European Journal Of Pediatrics[JOURNAL]
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200 papers
Higher IVIG resistance in Kawasaki disease patients treated early after fever onset: a single-center retrospective study of 2,988 cases.
Wen J, Wu Y, Huang P … +5 more , Zhang L, Li W, Wang Y, Xie X, Wang Z
Eur J Pediatr · 2026 Jun · PMID 42223674 · Publisher ↗
To investigate the impact of intravenous immunoglobulin (IVIG) timing on coronary artery outcomes and treatment response in children with Kawasaki disease (KD). This retrospective study analyzed 2,988 pediatric patients...
To investigate the impact of intravenous immunoglobulin (IVIG) timing on coronary artery outcomes and treatment response in children with Kawasaki disease (KD). This retrospective study analyzed 2,988 pediatric patients with Kawasaki disease (KD) who received initial IVIG treatment within 3-7 days of fever onset. Patients were categorized by IVIG initiation time: Group A (day 3 of fever, n = 134), Group B (day 4 of fever, n = 465), Group C (day 5 of fever, n = 1101), Group D (day 6 of fever, n = 833), and Group E (day 7 of fever, n = 455). We compared baseline characteristics, IVIG resistance, and convalescent-phase coronary artery lesions (CALs). Multivariate logistic regression analyzed the association between early initiation (days 3-4 of fever) of initial IVIG therapy and IVIG resistance or convalescent-phase CALs. Propensity score matching (PSM) was used to match the early (days 3-4 of fever, n = 590) and conventional (days 5-7 of fever, n = 590) treatment groups. Baseline data during the acute phase revealed that with delayed initiation of initial IVIG treatment, serum albumin (ALB), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels in children with KD showed a significant overall decreasing trend (P < 0.001), while platelet (PLT) counts and the incidence of acute-phase CALs showed a significant overall increase (P < 0.001). However, no significant difference was found in convalescent-phase CALs incidence among groups. IVIG resistance was more common among children who required early treatment (P < 0.001). PSM analysis showed no significant difference in acute or convalescent-phase CALs between the early and conventional groups. In the multivariate logistic regression analysis after adjusting for confounders, early IVIG initiation was not significantly associated with convalescent-phase CALs but was associated with a significantly increased risk of IVIG resistance (OR: 1.74; 95% CI: 1.32-2.29; P < 0.001).Conclusion: In this single-center retrospective study, initiating initial IVIG therapy within 3-7 days of fever onset showed no significant impact on the incidence of convalescent-phase CALs at different treatment timings. However, IVIG resistance was more common among children who required early treatment (days 3-4 of fever). Due to potential residual confounding by indication, these findings represent a non-causal association that may reflect differences in underlying disease severity and clinical presentation. Future prospective, multicenter, randomized controlled trials are needed to further clarify the optimal timing of initial IVIG therapy in KD patients, thereby providing evidence for developing individualized treatment strategies and improving long-term prognosis.
Clinical utility of a novel index for predicting metabolic dysfunction-associated steatotic liver disease risk in children.
Arslan G, Deveci M, Er E … +1 more , Dündar BN
Eur J Pediatr · 2026 Jun · PMID 42223658 · Publisher ↗
UNLABELLED: Visceral adiposity is a key driver of metabolic dysfunction. Although indices such as the Visceral Adiposity Index (VAI) are widely used in adults, no standardized, practical tool exists for assessing viscera...
UNLABELLED: Visceral adiposity is a key driver of metabolic dysfunction. Although indices such as the Visceral Adiposity Index (VAI) are widely used in adults, no standardized, practical tool exists for assessing visceral fat accumulation in children and adolescents. We aimed to develop a simple, clinically applicable model for the early identification of metabolic dysfunction-associated steatotic liver disease (MASLD) in pediatric obesity. We retrospectively analyzed 219 children and adolescents with obesity. Clinical, anthropometric, laboratory, and imaging data were collected. Hepatosteatosis and its severity were assessed by ultrasonography. Multivariable logistic regression models were constructed to identify independent predictors and to develop a parsimonious prediction model. The mean age was 13.34 ± 3.17 years, and 63% were female. Anthropometric measures (body weight, BMI, waist circumference, and waist-to-height ratio) increased across steatosis grades. Metabolic markers, including insulin, AST, ALT, and HOMA-IR, showed a progressive increase with disease severity. A parsimonious model (Model 1), incorporating only age, sex, BMI SDS, and waist circumference SDS, demonstrated robust discriminative performance and outperformed HOMA-IR and adult-derived indices (VAI and TyG), which showed limited predictive utility in this population. CONCLUSION: We present a novel, anthropometry-based model that accurately identifies MASLD in children with obesity using readily available clinical parameters. This pragmatic approach enables early risk stratification and may facilitate implementation in routine pediatric practice. WHAT IS KNOWN: • Visceral adiposity is closely associated with metabolic dysfunction and increased cardiometabolic risk in children with obesity. • Anthropometric and biochemical markers have been proposed as noninvasive tools for predicting metabolic associated steatotic liver disease (MASLD) in pediatric populations. WHAT IS NEW: • Visceral adiposity-related indices were significantly associated with the presence and severity of MASLD in children and adolescents with obesity. • The study highlights the potential utility of simple anthropometric and metabolic markers in the early identification of pediatric patients at higher risk for MASLD.
Interventions to improve neonatal and infant intubation success: a meta-analysis.
Tjurin W, Kiviranta P, Salmi H … +1 more , Kuitunen I
Eur J Pediatr · 2026 May · PMID 42215648 · Full text
UNLABELLED: The aim of this study is to synthesize and evaluate the effectiveness of interventions aimed at improving endotracheal intubation success in neonates and infants. PubMed, Scopus, and Web of Science were searc...
