European Journal Of Pediatrics[JOURNAL]
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200 papers
Associations of socioeconomic status and nurturing environment with developmental outcomes in very preterm children without sensorimotor impairment: a secondary analysis of the INTACT study.
Kono Y, Kusuda S, Nishida T … +7 more , Mori R, Toyoshima K, Sasaki H, Yonemoto N, Uchiyama A, Fujimura M, INTACT Study Group
Eur J Pediatr · 2026 May · PMID 42176065 · Publisher ↗
UNLABELLED: The objective of this study is to retrospectively evaluate the associations between socioeconomic status (SES), including nurturing environment, and developmental quotients (DQ) at age 3 in children born very...
UNLABELLED: The objective of this study is to retrospectively evaluate the associations between socioeconomic status (SES), including nurturing environment, and developmental quotients (DQ) at age 3 in children born very preterm with birth weight ≤ 1500 g. This secondary analysis used follow-up data from the Improvement of NICU Practices and Team Approach Cluster Randomized Controlled Trial. Participants born < 32 weeks' gestation without major sensorimotor impairments were stratified into three groups: 22-24, 25-27, and 28-31 weeks. Multiple linear regression evaluated the associations between prenatal SES and DQ scores of the Kyoto Scale of Psychological Development (KSPD), adjusted for sex, parity, gestational age, small for gestational age, multiple births, and facilities. Post-discharge SES variables were subsequently added to assess associations with nurturing environment. Of 2148 eligible survivors, 1978 underwent KSPD testing and 1846 caregivers completed SES questionnaires. Higher parental education was positively associated with total DQ across all groups: 22-24 weeks (β = 2.246, 95% CI 0.015-4.477), 25-27 weeks (β = 1.589, 95% CI 0.408-2.770), and 28-31 weeks (β = 1.299, 95% CI 0.315-2.282). Group childcare utilization was associated with higher total DQ: 22-24 weeks (β = 3.397, 95% CI 0.893-5.901), 25-27 weeks (β = 1.851, 95% CI 0.591-3.111), and 28-31 weeks (β = 2.617, 95% CI 1.613-3.620). These associations remained after adjustments for postnatal morbidities. CONCLUSION: Among children born very preterm without major sensorimotor impairments, parental education and group childcare utilization were independently associated with more favorable cognitive outcomes at age 3. These results suggest the importance of socioeconomic and environmental support in optimizing developmental outcomes for this vulnerable population. WHAT IS KNOWN: • Prenatal and postnatal SES are associated with developmental outcomes in both preterm and term children. In addition, daily group childcare environments influence child development in the general population. WHAT IS NEW: • Among very preterm children without major sensorimotor impairments, including those born at 22-24 weeks' gestation, parental education and group childcare utilization are independently associated with more favorable cognitive and language outcomes at age 3.
Early quantitative progression of café-au-lait macules and diagnostic threshold fulfilment by 24 months in neurofibromatosis type 1.
Alexopoulos A, Ntokos D, Kontara L … +5 more , Miligkos M, Dakoutrou M, Sarafis P, Kanaka-Gantenbein C, Nasi L
Eur J Pediatr · 2026 May · PMID 42174263 · Publisher ↗
UNLABELLED: Café-au-lait macules (CALMs) constitute a major diagnostic criterion for neurofibromatosis type 1 (NF1), yet infants presenting exclusively with CALMs often do not fulfill full diagnostic criteria in early li...
UNLABELLED: Café-au-lait macules (CALMs) constitute a major diagnostic criterion for neurofibromatosis type 1 (NF1), yet infants presenting exclusively with CALMs often do not fulfill full diagnostic criteria in early life. This retrospective cohort study aimed to quantify longitudinal changes in CALM burden during the first two years of life in children with NF1 and to assess the relevance of early lesion number for subsequent diagnostic threshold fulfillment. Sixty-three children with NF1 who initially presented with typical multiple CALMs were included. CALM counts were documented at 6, 12, and 24 months using standardized digital photography. CALM counts increased significantly over time (χ(2) = 124.097, p < 0.001; Kendall's W = 0.985), rising from a mean of 5.86 ± 2.63 at 6 months to 17.49 ± 7.75 at 24 months. While 38.1% of infants met the six-lesion diagnostic threshold (≥ 6 CALMs) at 6 months, 96.8% did so by 24 months, and 94.5% of those initially below the diagnostic threshold (< 6 CALMs) met the diagnostic threshold during follow-up by 24 months. CONCLUSION: CALM burden increases markedly during the first two years of life in children with NF1. By 24 months, nearly all children met the CALM-based diagnostic threshold (≥ 6 CALMs), indicating that this period represents a critical window for diagnostic threshold fulfillment. These findings support a time-dependent framework for the evaluation and follow-up of infants presenting with isolated multiple CALMs. WHAT IS KNOWN: • Multiple café-au-lait macules (CALMs) are a major diagnostic criterion for neurofibromatosis type 1 (NF1), with additional features often emerging later in childhood. • Infants presenting exclusively with CALMs frequently require longitudinal follow-up before diagnosis can be established. WHAT IS NEW: • Quantitative data on early longitudinal CALM progression in NF1 are limited. • This study demonstrates a marked increase in CALM burden during the first two years of life, with nearly all children meeting the diagnostic threshold by 24 months.
Prevalence and factors associated with acute kidney injury in children presenting to the emergency department with a first tonic-clonic seizure: an exploratory study.
Marzuillo P, Cerrone M, Di Sessa A … +7 more , Tirelli P, Rivetti G, Capasso G, Melone R, Miraglia Del Giudice E, Guarino S, Nunziata F
Eur J Pediatr · 2026 May · PMID 42171793 · Full text
UNLABELLED: We aimed to determine the prevalence of acute kidney injury (AKI) and to identify factors associated with its development in children presenting with a first febrile or non-febrile tonic-clonic seizure. We co...
