European Journal Of Pediatrics[JOURNAL]
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200 papers
Systemic versus intracranial immunotherapy delivery in pediatric malignant brain tumors: a systematic review, meta-analysis, and meta-regression.
Tykocki T
Eur J Pediatr · 2026 Jun · PMID 42283902 · Publisher ↗
UNLABELLED: Immunotherapy has emerged as a promising strategy for pediatric high-grade gliomas and diffuse midline gliomas, yet the clinical impact of delivery route remains uncertain. This study evaluated whether intrac...
UNLABELLED: Immunotherapy has emerged as a promising strategy for pediatric high-grade gliomas and diffuse midline gliomas, yet the clinical impact of delivery route remains uncertain. This study evaluated whether intracranial or systemic administration influences survival and toxicity outcomes. A systematic review and meta-analysis were conducted according to PRISMA guidelines. Clinical studies reporting survival or toxicity outcomes of immunotherapy in pediatric brain tumors were identified. Random-effects models were used to pool hazard ratios (HRs) for overall survival (OS) and 12-month survival (OS12), and odds ratios (ORs) for grade ≥ 3 neurotoxicity. Meta-regression assessed the influence of delivery route. Twenty-two studies were included in the quantitative synthesis. Intracranial delivery showed a pooled HR for OS of 1.12 (95% CI 0.88-1.42) with moderate heterogeneity (I = 27.3%), whereas systemic delivery showed HR 1.21 (95% CI 0.99-1.47) with minimal heterogeneity (I = 1.1%). No significant difference between delivery routes was observed (ratio of HRs 0.93, 95% CI 0.67-1.29). For grade ≥ 3 neurotoxicity, intracranial administration demonstrated markedly higher risk (OR 73.80, 95% CI 41.50-131.20) compared with systemic therapy (OR 6.20, 95% CI 1.80-20.90). Meta-regression confirmed that delivery route was not associated with OS or OS12 but was significantly associated with increased neurotoxicity (β = 3.064, p < 0.001). CONCLUSIONS: Immunotherapy delivery route does not appear to influence survival outcomes. Although intracranial administration was associated with higher reported rates of severe neurotoxicity, this finding should be interpreted cautiously given the heterogeneity of immunotherapy platforms and the potential confounding effect of treatment modality. Future studies should prioritize biologically guided therapeutic strategies while carefully balancing locoregional exposure and safety. WHAT IS KNOWN: • Locoregional (intracranial) immunotherapy has been proposed to improve CNS drug delivery in pediatric high-grade and diffuse midline gliomas, but its benefit over systemic administration is unproven. • Early-phase trials show biological activity with heterogeneous survival and toxicity, leaving the clinical impact of delivery route uncertain. WHAT IS NEW: • Across 22 studies, immunotherapy delivery route was not associated with overall or 12-month survival (rHR 0.93 and 0.87, both non-significant). • Intracranial delivery carried markedly higher severe neurotoxicity, but meta-regression showed this was largely driven by treatment platform (CAR-T/oncolytic) rather than route itself.
International variation in child healthcare practices and implications for childhood cancer diagnosis: a scoping review and cross-country clinician survey.
Lopez-Cortes A, Al-Mahdy A, Jakab Z … +12 more , Shimato M, Botta L, Didonè F, Cañete Nieto A, Desandes E, Hjalgrim LL, Polanco A, Stiller CA, Zeller B, Gatta G, Pritchard-Jones K, BENCHISTA Project Working Group
Eur J Pediatr · 2026 Jun · PMID 42283867 · Full text
UNLABELLED: Childhood cancer survival and stage at diagnosis vary internationally. Here, we explore differences in child health surveillance and healthcare practices across countries participating in the International Be...
