European Journal of Pediatrics最新文献

Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E-mediated food allergy that typically causes delayed gastrointestinal symptoms following the ingestion of a trigger food. FPIES is a rare condition with limited epidemiological data. This study aimed to investigate the demographic characteristics, triggers, clinical presentations, and outcomes of children with acute FPIES at the University Children's Hospital Zurich, a tertiary-level children's hospital in Switzerland, with a dual focus on confirmed and suspected FPIES cases. This retrospective study covered a 10-year period (2010-2020). Electronic medical records were screened for patients diagnosed with acute FPIES and those with symptoms suggestive of FPIES according to international diagnostic criteria. Those paediatric patients with an acute FPIES diagnosis or a history highly suggestive of FPIES were included. A total of 109 patients with acute FPIES were identified. Cow's milk (CM) was the most common food trigger (24%), followed by eggs (12%) and fish (10%). A single food trigger was identified in 56% of the patients. The median age of onset was 6 months (interquartile range (IQR), 4 months). Gender had no effect on observed FPIES cases. Data on FPIES tolerance and therefore resolution of FPIES symptoms and/or successful reintroduction of the triggering food were limited, with sufficient follow-up information available for only 37% of confirmed and 25% in suggestive cases: 27.5 months for CM (IQR, 15.75 months), 67.5 months for fish (IQR, 33.5 months), and 32 months for egg (IQR, 14.5 months).  Conclusion: The study contributes practical epidemiological and clinical insights into FPIES triggers, patterns, and patient characteristics, and provides further regional insights to navigate this complex condition. What is Known:  • FPIES is a rare, non-IgE-mediated food allergy, particularly affecting infants and young children. • FPIES is often under-recognized, resulting in delayed diagnosis and management. What is New: • By providing robust real-world data on acute FPIES, this study provides a decade-long overview of acute FPIES cases, detailing key food triggers, identifying gaps in clinical practice and delays in diagnosis, and contributing regional epidemiologic data that may not be apparent in short-term studies and underscore geographic variability in presentation and triggers.

The association between hypospadias, its severity, and anogenital distance remains inconsistent. This study aims to investigate the association between anogenital distance and hypospadias through a meta-analysis. We conducted a comprehensive search in international databases (PubMed, Web of Science, Cochrane Library, Embase, Medline) and Chinese databases (China National Knowledge Infrastructure, Wanfang Data, VIP database). We searched for studies on the association between anogenital distance and hypospadias. The search period extended until November 1, 2025. Thirteen studies involving 6905 male infants were included in the meta-analysis. We calculated the standardized mean difference and 95% confidence interval for anogenital distance using a random-effects model. The results indicated that children with hypospadias had a shorter anogenital distance (standardized mean difference, - 1.24; 95% confidence interval, - 1.74 to - 0.74). A negative correlation was observed between anogenital distance and hypospadias severity. Children with more severe hypospadias had a shorter anogenital distance. The standardized mean differences were - 1.05 (95% confidence interval, - 2.23 to 0.13) for distal hypospadias, - 1.66 (- 3.14 to - 0.18) for middle hypospadias, and - 3.00 (- 4.70 to - 1.31) for proximal hypospadias.

Conclusion:  Our study suggests that shortened anogenital distance is associated with hypospadias and may correlate with disease severity, consistent with the hypothesis of fetal androgen disruption. However, due to the observational nature of the included studies and significant heterogeneity, causal inference is limited. Anogenital distance may serve as a research endpoint, but prospective studies are needed to validate its etiological and clinical utility.

Trial registration: The study protocol has been registered in PROSPERO ( https://www.crd.york.ac.uk/prospero ) under the registration number CRD42023407183.

What is known: • In animal studies, anogenital distance is negatively correlated with hypospadias severity. • The association between anogenital distance and hypospadias has yielded inconsistent results in human studies.

What is new: • Anogenital distance is negatively correlated with the severity of hypospadias in human studies, which supports the role of impaired fetal androgen production/action in the pathogenesis of hypospadias. • Anogenital distance may serve as an indicator for reproductive health assessment endpoints.

