European Journal of Pediatrics最新文献

Cystic fibrosis (CF) is a chronic genetic disorder characterized by pancreatic insufficiency and lung disease. Advancements in highly effective modulator therapies (HEMTs) have improved life expectancy, shifting the focus to endocrine comorbidities, such as CF-related diabetes (CFRD) and bone disease (CFRBD). Therefore, current guidelines recommend routine screening for diabetes and osteoporosis in people with cystic fibrosis (PwCF) starting from age of 10 years. Increased risk of osteoporosis has been shown in type 1 and type 2 diabetes; however, there are limited studies evaluating the impact of glucose metabolism disorders on osteoporosis in children with cystic fibrosis. Therefore, this study investigates the impact of glucose metabolism disorders on PwCF. This cross-sectional retrospective study included 81 PwCF, aged between 10 and 21 years, who were screened routinely for diabetes and bone metabolism between 2019 and 2024. Data on demographics, CFTR variants, glucose metabolism, and biochemical bone parameters, including calcium, phosphorus, ALP, PTH, vitamin D levels with bone mineral density (BMD) of L1-L4 lumber spine were analyzed. Cases were categorized as normal, indeterminate, impaired glucose tolerance (IGT), or CFRD based on OGTT. Statistical analyses were conducted to determine factors affecting BMD, including pairwise comparison and multivariate regression analysis. Of the 81 cases, 55 (67.9%) had normal glucose tolerance, 9 (11.1%) had indeterminate (INDET), 9 (11.1%) had impaired glucose tolerance (IGT), and 8 (9.9%) had CFRD. IGT and CFRD cases demonstrated significantly lower body mass index (BMI), lung function, and BMD z-score than the normal group (p < 0.05). HbA1c had the negative association with BMD z-score (β = -0.36 per %1 increase in HbA1c, p < 0.001), while elevated BMI levels had positive relation (β = 0.28 per 1 kg/m² increase in BMI, p = 0.009). HEMT showed no significant impact on glucose or bone metabolism, likely due to short treatment durations.

Conclusions: Impaired glucose metabolism has a significant association with BMD in PwCF. Integrated monitoring of glucose and bone metabolism, along with a multidisciplinary approach is essential to optimize outcomes and reduce complications.

What is known: • Cystic fibrosis-related diabetes (CFRD) is the most common non-pulmonary comorbidity in CF. • Impaired glucose metabolism has been associated with reduced bone mineral density and increased fracture risk.

What is new: • This study demonstrates that even early glucose metabolism disorders are associated with reduced bone mineral density in CF patients. • Higher HbA1c levels were found to be associated with lower bone mineral density, highlighting the relationship between hyperglycemia and bone health in CF.

To evaluate the real-world impact of universal nirsevimab prophylaxis on the proportion of positive tests, seasonality, and severity of pediatric respiratory syncytial virus (RSV) infections and to explore the associated changes in respiratory virus seasonality. This is a retrospective, cohort study held in a single pediatric emergency department in a tertiary care hospital in Italy. We evaluated 758 children under 18 years of age presenting with respiratory symptoms who underwent multiplex PCR testing during three consecutive respiratory seasons (1 October to 30 April) from 2022 to 2025. Universal nirsevimab prophylaxis was implemented for infants in their first RSV season was broadly introduced in the 2024-2025 season starting November 1, 2024. Outcomes were compared between the pre-nirsevimab era (2022-2024) and the nirsevimab era (2024-2025). The primary outcome was the seasonal RSV positivity rate. Secondary outcomes included rates of hospitalisation, length of stay (LOS), requirement for respiratory support, and intensive care unit (ICU) admission. The proportion of RSV-positive tests decreased from a mean of 31.9% in the two pre-nirsevimab seasons to an overall 19.7% in the nirsevimab season. In infants aged 0-12 months, the rate fell from a mean of 45.4% to 19.9%. Among RSV-positive infants (0-12 months) in the 2024-2025 season, those who received nirsevimab (n = 12) had a shorter median hospital LOS (6.0 vs 8.5 days) and a lower requirement for high-level respiratory support (25.0% [3/12] vs 58.3% [14/24]) compared to unprotected infants (n = 24).

Conclusions: The introduction of a universal nirsevimab programme was associated with a substantial reduction in RSV positivity and the burden of severe disease. In this real-world setting, nirsevimab appeared to mitigate severe outcomes even in infants with breakthrough infections.

What is known: • Nirsevimab has demonstrated high efficacy in randomized controlled trials; however, real-world evidence regarding its impact onpopulation-level RSV positivity remains limited. • There is a paucity of data concerning the clinical characteristics and healthcare resource utilization associated with breakthrough infections following nirsevimab administration.