UNLABELLED: We aimed to determine the prevalence of acute kidney injury (AKI) and to identify factors associated with its development in children presenting with a first febrile or non-febrile tonic-clonic seizure. We conducted an exploratory retrospective study including children (< 18 years) presenting to the emergency department for a first episode of febrile or non-febrile tonic-clonic seizure between January 2021 and July 2025. AKI was defined according to KDIGO serum creatinine criteria, using back-calculating methods to estimate baseline creatinine. Clinical, laboratory, and therapeutic variables were collected. Logistic regression analyses were performed to identify factors associated with AKI. A total of 190 children (mean age 4.2 ± 3.7 years) were included; 112 (58.9%) presented with febrile seizures. AKI occurred in 23 patients (12.1%), with similar prevalence in febrile and non-febrile seizures (12.5% vs. 11.5%; p = 0.84). No patient required renal replacement therapy. Among children with febrile seizures, being born small for gestational age (SGA), elevated C-reactive protein (CRP) levels, and prior use of combined paracetamol and ibuprofen were independently associated with AKI. In the non-febrile seizure subgroup, longer seizure duration and higher CRP levels were associated with AKI in univariate analysis, but only CRP remained independently associated in multivariable model. CONCLUSION: AKI occurs in approximately 12% of children presenting with a first tonic-clonic seizure. Elevated CRP levels were associated with AKI in both febrile and non-febrile seizures, while SGA status and combined use of antipyretics were associated with AKI among children with febrile seizures. Given the limited number of events, these findings should be interpreted as exploratory. WHAT IS KNOWN: • Acute kidney injury (AKI) has been anecdotally reported in patients with status epilepticus, likely related to rhabdomyolysis-induced nephropathy. • No studies have systematically investigated this association in either adults or children. WHAT IS NEW: • Approximately 12% of children presenting with a fi rst febrile or non-febrile tonic-clonic seizure develop acute kidneyinjury (AKI). • Elevated C-reactive protein (CRP) levels are independently associated with AKI in both febrile and non-febrileseizures, whereas small-for-gestational-age status and prior combined use of paracetamol and ibuprofen areadditional factors associated with AKI in children with febrile seizures.
Standardizing HFNC for bronchiolitis: a quality improvement protocol in an Italian children's hospital.
Giugni C, Cecchi C, Nanni L … +1 more , Ricci Z
Eur J Pediatr · 2026 May · PMID 42171785 · Publisher ↗
UNLABELLED: Bronchiolitis is the leading cause of non-elective hospitalizations in infants, with an increasing use of high-flow nasal cannula (HFNC) therapy outside the Pediatric Intensive Care Unit (PICU). At our hospit...
UNLABELLED: Bronchiolitis is the leading cause of non-elective hospitalizations in infants, with an increasing use of high-flow nasal cannula (HFNC) therapy outside the Pediatric Intensive Care Unit (PICU). At our hospital, HFNC was used to treat pediatric bronchiolitis patients without a standardized protocol for initiation, flow titration, escalation, or a PICU alert system in cases of clinical deterioration. This quality improvement project aimed to evaluate the feasibility of a multidisciplinary protocol designed to standardize HFNC use for bronchiolitis in patients under 24 months of age, admitted to the emergency department (ED) during the 2021-2023 winter seasons and through the first 72 h of hospitalization. The primary outcomes were healthcare provider adherence and staff satisfaction. The protocol utilized the Clinical Respiratory Score (CRS) to guide therapy: low-flow oxygen for CRS < 4, HFNC with PICU notification for CRS 4-7, and consideration for non-invasive ventilation (NIV) and PICU transfer for CRS > 7. Satisfaction was assessed via a questionnaire stratified by clinical experience. As a secondary objective, CRS and clinical outcomes (length of stay [LOS] and PICU admission rates) of the per-protocol group were compared to a historical cohort admitted to our hospital during the two preceding winter seasons. The CRS used for comparison with the prospective group were retrospectively calculated from clinical chart review. Prospective data from 114 patients were analyzed; 97 were managed in full compliance with the protocol, yielding an adherence rate of 85.1%. Staff satisfaction was 100% among pediatric residents (n = 5) and junior physicians (< 5 years of experience, n = 15), while senior physicians (≥ 5 years of experience, n = 15) reported a 70% satisfaction rate. No significant differences were observed in LOS (6.13 ± 2.60 days per-protocol vs. 7.12 ± 8.95 days pre-protocol; p = 0.303) or PICU admission rates (20.6% per-protocol vs. 11.6% pre-protocol; p = 0.150). In the retrospective cohort (n = 86), the mean CRS at ED admission was significantly lower than in the per-protocol group (p < 0.001). However, the per-protocol group exhibited significantly lower CRS values at 48 h and 72 h (p < 0.001), despite higher baseline severity. CONCLUSIONS: The implementation of a structured HFNC protocol based on CRS scores is feasible in a tertiary pediatric setting, achieving high adherence (85%) and overall staff satisfaction (85.7%). While clinical outcomes remained comparable, the standardized approach encouraged early monitoring and was associated with earlier improvement in respiratory scores. Future initiatives should focus on optimizing adherence and addressing the specific concerns of senior clinical staff. WHAT IS KNOWN: • Current evidence does not support high-flow nasal cannula (HFNC) as a superior first-line therapy compared to standard low-flow oxygen. However, implementing a structured hospital protocol that reserves HFNC for selected patients who fail low-flow therapy can optimize clinical management and ensure timely intervention for those in urgent need. WHAT IS NEW: • This study demonstrates that a structured multidisciplinary protocol for HFNC - based on the Clinical Respiratory Score (CRS) and with a formal "PICU alert system" - is highly feasible in a tertiary Italian setting, achieving an overall adherence rate of 85.1%. The protocol was well-received by healthcare providers, with a global staff satisfaction rate of 85.7%.
Application of machine learning to predict bronchiolitis severity in children: a single-centre retrospective cohort study.
Manti S, Gambadauro A, Stocchero M … +2 more , Wasniewska M, Baraldi E
Eur J Pediatr · 2026 May · PMID 42171780 · Publisher ↗
UNLABELLED: Several severity scores have been developed to assess disease severity in infants with bronchiolitis, but they often lack objectivity and may not reliably reflect clinical outcomes. We performed a single-cent...