UNLABELLED: The aim of this study is to synthesize and evaluate the effectiveness of interventions aimed at improving endotracheal intubation success in neonates and infants. PubMed, Scopus, and Web of Science were searched from inception through July 2025. Randomized studies involving neonatal or infant endotracheal intubation were included regardless of intervention or comparator. Two reviewers independently extracted data and assessed risk of bias. Data were pooled using a random-effects inverse-variance model. Results are reported as risk ratios (RRs) with 95% confidence intervals (CIs). Certainty of evidence was assessed using the GRADE approach. Thirty studies published between 2002 and 2025 were included from 287 screened records. Most intubations were elective and performed in neonatal intensive care units or operating rooms. Video laryngoscopy improved first-attempt success compared with direct laryngoscopy (RR 1.13; 95% CI 1.06-1.20; high-certainty evidence). Pharmacologic interventions, particularly neuromuscular blocking agents and sedatives, generally increased success. Noninvasive respiratory support during intubation improved success (RR 1.18; 95% CI 1.02-1.38; moderate-certainty evidence). Time to successful intubation was similar across most interventions, except for neuromuscular blockade, which shortened intubation duration. Desaturation-related outcomes did not differ. CONCLUSION: Video laryngoscopy improves first-attempt intubation success with high-certainty evidence, and noninvasive respiratory support most likely improves success. These findings support their use during neonatal and infant intubation. WHAT IS KNOWN: • Intubation in neonates and infants carries a high complication risk, making fi rst-attempt successcritical. • Video laryngoscopy and pharmacological premedication each improve intubation conditions but have previouslybeen evaluated in isolation. WHAT IS NEW: • Pooled randomized evidence confi rms with high certainty that video laryngoscopy improves fi rst-attempt success over direct laryngoscopy without prolonging intubation time. • Non-invasive respiratory support during intubation most likely improves fi rst-attempt success and physiologicalsafety.
Clinical, economic, and organisational impact of the novel AAP 2022 neonatal hyperbilirubinemia guidelines in an Italian third-level neonatology unit.
Risso FM, Pintaldi S, Barovelli G … +14 more , Terminio C, Altomari M, Franzoni E, Ferrari S, Caffarone F, Guaragni B, Rodriguez Perez MDC, Zanchi D, Burato E, Nicoli F, Tomasi C, Spinoni V, Aversa S, Morotti F
Eur J Pediatr · 2026 May · PMID 42213232 · Publisher ↗
UNLABELLED: Neonatal hyperbilirubinemia (HB) is universally screened in Italy to reduce the risks of subsequent neurological damage. The 2022 American Academy of Paediatrics revised guidelines set higher phototherapy thr...
UNLABELLED: Neonatal hyperbilirubinemia (HB) is universally screened in Italy to reduce the risks of subsequent neurological damage. The 2022 American Academy of Paediatrics revised guidelines set higher phototherapy thresholds and offer follow-up recommendations that ultimately reduce HB overtreatment in newborns born at ≥ 35 weeks' gestational age. While assessing the implementation of AAP guidelines at our centre, we compared the clinical and economic outcomes between the AAP 2022 guidelines and current Italian recommendations. We retrospectively applied the American guidelines to newborns managed according to current Italian recommendations, born at our centre between November 2024 and February 2025. Clinical characteristics, bilirubin levels, and interventions were recorded. The Institutional Treasury provided healthcare costs for hospitalisation and interventions. Clinical decisions and subsequent costs were compared. Nine-hundred and four newborns (50% females, median gestational age 39 weeks) were enrolled. Forty-eight (5.3%) patients presented bilirubin-induced risk factors. The bilirubin level informing a clinical decision was performed at a median of 51 (interquartile range 44-58) hours-of-life. AAP guidelines potentially reduced phototherapy by 69.8% (p < 0.001), accounting for a 98 bed-days reduction. Post-discharge bilirubin checks increased by 37.9% (p = 0.004). A 4-month reduction of 16,591.58 € in variable costs and a significant improvement in resource rationalisation were calculated. CONCLUSION: The AAP 2022 guidelines potentially reduce HB treatment and shift bilirubin surveillance to the outpatient department, enhancing neonatal care efficiency and reducing healthcare costs. These analytical outcomes encouraged the adoption of the AAP guidelines at our centre. Longitudinal surveillance will clarify the safety and actual extent of this change of reference guidelines in our practice. WHAT IS KNOWN: • The risk of bilirubin-induced neurological damage (BIND) in healthy term and near-term newborns has been overestimated in the past. The AAP revised its hyperbilirubinemia guidelines, providing higher hourly bilirubin thresholds for newborns without risk factors for BIND. • Despite reports on the safety and efficacy of the AAP 2022 guidelines, their implementation was not officially encouraged in Italy, making their adoption a choice to be evaluated at a facility level. WHAT IS NEW: • Simulation on retrospective data of AAP 2022 guidelines promises a reduction in healthcare costs and rationalisation of healthcare system resources. • The favourable cost-effectiveness analysis prompted the adoption of AAP 2022 guidelines at our centre. Longitudinal surveillance will help clarify the actual extent of economic impact and to assess real-life safety and efficacy of the guidelines.
Cenobamate in pediatric drug-resistant epilepsy: real-world evidence from a two-center retrospective study.
Taximi S, Angeli M, Chranioti I … +3 more , Dimopoulou D, Vartzelis G, Dinopoulos A
Eur J Pediatr · 2026 May · PMID 42213138 · Publisher ↗
UNLABELLED: Epilepsy is common in children and is often manageable. However, only about one-third of individuals remain seizure-free. Drug-resistant epilepsy (DRE) is associated with poor quality of life, an increased ri...