UNLABELLED: Childhood cancer survival and stage at diagnosis vary internationally. Here, we explore differences in child health surveillance and healthcare practices across countries participating in the International Benchmarking of Childhood Cancer Survival by Stage (BENCHISTA) collaboration-with a focus on timely cancer diagnosis. We conducted a scoping review of five databases (MEDLINE, Embase, SCOPUS, Web of Science, and ProQuest Central) for articles published in English or Spanish between 1 Jan 2012 and 15 Oct 2025, describing child health surveillance and acute care pathways, limited to the 29 countries involved in the BENCHISTA collaboration. Two reviewers independently screened abstracts; a third resolved conflicts. In parallel, a semi-structured questionnaire was distributed (to one general practitioner, one paediatrician) in 27 countries who contributed to the BENCHISTA database. We collected standardised information on national child health practices and validated against published national guidance. Of 2,963 articles screened, 33 were included. Three key themes emerged: (1) healthcare-seeking behaviour of families and their interaction with frontline professionals, (2) awareness of alarm symptoms by caregivers and clinicians, and (3) system-level and training-related factors affecting timely diagnosis. Studies highlighted challenges such as low symptom recognition, variation in paediatric training, and limited referral guidance. Questionnaire responses showed variation in the number of routine child health checks with physical examination for children < 5 years (median 10; range 2-21), paediatric training, and access to diagnostic tools. CONCLUSION: There is substantial international variation in routine child health surveillance and acute illness assessment. These findings will inform interpretation of BENCHISTA data and may guide future strategies to support early cancer diagnosis. WHAT IS KNOWN: • Childhood cancer survival and stage at diagnosis vary internationally. • Early recognition of alarm symptoms is critical but often delayed due to system-level gaps. WHAT IS NEW: • This study combines a scoping literature review and clinician survey across 27 countries, identifying shared barriers to timely diagnosis. • It reveals variation in paediatric training of front-line healthcare practitioners, referral pathways, and child health surveillance practices, even among high-income countries.
Ambulatory hypertension and left ventricular hypertrophy in pediatric chronic kidney disease: a systematic review and meta-analysis.
Chung J, Yu A, Robinson C … +11 more , Dionne JM, Ewusie J, Lawson DO, Mitsnefes M, Noone DG, Parekh RS, Sinha M, South AM, Thabane L, Chung Z, Chanchlani R
Eur J Pediatr · 2026 Jun · PMID 42283864 · Publisher ↗
UNLABELLED: Cardiovascular disease is the leading cause of mortality in pediatric patients with chronic kidney disease (CKD). In the general pediatric population, hypertension is associated with an increased risk of left...
UNLABELLED: Cardiovascular disease is the leading cause of mortality in pediatric patients with chronic kidney disease (CKD). In the general pediatric population, hypertension is associated with an increased risk of left ventricular hypertrophy (LVH); however, the strength of this association varies in the pediatric CKD literature. A lack of consensus on optimal blood pressure (BP) targets for this population contributes to variability in clinical practice. This study aims to determine the association between ambulatory hypertension and LVH in pediatric CKD. A systematic literature search was conducted on five databases from 1974 to 2025. The mean left ventricular mass index (LVMI) and odds of LVH was compared between normotensive and hypertensive groups. The association between LVMI and 24-h systolic/diastolic blood pressure, day/night systolic/diastolic blood pressure, and 24-h mean arterial pressure (MAP), was determined. Fifty-one full text studies (n = 6509 children) were eligible for inclusion in the meta-analysis. Pediatric CKD patients with ambulatory hypertension demonstrated increased LVMI (mean difference 5.15 g/m (95% CI 3.16, 7.15) and increased risk of LVH odds ratio 2.82 (95% CI 2.18, 3.65) to normotensive controls. LVMI was significantly lower among children with a 24-h MAP < 50th percentile (- 8.2 g/m, 95% CI - 16.0, - 0.4) and 24-h SBP between the 50 and 90th percentiles (- 10.8 g/m, 95% CI - 20.8, - 0.8) compared to those with 24-h MAP or 24 h SBP > 90th percentile, respectively. CONCLUSION: In children with CKD, ambulatory hypertension is associated with elevated risk of LVH and increased LVMI. However, there was significant heterogeneity among the included studies with respect to study design and definition of outcomes. Timely detection of hypertensive target organ injury is imperative to mitigate future cardiovascular disease in pediatric CKD patients.Prospero Registration: CRD 42023426891. WHAT IS KNOWN: • Hypertension is a critical predictor of adverse cardiovascular outcomes in children with CKD. Hypertension-induced target organ damage such as LVH may predict future cardiovascular outcomes in high-risk populations. Despite this, there remains considerable variability in clinical blood pressure targets and monitoring practices. Our findings highlight the importance of ambulatory blood pressure monitoring (ABPM) in detecting subclinical cardiovascular injury, supporting its integration into routine CKD care to improve risk stratification and treatment decisions. WHAT IS NEW: • This meta-analysis establishes a robust association between ambulatory hypertension and left ventricular hypertrophy (LVH) in children with CKD, demonstrating that higher blood pressure burden is linked to increased left ventricular mass index (LVMI). Notably, children with 24-h mean arterial pressure (MAP) and systolic blood pressure (SBP) above the 90th percentile exhibited significantly greater LVMI, reinforcing the impact of sustained hypertension on cardiac remodelling in pediatric CKD. • The strong association between ambulatory hypertension and LVH underscores the urgent need for evidence-based BP thresholds that minimize cardiovascular risk in pediatric CKD. Early identification of hypertensive target organ damage may enable timely therapeutic interventions to prevent long-term cardiovascular complications. Future studies should focus on defining optimal BP targets and evaluating the efficacy of antihypertensive strategies tailored to pediatric CKD. Standardizing BP measurement approaches may further refine hypertension management and improve cardiovascular outcomes in this vulnerable population.
