepressants (e.g. imipramine) and selective serotonin reuptake inhibitor (e.g. fluoxetine) improved both partial response (PR) and complete response (CR) at varying rates across highly heterogeneous interventions and study populations. However, the evidence does not strongly support a treatment algorithm. Furthermore, reports on electro-acupuncture, furosemide, onabotulinumtoxin A injections or the herbal medicine 'shokenchuto' were considered unreliable for pure refractory MNE, despite improvements in PR and CR occurring at different rates. Conclusion: The question of which treatment strategy should be used for refractory cases remains unanswered due to a lack of sufficiently unbiased, prospective, randomized, controlled studies involving long-term follow-up. Some second- and third-line treatment options may improve PR and CR rates, despite the limited available evidence to support a treatment algorithm. However, further research is needed to confirm these benefits.
Childhood obesity is associated with an increased risk of metabolic associated fatty liver disease (MAFLD) and intra-pancreatic fat deposition (IPFD). Recent studies in adults suggest that pancreatic fat distribution is heterogeneous and that fat deposition in different regions may have distinct metabolic implications. However, data on regional IPFD patterns and their association with insulin resistance in children with obesity remain limited. This study aimed to investigate the regional distribution of pancreatic fat and its association with insulin resistance in children and adolescents with obesity. This retrospective study included 231 children and adolescents with obesity (156 boys, 75 girls; age range 8-18 years). All participants underwent magnetic resonance imaging (MRI) using the qDixon technique to quantify fat fractions in the pancreatic head, body, and tail, as well as in the liver. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Statistical analyses included Spearman correlations, logistic regression, and receiver operating characteristic (ROC) curve analysis. The prevalence of high IPFD was higher in the pancreatic head than in the body and tail across all cutoff values (> 10%, > 15%, and > 20%) in both sexes (p < 0.01). Pancreatic head fat, but not body or tail fat, was significantly correlated with insulin levels and HOMA-IR (p < 0.01). In logistic regression models adjusted for confounders, pancreatic head fat (as a continuous variable and with a > 20% cutoff) was independently associated with high insulin (odds ratio (OR) = 1.02, 95% confidence interval (CI):1.002-1.043, and OR = 2.10, 95%CI: 1.00-4.47) and insulin resistance (OR = 1.02, 95% CI: 1.002-1.044; and OR = 2.31, 95% CI: 1.13-4.78, respectively). ROC analysis showed that pancreatic head fat had a significantly higher area under the curve (AUC = 0.65) for predicting insulin resistance than body, tail and liver fat (AUC = 0.60)(p = 0.02). In children and adolescents with obesity, the deposition of pancreatic fat is heterogeneous, with the greatest accumulation observed in the pancreatic head. Fat in the pancreatic head is independently associated with high insulin resistance, whereas fat in the body and tail is not. What is Known? • Obesity is associated with an increased risk of intra-pancreatic fat deposition (IPFD). • IPFD may be associated with metabolic risk. What is New? • This is the first study reporting the spatial heterogeneity of IPFD in children and adolescents with obesity. • Fat accumulation in the pancreatic head, but no in body and tail is associated with high level of insulin resistance.
