European Journal of Pediatrics最新文献

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.

Vascular access is a cornerstone of neonatal intensive care, yet current practice remains heterogeneous due to the lack of harmonized international guidelines. In this article, we present a position paper developed by a group of European experts - the Neonatal European Vascular Access Teams (NEVAT) - designed as a guide in planning, inserting, and maintaining vascular access in neonates. The position paper was developed using a not anonymous consensus method. Seven working groups prepared preliminary drafts on seven specific topics: peripheral venous devices, umbilical catheters, epicutaneo-cava catheters, ultrasound-guided central catheters, intraosseous access, peripheral arterial catheters, and infusion line management. The drafts were analyzed, modified, and validated through multiple rounds of open discussion, until full agreement was reached. The resulting position paper advocates a proactive, individualized, and standardized approach. Key elements include evidence-based selection of the device, structured preprocedural evaluation, maximal aseptic precautions, systematic use of ultrasound, securement with cyanoacrylate and semipermeable dressings, and structured post-insertion surveillance. Infusion line management emphasizes the use of closed systems, passive disinfection caps, and checklists. The NEVAT developed this position paper with the purpose of combining best evidence with expert agreement, so as to reduce variability in clinical practice, enhance safety, and improve neonatal outcomes, while encouraging multidisciplinary collaboration and family-centered care. What is Known: • Neonates are highly vulnerable to vascular access complications, but current practice is heterogeneous, with limited evidence-based guidance and significant variability across NICUs. What is New: • The NEVAT group provides the first European position paper on neonatal vascular access, aiming to improve homogeneity in device selection, insertion, and maintenance, promoting a safer and more consistent care.

Clinical studies have shown that Elexacaftor-Tezacaftor-Ivacaftor (ETI) improves lung disease and body weight in individuals with cystic fibrosis (CF); however, gastrointestinal system effects remain unclear. The purpose of this study was to evaluate exocrine pancreatic function using fecal elastase-1 (FE-1) levels in CF patients receiving ETI therapy and to assess changes in fat-soluble vitamin levels specifically within the pancreatic-insufficient (PI) subgroup. We retrospectively evaluated FE-1 levels before and during ETI treatment in the entire study group. Additionally, sweat chloride levels and growth parameters were assessed before and after follow-up ETI therapy in the entire study group. Also, vitamin A, D, E, PT, and INR levels were evaluated in PI patients before and after follow-up ETI treatment. The study included 20 pediatric CF patients with baseline FE-1 values. PI was present in 18 patients. The median age at the start of ETI therapy was 9.5 years (IQR 7.7-13.5; range 3-21 years). The median time between the baseline FE-1 test and the last FE-1 test was 12.0 months (IQR 12.0-19.5). The median FE-1 value before ETI therapy was 20.6 mcg/g (IQR 20.6-31.9), and after follow-up, 20.6 mcg/g (IQR 20.6-32.5) in 18 PI patients. Both PS patients maintained FE-1 levels ≥ 200 mcg/g before and after follow-up on ETI therapy. A significant increase in vitamin A levels was observed in PI patients, with a mean rise of 122.8 µg/L (p = 0.016). No significant change was observed in vitamin E levels (mean change 0.63 ± 4.14 µg/L; p = 0.304). Conclusion: In our study, no significant improvement in FE-1 levels was observed in pediatric CF patients receiving ETI therapy, whereas a substantial increase in vitamin A levels was found in patients with PI. These findings suggest that the effect of ETI therapy on pancreatic function may be limited and that its impact on exocrine pancreatic function should be further investigated. What is Known: • Exocrine pancreatic insufficiency is common in cystic fibrosis and is typically assessed using fecal elastase-1 (FE-1). • CFTR modulator therapies, especially ETI, improve respiratory and nutritional outcomes by targeting CFTR function, but their impact on pancreatic exocrine function in pediatric patients remains unclear. C What is New: • In this real-life pediatric cohort, no significant increase in FE-1 levels was observed during ETI treatment. • Despite improvements in CFTR function and nutritional status, these changes were not accompanied by recovery of pancreatic exocrine function.

Ultra-short celiac disease (USCD) represents a histopathological variant with selective involvement of the duodenal bulb. The mechanisms underlying the sparing of the second duodenal portion remain unclear. The histopathological progression of USCD under continued gluten exposure is not yet defined and represents a significant gap in current understanding. This retrospective study assessed histological changes in the duodenal bulb and second portion of the duodenum in pediatric patients who maintained gluten consumption until a definitive USCD diagnosis. Inclusion criteria required persistent dietary gluten intake, initial diagnosis confirmed by Marsh-Oberhuber classification, and elevated tissue transglutaminase (tTG) antibody levels. Fifteen out of 35 patients with USCD underwent repeat endoscopies. Villous atrophy was consistently confined to the first portion of the duodenum, with preservation of the second portion despite gluten exposure. Extensive celiac disease (ECD), characterized by involvement of the second portion of the duodenum, was associated with a significantly increased prevalence of short stature (p < 0.001) and iron deficiency anemia (p = 0.010), as well as substantially higher titers of tTG antibodies (p < 0.001). Both the USCD and ECD groups had similar rates of additional autoimmune diseases.  Conclusion: In children, USCD presents with a distinct and localized duodenal response to gluten. Although USCD presents with a milder clinical and serological profile, the comparable autoimmune burden underscores the necessity for accurate diagnosis and timely treatment. What is Known: • Patients with USCD typically demonstrate milder clinical symptoms and lower serological markers compared to those with more extensive small-intestinal involvement. • The histopathological response to ongoing gluten exposure in USCD has not been characterized to date. What is New: • USCD remains histologically confined to the duodenal bulb, with no progression to the second portion of the duodenum observed over time, even with continued gluten intake. • Isolated duodenal bulb involvement may be sufficient to initiate systemic autoimmunity in celiac disease, despite mild clinical and serological features.