Lung ultrasound findings in neonatal viral pneumonia: case series and literature review.
Res G, Alonso-Ojembarrena A, García-Acevedo M … +4 more , Sartorius V, Davis A, Bhombal S, De Luca D
Eur J Pediatr · 2026 Jun · PMID 42283854 · Publisher ↗
UNLABELLED: Viral pneumonia (VP) is uncommon and may be underdiagnosed in neonates due to unspecific clinical course and radiological appearance. Lung ultrasound (LUS) is a well-known technique to diagnose and manage bro...
UNLABELLED: Viral pneumonia (VP) is uncommon and may be underdiagnosed in neonates due to unspecific clinical course and radiological appearance. Lung ultrasound (LUS) is a well-known technique to diagnose and manage bronchiolitis due to respiratory syncytial virus (RSV) but its role in neonates with VP caused by other viruses remains unclear due to the rarity of this condition. We report five cases of microbiologically confirmed, neonatal VP caused by viruses other than RSV along with their LUS findings. Abnormal but not specific ultrasound findings were present in all patients, and they widely varied in parallel with the clinical course. LUS findings spanned the whole spectrum of LUS semiology and reflected severity but did not identify or suggest the aetiology. These cases illustrate the LUS findings of uncommon cases of neonatal VP and highlight the need to incorporate clinical and laboratory data with lung imaging to refine the diagnosis. CONCLUSION: Neonates with VP have a wide range of LUS appearances. LUS findings are not pathognomonic but can be usefully integrated with clinical and laboratory data. WHAT IS KNOWN: • Lung ultrasound is helpful to diagnose pneumonia in the paediatric population. However, its findings in neonates with viral pneumonia have not been formally described yet and its role to differentiate the aetiology remains unclear. WHAT IS NEW: • We report five cases of neonatal viral pneumonia describing their lung ultrasound findings. They present the whole spectrum of lung ultrasound semiology and are unspecific for the viral aetiology or the patient age. Lung ultrasound findings are consistent with the clinical severity (i.e. worse ultrasound findings were observed in patients with worse clinical course).
Long-term comorbidity associated with childhood periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a case-control study.
Uosukainen H, Kettunen S, Ruuska-Loewald T … +4 more , Palmu S, Linnola S, Renko M, Lantto U
Eur J Pediatr · 2026 Jun · PMID 42283846 · Full text
UNLABELLED: The aim of this study was to evaluate the long-term morbidity of patients with PFAPA compared with controls selected from the general population. We identified 244 patients treated for PFAPA at Tampere, Oulu,...
UNLABELLED: The aim of this study was to evaluate the long-term morbidity of patients with PFAPA compared with controls selected from the general population. We identified 244 patients treated for PFAPA at Tampere, Oulu, and Kuopio University hospitals between 2008 and 2018. In May 2023, and January 2024, these patients were invited to complete a detailed questionnaire regarding their past and current health and lifestyle. A total of 2433 controls, matched for age, sex, and birthplace, were randomly selected from the Population Register Center of Finland and completed the same survey. We compared the occurrence of acute and chronic illnesses and childhood environmental exposures between PFAPA patients and controls 5-16 years after the initial PFAPA diagnosis. Responses were obtained from 98 PFAPA patients (40.1%) and 490 controls (20.1%). Atopy was the only chronic condition significantly more common among PFAPA patients than controls (14.3% vs 7.9%; OR 2.0, 95% CI 1.0-3.9). PFAPA patients more frequently reported recurrent otitis media (36.2% vs 20.9%; OR 2.3, 95% CI 1.4-3.8), tympanostomy (24.5% vs 15%; OR 1.9, 95% CI 1.1-3.2), bronchitis (4.2% vs 1.2%; OR 4.0, 95% CI 1.1-14.9) and hospitalization due to infections (30.2% vs 17.9%; OR 1.9, 95% CI 1.2-3.2). Fungal infections were also more common among PFAPA patients (8.5% vs 3.7%; OR 2.4, 95% CI 1.0-5.9). No differences were found in other chronic conditions or environmental exposures. CONCLUSION: Children with PFAPA did not exhibit greater long-term morbidity than controls, except for a higher prevalence of atopy. Respiratory infections, recurrent otitis media, and fungal infections were more frequent among cases than controls. These findings may reflect greater healthcare use rather than true susceptibility to infections. Environmental risk factors were similar between the groups. WHAT IS KNOWN: • Current evidence does not suggest an association between PFAPA and other chronic conditions. • Prior evidence on infection susceptibility in PFAPA has been inconsistent. WHAT IS NEW: • Children with a history of PFAPA show no increased long-term morbidity except for atopy. • PFAPA patients have more childhood AOM, bronchitis, and fungal infections than controls from the general population. Increased rates of diagnosed infections and hospitalizations in PFAPA patients may be influenced by healthcare‑seeking behavior and diagnostic practices, rather than reflecting true infection susceptibility.