Empirical data on post-injury disability in children is limited and deriving disability weights is urgently needed. The aim of this study is to utilise pooled data to determine adequate disability weights in children and adolescents. Five longitudinal prospective cohort studies of pediatric injury survivors aged 5-17 years were pooled (N = 1972) to create case-based pediatric weights for established nature-of-injury classifications using four types of EQ-5D utility scores to represent overall health-related quality of life. Healthy population norms from seven countries formed a sensitivity analysis. Disability weights (DW) were calculated at 1 month, 4 months, 6 months, and 12 months post injury to produce two disability weights per injury class: 12-month residual disability weights (12dw) and 12-month annualised weights (12aw). DW for asphyxiation/non-fatal submersion, spinal cord lesion, fracture of the femur, fracture of pelvis, and fracture of vertebral column, were more than twice that of the lowest DW for fracture of clavicle, scapula, or humerus, and fracture of radius or ulna. 12dw for moderate/severe traumatic brain injury (TBI) was 19% higher than minor TBI and 25% higher for 12aw. Conclusion: Different DW should be applied to DALY calculations for children and adolescents compared to adults. The calculation of these DWs is complex and warrants further investigation. This study confirms that injury is often a chronic disorder and burden of disease for children and adolescents and estimates should reflect this situation. What is Known: • Traumatic injuries pose substantial threats to children's health, education and social inclusion • Much-needed disability weights, used in calculating the years lived with disability (YLDs), has been limited by the lack of empirical data on postinjury disability in children What is New: • This study confirms injury is often a chronic disorder and burden of disease for children and adolescents • Injury-group disability weights for children and adolescents are provided for YLD calculations, and these weights differ to those used for adults.

Diaphragmatic ultrasound (DUS) and lung ultrasound (LUS) are increasingly applied to evaluate neonatal respiratory muscle performance and lung aeration, respectively. This prospective, observational, single-center study assessed DUS of both hemi-diaphragms and LUS in healthy full-term neonates on days of life (DOL) 1 and 3 to profile postnatal physiology and establish normative values. DUS metrics included diaphragmatic excursion (DE), contraction velocity (DCV), inspiratory diaphragm (DTi) and expiratory diaphragm (DTe) thickness, diaphragmatic thickening fraction (DTF), and inter-hemi-diaphragm DTF difference (ΔDTF). A six-zone, 3-point scoring system was used to evaluate LUS aeration. Twenty newborns (gestational age 39.0 ± 1.2 weeks, birth weight 3334 ± 343 g) were evaluated. No significant differences were observed in DE, DCV, DTi, DTe, DTF, or ΔDTF between DOL 1 and 3. Sex had no effect on DUS parameters. Cesarean-born neonates demonstrated significantly lower DE and DTF on DOL 1, but values were comparable by DOL 3. LUS aeration scores were similar between DOL 1 and DOL 3 (medians (Q1-Q3): 1 (0-1.3) and 1 (0-1), respectively, p = 0.244), with no differences by delivery mode or sex. Intra-observer reliability was excellent for nearly all DUS metrics on DOL 1 and DOL 3 (intraclass correlation coefficients > 0.90).

Conclusion: Diaphragmatic function is stable in healthy neonates without significant pulmonary involvement on LUS during the first three postnatal days. Mode of delivery appears to transiently influence diaphragmatic performance on DOL 1. Combined DUS and LUS provide complementary insights into neonatal respiratory adaptation and may serve as reference values for clinical practice and research.

What is known: • Point-of-care diaphragmatic ultrasound (DUS) and lung ultrasound (LUS) are increasingly utilized as safe, bedside tools for assessing neonatal respiratory distress and supporting clinical decision-making.

What is new: • This is the first study to evaluate both DUS and LUS together in healthy term newborns during the first 3 days of life, demonstrating stable diaphragmatic function transiently influenced by delivery mode but independent of newborn sex.