What is new: • Implementation of a universal program was associated with a significant decrease in RSV positivity and markedly milder breakthrough infections, characterized by shorter hospital stays and reduced need for respiratory support. • Protection was consistently observed across the 0-12 and 0-6 month cohorts, supporting the role of nirsevimab in mitigating severe disease and justifying its broad implementation to alleviate healthcare system burden.

Neurofibromatosis type 1 (NF1) is an autosomal dominant syndrome caused by mutations in the NF1 gene. Although cardiac abnormalities have been observed in NF1, they are frequently overlooked due to a lack of routine cardiac surveillance. Myocardial strain imaging offers a sensitive and non-invasive method for detecting early subclinical myocardial dysfunction. This study aims to detect cardiac abnormalities in children with NF1 using conventional echocardiography, Doppler tissue imaging (DTI), and myocardial strain analysis. A case-control study was conducted on 38 asymptomatic children with clinically confirmed NF1 and 35 healthy, age- and sex-matched controls. All patients underwent ECG, conventional echocardiography, DTI, and two-dimensional speckle-tracking echocardiography. NF1 patients showed significantly decreased ejection fraction (p = 0.0009) and higher interventricular septal and posterior wall thickness during systole (p < 0.0001). DTI revealed reduced mitral systolic (Sm) and early diastolic (Em) velocities, longer isovolumic contraction and relaxation periods, and increased LV Tei index values (p < 0.0001), indicating combined systolic and diastolic dysfunction. Also, myocardial strain analysis in NF1 children revealed considerably lower peak systolic left ventricular global longitudinal strain (LVGLS) (p 0.0014), as well as lower peak systolic septal and lateral wall strain values (p 0.0046, 0.0027), respectively. Conclusion: Children with NF1 show early subclinical myocardial dysfunction, even when there is no hypertension or overt cardiac symptoms. These findings highlight the significance of frequent echocardiographic screening, including strain imaging, for the early diagnosis and longitudinal monitoring of heart function in NF1 children.  What is Known: • Neurofibromatosis type 1 (NF1) is a multisystem syndrome that can involve the cardiovascular system. • Previous studies showed hypertrophic cardiac changes in NF1 patients, but data in children, especially those without hypertension, are limited, as routine echocardiography is not involved in NF1 management. What is New: • Our study revealed early subclinical myocardial dysfunction in NF1 children without the presence of hypertension or overt cardiac symptoms. • This emphasizes the potential of myocardial strain imaging as a sensitive tool for early detection of myocardial dysfunction in NF1 children, thereby supporting the need for routine echocardiographic surveillance in these patients.

Intra-amniotic inflammation and infection are common intrapartum conditions at term and represent a major cause of fetal and neonatal morbidity independent of hypoxia. These conditions trigger the fetal inflammatory response syndrome (FIRS), characterized by systemic cytokine activation, cardiovascular dysfunction, impaired thermoregulation, and neuroinflammation, which substantially increase the risk of early-onset neonatal sepsis, encephalopathy, and long-term neurological injury. The coexistence of inflammation and intrapartum hypoxic stress markedly amplifies fetal brain vulnerability. During labor, fetal inflammation is associated with specific cardiotocographic patterns that may precede metabolic acidemia. Early signs include unexplained fetal tachycardia or a progressive rise in baseline heart rate, often without preceding decelerations. With progression, loss of accelerations, abnormalities of baseline variability-including increased, reduced, or atypical sinusoidal patterns-and absence of sleep-wake cycling become evident. Decelerations may develop secondary to inflammation-related placental dysfunction, altered umbilical blood flow, and abnormal uterine contractility.

Conclusion:  Prompt recognition of these intrapartum features allows early intervention through maternal temperature control, antibiotic therapy, and timely delivery when indicated. Early identification and management of fetal inflammation are essential to mitigate inflammation-mediated neonatal morbidity and adverse neurological outcomes.

What is known: • Intra-amniotic inflammation and infection during labor are common at term and are major contributors to fetal and neonatal morbidity. • Traditional intrapartum cardiotocography (CTG) interpretation is primarily focused on detecting hypoxia-related fetal compromise and may fail to recognize non-hypoxic inflammatory insults.

What is new: • Fetal exposure to intra-amniotic inflammation during labor can be identified antenatally through specific intrapartum cardiotocographic patterns, even in the absence of maternal clinical signs of infection. • The recognition of CTG features suggestive of fetal inflammation provides an opportunity for earlier intrapartum intervention, with potential to reduce neonatal sepsis, encephalopathy, and long-term neurological injury.