The FARSA gene encodes the catalytic α-subunit of cytoplasmic phenylalanyl-tRNA synthetase (FARS1), a key enzyme in protein biosynthesis. Biallelic pathogenic variants cause a rare multisystemic disorder of variable severity, usually characterized by early-onset interstitial lung disease (ILD) with neurological and hepatic involvement. We present two genetically confirmed cases of FARSA deficiency and one additional patient with FARSA-related ILD carrying two rare heterozygous variants of uncertain significance and compare their phenotypes with previously reported patients. Clinical, radiologic, laboratory, and genetic features of three pediatric patients were retrospectively reviewed. Whole-exome sequencing confirmed the molecular diagnosis in two patients and identified two rare candidate FARSA variants in one putative case. The results were systematically compared with published cases. Two patients carried homozygous R295W variants, whereas Case 3 carried two rare heterozygous candidate variants, p.Ala90Val and p.Gln341Arg, with unconfirmed phase. Cases 1 and 2 developed ILD during early infancy, whereas Case 3 developed interstitial lung disease after severe RSV pneumonia at 15 months. Imaging showed diffuse ground-glass opacities with interlobular septal thickening in Cases 1 and 2 and a mosaic perfusion pattern in Case 3. Neurologic features included hypotonia, corpus callosum hypoplasia, and periventricular cysts. Liver abnormalities ranged from persistent hypoalbuminemia to intermittent enzyme elevations. Cases 1 and 2 showed persistently elevated inflammatory markers independent of infection. Corticosteroids were ineffective. Rituximab and ruxolitinib were associated with variable clinical benefit: partial stabilization in the severe cases and sustained clinical improvement in the milder pulmonary case. Overall, these patients illustrate a broad phenotypic spectrum of FARSA-related disease, ranging from severe, ventilator-dependent multisystem disease to a milder, lung-dominant form with sustained stabilization.  FARSA-related disease is characterized by severe early-onset ILD, persistent inflammatory activity, and multisystem involvement, but with poor response to current therapies. Our cases emphasize that the pathogenesis probably involves both impaired protein synthesis and chronic inflammatory mechanisms. International collaboration and longitudinal studies are needed to refine the genotype-phenotype correlation and develop innovative treatment strategies that could ultimately improve prognosis and survival. • FARSA deficiency is a rare cause of pediatric interstitial lung disease with multisystem involvement, and only a limited number of cases have been reported. • We report two genetically confirmed cases and one putative FARSA-related ILD case, together with an updated literature review demonstrating the broad phenotypic spectrum and current therapeutic experience.
Acute skin failure in children encompasses several life-threatening conditions that can present with strikingly similar, extensive skin detachment despite fundamentally different causes. Staphylococcal scalded skin syndrome (SSSS), toxic epidermal necrolysis (TEN), and severe cutaneous bacterial infections may look almost identical at the bedside, yet differ profoundly in mechanism, treatment, and prognosis. The objective of this study is to describe four consecutive pediatric cases of acute skin failure and to derive a practical, bedside diagnostic approach that helps distinguish infectious from immune-mediated causes early, when therapeutic decisions must be made. We performed a retrospective analysis of four children managed in our Pediatric Intensive Care Unit between 2023 and 2024, comparing clinical presentation, diagnostic work-up, treatment, and outcome. The report follows the CARE (CAse REport) guidelines. Three children with SSSS or severe cutaneous bacterial infection recovered completely with antibiotic therapy within 4-7 days. One child with lamotrigine-induced TEN required 42 days of intensive care and multimodal immunomodulation before complete recovery. All four children survived and recovered fully. The extent of skin detachment alone cannot establish the diagnosis. Careful assessment of mucosal involvement, a detailed medication history, and microbiological findings-together with the treatment response at 48-72 h-were the most useful discriminators, determining whether antibiotic therapy or immunomodulation was required. • SSSS, TEN, and severe cutaneous bacterial infections can all cause extensive skin detachment in children and may be difficult to distinguish at first presentation. • The treatments for these conditions differ fundamentally, and inappropriate therapy can worsen the outcome. • In a comparative series of four children, the extent of skin involvement did not discriminate between causes: two children with 90% body-surface involvement required opposite treatments. • We propose a pragmatic, time-anchored bedside approach-systematic mucosal examination, a structured medication history, and reassessment of treatment response at 48-72 h-to help distinguish infectious from immune-mediated acute skin failure.