A hallmark of Prader-Willi syndrome (PWS) is hypothalamic-pituitary axis dysfunction, which can result in reduced growth hormone (GH) production. While GH replacement therapy is common in children with PWS, it has also been implicated in the development of obstructive sleep apnoea (OSA) in some children. The mechanisms underlying this development are poorly understood but may be related to alterations in ventilatory control. Our study investigated the impact of GH treatment on ventilatory control stability during sleep in children with PWS. Polysomnographic data pre- and post-GH therapy in 25 children (aged 2mo-18y) were used to assess ventilatory control using a validated method that estimates loop gain (dimensionless ratio) from ventilation changes following spontaneous sighs during sleep. Data were analysed using linear mixed-effects modelling with GH as a fixed effect and participant as a random intercept. Covariates that could impact loop gain including age, obstructive-apnoea hypopnoea index (OAHI) and central apnoea-hypopnoea index (CAHI) were each added separately to the base model in a stepwise, manual forward selection approach. Loop gain was not altered by GH treatment (β = 0.003, 95% CI: [-0.042, 0.049], p = 0.878, Cohen's d = 0.031). Age, OAHI and CAHI did not alter the impact of GH on loop gain. No difference in sleep or respiratory characteristics were found, however 20% of children developed OSA post-GH.

Conclusion: Initiation of GH therapy was not associated with a change in loop gain, suggesting that changes in ventilatory control are unlikely to contribute to the development of OSA in children with PWS.

What is known: • Prader-Willi syndrome is associated with abnormal ventilatory control and increased risk of sleep-disordered breathing. • Growth hormone therapy may influence respiratory physiology but its effect on the stability of ventilatory control (loop gain) remains unclear.

What is new: • In this cohort of children with Prader-Willi syndrome, growth hormone therapy did not alter loop gain despite inter-individual variability. • Our findings suggest that any sleep-disordered breathing that emerges following growth hormone therapy is likely driven by mechanisms other than altered loop gain.

Antimicrobial resistance (AMR) among Gram-negative (GN) pathogens has emerged as a critical global threat, particularly in low- and middle-income countries where access to novel antimicrobials is limited. In Türkiye, colistin (CST) remains a last-resort therapy against multidrug-resistant (MDR) and carbapenem-resistant Gram-negative bacteria (CR-GNB) despite its nephrotoxic potential. This study aimed to evaluate the clinical characteristics, microbiological outcomes, and adverse events associated with CST therapy in pediatric patients over a nine-year period. We conducted a single-center retrospective cohort study including pediatric patients treated with CST for nosocomial MDR-GN infections at a tertiary university hospital between January 2016 and March 2025. Demographic, clinical, microbiological, and treatment-related data were collected. Univariable comparisons and multivariable logistic regression analyses were performed to identify factors associated with nephrotoxicity, treatment failure, and mortality. A total of 117 treatment episodes were identified among 112 patients (mean age: 75.9 ± 69.5 months; 65% male). The predominant pathogens were Klebsiella pneumoniae (39.7%), Pseudomonas aeruginosa (26.4%), and Acinetobacter baumannii (22.0%). CST was used in combination regimens in all episodes, most commonly with carbapenems (73.5%). Microbiological eradication was achieved in 70% of culture-confirmed episodes. The overall sepsis-related mortality rate was 18.8%. Nephrotoxicity occurred in 12.8% of patients and was associated with mortality and severity indicators in univariable analyses. In multivariable analysis, endotracheal intubation remained the only independent predictor of mortality (adjusted OR 23.98, 95% CI 4.47-128.52). Conclusions: CST remains a last-resort agent for MDR and CR-GNB infections in pediatric settings with limited access to novel antimicrobials. Although microbiological eradication was achieved in most cases, treatment outcomes were primarily driven by disease severity and host-related factors rather than antimicrobial combinations. Endotracheal intubation emerged as the strongest independent predictor of mortality. What is Known - What is New •CST is widely used as a last-resort option for pediatric MDR-GN infections. •Nephrotoxicity and variable clinical outcomes remain major concerns. •This study provides long-term real-world pediatric data on CST use. • Disease severity and host-related factors were the main determinants of treatment failure and mortality.