UNLABELLED: Epilepsy is common in children and is often manageable. However, only about one-third of individuals remain seizure-free. Drug-resistant epilepsy (DRE) is associated with poor quality of life, an increased risk of sudden death, and adverse neurodevelopmental outcomes. Cenobamate is a new promising antiepileptic drug approved for adults with refractory focal epilepsy, but data from pediatric subjects are limited. This study aims to provide data on cenobamate's use in this population. We performed a two-center retrospective study of pediatric individuals with focal DRE treated with cenobamate as adjunctive therapy, comparing seizure frequency before treatment and after reaching the maximum tolerated dose using routine clinical records. A total of 65 subjects (median age of 11.5 years) were followed for a median of nine months. The median initiation dose was 0.3 mg/kg/day and the median final dose was 2.34 mg/kg/day. At treatment initiation, the participants were receiving a median of 2 anti-seizure medications (IQR: 1 - 3) and had previously been exposed to a median of 5 different medications (IQR: 4 - 7). Twenty individuals had previously been on a ketogenic diet and thirty-two were diagnosed with developmental and epileptic encephalopathy (DEE). Seizure frequency significantly reduced post treatment (p < 0.001): 75% of participants improved, 44.6% had > 50% reduction of seizure episodes and 20% became seizure free. Adverse events were reported in 52.3% of participants, most commonly drowsiness, fatigue, dizziness, ataxia and appetite loss and these were generally mild, well tolerated and mostly self-limiting. CONCLUSION: In conclusion, cenobamate appears to be effective and well-tolerated adjunctive therapy in children with DRE, especially in individuals with structural or unknown etiologies. WHAT IS KNOWN: • Approximately one third of children with epilepsy develop drug-resistant epilepsy. • Cenobamate (CNB) is a novel anti-seizure medication (ASM) used successfully as an adjunctive therapy for refractory focal epilepsy in adults. Only a few studies are available for children. WHAT IS NEW: • This study is one of the limited multicenter studies showing CNB's efficacy and safety in children. • Cenobamate is generally safe and well-tolerated and best responses are observed in individuals with structural abnormalities or epilepsy of unknown etiology, particularly in the absence of developmental and epileptic encephalopathy.
Organ size in small infants (The OSSI Study): establishing sonographic reference intervals for abdominal organs in preterm infants.
Rahn A, Pirr S, Peter C … +8 more , Böhne C, Klischke L, Ringlstetter R, Theis L, Brodowski L, Bohnhorst B, Franke D, Müller T
Eur J Pediatr · 2026 May · PMID 42209833 · Full text
UNLABELLED: Accurate ultrasound assessment of abdominal organ size in preterm infants is essential for evaluating growth and detecting abnormalities. However, standardized reference intervals for liver, spleen, and kidne...
UNLABELLED: Accurate ultrasound assessment of abdominal organ size in preterm infants is essential for evaluating growth and detecting abnormalities. However, standardized reference intervals for liver, spleen, and kidney dimensions in preterms below 40 cm body length are lacking. This study aimed to establish reference intervals for these organs. 57 eutrophic preterm infants with a body length below 40 cm (gestational age: 23 /-31 / weeks; birth length: 29-39.5 cm) were prospectively examined using a standardized ultrasound protocol recommended by the German Society for Ultrasound in Medicine (DEGUM). Craniocaudal liver length, spleen length, and renal volume were measured and correlated with corrected gestational age, body weight, and body length. Reference intervals were calculated from log-transformed data with 95% confidence intervals for reference limits. Portal vein peak velocity before feeding and presence of a patent ductus venosus (PDV) were additionally assessed. Organ dimensions correlated most closely with body weight, followed by body length and corrected gestational age, with renal volume showing the highest correlations overall. Reference intervals for liver, spleen, and renal size showed tight 95% confidence intervals. Portal vein peak velocity ranged from 9-29 cm/s. A PDV was present in 56%; these infants were younger at examination (10.9 vs. 17 days, p = 0.01). CONCLUSION: This study provides clinically relevant ultrasound reference intervals for abdominal organs in small preterm infants. These measurements may help distinguish physiological from pathological findings and guide clinical decision-making in neonatal care. WHAT IS KNOWN: • Ultrasound is the preferred imaging modality for abdominal organ assessment in preterm infants, but standardized sonographic reference intervals for infants with a body length below 40 cm are lacking. WHAT IS NEW: • This study provides the first standardized sonographic reference intervals for liver length, splenic length, and renal volume in preterm infants below 40 cm body length, using a prospective, reproducible protocol aligned with DEGUM recommendations. • Organ size correlated most strongly with body weight, followed by body length and corrected gestational age, with renal volume showing the highest overall correlations across all parameters.
Effect of probiotics on allergic rhinitis in children; A systematic review and meta-analysis.
Bakhshi A, Poursadegh F, Salari M … +4 more , Eidgahi ES, Shazdehahmadi S, Mahmoudi M, Faridzadeh A
Eur J Pediatr · 2026 May · PMID 42209809 · Publisher ↗
BACKGROUND: Allergic rhinitis (AR) is a prevalent chronic inflammatory disorder in children, often undiagnosed and associated with reduced quality of life and risk of comorbidities such as asthma. Probiotics have been fo...
BACKGROUND: Allergic rhinitis (AR) is a prevalent chronic inflammatory disorder in children, often undiagnosed and associated with reduced quality of life and risk of comorbidities such as asthma. Probiotics have been found to be potential modulators of immune responses in allergic conditions. This systematic review and meta-analysis evaluated the efficacy of probiotics compared with placebo in the management of pediatric AR. METHODS: Searches were conducted in accordance with a pre-registered protocol using MEDLINE (PubMed), the Web of Science, Scopus, and Embase through April 8, 2025. Randomized controlled trials (RCTs) of children aged < 18 years that compared probiotics, prebiotics, or synbiotics with a placebo were considered for inclusion. Outcomes of interest included clinical and laboratory parameters. Random-effects models with Hedges' g were used; heterogeneity was assessed via I. RESULTS: Fourteen RCTs involving 1,739 children were included. Meta-analysis revealed a significant reduction in nasal symptom scores (SMD = -1.40; 95% CI: -2.26 to -0.54; I = 91.3%) and eye symptom scores (SMD = -3.59; 95% CI: -5.84 to -1.33; I = 94.3%). Quality of life (RQLQ) was also significantly improved (SMD = -2.98; 95% CI: -4.85 to -1.12; I = 95.7%). Among laboratory markers, a small but significant increase in serum eosinophils was observed (SMD = 0.29; 95% CI: 0.06 to 0.52; I = 0%). CONCLUSION: Probiotics were associated with improvements in nasal and ocular symptoms and quality of life in children with AR; however, these findings should be interpreted with caution due to substantial heterogeneity across studies. Probiotics may have a potential role as an adjunctive therapy, but further high-quality, standardized trials are needed. PROSPERO registration code: CRD420250654461 on 24 February 2025. What is Known • Probiotics have been investigated as adjunctive therapy for pediatric allergic rhinitis because of their potential immunomodulatory effects. • Previous studies and meta-analyses have reported inconsistent findings regarding the clinical and immunological effects of probiotics in allergic rhinitis. What is New •This meta-analysis demonstrated significant improvements in nasal symptoms, ocular symptoms, and quality of life in children with allergic rhinitis receiving probiotics versus placebo. • Probiotic supplementation showed no consistent beneficial effects on immunological markers, while substantial heterogeneity remained across studies.