UNLABELLED: Several severity scores have been developed to assess disease severity in infants with bronchiolitis, but they often lack objectivity and may not reliably reflect clinical outcomes. We performed a single-centre retrospective cohort study including infants younger than 12 months admitted with a clinical diagnosis of bronchiolitis over three epidemic seasons (2021-2024). Cluster analysis was applied to identify groups of infants with similar clinical patterns, which were subsequently mapped to severity levels. A machine learning (ML) model was then trained to predict these severity levels using anamnestic and clinical variables available at admission. For comparison, the bronchiolitis risk of admission score (BRAS) and the respiratory severity score-heart rate (RSS-HR) were also calculated at admission. A total of 112 infants were included, and three severity levels were identified. Mild bronchiolitis corresponded to infants not requiring NICU admission or supplementary ventilation. Moderate cases involved infants needing supplementary ventilation without NICU admission. Severe bronchiolitis was associated with both NICU admission and supplementary ventilation. BRAS showed only a weak association with the newly defined clinical severity score (τ = 0.354, p < 0.001), while RSS-HR showed no significant correlation. In contrast, the ML model demonstrated strong predictive performance (τ = 0.731, p < 0.001 in the test set). A simplified decision tree based on three admission variables-age, retractions, and oxygen saturation-also showed good predictive ability (τ = 0.654, p < 0.001). CONCLUSIONS: A new dynamic approach for assessing bronchiolitis severity at hospital admission, capable of robust and adaptable prediction across clinical settings, has been elaborated. WHAT IS KNOWN: • Several bronchiolitis severity scores exist, but many lack validation, are subjective, and have limited applicability across settings, making early and accurate severity prediction difficult. WHAT IS NEW: • Our study introduces a three-level, outcome-based severity score and a dynamic ML tool, plus a simplified ARS decision tree, all outperforming conventional scores in predicting severity at admission.
Childhood body mass index trajectories and risk of overweight and obesity in young adulthood: a population-based prospective cohort study.
de Groot JM, Felix JF, Gaillard R … +1 more , Jaddoe VWV
Eur J Pediatr · 2026 May · PMID 42168653 · Full text
UNLABELLED: Childhood body mass index (BMI) change is associated with obesity in adulthood but is often investigated in isolated age windows. This study aimed to identify age windows of BMI changes that are associated wi...
UNLABELLED: Childhood body mass index (BMI) change is associated with obesity in adulthood but is often investigated in isolated age windows. This study aimed to identify age windows of BMI changes that are associated with overweight, including obesity, in young adulthood. This study was embedded in a population-based, prospective cohort study among 3528 participants born in Rotterdam, the Netherlands, between 2002 and 2006. Data on gestational-age-adjusted birth weight and sex- and age-adjusted BMI (BMI-SDS) was repeatedly collected between 2 and 20 years in a dedicated research center. Associations between childhood BMI-SDS and young adult (from 17 to 21 years of age) BMI-SDS and overweight/obesity were analyzed. Of children with overweight, including obesity, at 2, 6, 10, and 14 years, 32.6%, 54.0%, 57.4%, and 70.3%, respectively, had overweight around 18 years of age. Positive deviations from the expected BMI at any age were positively associated with odds of overweight at 18, with the strongest effect estimate at 6 years (p-values < 0.05). Of children in the highest BMI tertile between 2 and 10 years, only those with BMI growth deceleration, defined as a decrease comparable to crossing a major percentile line on a growth chart, between 2 and 6 years did not have increased risk of overweight at 18 years, whereas all other children in the highest BMI tertile did. CONCLUSION: Optimizing healthy and reversing unhealthy BMI trajectories in early childhood, especially before 6 years, may be a great opportunity for the prevention of overweight and obesity. WHAT IS KNOWN: • Childhood growth and body mass index (BMI) are strongly related to obesity in adulthood. • Rapid weight gain in infancy, early childhood, and adolescence has all been found to be associated with risk of obesity in both childhood and adulthood. WHAT IS NEW: • Based on repeated growth data of 3,528 children from a prospective cohort, associations of childhood BMI with young adult BMI are strongest around age 6, compared to ages 2, 10, and 14 years old. • The increased risk of adult overweight/obesity in children in the highest BMI tertile was attenuated in those with growth deceleration before 6 years. After this age, regardless of growth velocity, risk remained increased for children in the highest BMI tertile.
Traumatic intraventricular haemorrhages: clinical indicators determining morbidity and mortality in paediatric patients.
Mart ZÖ, Ulusoy E, Uyuşkan B … +7 more , Akansu İ, Er A, Ur K, Eser Ö, Canbeldek ME, Günal Ö, Duman M
Eur J Pediatr · 2026 May · PMID 42168612 · Full text
UNLABELLED: Intracranial haemorrhages and traumatic brain injury are significant causes of morbidity and mortality in paediatric patients. Traumatic intraventricular haemorrhage (tIVH) is the least common type of intracr...
UNLABELLED: Intracranial haemorrhages and traumatic brain injury are significant causes of morbidity and mortality in paediatric patients. Traumatic intraventricular haemorrhage (tIVH) is the least common type of intracranial haemorrhage and typically occurs in association with other intracranial injuries. This study aimed to describe the clinical characteristics of children diagnosed with tIVH, and to identify risk factors associated with poor prognosis. Paediatric patients diagnosed with tIVH in the paediatric emergency department between January 2010 and December 2024 were retrospectively reviewed. Demographic and clinical characteristics, laboratory and imaging results, treatment modalities, and outcomes were analysed. Neurological status at discharge was assessed using the Glasgow Outcome Scale-Extended (GOSE). Among the 785 patients with traumatic intracranial haemorrhage, tIVH was identified in 41 (5.2%). Most patients were male (68.3%), with a median age of 12.8 years (6.6-15.7). The most common mechanism of injury was traffic-related trauma (78.1%). Altered consciousness was observed in 87.8% (n = 36), convulsive seizures in 17.1% (n = 7), and a Glasgow Coma Scale (GCS) score below 9 on admission in 80.5% (n = 33). Isolated tIVH was observed in only three patients (7.3%). Overall, 82.9% of patients (n = 34) required admission to the intensive care unit, and the mortality rate was 34.1% (n = 14). Only 31.6% of patients achieved a good neurological outcome; notably, all patients with isolated tIVH had favourable outcomes. Low admission GCS, coagulopathy, concomitant subdural haemorrhage, and cerebral herniation were significantly associated with both poor neurological outcome and mortality. In addition, bilateral haemorrhage, cerebral oedema, and midline shift were associated with poor neurological outcome, whereas fourth ventricular haemorrhage, concomitant skull fracture, maxillofacial trauma, and abdominal trauma were significantly associated with mortality (p < 0.05). CONCLUSION: Low admission GCS, coagulopathy, and associated cranial or extracranial injuries are strong predictors of poor prognosis in pediatric tIVH, whereas isolated tIVH is associated with favourable neurological outcomes. Early identification of high-risk features may improve outcomes in pediatric tIVH. WHAT IS KNOWN: • Traumatic intraventricular haemorrhage (tIVH) is a rare complication of paediatric traumatic brain injury, typically resulting from high-energy trauma such as traffic accidents, and frequently coexists with other severe intracranial injuries. • While isolated tIVH is known to follow a favourable and self-limited course, the presence of tIVH in the context of multitrauma is generally associated with high rates of morbidity and mortality. WHAT IS NEW: • This study demonstrates that poor neurological outcomes and mortality in paediatric tIVH are driven primarily by the severity of concomitant injuries rather than the tIVH itself. • Specific clinical and radiological features, such as coagulopathy, concomitant subdural haemorrhage, bilateral haemorrhagic involvement, midline shift, cerebral oedema, fourth ventricular involvement, and concurrent abdominal trauma, were identified as strong prognostic markers in this population.