Background: Preeclampsia (PE) is associated with long-term cardiovascular risks in offspring, but its subclinical cardiac impact remains underexplored. This study aimed to evaluate the long-term cardiac function in children born to preeclamptic mothers using conventional and two-dimensional speckle tracking echocardiography (2D-STE).

Methods: In this prospective cross-sectional study, 48 offspring (aged 2-12 years) of preeclamptic pregnancies were compared with 48 age- and sex-matched controls. Standard echocardiographic measurements and advanced myocardial strain parameters (total global longitudinal strain [TGLS], total global circumferential strain [TGCS]) were assessed. Subgroup analyses were performed based on the timing of PE onset (early vs. late). Statistical significance was set at p < 0.05.

Results: No significant differences were observed in conventional echocardiographic systolic indices (EF, FS, TAPSE). However, the mitral E/A ratio was significantly lower in the PE group (p = 0.0099), suggesting early diastolic dysfunction. 2D-STE revealed significantly reduced total GLS (- 25.8 ± 1.5 vs - 28.3 ± 2.3, p < 0.0001) and mid-level GCS (- 25.0 ± 3.5 vs - 26.9 ± 4.4, p = 0.0175) in the PE group. No differences in strain parameters were observed between early-onset and late-onset PE subgroups. Although anthropometric measures (weight and height) were lower in the PE group, SDS values were not statistically different.

Conclusions: Children exposed to PE in utero demonstrate subclinical alterations in left ventricular systolic and diastolic function, detectable only via advanced echocardiographic methods. Conventional echocardiographic parameters may fail to detect these early functional impairments. Long-term cardiac monitoring using 2D-STE could be crucial for this at-risk population, regardless of PE onset timing.

What is known: • Prenatal exposure to preeclampsia may affect cardiovascular structure and function in offspring. • Speckle-tracking echocardiography is a sensitive method for detecting subclinical myocardial dysfunction.

What is new: • Myocardial strain abnormalities were detected by speckle-tracking echocardiography despite normal conventional echocardiographic parameters. • These findings highlight the value of speckle-tracking echocardiography in identifying subclinical myocardial dysfunction in children exposed to preeclampsia.

Children are highly vulnerable to air pollution, yet most studies rely on single-pollutant approaches. This study examined associations between individual and joint exposure to multiple air pollutants and cognitive outcomes in preschoolers, with attention to potential sex differences. Traffic-related pollutants (PM_2.5, PM₁₀, PM_coarse, PM_{2.5absorbance}, NO₂, NO_x, O₃) were estimated at schools from the cross-sectional study among 286 children. Cognitive function was assessed with the Wechsler Preschool and Primary Scale of Intelligence-IV. Linear and weighted quantile sum (WQS) regression were conducted, adjusting for relevant child and family covariates. PM_coarse (β = -2.71, 95% CI -4.23, -1.20) and PM₁₀ (β = -2.39, 95% CI -4.09, -0.70) were inversely associated with the working memory index (WMI), with stronger associations observed in boys (PM_coarse: β = -3.32, 95% CI -5.77, -0.88; PM₁₀: β = -3.79, 95% CI -6.50, -1.09). WQS analysis indicated a negative association between the pollutant mixture and WMI (estimate = - 3.60, 95% CI -5.92, -1.28), with PMcoarse contributing most to the index. Sex-stratified WQS analyses suggested associations between air pollution mixture and lower verbal comprehension in girls and lower WMI in boys.

Conclusion:  School-age exposure to ambient air pollution mixtures was associated with differences in cognitive performance among preschool children, with patterns varying by sex. These findings highlight the importance of considering pollutant mixtures and potential sex differences when evaluating associations between air pollution and early childhood cognition.

Clinical trial registration: EUCTR-2012-005480-28 ( www.clinicaltrialsregister.eu ). NCT03196882 ( www.

Clinicaltrials: gov ).

What is known: • Ambient air pollution is linked to impaired neurodevelopment in children, but evidence using multi-pollutant mixture models in preschoolers remains limited.

What is new: • Air pollutant mixture was negatively associated with working memory index in preschoolers. • Sex-stratified analyses suggested potential associations with lower verbal comprehension in girls and lower working memory in boys.