Incidental esophageal eosinophilia (EE) can be detected in children investigated for suspected celiac disease (CD), but the relationship between CD and eosinophilic esophagitis (EoE) remains unclear. This study describes the characteristics of these patients and evaluates whether EE resolves on a gluten-free diet (GFD). This retrospective study included all patients < 18 years biopsied for suspected CD (2018-2025). When esophageal abnormalities were observed, additional biopsies were taken. Cases (CD + EE) had positive antitransglutaminase antibodies-classified as active CD (ACD) or potential CD (PCD) if presented or not intestinal damage- and biopsy-proven EE (≥ 15 eos/HPF). Comparators were randomly selected among CD-diagnosed patients without macroscopical esophageal abnormalities (CD + EE -). Clinical, immunological, and histological features were compared. EE remission (< 15 eos/HPF) was assessed in cases after treatment. PCD patients received proton pump inhibitors (PPIs) for 8 weeks, with GFD prescribed only if PPIs failed. ACD patients received a 6-month GFD first, with PPIs added if esophageal remission was not achieved. 14/520 children (2.7%) had confirmed EE (9 ACD, 5 PCD). Only 2/14 (14%) were symptomatic. Compared to 100 CD + EE - subjects, cases were significantly more likely to be male (86% vs. 34%; p = 0.0003), atopic (57% vs. 22%; p = 0.009), and having peripheral eosinophilia (86% vs. 12%; p < 0.0001). Overall, GFD induced EE remission in 5/11 (45%) of cases. Most ACD patients required additional PPI therapy after GFD failure.   Incidental EE affects ~ 3% of pediatric CD evaluations. These patients typically fulfill histological EoE criteria and are often asymptomatic. Male sex, atopy, and peripheral eosinophilia are strongly associated to this condition. While GFD resolves EE in nearly half of cases, the persistence in others suggests EE is frequently an independent comorbidity. Nonetheless, a GFD is a viable first-line approach in dual-diagnosis patients. • Incidental esophageal eosinophilia (EE) is sometimes found in children being evaluated for celiac disease (CD). • The precise clinical relationship and overlap between celiac disease and eosinophilic esophagitis (EoE) remain unclear. • Incidental EE affects ~3% of pediatric CD cases; patients are often asymptomatic but strongly linked to male sex, atopy, and peripheral eosinophilia. • A gluten-free diet solves EE in aroung 45% of cases, making it a viable first-line approach in dual diagnosis of EE and celiac disease, though others additional, EE specific therapies.
Pediatric traumatic brain injury (TBI) is a major public health concern requiring coordinated management within an organized trauma system. This study aimed to analyze the epidemiology and temporal trends of pediatric TBI in Lombardy (Italy) and to evaluate centralization patterns within the regional hub-and-spoke trauma network. We conducted a retrospective, population-based study using regional administrative healthcare databases. All healthcare episodes of children (< 18 years) with a diagnosis of TBI residing in Lombardy (Italy) who presented to emergency departments (EDs) between January 2012 and December 2022 were included. ED visits, hospital admissions, and intensive care unit (ICU) admissions were analyzed. Temporal trends in ED visits, hospital admissions, and ICU admissions were evaluated using standardized rates and regression models. Centralization was assessed through temporal changes in ICU referral patterns within the regional trauma network. A total of 143,961 ED visits and 14,223 hospital admissions for pediatric TBI were recorded. ED visit rates declined significantly over time (adjusted annual reduction ≈1%), while hospital admission rates also declined significantly (adjusted annual reduction ≈4%). In contrast, no significant temporal trend was observed for ICU admissions after multivariable adjustment. The proportion of ICU admissions managed at the designated regional referral center increased progressively over time.  This population-based study identified declining recorded ED visits and hospital admissions for pediatric TBI, alongside increasing concentration of ICU-managed pediatric TBI cases at a high-volume referral center within a structured trauma system. These findings are consistent with the evolution of the regional hub-and-spoke trauma system. • Pediatric traumatic brain injury (TBI) is a major cause of emergency department visits and trauma-related hospitalizations in children. • Specialized pediatric trauma systems and referral to high-volume centers are recommended for severe pediatric TBI management. • This population-based study provides an 11-year assessment of pediatric TBI epidemiology and temporal trends across an entire regional trauma network. • Over time, pediatric TBI cases requiring intensive care were increasingly managed at the regional referral center, consistent with the evolution of a regional hub-and-spoke trauma system.