Cognitive ability following exposure to parental mental disorders and other childhood adversities: a population-based cohort study of Danish males in late adolescence.
Petersen TG, Okholm GT, Davidsen K … +4 more , Wesselhoeft R, Osler M, Munk-Olsen T, Bliddal M
Eur J Pediatr · 2026 May · PMID 42209802 · Full text
UNLABELLED: The purpose of the study is to examine the association between parental mental disorders diagnosed before age six and cognitive ability at age 18, using data from a population-based cohort of male adolescents...
UNLABELLED: The purpose of the study is to examine the association between parental mental disorders diagnosed before age six and cognitive ability at age 18, using data from a population-based cohort of male adolescents attending military conscription. Further, we tested whether other childhood adversities modified this association. All males born in Denmark 1996-2001 were linked to national registers. Parental mental disorders were identified from psychiatric hospital diagnoses. We assessed other childhood adversities before age six, including family health-related, socioeconomic, and family instability, as well as the number of adversities experienced. Cognitive scores from the mandatory military conscription were standardized (mean 100, SD = 15). Associations were estimated using multiple linear regression, and effect modification was evaluated using Wald tests. We included 125,791 males (mean age 18 years, SD = 0.66), of whom 6708 had a parent with a mental disorder. Parental mental disorders were associated with a 0.91-point reduced cognitive ability score (95% confidence interval - 1.3, - 0.53). This association was not observed in adolescents who lived with only one parent (- 0.35 (- 0.85, 0.15)), those placed in out-of-home care (3.2 (0.59, 5.8)), and those with ≥ 3 additional adversities before age six. Effect modification tests were statistically significant for these groups (p < 0.01). CONCLUSION: Parental mental disorders before age six were associated with a modest reduction in cognitive ability in males at age 18, compared with those without parental mental disorders. Our findings show the association varies across family contexts, although unmeasured genetic and environmental confounding should be considered in interpreting these results. WHAT IS KNOWN: • Parental mental disorders are common and linked to lower cognitive ability in offspring. • Childhood adversities often cluster within families and are associated with poorer cognitive outcomes. WHAT IS NEW: • In this nationwide Danish cohort, parental mental disorders before age six were associated with slightly lower cognitive ability at age 18. • This association was not observed among adolescents with > 2 additional adversities, those who lived with only one parent, or those placed in out-of-home care before age six, suggesting the association varies across family context.
Pathogen-specific clinical and inflammatory phenotypes in pediatric catheter-related infections.
Budağ MÖ, Tural-Kara T
Eur J Pediatr · 2026 May · PMID 42209801 · Full text
UNLABELLED: Early empirical management of pediatric catheter-related infections (CRI) is complicated by delayed microbiological confirmation and heterogeneous local pathogen epidemiology. Pathogen-specific clinical and i...
UNLABELLED: Early empirical management of pediatric catheter-related infections (CRI) is complicated by delayed microbiological confirmation and heterogeneous local pathogen epidemiology. Pathogen-specific clinical and inflammatory profiling may facilitate contextual risk assessment at the time of clinical suspicion. In this retrospective single-center cohort study, 291 CRI episodes contributed by 177 pediatric patients between March 1, 2020, and February 29, 2024, were analyzed. Clinical variables at catheter insertion and inflammatory biomarkers at infection onset were evaluated. CRI episodes were classified according to the first clinically significant isolate. Multivariable logistic regression models explored predictors of (i) Gram-negative versus Gram-positive CRI and (ii) fungal versus bacterial CRI. During 24,846 catheter days of follow-up, the incidence density (rate per 1000 catheter days) was 11.7 per 1000 catheter days (95% CI 10.4-13.1). A causative pathogen was identified in 94.2% of episodes: 51.1% Gram-positive, 40.5% Gram-negative, and 8.4% fungal. Gram-negative infections were associated with higher CRP, PCT, and NLR levels. PCT demonstrated the highest discriminatory capacity for Gram-negative CRI (AUC 0.663, 95% CI 0.593-0.734). Lymphocyte count showed moderate discrimination for fungal CRI (AUC 0.711). CONCLUSIONS: Pediatric CRI exhibit pathogen-associated inflammatory and device-related patterns; however, discriminatory performance of individual biomarkers remains modest. These findings may support contextual risk assessment at first suspicion but do not justify modification of guideline-based empirical therapy without prospective validation. WHAT IS KNOWN: •Pediatric catheter-related infections (CRI) are prevalent in tertiary care settings, particularly among children with hematologic or oncologic disorders. •The early clinical presentation of the condition is often non-specific, and microbiological confirmation is frequently delayed, necessitating empirical therapy. •Gram-positive organisms predominate; however, Gram-negative and fungal pathogens are increasingly reported. •Inflammatory biomarkers, including CRP and procalcitonin, are frequently utilized in clinical practice, though their capacity to differentiate among different pathogen classes remains equivocal. WHAT IS NEW: •In a cohort of 177 children, contributing 291 CRI episodes, the incidence density was 11.7 per 1000 catheter days. •Distinct pathogen-associated phenotypes were identified: Gram-negative CRI exhibited a more pronounced inflammatory profile, while fungal CRI were more frequently associated with temporary and multi-lumen devices. •Despite the presence of statistically significant associations, the capacity for discrimination between pathogen classes based on biomarkers was modest (AUC ≤ 0.66 for Gram-negative differentiation), underscoring the limitations of relying on a solitary biomarker. •These findings support the implementation of structured, multivariable contextual assessment as a preferred approach over decision-making based exclusively on biomarkers at the initial stage of clinical suspicion.
Clinical delineation and genotype-phenotype correlation of 84 pediatric patients with Cornelia de Lange syndrome: insights from a single-center Chinese study.