This study examined self-esteem, body image, alexithymia, and aggression in adolescents with idiopathic/genetic generalized epilepsy (IGE). These domains were selected because they may be affected not only by epilepsy itself but also by stigma, difficulties in emotional regulation, or treatment-related effects. Assessing these domains together was intended to examine whether IGE might be associated with additional psychosocial strain in otherwise clinically stable adolescents. We carried out a case-control study including 45 adolescents with IGE and 45 controls matched for age and sex. Controls were selected from outpatient services and were required to have no neurological disorders. Psychiatric disorders were assessed using the K-SADS (Kiddie Schedule for Affective Disorders and Schizophrenia) interview; no clinically significant psychiatric diagnoses were identified in the control group. All participants completed standardized Turkish questionnaires on the same day.Within the epilepsy group, 20.0% were diagnosed with juvenile absence epilepsy (JAE), 22.2% with juvenile myoclonic epilepsy (JME), and 57.8% with epilepsy with generalized tonic-clonic seizures alone (EGTCSA). Across all four psychological measures, the epilepsy and control groups showed no statistically significant differences (all p > 0.05). No significant differences were found in subgroup analyses based on epilepsy syndrome or seizure frequency.

Conclusion: Adolescents with well-controlled IGE and minimal psychiatric comorbidities demonstrated comparable levels of psychosocial functioning to their healthy peers. This finding is consistent with evidence suggesting that psychosocial difficulties in epilepsy are often linked to comorbidity and contextual factors rather than to the diagnosis alone. Studies conducted in broader settings and with larger, more varied samples will be needed to better understand how medical, emotional, and environmental factors jointly influence psychosocial outcomes in this population.

What is known: • Adolescents with epilepsy are frequently considered at increased risk for psychosocial difficulties, including lower self-esteem, emotional instability, and body image concerns.

What is new: • In this study, no significant differences were found in self-esteem, body image, alexithymia, or aggression among Turkish adolescents with idiopathic/genetic generalized epilepsy compared with healthy controls. These findings suggest that, when seizures are well controlled and psychiatric comorbidities are limited, epilepsy itself may not confer additional psychosocial vulnerability.

Early detection of developmental dysplasia of the hip (DDH) is essential to prevent late presentation and long-term morbidity. Universal neonatal hip ultrasound screening using the Graf method improves early diagnosis. However, evidence-based training requirements for paediatricians remain unclear. This study aimed to determine the duration of training and the number of examinations required for paediatricians to achieve diagnostic competency in neonatal hip ultrasound. An analytical cross-sectional observational study was conducted. Fourteen paediatricians completed a standardized 40-h theoretical and practical training course and performed neonatal hip ultrasound examinations using the Graf method. A total of 467 newborns were screened between 4-6 and 12-16 weeks of age over a 10-month period. Images were compared with a blinded external expert reference standard. Diagnostic agreement was assessed using weighted κ statistics and learning curves and competency thresholds were evaluated using cumulative sum (CUSUM) analysis. A total of 3752 ultrasound images were obtained, of which 3182 (84.8%) met Graf standardization criteria. CUSUM analysis showed that diagnostic competency thresholds were reached after approximately 50 examinations, with performance consolidating between 50 and 100 examinations. Paediatricians completing around four months of supervised practice and at least 180 examinations achieved substantial interobserver agreement comparable to expert reviewers (weighted κ, 0.60-0.75). Diagnostic discrepancies occurred mainly during early training and involved borderline hip classifications (Graf IIa-IIc).

Conclusion: Paediatricians can achieve reliable diagnostic competency in neonatal hip ultrasound using the Graf method following structured training and adequate supervised clinical experience.

What is known: • Universal ultrasound screening using the Graf method improves early detection of developmental dysplasia of the hip (DDH). • Training requirements for paediatricians performing neonatal hip ultrasound remain poorly defined.

What is new: • This study defines learning curve thresholds for paediatricians performing neonatal hip ultrasound using the Graf method. • Competency was achieved after 50 examinations, with consolidated performance after 4 months of practice and180 examinations.