Maternal PPI therapy during lactation: pantoprazole levels in human milk and possible neonatal implications.
Bor S, Ergun P, Sahin S … +3 more , Kipcak S, Tuncal A, Karasulu E
Eur J Pediatr · 2026 May · PMID 42168392 · Full text
UNLABELLED: Proton pump inhibitors (PPIs) are widely used for acid-related disorders, but limited data exist regarding their excretion into human breast milk. This study aimed to quantify pantoprazole levels in plasma an...
UNLABELLED: Proton pump inhibitors (PPIs) are widely used for acid-related disorders, but limited data exist regarding their excretion into human breast milk. This study aimed to quantify pantoprazole levels in plasma and breast milk of lactating women and to assess potential infant exposure. Sixteen mothers who had discontinued breastfeeding and were prescribed 40 mg pantoprazole once daily participated. Blood and breast milk samples were collected on days 1 and 7 at 0, 1.5, 3, 4.5, and 6 h post-dose. Pantoprazole was quantified using a validated high-performance liquid chromatography (HPLC) method with omeprazole as the internal standard. Samples were extracted via liquid-liquid extraction, and the method was validated over a linear range of 0.03-1 µg/mL (LOQ 0.03 µg/mL). Pantoprazole was detected in 46% (69/150) of plasma samples and 17.4% (26/149) of breast milk samples. Plasma levels peaked at ~ 4.5 h, whereas breast milk concentrations peaked at 3-4.5 h on day 1 and at 3 h on day 7. The low detectability and consistently lower breast milk concentrations suggest limited transfer into breast milk. Pantoprazole levels in breast milk were consistently lower than plasma and infrequently detectable. CONCLUSION: This study, representing the largest series to date examining pantoprazole excretion during lactation, suggests that infant exposure via breast milk is low. These findings suggest that breastfeeding may be compatible with pantoprazole therapy, although caution is warranted. The data provide supportive evidence for clinical decision-making. WHAT IS KNOWN: • Proton pump inhibitors (PPIs) are widely prescribed during lactation, but robust safety and pharmacokinetic data for pantoprazole transfer into breast milk remain limited. • Current breastfeeding recommendations for PPIs are based largely on expert opinion and isolated case reports with limited milk sampling. WHAT IS NEW: • Peak concentrations occurred 3-4.5 hours post-dose, and milk levels were consistently much lower than plasma levels. • Pantoprazole was detected in few milk samples and at concentrations markedly lower than plasma levels, indicating negligible infant exposure and supporting breastfeeding compatibility during therapy.
Contrasting BMI and height z-score trajectories in children with new-onset T1DM: a case-control study across Latin American Centers.
Hirschler V, Molinari C, Gonzalez C … +2 more , Witte DR, CODIAPED Study Group
Eur J Pediatr · 2026 May · PMID 42165904 · Publisher ↗
UNLABELLED: Children with new-onset type 1 diabetes (T1DM) may experience some growth delay. To compare growth trajectories assessed by z-height and z-BMI over a 3-year follow-up period between children with new-onset T1...
UNLABELLED: Children with new-onset type 1 diabetes (T1DM) may experience some growth delay. To compare growth trajectories assessed by z-height and z-BMI over a 3-year follow-up period between children with new-onset T1DM and a control group without T1DM across multiple Latin American centers. A retrospective analysis of medical records was conducted over 3 years (2021-2024) in children with new-onset T1DM and their controls from ten Latin American centers, including age, sex, and anthropometric measures. A mixed-effects model was used to analyze z-height and z-BMI over three years. A total of 534 participants were included, comprising 245 children with T1DM (51.4% female; mean age, 8.8 years) and 289 controls (45.7% female; mean age, 8.1 years). The mean z-BMI in children with T1DM compared to controls was at years 0 (- 0.12 vs. 0.54), 1 (0.36 vs. 0.63), 2 (0.32 vs. 0.55), and 3 (0.34 vs. 0.47). Children with T1DM had a significantly lower z-BMI than controls, with mean differences of - 0.71, - 0.33, and - 0.28 in years 0, 1, and 2, respectively. However, by year 3, the mean difference (- 0.18) was no longer significant. z-height in children with T1DM vs. controls was at years 1 (- 0.08 vs. - 0.09), 2 (- 0.24 vs. - 0.12), and 3 (- 0.35 vs. - 0.12). z-height remained stable in controls but declined in the T1DM group, reaching a mean difference of - 0.25 (p < 0.01) by year 3. CONCLUSIONS: This study demonstrated that despite treatment and equalization of z-BMI, children with T1DM in Latin America experience a progressive decline in linear growth. WHAT IS KNOWN: • Children with type 1 diabetes may experience impaired linear growth and lower BMI at disease onset, particularly in association with poor metabolic control. WHAT IS NEW: • This multicenter Latin American study showed that although BMI normalized after treatment initiation, children with type 1 diabetes exhibited a progressive decline in height z-scores over the first three years after diagnosis compared with healthy controls.
From pathology back to the clinic: refining indications for paediatric cervical lymph node biopsy.
Viard E, Gazagne C, Petit P … +4 more , Appay R, Nicollas R, Saultier P, Moreddu E
Eur J Pediatr · 2026 May · PMID 42165847 · Publisher ↗
UNLABELLED: Cervical lymphadenopathy is common in children, yet indications for open biopsy remain debated. Most studies analyse clinical cohorts in which only a subset of patients undergo biopsy, limiting correlation wi...