Li Q, Chang G, Huang Y … +9 more , Li X, Yu T, Ding Y, Wang Y, Feng B, Ying L, Chen Y, Li J, Wang X
Eur J Pediatr · 2026 May · PMID 42207311 · Publisher ↗
Cornelia de Lange syndrome (CdLS) is a rare genetic disorder, which has clinical and genetic heterogeneity. This study investigated the clinical and genetic characteristics of a large cohort of CdLS in China and elucidat...
Cornelia de Lange syndrome (CdLS) is a rare genetic disorder, which has clinical and genetic heterogeneity. This study investigated the clinical and genetic characteristics of a large cohort of CdLS in China and elucidated genotype-phenotype correlations. The clinical manifestations, laboratory tests, and genetic testing of pediatric participants from January 2011 to December 2025 were retrospectively analyzed. We compared clinical phenotypes of patients with NIPBL variants versus those with variants in other causative genes, as well as among patients with different types of NIPBL variants. A total of 84 Chinese patients diagnosed with CdLS were included in this cohort. Growth curve analysis delineated distinct sex-specific patterns. Male patients experience severe growth faltering during puberty, suggesting an underlying deficit in sex hormone drive. This is further corroborated by the significant growth acceleration achieved with hormone replacement therapy in a male patient diagnosed with hypogonadotropic hypogonadism. NIPBL variants were the predominant cause, accounting for 66.7% of cases, and correlated with the most severe phenotypic spectrum. Notably, this subgroup exhibited significantly more severe growth retardation and a higher frequency of classic facial features (p < 0.001). Furthermore, severe upper limb deformities, such as oligodactyly, were identified exclusively in the NIPBL subgroup.Conclusion: This study characterized a Chinese CdLS cohort, establishing its first growth curves and observing a positive growth response to hormone therapy. Our findings confirm the link between NIPBL variants and the most severe phenotype, thereby underscoring the necessity of a genotype-stratified approach for clinical management and counseling.
Objective sleep parameters in children with nocturnal enuresis: a scoping review of polysomnographic evidence.
Hougaard NB, Borg B, Jørgensen CS … +1 more , Kamperis K
Eur J Pediatr · 2026 May · PMID 42201571 · Publisher ↗
Nocturnal enuresis (NE) is a common condition in childhood, yet the role of sleep in its pathophysiology remains unclear. While failure to awaken during sleep is a key feature, objective evidence from polysomnography (PS...
Nocturnal enuresis (NE) is a common condition in childhood, yet the role of sleep in its pathophysiology remains unclear. While failure to awaken during sleep is a key feature, objective evidence from polysomnography (PSG) has yielded inconsistent results. This scoping review aimed to systematically map studies reporting objective sleep parameters in children and adolescents with NE. The review followed the PRISMA-ScR guideline and was preregistered on the Open Science Framework. PubMed EMBASE, and Web of Science, were systematically searched for peer-reviewed English-language articles reporting objective sleep measures in participants under 18 years, evaluated for NE. Eighteen studies using PSG were included, most employing hospital-based recordings. Findings on sleep architecture in children with NE were heterogeneous. Several studies reported alterations in sleep stage distribution, including reduced slow-wave sleep, whereas others found no differences compared with controls. Periodic limb movements were elevated in some cohorts, particularly in treatment-refractory cases, but were not consistently reported. Some studies suggested a higher prevalence of obstructive sleep apnoea. Treatment studies indicated that successful therapy may be accompanied by changes in sleep stage distribution, cortical arousals, and limb movements. Conclusion: Evidence suggests that alterations in sleep regulation and fragmentation may be present in at least a subset of patients with NE. Although the evidence remains heterogeneous, emerging patterns indicate that sleep physiology could play a role in the pathophysiology of enuresis. The data suggest that disturbed arousal regulation and PLMS may be related to NE, underscoring the need for standardised, multimodal sleep assessments. What is Known-What is New: • Children with nocturnal enuresis fail to awaken to bladder signals during sleep. Prior polysomnography studies have produced inconsistent findings on sleep stages, cortical arousals, and periodic limb movements. • This scoping review synthesises 18 polysomnographic studies and highlights heterogeneous yet suggestive evidence of altered sleep regulation, fragmentation, and limb movements in children with nocturnal enuresis. The findings underscore the need for standardised PSG studies and indicate that sleep physiology may represent a relevant target for future phenotyping and research.
Characteristics of children with first febrile urinary tract infection caused by Staphylococcus species.
Hennaut E, Gubbelmans N, Martiny D … +5 more , Lolin K, Guillaume-Gentil P, Tram N, Chiodini B, Ismaili K
Eur J Pediatr · 2026 May · PMID 42201565 · Publisher ↗
Staphylococci are uncommon causes of febrile urinary tract infections (UTIs) in children and are often dismissed as contaminants in urine cultures. Data on their clinical significance in pediatric febrile UTIs are scarce...
Staphylococci are uncommon causes of febrile urinary tract infections (UTIs) in children and are often dismissed as contaminants in urine cultures. Data on their clinical significance in pediatric febrile UTIs are scarce. This study aimed to characterize the clinical features of children treated for a first febrile staphylococcal UTI at Hôpital Universitaire des Enfants Reine Fabiola (HUDERF) in Brussels. We performed a retrospective observational study including children aged < 16 years diagnosed with a first febrile staphylococcal UTI between January 2010 and December 2023. Twenty-five children were included; 56% had no prior history of febrile UTI. The male-to-female ratio was 3.2. At admission, median age was 6.5 years (interquartile range [IQR] 2.6-7.9), median temperature 39 °C (IQR 38.5-39.5), and median C-reactive protein level 31.6 mg/L (IQR 7.2-66.9). Congenital anomalies of the kidney and urinary tract (CAKUT) were present in 84% of cases, with vesicoureteral reflux (VUR) in 57%. Identified species included Staphylococcus epidermidis (44%), S. aureus (28%), S. saprophyticus (16%), S. haemolyticus (8%), and S. hominis (4%). S. epidermidis was mainly associated with VUR, whereas S. aureus was associated with obstructive uropathies and severe complications. S. saprophyticus was predominantly identified in girls without anatomical predisposition. UTI recurrence was observed in 20%, exclusively in boys with CAKUT. Conclusions: Although rare, staphylococci may cause febrile UTIs in children, particularly in those with underlying urinary tract anomalies. Such isolates should not be systematically considered contaminants and warrant careful clinical investigation.