Congenital heart disease (CHD) is the most common major birth defect, affecting nearly 1% of live-born infants. There is a high prevalence of CHD among premature neonates, with prematurity and low birth weight compounding the risks associated with CHD and leading to increased morbidity and mortality. Despite advances in diagnosis, surgery, and intensive care, outcomes for preterm infants with CHD remain guarded, particularly in the earliest gestational age groups. These infants face heightened risks of neonatal decompensation, cardiac arrest, and early mortality, but also long-term complications including neurodevelopmental impairment. The interplay between maternal-fetal factors, perinatal environment, and the complex physiology of both prematurity and CHD underscores the need for multidisciplinary care. Prenatal diagnosis, careful delivery planning, specialized postnatal management, and tailored surgical timing are critical to optimizing outcomes. Neonatal and cardiac intensivists, cardiologists, surgeons, anesthesiologists, and allied professionals must collaborate closely to address diverse challenges including hemodynamic instability, respiratory support, nutrition, neuroprotection, and social disparities. This review synthesizes current evidence on the epidemiology, pathophysiology, and management of neonates with CHD with a focus on prematurity. We highlight evolving models of interdisciplinary care and outline priorities for research. A physiology-based, team-oriented approach is essential to improve both survival and long-term quality of life for this vulnerable population. What is Known: • CHD is the most common birth defect and a leading cause of neonatal morbidity and mortality. • Prematurity and low birthweight worsen outcomes, with complications and surgical risk inversely related to gestational age. What is New: • Pregnancies with CHD carry up to a threefold higher risk of preterm delivery. • Outcomes reflect maternal-fetal and neonatal factors, highlighting the need for tailored timing, evaluation, and surgical strategies, with a key role for multidisciplinary care.

Achieving optimal vancomycin trough concentrations in vivo is crucial to its therapeutic effectiveness. This study was a retrospective, single-center, observational cohort analysis designed to further investigate factors affecting vancomycin trough levels and adverse reactions in pediatric patients with infections, building upon previous research on the rational pediatric use. Additionally, we explored the relationship between vancomycin trough levels and clinical symptom improvement in children infected with Methicillin-resistant Staphylococcus aureus (MRSA). The findings demonstrated that initial vancomycin dosing regimens, as well as serum albumin, hemoglobin, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels, did not differ significantly among the three trough concentration groups: target (10-20 mg/L), high (≥ 20 mg/L), and low (< 10 mg/L) (P > 0.05). The estimated glomerular filtration rate (GFR) values at treatment initiation were 108.4 (87.8-163.7), 95.2 (65.8-144.3), and 149.8 (95.3-201.6) for the three groups, respectively (P < 0.05). Multiple linear regression identified GFR as the most predictive variable for vancomycin trough concentration, showing a negative linear correlation with the initial GFR value in children undergoing vancomycin treatment (R² = 0.1565, P = 0.014). For children with MRSA infections, the time to normalization of infection markers and the time to negative microbial cultures were shorter in the target and high trough concentration groups compared to the low trough concentration group (P < 0.05). However, the incidence of acute kidney injury during hospitalization was higher in the high concentration group compared to the target and low concentration groups. Therefore, vancomycin trough concentrations in pediatric patients are inversely related to GFR levels. There were no statistically significant differences in the rates of acute liver injury, thrombocytopenia, neutropenia, or 30-day mortality among the three groups (P > 0.05).Conclusion: For children with MRSA infections, clinical effectiveness is superior at target and high vancomycin trough concentrations; however, elevated trough concentrations are linked to an increased risk of acute kidney injury. Clinically, vancomycin should be administered at lower doses as recommended by guidelines.

The aim of the study was to compare the effectiveness of daycare-simulated interrupted phototherapy versus continuous phototherapy for treating neonatal jaundice. A parallel randomized controlled trial with one-to-one allocation was conducted involving low-risk jaundiced neonates. The neonates in the intervention group received 10 h of phototherapy, while the control group received continuous phototherapy for 24 h. Total serum bilirubin (TSB) was measured before the start of phototherapy and at 24 h of treatment. Seventy-four neonates were recruited, and 37 neonates were randomly allocated to each group. The mean rate of fall of TSB per hour was not statistically significantly different between the intervention and control groups (1.71 versus 1.9 µmol/L/h; p = 0.529). The mean of TSB post-treatment in the intervention group was higher than in the control group and statistically significant (182 versus 158 µmol/L; p = 0.045) but not clinically significant, as none of the neonates required reinstitution or continuation of phototherapy.

Conclusion:  Ten hours of phototherapy which could be given in daycare may be effective and safe.

Trial registration: This trial wasregistered with Australian New Zealand Clinical Trials (trial ID: ANZCTR 12624000860561) prospectively on 12 July 2024.

What is known: • Intermittent phototherapy is known to be as effective as continuous phototherapy.

What is new: • We designed a study in which phototherapy was interrupted after 10 h, simulating daycare phototherapy. • Daycare phototherapy for 10 h may be feasible in treating neonatal hyperbilirubinemia in low-risk neonates.