To assess the validity of the SENS motion® system (SENS) for measuring postures and movements in school-aged children with functional disabilities, using direct video observation as the criterion method. In this cross-sectional-study, 29 children (51.7% male, mean age 10.8 ± 2.9 years) from two special schools in Denmark participated. Each child wore a SENS device on the thigh while completing a standardized protocol of six categories: lying/sitting, standing, walking, running, cycling, and step count. All activities were video recorded. Video data were coded in 5-s epochs and aligned with SENS output. Agreement was assessed by comparing the observed time spent in each activity with the corresponding time estimated by SENS, expressed as mean values, standard deviations, mean differences, and percentage agreement. SENS showed excellent agreement for walking (93.2%) and lying/sitting (96.2%), good agreement for running (89.2%), and moderate agreement for standing (74.1%). Cycling was poorly detected, with only 6.4% agreement, as it was frequently misclassified as walking (50.8%) or lying/sitting (42.7%). Step counts were slightly overestimated by SENS (mean difference 7.2 steps). Overall, SENS tended to underestimate activity duration compared with the observation.

Conclusion:  SENS demonstrated excellent to good validity for detecting lying/sitting, walking, and acceptable validity for running in children with functional disabilities, but moderate validity for standing and limited validity for cycling. These findings indicate that SENS may be useful for monitoring several common postures and activities in this population, though further algorithm refinement and broader validation are needed, particularly for cycling and postural transitions.

What is known: • Children with disabilities engage in less dynamic postures and more lying/sitting time than their peers without disabilities. • Accelerometer systems are typically validated in healthy populations, limiting accuracy in children with disabilities.

What is new: • SENS shows excellent to good validity for lying/sitting, walking, and running in children with functional disabilities. • SENS performs poorly for cycling and moderately for standing, highlighting the need for algorithm refinement.

Dysbiosis in early life has been associated with the development of atopic diseases. In the INCA study, antibiotic treatment in the first week of life was associated with wheezing at 1 year and food allergies at 4-6 years. This follow-up study investigates whether these associations persist at age 9-12, and whether new associations with other atopic diseases have developed. The INCA cohort consisted of 436 children included in 2012-2015 to investigate the long-term effects of antibiotic treatment in the first week of life. Term-born infants from four Dutch hospitals were included, of which 151 received intravenous antibiotics in their first week of life due to suspected early-onset sepsis (AB+), and 285 were unexposed infants (AB-). In the 9-12-year follow-up study, parents and children filled out questionnaires on atopic diseases. Furthermore, general practitioners' diagnoses were collected. The follow-up questionnaire was completed by 314 participants. Parental-reported and test-confirmed food allergies were more prevalent in AB+ children compared to AB- (unadjusted odds ratio (OR) 3.52, 95% confidence interval (CI) 1.50-8.25 and OR 6.6, 95% CI 1.3-32, respectively). However, no significant differences existed between AB+ and AB- in the incidence of asthma (OR 0.73, 95% CI 0.25-2.1) or inhalant allergies (OR 1.03, 95% CI 0.554-1.91). The "any allergy" diagnosis by general practitioners was more prevalent in AB+ than AB- (OR 3.0, 95% CI 1.2-7.6).

Conclusions:  Antibiotic treatment in the first week of life is associated with food allergies at ages 9-12, but not with asthma, inhalant allergies, or eczema.

What is known: • Correlations have been observed between early life antibiotics exposure (< 2 years of age) and the development of atopic diseases such as asthma, eczema, and allergies. • Antibiotics exposure specifically in the first week of life has been associated with an increased risk of wheezing at age 1 and food allergies at ages 4-6.

What is new: • Antibiotics in the first week of life are still associated with food allergies at ages 9-12, but not with airway atopy (asthma, hay fever, or inhalant allergies). • The results of this study suggest that there may be different mechanisms involved in the development of food vs. inhalant allergies, and further research is needed to determine how these diseases develop and how to prevent this.

Childhood vaccination is a very effective public health intervention. Fear of pain during vaccination reduces vaccine willingness and can be addressed by interventions. We aimed to identify behavioural determinants of the use of pain-reducing interventions by Preventive Child Healthcare (PCH) physicians and nurses and the associations of sociodemographic characteristics with these behavioural determinants. We invited all PCH professionals of one municipal health service (Groningen, the Netherlands; n = 180) to fill in an online questionnaire on behavioural determinants of the use of pain-reducing interventions, based on the ASE (Attitude-Social influence-self-Efficacy) model of behaviour. We evaluated the associations of their background characteristics with their responses using logistic regression analyses. Of the 83 PCH professionals, 95% considered it important to reduce pain during vaccination, 90% intended to liaise with children and parents about pain mitigation, and 85% reported a high self-efficacy regarding the use of pain-reducing interventions. Lack of time and knowledge about pain reduction, and difficulties in the use of pain mitigation were negatively associated with the use of pain-reducing interventions. Nurses were more likely than physicians to liaise with children and parents about pain mitigation during vaccination (odds ratio, 95% confidence interval 8.86, 1.62 to 48.4) and believe they are competent to mitigate pain during vaccination (6.27, 1.65 to 23.9).