Pentoxifylline in children with acute encephalitis syndrome: a randomized control trial.
S YK, Dwibedi B, Das RR
Eur J Pediatr · 2026 May · PMID 42201544 · Publisher ↗
Because of the excessive endogenous inflammatory mediators, acute encephalitis syndrome (AES) results in death, or sequelae in survivors. Pentoxifylline, a modulator of inflammation, can have beneficial role in AES. The...
Because of the excessive endogenous inflammatory mediators, acute encephalitis syndrome (AES) results in death, or sequelae in survivors. Pentoxifylline, a modulator of inflammation, can have beneficial role in AES. The primary objective was to assess the efficacy of pentoxifylline in terms of time taken for improvement in Glasgow coma scale (GCS) from baseline, in children with AES. The secondary objectives were adverse effects of pentoxifylline and frequency of sequelae among the survivors. This open-label randomized controlled trial (RCT) was conducted in a tertiary care teaching institution for 2 years (January 2022 to December 2023). Children aged 1 month to 14 years with a clinical diagnosis of AES were randomized to receive either standard treatment along with pentoxifylline or standard treatment alone. The data were recorded in case record forms. Forty-four children were randomized (median age, 77 months; male 72.7%). There was no significant difference in the time (median, IQR) taken for improvement of Glasgow coma scale (GCS) by 3 points or normalization between the pentoxifylline group [26 (19-50) hours] and control group [28 (16-52) hours] (p = 0.92). Other outcomes like requirement of mechanical ventilation, mortality, and sequalae were not significantly different between the two groups. The adverse event rate was also not different. Conclusion: Adjunctive pentoxifylline did not provide significant clinical benefit in children with AES, although it was safe and well tolerated. Larger, adequately powered multicenter trials with etiological stratification and biomarker integration are needed to identify potential subgroup benefits. What is Known: • Acute encephalitis syndrome (AES) is associated with high mortality and significant neurological sequelae, largely driven by host-mediated inflammatory responses. • No immunomodulatory adjunct therapy has yet shown proven benefit in pediatric AES. What is New: • Adjunctive pentoxifylline did not significantly improve neurological recovery or clinical outcomes in children with AES. • Pentoxifylline was safe and well tolerated, supporting further evaluation in larger, etiology-stratified trials.
Parental vaccine hesitancy and immunization practices in children with food allergy.
Yiğit EŞ, Bağ Ö, Tunca S … +1 more , Tuncel T
Eur J Pediatr · 2026 May · PMID 42201433 · Publisher ↗
UNLABELLED: The objective is to assess vaccine hesitancy among parents of children with food allergy compared with parents of healthy children, and to examine immunization practices in this population. In this cross-sect...
UNLABELLED: The objective is to assess vaccine hesitancy among parents of children with food allergy compared with parents of healthy children, and to examine immunization practices in this population. In this cross-sectional analytic study conducted between March and October 2025, parents of children aged 0-36 months with food allergy completed a validated Vaccine Hesitancy Scale (VHS) in their native language. Vaccine hesitancy subscales-including perceived benefits and protective value of vaccination, anti-vaccine attitudes, non-vaccination strategies, and legitimization of hesitancy-along with immunization practices were compared with healthy controls. The study included 250 children with food allergies and 250 healthy controls. Total VHS scores were similar between groups (42.8 ± 15.4 vs 41.5 ± 14.0, p = 0.54). However, subscale scores for "strategies for non-vaccination" and "legitimization of vaccine hesitancy" were significantly higher among parents of children with food allergies. The rate of delayed or incomplete vaccination was significantly higher in children with food allergies (25 vs 4, p < 0.001), particularly for the measles-mumps-rubella vaccine among children with egg allergies. CONCLUSION: The total VHS scores between parents of FA and healthy controls were similar, indicating that parents of children with food allergy do not exhibit a distinct or heightened level of VH. However, even if it does not reflect in the total scores, due to the higher scores in subscales of "strategies to avoid vaccination" and "legitimization of vaccine hesitancy," parents of children with FA should be evaluated carefully to promote vaccination in their children. WHAT IS KNOWN: • Childhood vaccine hesitancy and refusal are a secular trend affecting both the healthy population and individuals with chronic diseases. WHAT IS NEW: • Children with food allergies are at increased risk of under-vaccination, particularly for the MMR vaccine, but this situation is not directly associated with parental vaccine hesitancy.
Efficacy of Intravenous Immunoglobulin and Corticosteroids in Pediatric Myocarditis: A Comprehensive Prospective Analysis from a Middle Eastern Tertiary Care Center.
Essmaeel A, Mohammad H, Darwish M
Eur J Pediatr · 2026 May · PMID 42189291 · Publisher ↗
Pediatric myocarditis remains a rare but serious condition with high morbidity and mortality. The potential role of intravenous immunoglobulin (IVIG) and corticosteroids remains debated. In this prospective cohort study,...
Pediatric myocarditis remains a rare but serious condition with high morbidity and mortality. The potential role of intravenous immunoglobulin (IVIG) and corticosteroids remains debated. In this prospective cohort study, 84 children with clinically diagnosed myocarditis were enrolled and followed for one year. Patients received supportive therapy (n = 29), corticosteroids (n = 21), IVIG (n = 19), or combination therapy (IVIG + corticosteroids, n = 15), according to clinical judgment. Short- and long-term outcomes were compared. Improvement was defined as LVEF ≥ 55% or, for baseline LVEF < 45%, an absolute increase ≥ 10 percentage points with normalization of wall motion/fractional shortening. Outcomes were analyzed using chi-square/Fisher's exact tests, with risk ratios (RR), odds ratios (OR), and 95% confidence intervals (CIs) reported. Survival was assessed by Kaplan-Meier analysis. At one year, improvement occurred in 35% of supportive, 48% of corticosteroid, 58% of IVIG, and 67% of combination therapy patients (global χ p = 0.177). Compared with supportive care, the point estimate for improvement was highest in the combination therapy group (RR 1.93, 95% CI 0.98-3.83; OR 3.68, 95% CI 0.86-17.91), however, the difference was not statistically significant (Fisher p = 0.059). Mortality rates were 35%, 24%, 26%, and 20%, respectively, also without significant differences between groups. Conclusions: No statistically significant differences in improvement or survival were observed between treatment strategies. The reported point estimates are descriptive and should not be interpreted as evidence of treatment superiority. Larger multicenter or randomized studies are needed.