Neurological involvement is rare in paediatric thrombotic microangiopathies (TMAs), with scarce information to guide clinical management. Therefore, this study aimed to describe and compare the characteristics, risk factors, and outcomes between children with and without severe neurological involvement in the context of TMA requiring intensive care. This was a prospective multicentre observational study in 20 paediatric intensive care units (PICUs) in Spain, the MATUCIP Registry, from January 2017 to December 2025 including children aged more than 1 month with TMAs, who were followed up through discharge from the PICU. We collected routine care data and management was performed according to local practice. The main outcome was the incidence of severe neurological involvement, and secondary ones were its relation with supportive care, length of PICU stay, and laboratory findings. We included 160 patients (50.6% female) with a median age of 2.8 years (interquartile range [IQR], 1.6-6). At baseline, 121/160 presented with gastrointestinal (75.6%), 22/160 respiratory (13.8%), manifestations. Only 3 out of 160 (1.9%) patients presented initially with neurological manifestations, but up to 46 developed them during follow-up (28.7%). Most neurological cases were severe (31 out of 46, 67%), including altered level of consciousness (n = 22, 70.9%) and seizures (n = 14, 45.2%). Patients with neurological involvement required renal replacement therapy more frequently, eculizumab/ravulizumab administration, and had longer PICU length of stay. In our cohort, almost one-third of participants developed neurological manifestations, most of them severe, during a PICU admission for TMA, and this was associated with prolonged recovery times and an increased need for supportive interventions. This warrants close neurological surveillance by PICU staff for the timely introduction of protective measures, although the impact of such measures on mortality and long-term outcomes needs further research. • TMA is a group of multisystemic diseases, and even though neurological involvement is not the most common manifestation, it has been associated with higher mortality and morbidity, making early detection and treatment crucial. • In our registry, neurological impairment occurred in one-third of TMA cases, and it was associated with poorer outcomes and a longer PICU stay. • Although the treatment is mainly supportive care, the onset of neurological manifestations may determine the indication for complement-inhibitor drugs.
The purpose of the study is to compare the efficacy and safety of available interventions for infantile hemangioma against oral propranolol and to evaluate the certainty of the comparative evidence. We conducted a Bayesian network meta-analysis in accordance with PRISMA-NMA guidelines and systematically searched PubMed, Embase, the Cochrane Library, and CNKI from January 2008 to June 2026. A random-effects consistency model was fitted using the BUGSnet package. Evidence certainty was assessed using the CINeMA framework, and risk of bias was evaluated using the revised Cochrane RoB 2 tool. Thirty randomized controlled trials (RCTs) including 2,639 patients across nine treatment nodes were included in the efficacy analysis, and 12 RCTs involving 1,143 patients across eight nodes were included in the safety analysis. Using oral propranolol as the reference treatment, no active intervention demonstrated statistically significant superiority in efficacy, whereas placebo was significantly inferior. Corticosteroids were the only intervention associated with substantially higher adverse event rates, whereas atenolol showed a trend toward fewer adverse events. By anchoring all comparisons to oral propranolol and integrating CINeMA certainty assessments with inconsistency testing, these findings are consistent with the continued role of oral propranolol as the reference systemic treatment for infantile hemangioma. For patients intolerant to propranolol, atenolol may represent a reasonable alternative.  By anchoring all comparisons to oral propranolol and integrating CINeMA certainty assessments with inconsistency testing, these findings are consistent with the continued role of oral propranolol as the reference systemic treatment for infantile hemangioma. For patients intolerant to propranolol, atenolol may represent a reasonable alternative. • Oral propranolol is the established first-line systemic therapy for infantile hemangioma. • Previous network meta-analyses have reported treatment rankings, but the clinical meaning of these rankings relative to oral propranolol remains uncertain. • Despite favorable point estimates for combination therapy and nadolol, this benchmark-anchored analysis found no included active intervention statistically superior to oral propranolol. • Certainty assessment showed that treatment rankings were limited by heterogeneity, inconsistency, risk of bias, and imprecision; atenolol had the largest body of direct comparative evidence among the alternatives.