Conclusion:  Most PCH professionals acknowledge the importance of reducing pain during vaccination but experience various barriers in the use of pain-reducing interventions. Education of professionals might contribute to the adherence to guidelines regarding pain reduction.

What is known: • Childhood vaccination is a very effective public health intervention. • Fear of pain during vaccination reduces vaccine willingness and can be addressed by interventions.

What is new: • Most Preventive Child Healthcare physicians and nurses acknowledge the importance of reducing pain during vaccination but experience various barriers in the use of pain-reducing interventions. • Education of professionals might contribute to the adherence to guidelines regarding pain reduction.

Early identification of children at high risk for moderate-to-severe obstructive sleep apnea (OSA) is crucial for timely intervention, yet is often hindered by limited access to polysomnography (PSG). We aimed to develop an interpretable clinical prediction model using easily obtainable clinical and inflammatory biomarkers to distinguish moderate-to-severe from mild pediatric OSA. We conducted a retrospective study of 164 children diagnosed with OSA by PSG. From multiple biomarkers and clinical variables, least absolute shrinkage and selection operator (LASSO) regression was employed to select the most predictive features. A multivariable logistic regression model was built and presented as an interpretable nomogram. Model performance was evaluated via bootstrap validation assessing discrimination, calibration, and clinical utility. The LASSO algorithm identified eight core predictors: female, tonsil size grades 3 and 4, adenoid-to-nasopharynx ratio (A/N ratio), IgE, IL-4, IL-6, and IL-10. The final model demonstrated robust performance, with a bootstrap-corrected AUC of 0.763 (95%CI 0.690-0.836). Decision curve analysis confirmed the model's clinical utility.

Conclusion:  We developed an explainable nomogram that integrates upper airway anatomy, allergic, sex, and specific inflammatory cytokines. This tool provides clinicians with a practical, non-invasive method for individualized risk assessment, facilitating the identification of children with moderate-to-severe OSA who may benefit from prioritized diagnosis and intervention.

What is known: • Polysomnography(PSG) is the gold standard for diagnosing pediatric obstructive sleep apnea (OSA) but has limited accessibility, hindering the early identification of children at risk for moderate-to-severe disease.

What is new: • We developed an explainable nomogram that integrates sex, tonsil size, adenoid hypertrophy, allergy (IgE), and specific inflammatory cytokines (IL-4, IL-6, IL-10) to provide a practical, noninvasive tool for individualized risk assessment of moderate-to-severe OSA in children.

The aim of this study is to systematically compare binocular gaming with conventional occlusion therapy for visual acuity improvement in childhood amblyopia. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines (PROSPERO CRD420251080735). PubMed, Scopus, Cochrane Library, and Google Scholar were searched through June 2025 for randomized controlled trials in children aged 3-18 years with unilateral amblyopia. The primary outcome was best-corrected visual acuity improvement, expressed as standardized mean difference (SMD). A random-effects model was applied with subgroup analyses by treatment duration, sample size, and patient characteristics. Nine RCTs, including 986 children, met the inclusion criteria. Pooled analysis showed no significant difference between binocular gaming and patching (SMD 0.05, 95% CI - 0.2 to 0.3, p = 0.68) with substantial heterogeneity (I² = 65%). Subgroup analyses revealed time-dependent effects: short-duration trials (≤ 6 weeks) favored binocular gaming (SMD 0.35, 95% CI 0.05-0.65, p = 0.02), medium-duration trials (8-12 weeks) showed no significant benefit, while long-duration trials (> 12 weeks) favored patching (SMD - 0.47, 95% CI - 0.72 to - 0.22, p < 0.001). Larger, high-quality trials consistently supported patching. Publication bias analysis indicated small-study effects, with trim-and-fill suggesting the true effect may favor patching (adjusted SMD - 0.15).

Conclusion: Binocular gaming may provide short-term benefits, but robust evidence indicates patching is superior for long-term outcomes. After adequate refractive correction, conventional occlusion therapy remains the recommended first-line active treatment for amblyopia. Binocular gaming may be considered as an adjunct or alternative for children who are unable to comply with patching.

What is known: • Patching is an effective standard treatment for childhood amblyopia. • Evidence for binocular gaming compared with patching has been inconsistent.

What is new: • Binocular gaming shows short-term benefit, but patching is superior long term. • High-quality trials support patching as first-line; gaming may be an adjunct.