Gut microbiota-modulating interventions in paediatric type 1 diabetes: a systematic review and meta-analysis.
Llopis-Alonso I, Correa-Bares M, Mercader-Ros MT … +3 more , Lucas-Abellán C, García-Muñoz AM, Victoria-Montesinos D
Eur J Pediatr · 2026 May · PMID 42184054 · Publisher ↗
To evaluate the efficacy and safety of gut microbiota-modulating interventions in children and adolescents with type 1 diabetes. A systematic review and meta-analysis was conducted according to PRISMA 2020. PubMed/MEDLIN...
To evaluate the efficacy and safety of gut microbiota-modulating interventions in children and adolescents with type 1 diabetes. A systematic review and meta-analysis was conducted according to PRISMA 2020. PubMed/MEDLINE, Scopus, Web of Science, and CENTRAL were searched from inception to 28 February 2026 for randomised controlled trials of oral probiotics, prebiotics, or synbiotics in participants aged ≤ 19 years with type 1 diabetes. Primary outcomes were glycated haemoglobin, fasting blood glucose, total daily insulin dose, and C-peptide. Immune-inflammatory, microbiota-related, intestinal permeability, and safety outcomes were narratively synthesised. Twelve randomised controlled trials involving 808 paediatric participants were included. Interventions varied in formulation, dose, and duration. Pooled analyses showed significant reductions in glycated haemoglobin and fasting blood glucose, whereas no significant effects were found for total daily insulin dose or C-peptide. Immune-inflammatory, microbiota-related, and intestinal permeability outcomes suggested possible benefits, but reporting was inconsistent and quantitative pooling was not feasible. Overall, the evidence was limited by substantial clinical and methodological heterogeneity. Conclusion: Gut microbiota-modulating interventions may improve glycaemic control in children and adolescents with type 1 diabetes, particularly glycated haemoglobin and fasting blood glucose. However, current evidence is insufficient to support any specific formulation, dose, or duration, and larger well-designed paediatric trials are still needed. What is Known: • Gut microbiota-modulating interventions are biologically plausible adjunctive strategies in paediatric type 1 diabetes. • Earlier paediatric reviews included few randomised trials and reported inconsistent glycaemic findings. What is New: • This updated review included 12 randomised controlled trials involving 808 children and adolescents. • It adds a structured synthesis of immune-inflammatory, microbiota/barrier, metabolite-related and safety outcomes beyond glycaemic endpoints.
Treatable traits in paediatric bronchiectasis: current practice and a proposed checklist.
Annereau J, Gonsard A, Abou Taam R … +6 more , Delacourt C, Roy C, Le A, Sermet-Gaudelus I, Hadchouel A, Drummond D
Eur J Pediatr · 2026 May · PMID 42184004 · Publisher ↗
UNLABELLED: We recently published a treatable traits (TT) framework for children with non-cystic fibrosis bronchiectasis (NCFB). Whether these traits are routinely documented as assessed and identified in clinical practi...
UNLABELLED: We recently published a treatable traits (TT) framework for children with non-cystic fibrosis bronchiectasis (NCFB). Whether these traits are routinely documented as assessed and identified in clinical practice is unknown. We conducted a retrospective study of children (< 18 years) with CT-confirmed NCFB followed at a tertiary referral centre (2010-2024). For each patient, we determined which of 41 predefined TTs across four domains-aetiological (n = 6), pulmonary (n = 15), extrapulmonary (n = 9), and behavioural/environmental (n = 11)-were documented as assessed, and among those assessed, which were identified. Among 121 children (median age 10.1 years; median 2 exacerbations/year), only 20 out of 41 TTs (49%) were documented as assessed per patient, and a median of 6 were identified. Aetiological and pulmonary traits were more frequently documented as assessed than extrapulmonary and behavioural. Anxiety and depression in children or parents, as well as viral prevention measures, were never documented, and treatment adherence was rarely recorded. When traits were documented as assessed, several were frequently identified: neutrophilic inflammation was found in 93%, eosinophilic inflammation in 35%, and short-acting beta-agonist overuse in 47% of assessed patients. CONCLUSION: Even in a tertiary referral centre, half of TTs lacked documented assessment in children with NCFB, particularly psychosocial and behavioural factors. Based on these findings, we propose a pragmatic TT checklist, used as a flexible clinical guide, to support structured, clinically relevant, and traceable assessment of children with NCFB in routine care. WHAT IS KNOWN: • Paediatric non-cystic fibrosis bronchiectasis is a heterogeneous disease requiring individualised management. • A "treatable traits" approach has been proposed to guide precision medicine beyond standard guidelines. WHAT IS NEW: • In real-life paediatric practice, only half of treatable traits are documented as assessed, with psychosocial and behavioural factors particularly infrequently documented. • We propose a pragmatic checklist to support structured, clinically guided assessment and improve routine care.
Rethinking monosymptomatic nocturnal enuresis as a developmental variation.
Uemura O
Eur J Pediatr · 2026 May · PMID 42183884 · Publisher ↗
Monosymptomatic nocturnal enuresis (MNE), defined as nocturnal bedwetting in children without daytime lower urinary tract symptoms, is a frequent concern in general pediatric practice. It is common in early childhood and...