UNLABELLED: Cervical lymphadenopathy is common in children, yet indications for open biopsy remain debated. Most studies analyse clinical cohorts in which only a subset of patients undergo biopsy, limiting correlation with definitive diagnoses. We adopted a pathology-first approach to identify the clinical and imaging features associated with malignant haematologic disease among children undergoing cervical lymph node biopsy. We performed a retrospective review of 160 consecutive paediatric cervical lymph node biopsies conducted at a tertiary referral centre. Demographic, clinical, laboratory, radiological, and pathological data were collected. Benignity and malignancy criteria guided the analysis, and associations were summarised using odds ratios. Among the 160 biopsies, 81 (50.6%) revealed malignant haematologic disease, predominantly Hodgkin lymphoma. Infectious lymphadenopathy and reactive lymphoid hyperplasia were the most frequent benign diagnoses. No metastatic lymph nodes were identified. Clinical signs associated with malignancy included lymph node fixation, dyspnoea, and fever. Imaging features suggestive of malignancy included dedifferentiated and hypoechoic lymph nodes, compression of the internal jugular vein, abdominopelvic lymphadenopathy, cardiomediastinal enlargement, and confluent cervical nodes. The risk of malignancy increased progressively with the number of involved cervical nodal levels. Lower cervical and, in particular, supraclavicular locations were strongly associated with malignancy. CONCLUSION: In children undergoing cervical lymph node biopsy, malignant lymphadenopathy is overwhelmingly dominated by lymphoma rather than metastatic disease. A combination of clinical findings and high-quality ultrasound evaluation can help identify children at higher risk of malignant haematologic disease and support more selective use of surgical biopsy. WHAT IS KNOWN: • Paediatric cervical lymphadenopathy is common; although most cases are benign, some may indicate serious underlying disease. • Several studies have described clinical and paraclinical prognostic factors associated with paediatric cervical lymphadenopathy. WHAT IS NEW: • High-quality ultrasound triage can substantially reduce unnecessary cervical lymph node biopsies. • By adopting a pathology-first approach, this study identifies preoperative clinical and imaging criteria associated with malignancy, helping to determine which children truly require biopsy and which could be safely observed.
Lung ultrasound evolution after interventional closure of the ductus in preterm babies.
Arriaga-Redondo M, Gregorio-Hernández R, Rodríguez-Sánchez de la Blanca A … +5 more , Rodriguez-Corrales E, Vigil-Vázquez S, Pérez-Pérez A, Ramos-Navarro C, Sánchez-Luna M
Eur J Pediatr · 2026 May · PMID 42162517 · Publisher ↗
Interventional closure of patent ductus arteriosus (PDA) in preterm infants may result in significant hemodynamic and pulmonary changes. Lung ultrasound (LU) is increasingly used to assess pulmonary aeration; however, da...
Interventional closure of patent ductus arteriosus (PDA) in preterm infants may result in significant hemodynamic and pulmonary changes. Lung ultrasound (LU) is increasingly used to assess pulmonary aeration; however, data on early respiratory changes following PDA closure remain limited. A prospective observational study was conducted including preterm infants born at ≤ 32 weeks' gestation with hemodynamically significant PDA undergoing surgical or catheter-based closure between May 2022 and November 2025. LU was performed the day before intervention and at 1-2 h, 6-12 h, 24 h, and 2-3 days after closure. Oxygenation (S/F ratio) and invasive mechanical ventilation (IMV) use were also evaluated. Seventeen infants were included (15 catheter-based, 2 surgical closures). A transient deterioration in oxygenation and increased odds of IMV were observed within the first hours after ductal closure. This was followed by a significant improvement in lung ultrasound score at 2-3 days. Conclusion: Lung aeration improved 2-3 days after interventional PDA closure in preterm infants. Lung ultrasound may be a useful bedside tool to monitor dynamic pulmonary changes during the early post-closure period.
Microvascular ultrasound imaging of the neonatal brain: a scoping review.
Ramana A, Zhu J, Acimovic K … +3 more , Mitra K, Tang MX, Banerjee J
Eur J Pediatr · 2026 May · PMID 42162396 · Full text
Microvascular changes in the developing neonatal brain often precede clinically detectable injury. Advanced ultrasound techniques such as microvascular Doppler (MVD), contrast-enhanced ultrasound (CEUS), and super-resolu...
Microvascular changes in the developing neonatal brain often precede clinically detectable injury. Advanced ultrasound techniques such as microvascular Doppler (MVD), contrast-enhanced ultrasound (CEUS), and super-resolution ultrasound (SRUS) offer the potential for bedside assessment of microvascular flow and perfusion without sedation, organotoxic contrast agents, or ionising radiation. Using Joanna Briggs Institute methodology and PRISMA-ScR guidance, MEDLINE, EMBASE, Web of Science, trial registries, and grey literature were searched for original in vivo neonatal studies reporting microvascular or perfusion data using MVD, CEUS, or SRUS-based approaches. Extracted data included study metadata, population characteristics, ultrasound systems and protocols, and key feasibility, safety, and performance outcomes. Of 3028 screened records, 23 studies met the inclusion criteria (1 SRUS, 8 CEUS, 14 MVD). Using SonoVue/Lumason microbubbles, the CEUS studies reported 163 neonatal brain scans in 91 neonates (25 to 41 weeks' gestation). A total of 263 infants were studied across 14 MVD studies. All studies demonstrated safe ultrasound techniques that can be used to assess brain perfusion and cerebrovascular pathologies in preterm and term neonates, particularly in understanding changes in cerebral microvasculature, mainly in infants with hypoxic-ischaemic encephalopathy (HIE), neurovascular, and congenital cardiac conditions. Conclusions: Advanced ultrasound techniques show promise as adjuncts in neonatal neuroimaging, enabling assessment of perfusion and microvascular haemodynamics. Future clinical translation would require standardised protocols, normative datasets, longitudinal outcome linkage, governance and training standards, and diagnostic effectiveness.
Performance of PRISM III and pediatric early warning score for predicting patients needing increased level of care in a pediatric intermediate care unit.