Peripartum depression (PPD) is a serious public health issue associated with adverse maternal and infant outcomes. Healthcare providers (HCPs)-including pediatricians, family medicine physicians (FMPs), and obstetricians-are well-placed to screen for and manage PPD. This study aims to investigate the knowledge, attitudes, and experience regarding PPD among pediatricians and compare them with those of FMPs and obstetricians in Turkey. This cross-sectional study included HCPs from multiple cities across Turkey. Data were gathered through an online structured questionnaire designed by the researchers. The sample comprised 200 pediatricians, 158 FMPs, and 76 obstetricians. Pediatricians exhibited the lowest level of awareness regarding PPD screening tools (p < 0.001), the lowest utilization rate of standardized PPD screening tools (2%), and the lowest rate of prior PPD training (1.5%). Although the majority of pediatricians agreed that PPD should be assessed, only 39% perceived postnatal PPD assessment as part of their professional responsibility (p < 0.001). After adjusting for confounders, being a pediatrician was independently associated with lower awareness of PPD screening scales (aOR = 0.50; 95% CI:0.30-0.83; p = 0.007) and a higher likelihood of strongly disagreeing with PPD screening responsibility (aOR = 5.82; 95% CI:1.31-25.84; p = 0.021). Pediatricians demonstrated the lowest levels of knowledge, experience, and unfavorable attitudes toward managing PPD. A clear discrepancy exists between recognizing the importance of PPD management and acting on PPD. Incorporating PPD training into medical education and pediatric residency programs, as well as developing standardized PPD guidelines that include pediatricians, could enhance PPD screening and management in Turkey. • Although a growing body of literature has documented a rise in peripartum depression (PPD) screening by pediatricians, current PPD screening rates remain profoundly inadequate. • Healthcare providers have limited knowledge, negative attitudes, and insufficient clinical experience regarding PPD. • This study is the first in Turkey to highlight the significant gaps in postpartum PPD awareness among pediatricians, revealing limited knowledge, negative attitudes, and insufficient clinical experience. • Pediatricians had the lowest rate of prior training among healthcare professionals, despite expressing a strong need for education.
Although the role of dopaminergic dysfunction and iron metabolism in the pathophysiology of restless legs syndrome (RLS) has been widely investigated, the potential association between vitamin B12 status and RLS remains insufficiently explored. In particular, data in pediatric and adolescent populations are limited and inconsistent. Moreover, while sleep disturbance is a well-recognized feature of RLS, the combined relationship between vitamin B12 levels, RLS, and sleep quality has not been adequately evaluated in adolescents. Therefore, the present study aimed to investigate the association between vitamin B12 levels and the presence of RLS, and to assess sleep quality in adolescents with and without RLS. Dysfunction of the dopaminergic system is known to play a role in the pathophysiology of patients with restless legs syndrome (RLS). Vitamin B12 functions as a cofactor in pathways involved in dopamine synthesis. This study was conducted to investigate the association between vitamin B12 levels and restless legs syndrome (RLS) and to evaluate the relationship between RLS and sleep quality. The study was conducted with 146 pediatric patients aged 10-16 years who applied to pediatric outpatient clinics. All patients were evaluated for RLS according to the diagnostic criteria established by the International RLS Study Group (IRLSSG). Patients with symptoms of RLS were scored using the disease symptom severity scale defined by the same group, and comparisons were made between the groups. To assess sleep quality, the Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered to all patients, and the results were recorded and compared across all groups. There were no statistically significant differences in hemoglobin, hematocrit, ferritin, folic acid, or glucose levels. Serum vitamin B12 levels were found to be significantly lower in patients with RLS compared to those without the syndrome. Our total PSQI scores were statistically higher in the RLS group than in the non-restless legs syndrome group. Patients were divided into three groups according to their vitamin B12 levels: "deficient," "borderline," and "sufficient." When these three groups were compared in terms of the frequency of restless legs syndrome, its prevalence was statistically higher in the group with insufficient vitamin B12 levels. Conclusion: Our findings suggest an association between lower vitamin B12 levels and the presence of RLS in adolescents. However, due to the cross-sectional design of the study, causality cannot be established and further prospective studies are needed to confirm these findings. In addition, consistent with the literature, sleep quality was found to be impaired in patients with RLS in our study. What is known • RLS is associated with sleep disturbance and reduced quality of life • Evidence on the relationship between vitamin B12 and RLS is limited, especially in adolescents What is new • Lower vitamin B12 levels were associated with a higher frequency of RLS in unadjusted analyses • Vitamin B12 status may be related to sleep quality in this population.