Monosymptomatic nocturnal enuresis (MNE), defined as nocturnal bedwetting in children without daytime lower urinary tract symptoms, is a frequent concern in general pediatric practice. It is common in early childhood and typically resolves spontaneously with increasing age, indicating a strong maturational component. Nevertheless, MNE is often conceptualized as a pathological disorder requiring active medical intervention. This mini-review proposes that MNE may be more appropriately interpreted as a developmental variation reflecting delayed maturation of nocturnal arousal mechanisms rather than a primary structural disorder. From a developmental perspective, nocturnal urine production, bladder storage capacity, and sleep-arousal mechanisms mature at different rates, and enuresis occurs when arousal maturation lags behind other components. Current therapeutic approaches mainly provide symptomatic control or facilitate adaptation rather than correcting a structural abnormality. Reframing MNE within a developmental framework may help support reassurance, shared decision-making, and more balanced clinical discussions regarding management in routine pediatric practice. What is Known: • Monosymptomatic nocturnal enuresis (MNE) is generally regarded as a functional disorder related to delayed maturation of nocturnal continence mechanisms. • Multiple factors, including nocturnal urine production, bladder capacity, and sleep-arousal function, contribute to the pathophysiology of MNE. What is New: • This article proposes that MNE may be better understood as a developmental variation caused by temporal mismatch among continence-related maturation processes, particularly sleep-arousal maturation. • The developmental perspective presented here may help reduce unnecessary medicalization and promote a more individualized understanding of children with MNE.
Safety and efficacy of liposomal iron for iron deficiency anemia in pediatric population: A systematic review and meta-analysis of randomized controlled trials.
Alharran AM, Almutairi EY, Alazemi WB … +10 more , Alnejadah FA, Hasan HS, AlOufan L, Alsultan AM, AlOmar H, Alqayem M, Maasarani J, Alohaly A, Awad P, Alfehaid A
Eur J Pediatr · 2026 May · PMID 42183880 · Publisher ↗
Iron deficiency anemia (IDA) remains a public health problem in children. Conventional iron therapy is effective but often causes gastrointestinal adverse effects that reduce adherence. Liposomal iron has been developed...
Iron deficiency anemia (IDA) remains a public health problem in children. Conventional iron therapy is effective but often causes gastrointestinal adverse effects that reduce adherence. Liposomal iron has been developed to enhance absorption and improve tolerability. This systematic review and meta-analysis evaluated the efficacy and safety of liposomal iron compared with conventional iron formulations in pediatric patients with IDA. We searched PubMed, Scopus, Web of Science, and the Cochrane Library up to February 21, 2026 for randomized controlled trials (RCTs) comparing liposomal iron with conventional oral iron in children with IDA. Analyses were performed using R software with the meta package. Continuous outcomes were pooled as mean differences (MDs) and dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs) using a random-effects model. Subgroup analyses according to follow-up duration. Four RCTs involving 454 children were included. At 6 months, liposomal iron produced a significantly greater increase in hemoglobin compared with conventional iron (MD 0.96 g/dL, 95% CI 0.09-1.82; P = 0.03), although heterogeneity was substantial (I = 92.9%). No significant differences were observed at earlier time points. Liposomal iron significantly reduced total iron-binding capacity (MD - 35.52 μg/dL; P < 0.0001) and increased mean corpuscular hemoglobin (MD 1.83 pg; P < 0.0001). Liposomal iron was associated with fewer adverse events (RR 0.29; P = 0.02) and lower risk of constipation (RR 0.56; P = 0.02).Conclusion: Liposomal iron offered better tolerability and was non-inferior to conventional iron for most hematologic outcomes. Evidence remains preliminary and larger RCTs are needed to confirm its efficacy in pediatric IDA.
Pediatric Trauma Score (PTS) combined with blood lactate measurement provides clinical treatment guidance and prognosis prediction for children with compound injuries: a prospective study.
Gao W, Song X, Xing Y … +2 more , Liang L, Feng Y
Eur J Pediatr · 2026 May · PMID 42176112 · Publisher ↗
UNLABELLED: Compound injuries in children are the leading cause of death and disability, and early and accurate assessment is crucial to optimize treatment. This study aimed to explore the clinical value of Pediatric Tra...
UNLABELLED: Compound injuries in children are the leading cause of death and disability, and early and accurate assessment is crucial to optimize treatment. This study aimed to explore the clinical value of Pediatric Trauma Score (PTS) combined with blood lactate measurement in the triage, treatment guidance and prognosis prediction of pediatric compound injuries. From January 2023 to December 2024, a randomized, single-blind controlled trial was conducted in the emergency department of Hebei Provincial Children's Hospital (the only tertiary pediatric medical center in Hebei Province), China. A total of 546 children with compound injuries who presented to the hospital were included and randomly divided into the intervention group (n = 273, managed by PTS combined with dynamic monitoring of blood lactate) and the control group (n = 273, managed by PTS only). The main outcomes were the timeliness of rescue (time to critical intervention) and the accuracy of prognosis prediction (predictive effectiveness of mortality and major complications). Secondary outcomes included emergency department length of stay, unplanned Intensive Care Unit (ICU) admission, and 30-day complication rate. The median time from admission to initiation of key interventions was significantly shorter in the intervention group compared with the control group (45 [interquartile range (IQR): 30-65] min vs. 68 [IQR: 45-95] min, P < 0.001). The area under the receiver operating characteristic (ROC) curve (AUC) of the combined indicator (PTS + initial lactate) to predict 30-day mortality was 0.936 (95% CI: 0.902-0.970), which was significantly higher than PTS alone (AUC: 0.812, P < 0.001) or initial lactate (AUC: 0.855, P = 0.002). The emergency department length of stay, unplanned ICU admission rate and 30-day complication rate of the intervention group were significantly lower than those of the control group (all P < 0.05). Dynamic monitoring showed that 6-h lactate clearance < 30% was a strong independent predictor of the occurrence of multiple organ dysfunction syndrome (MODS) (odds ratio (OR) = 5.42, 95% CI: 2.88-10.21,P < 0.001. CONCLUSION: The combined application of PTS and blood lactate integrates physiological status and metabolic information, which can significantly improve the accuracy of early triage of pediatric compound injuries, guide the implementation of rescue measures, and effectively predict prognosis through dynamic monitoring, providing a reliable basis for precise personalized management. WHAT IS KNOWN: • Compound injuries in children are the leading cause of death and disability, and early and accurate assessment is crucial to optimize treatment. WHAT IS NEW: • The combined application of the Pediatric Trauma Score (PTS) and blood lactate signifi cantly improves the accuracy of early triage and 30-day mortality prediction, shortens the time to critical intervention, and reduces unplanned ICU admission and 30-day complication rates in pediatric compound injuries. • Dynamic monitoring shows that 6-hour lactate clearance 30% is a strong independent predictor of multiple organ dysfunction syndrome (MODS).
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