Pérez-Porra S, Delgado A, Redondo E … +3 more , Andrés P, Cano A, Granda E
Eur J Pediatr · 2026 May · PMID 42159847 · Publisher ↗
UNLABELLED: The aim of this study is to evaluate the performance of PRISM III and pediatric early warning score (PEWS) for predicting increased level of care in an intermediate care unit (IMCU) and to describe the factor...
UNLABELLED: The aim of this study is to evaluate the performance of PRISM III and pediatric early warning score (PEWS) for predicting increased level of care in an intermediate care unit (IMCU) and to describe the factors associated with it. This was a retrospective observational study in an IMCU of a tertiary university hospital without an on-site pediatric intensive care unit (PICU). Patients younger than 14 years old admitted to IMCU (June 2021 to September 2024) were included. Area under the curve (AUC) for "increased level of care"-composite outcome including high respiratory support, invasive procedures, prolonged length of stay, or PICU-transfer-was calculated for both scores. Of 567 patients included (median age 15 months [IQR 3-49]; 57.8% male), 269 (47.4%) needed increased level of care. AUC of PRISM III was 0.545 (CI95% 0.497-0.592), whereas AUC of PEWS was 0.697 (CI95% 0.654-0.740); sensitivity was 43.5% (CI95% 37.8-49.3) and specificity was 86.6% (CI95% 82.3-90.1). Results were consistent in sensitivity analyses. Healthcare workers or family concern was associated with increased level of care [aOR 4.127 (CI95% 2.492-6.835)] and PICU-transfer [aOR 8.180 (CI95% 2.920-22.912)]. CONCLUSIONS: Neither PRISM III nor PEWS was accurate to predict increased level of care in IMCU. Healthcare worker or family concern was associated with both increased level of care and PICU-transfer. These findings highlight the need for IMCU-specific severity tools and the importance of individual assessment. WHAT IS KNOWN: • Early warning scores (PEWS) and PRISM III are widely used in general wards and PICU, respectively. • However, their performance in intermediate care units (IMCU) remains poorly defined. WHAT IS NEW: • Both PRISM III and PEWS have limited accuracy in predicting the need for increased level of care within an IMCU. • The subjective concern of staff or family members was associated with clinical worsening and PICU-transfer.
Early post-IVIG serum IgG concentration does not explain IVIG non-response in Kawasaki disease.
Hashimoto I, Okabe M
Eur J Pediatr · 2026 May · PMID 42159808 · Publisher ↗
Intravenous immunoglobulin (IVIG) at 2 g/kg is the standard first-line therapy for acute Kawasaki disease (KD), yet a subset of patients remains febrile after treatment. Whether IVIG non-response is primarily explained b...
Intravenous immunoglobulin (IVIG) at 2 g/kg is the standard first-line therapy for acute Kawasaki disease (KD), yet a subset of patients remains febrile after treatment. Whether IVIG non-response is primarily explained by a low early post-infusion IgG concentration remains uncertain. We retrospectively reviewed consecutive patients with KD at a single center (2009-2019). Patients receiving initial IVIG 2 g/kg without adjunctive therapy were included (N = 109; responders = 86, non-responders = 23). Serum IgG was measured at admission and within 24 h after completion of IVIG. Associations with non-response were examined using multivariable Firth penalized logistic regression, with IgG scaled per 100 mg/dL and adjustment for prespecified clinical covariates. Sensitivity analyses included additional adjustment for the Kobayashi score and exclusion of one non-responder treated without meeting the objective fever criterion. Baseline IgG was correlated with early post-IVIG IgG (Spearman's ρ = 0.481, P < 0.001). In multivariable Firth penalized logistic regression model, higher post-IVIG IgG was independently associated with non-response (OR 1.26 per 100 mg/dL; 95% CI 1.06-1.53), whereas baseline IgG was not significant in the same model. Neutrophil percentage (pre-IVIG) was also independently associated with non-response (OR 1.08 per 1% increase; 95% CI 1.02-1.16). Sensitivity analyses yielded consistent direction and significance of the main associations. Conclusions: Under the standard 2 g/kg regimen, IVIG non-response in Kawasaki disease was not explained by a low early post-infusion serum IgG concentration. Non-response occurred even at early post-IVIG IgG concentrations within-and above-the range observed among responders, suggesting escalation strategies beyond simply repeating IVIG to further increase IgG.
Comparison of Masimo O3 and INVOS 7100 cerebral oxygenation during immediate neonatal transition.
Sintupech P, Anantho A, Songnok K … +1 more , Kitsommart R
Eur J Pediatr · 2026 May · PMID 42159790 · Full text
UNLABELLED: This study aims to compare CrSO measured simultaneously by Masimo O3 and INVOS during the first 15 min after birth in healthy term infants and to evaluate agreement and derived cerebral fractional tissue oxyg...
UNLABELLED: This study aims to compare CrSO measured simultaneously by Masimo O3 and INVOS during the first 15 min after birth in healthy term infants and to evaluate agreement and derived cerebral fractional tissue oxygen extraction (cFTOE). In this prospective observational study, 65 healthy term infants were monitored immediately after birth using Masimo O3 and INVOS 7100 applied simultaneously with randomized hemispheric placement. Pre-ductal oxygen saturation (SpO) was recorded continuously. Minute-specific values were derived from aggregated measurements during the final 30 s of each minute. Paired comparisons were performed using Wilcoxon signed-rank test. Agreement was assessed using Bland-Altman analysis with regression evaluation for proportional bias. Both devices demonstrated a similar temporal increase in CrSO during the first 5 min, with relative stabilization thereafter. From minute 4 onward, Masimo O3 values were lower than INVOS, with significant differences at minutes 5 to 11 and min 14 (p < 0.05). Overall mean bias was - 2.8%, with 95% limits of agreement from + 18.0 to - 23.6%. Significant proportional bias was present (R = 0.11, p < 0.001). When CrSO was < 60%, mean bias was + 28.7% with wide limits of agreement. Masimo O3 derived cFTOE values were consistently higher at several time points. No significant hemispheric differences were detected. CONCLUSION: Masimo O3 and INVOS show similar temporal patterns but an oxygenation-dependent proportional bias. CrSO values are device-specific and not interchangeable, particularly at lower saturation levels during early transition. WHAT IS KNOWN: • Cerebral oxygenation during neonatal transition increases rapidly after birth and can be monitored using near-infrared spectroscopy. • Absolute values differ between devices, limiting comparability across NIRS systems. WHAT IS NEW: • This study provides a simultaneous head-to-head comparison of Masimo O3 and INVOS during immediate neonataltransition, demonstrating oxygenation-dependent proportional bias. • CrSO2 values are device-specific and and should not be directly translated between monitoring platforms.
Interdisciplinary collaboration in pediatric palliative care: a qualitative study on barriers and facilitators as perceived by parents and healthcare professionals.
Kemna MM, Aris-Meijer JL, Verhagen AAE … +3 more , Teunissen SCCM, Engel M, Kars MC
Eur J Pediatr · 2026 May · PMID 42159767 · Full text
UNLABELLED: Pediatric palliative care (PPC) requires involvement of various healthcare professionals (HCPs) across home and hospital settings to address the complex needs of children and families. Interdisciplinary colla...
UNLABELLED: Pediatric palliative care (PPC) requires involvement of various healthcare professionals (HCPs) across home and hospital settings to address the complex needs of children and families. Interdisciplinary collaboration (IDC) among HCPs and parents is crucial for the coordination, continuation, and quality of PPC. Yet, IDC remains difficult to achieve in practice. We aimed to identify barriers and facilitators to IDC in PPC as experienced by expert parents and HCPs in order to strengthen PPC. An exploratory multiple-case study was conducted using semi-structured interviews. Cases consisted of (non-)bereaved parents of a child qualifying for PPC and their involved HCPs. Data was thematically analyzed using the QUAGOL method. Nine cases, representing nine children, were included, comprising interviews with 14 parents and 39 HCPs. Barriers and facilitators to IDC were context-dependent and spanned seven domains: network, interdependence, goals of care, roles and tasks, added value, responsibility, and urgency. IDC typically developed slowly after diagnosis due to barriers such as negative perceptions on collaborative partners or IDC. Collaboration intensified during crisis and the terminal phase due to facilitators such as awareness of being a network. CONCLUSION: IDC in PPC cases is best understood as occurring in situational care networks (SCNs): temporary, child-specific constellations of parents and fluctuating non-standard and transmural collaborating HCPs. This conceptualization exposes vulnerabilities, but also opportunities of support and complementary HCP expertise in PPC collaboration. Early initiation of SCNs seems to better strengthen structural IDC than reactive reliance on parental coordination or crisis-driven senses in PPC. WHAT IS KNOWN: • Interdisciplinary collaboration among healthcare professionals and parents is crucial for coordination, continuation, and quality of pediatric palliative care. • Parents and healthcare professionals report challenges regarding collaboration in pediatric palliative care. WHAT IS NEW: • Besides facilitators and barriers in interpersonal interactions, individual attitudes and perceptions affect interdisciplinary collaboration in pediatric palliative care. • Conceptualizing collaboration as situational care networks of non-standard, transmural collaboration between healthcare professionals and parents may strengthen interdisciplinary collaboration.
Correction to: Predicting coronary artery abnormalities in Kawasaki disease: Model development and validation.
Wang Q, Kimura Y, Oba J … +8 more , Ishikawa T, Ohnishi T, Akahoshi S, Iio K, Morikawa Y, Sakurada K, Kobayashi T, Miura M
Eur J Pediatr · 2026 May · PMID 42159634 · Publisher ↗
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Frequency and outcomes of surgical and transcatheter closure of patent ductus arteriosus in preterm infants in Germany-a prospective nationwide hospital-based surveillance study.
Adelheid K, Leonie A, S UM … +6 more , Andreas M, Dominique S, D GV, A HN, W FA, André J
Eur J Pediatr · 2026 May · PMID 42156592 · Full text
UNLABELLED: Treatment strategies in patent ductus arteriosus (PDA) in preterm infants (PIs) have evolved in recent years and vary substantially between centers. While recent recommendations increasingly advocate for a mo...
UNLABELLED: Treatment strategies in patent ductus arteriosus (PDA) in preterm infants (PIs) have evolved in recent years and vary substantially between centers. While recent recommendations increasingly advocate for a more conservative approach to PDA management, transcatheter PDA closure (TCPC) has simultaneously become a well-established alternative to surgical ligation-even in very small PIs-after failure of medical treatment. Particularly in light of the ongoing conflicting perspectives in the field of optimal PDA management in PIs, our objective was to compare frequency, efficiency, and complications of surgical closure versus TCPC in a real-world setting. Between 2022 and 2023, we conducted a prospective nationwide hospital-based surveillance study including preterm infants < 32 weeks gestation and < 1500 g birthweight who underwent either surgical or transcatheter PDA closure. Standardized data on PDA treatment strategies, including medical therapy and complications, were collected by the German Paediatric Surveillance Unit (GPSU) and outcomes evaluated using the Desirability of Outcome Ranking (DOOR) method. Data from 110 infants were analyzed. Ninety-three percent (102/110) received at least one kind of medical treatment before definite mechanical closure with ibuprofen most widely used followed by paracetamol. Surgical closure was performed in 70 infants and transcatheter closure in 40 infants. Infants in the surgical group were more immature at birth (24 + 3 weeks [IQR 23 + 5-25 + 3] vs. 25 + 3 weeks [IQR 24 + 3-27 + 0], p 0.001), had lower birthweight (635 g vs. 733 g, p 0.009), and had lower weight at the time of surgery compared to catheterization (915 g vs. 1200 g, p < 0.001). Complications were reported in 15% (10/68) after surgical closure and in 26% (10/39) after TCPC but did not differ in the DOOR analysis. CONCLUSION: In this nationwide study from Germany, transcatheter PDA closure was performed in approximately one-third of preterm infants, whereas surgical closure remained the predominant approach, particularly in smaller and more immature infants. The high incidence of adverse events following both methods-TCPC and surgical closure-warrants close ongoing surveillance. Substantial off-label use of paracetamol reflects evolving medical practice. WHAT IS KNOWN: • PDA in PIs remains a common clinical challenge, with a wide range of treatment strategies across NICUs. • New transcatheter PDA closure (TCPC) devices have recently been approved for use in preterm infants weighing > 700 g, expanding interventional options in this vulnerable population. WHAT IS NEW: • Surgical PDA closure seems to be still the preferred PDA treatment option in Germany especially in more immature infants. • Overall safety demonstrated no meaningful difference between TCPC and surgical PDA closure.
Trefoil factor 3 as a marker of gastrointestinal cell injury during sepsis.
Behairy OGA, El-Gaffar AOA, Ali BG … +2 more , Abdel-Gayed ES, Zakaria RM
Eur J Pediatr · 2026 May · PMID 42154329 · Full text
UNLABELLED: The purpose of this study is to evaluate trefoil factor 3 (TFF3) as a biomarker of gastrointestinal cellular injury in children with sepsis. This case-control study included 100 children admitted to the Pedia...
UNLABELLED: The purpose of this study is to evaluate trefoil factor 3 (TFF3) as a biomarker of gastrointestinal cellular injury in children with sepsis. This case-control study included 100 children admitted to the Pediatric Intensive Care Unit (PICU) with sepsis. They were divided into two groups according to gastrointestinal involvement, in addition to 30 age- and sex-matched healthy children who served as a control group. All participants underwent laboratory investigations, including complete blood count (CBC), liver, and kidney function tests. The Pediatric Logistic Organ Dysfunction (PELOD) score was applied to assess organ dysfunction severity, and TFF3 levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. TFF3 levels were markedly elevated in sepsis with gastrointestinal involvement compared to sepsis without gastrointestinal involvement and controls (P < 0.001). In these patients, levels were significantly higher in those with ileus, bleeding per rectum, and melena compared to those without. Non-survivors had higher TFF3 levels than survivors. Regarding blood culture results, patients with Klebsiella had the highest TFF3 levels compared to those with Staphylococcus aureus and those with no growth. In the multinomial logistic regression analysis using the control group as the reference category, TFF3 emerged as a significant predictor of sepsis outcomes. For patients with sepsis without gastrointestinal involvement, higher TFF3 levels were significantly associated with increased odds of sepsis (OR = 1.814, 95% CI 1.282-2.567, P = 0.001). Among patients with sepsis and gastrointestinal involvement, TFF3 demonstrated a more pronounced association (OR = 3.095, 95% CI 2.044-4.686, P < 0.001). CONCLUSION: TFF3 is a valuable tool in the PICU setting, providing an objective measure of intestinal damage and assisting clinicians in the anticipation, diagnosis, and management of gastrointestinal failure in vulnerable pediatric patients. WHAT IS KNOWN: • Trefoil factor 3 (TFF3) is a mucosal protective peptide involved in epithelial restitution and gut barrier integrity and has been investigated as a potential biomarker of intestinal injury. WHAT IS NEW: • This study demonstrates that serum TFF3 levels are significantly elevated in pediatric sepsis, particularly in children with gastrointestinal involvement, ileus, rectal bleeding, or melena. • Elevated TFF3 levels were associated with poor outcomes and independently predicted sepsis severity and gastrointestinal dysfunction in critically ill children.
A comparative analysis of corticosteroids and exclusive enteral nutrition induction therapy in children with small bowel Crohn's disease: results of two prospective cohorts.
Klomberg RCW, Griffiths AM, Aloi M … +15 more , Kiparissi F, Lawrence S, Otley AR, Critch J, van der Feen C, Rodrigues A, Mack DR, Huynh HQ, Church PC, Rizopoulos D, Croft NM, de Ridder L, Walters TD, European Paediatric IBD Network for Safety, Efficicacy of Treatment and Quality Improvement of Care (PIBD-SETQuality), Canadian Children IBD Network (CIDsCaNN)
Eur J Pediatr · 2026 May · PMID 42154069 · Publisher ↗
UNLABELLED: Corticosteroids (CS) and exclusive enteral nutrition (EEN) are effective induction therapies for pediatric Crohn's disease (CD), but comparative studies evaluating long-term outcomes in small bowel CD are lac...
UNLABELLED: Corticosteroids (CS) and exclusive enteral nutrition (EEN) are effective induction therapies for pediatric Crohn's disease (CD), but comparative studies evaluating long-term outcomes in small bowel CD are lacking. Children (2-18 years) with newly diagnosed small bowel CD involving the ileum prospectively enrolled in the multicenter Canadian CIDsCaNN or European PIBD-SETQuality inception cohorts receiving CS or EEN induction treatment were evaluated longitudinally. The primary outcome was sustained steroid-free remission (SSFR) at 1 year. Secondary outcomes included changes in height z-scores, time-to-first-biologic and time-to-luminal-resection. Results were confirmed after propensity score matching (PSM). In total, 208 children (61% CIDsCaNN, 39% PIBD-SETQuality) treated with CS (n = 60) or EEN (n = 148) were eligible for analysis. Baseline clinical characteristics were comparable. Immunomodulator monotherapy and anti-TNF-based regimens were implemented as maintenance therapy in 64% and 22%, respectively, following EEN induction and in 75% and 15% following CS induction (p = 0.51). At 1 year, SSFR was achieved in 48% [23/48] in CS vs. 37% [46/124] in EEN (p = 0.19). Delta height z-scores at 1 year were comparable (- 0.05 [IQR - 0.23 to 0.21] with CS vs. + 0.01 [IQR - 0.18 to 0.25] with EEN, p = 0.26). Time to first biologic (39% [CS] vs. 50% [EEN] at 1 year) and time to luminal resection (6% [CS] vs. 11% [EEN] at 1 year) were similar. In the PSM cohort of 114 children (75 EEN, 39 CS), the RR (95% CI) for SSFR with CS (1.46 [0.86-2.49]) was comparable to that of the unmatched cohort (1.29 [0.89-1.88]). CONCLUSIONS: CS and EEN induction therapy demonstrate comparable effectiveness in pediatric small bowel CD, supporting the importance of shared decision-making. TRIAL REGISTRATION: The PIBD-SETQuality inception cohort was registered under trial registration number NCT03571373 (clinicaltrials.gov). The CIDsCaNN Network was registered under trial registration number NCT02308917 (clinicaltrials.gov). WHAT IS KNOWN: • Studies suggested better efficacy of exclusive enteral nutrition (EEN) in small bowel CD than colonic CD, and it is thought to favor growth, making it the preferred treatment option by physicians for small bowel CD. WHAT IS NEW: • This research demonstrated that both therapies are equally effective in achieving long-term outcomes, including sustained remission, growth, time to surgery or biologics, when followed by maintenance therapy.
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