Nationwide variability in sedation, analgesia, and developmental care practices during neonatal therapeutic hypothermia: A French national survey.
Osswald C, Le Duc K, Chaton L … +4 more , Joriot S, Storme L, Flamein F, Boukhris MR
Eur J Pediatr · 2026 Jun · PMID 42277340 · Full text
UNLABELLED: Analgesia, sedation and developmental care are key components of supportive management for newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). However, evidence-based...
UNLABELLED: Analgesia, sedation and developmental care are key components of supportive management for newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). However, evidence-based recommendations remain limited, and practices may vary substantially between centers. We aimed to describe current practices in analgesia, sedation, and developmental care during TH across French neonatal intensive care units (NICUs). We conducted a nationwide cross-sectional survey using a standardized electronic questionnaire distributed to all NICUs performing TH in France. Each center provided a single consolidated response. Descriptive statistics were used. Fifty-one of 63 eligible NICUs responded (80%), including 33 university and 18 general hospitals. Formal developmental care programs were available in 88% of centers. Routine endotracheal intubation during TH was reported by 71%. The most frequently used medications were midazolam (94%), sufentanil (88%), morphine (84%), and paracetamol (82%). Analgesia-sedation regimens and dosing strategies varied markedly across centers. Most NICUs (75%) expressed interest in developing protocols allowing TH without routine intubation. CONCLUSIONS: Substantial inter-center variability exists in analgesia, sedation, and developmental care practices during neonatal TH. These findings support the need for standardized, evidence-based protocols to optimize neonatal comfort and reduce practice heterogeneity. WHAT IS KNOWN: • Therapeutic hypothermia is the standard neuroprotective treatment for moderate-to-severe neonatal hypoxic-ischemic encephalopathy. • Analgesia, sedation, and supportive care during therapeutic hypothermia are widely used, but evidence-based recommendations remain limited. WHAT IS NEW: • This first nationwide French survey demonstrates marked inter-center variability in analgesia, sedation, developmental care, and routine intubation practices during neonatal therapeutic hypothermia. • These findings highlight the need for standardized, pharmacologically informed protocols during therapeutic hypothermia, prioritizing medications with more predictable metabolism and clearer pharmacokinetic-based dosing strategies.
Incidence and associated factors of metachronous contralateral cryptorchidism after unilateral cryptorchidism: a retrospective cohort study.
Grande-Moreillo C, Pérez-López C, Vicente-Sánchez N … +1 more , Fuentes-Carretero S
Eur J Pediatr · 2026 Jun · PMID 42274851 · Publisher ↗
UNLABELLED: Acquired cryptorchidism is an increasingly recognized condition and may present bilaterally with a metachronous pattern. The objective of this study was to evaluate the incidence of acquired contralateral met...
UNLABELLED: Acquired cryptorchidism is an increasingly recognized condition and may present bilaterally with a metachronous pattern. The objective of this study was to evaluate the incidence of acquired contralateral metachronous cryptorchidism and to identify associated factors in patients undergoing surgery for unilateral cryptorchidism. This retrospective cohort descriptive study included patients who underwent surgery for unilateral cryptorchidism in the Paediatric Surgery departments of Consorci Sanitari Alt Penedès-Garraf and Hospital Universitari Mútua Terrassa between 2005 and 2024. Demographic data, characteristics of cryptorchidism, and intraoperative findings from the initial surgery were recorded. A history of prematurity and obesity were also collected. A total of 275 patients were included. Contralateral acquired cryptorchidism developed in 11 of 111 patients with congenital cryptorchidism (9.9%; 95% CI 5.1%-17%) and in 29 of 164 patients with acquired cryptorchidism (17.7%; 95% CI 12.2%-24.4%). Multivariate analysis identified the following associated factors for metachronous contralateral cryptorchidism: acquired cryptorchidism at initial presentation (aOR = 4.00, 95% CI 1.60-9.99; p = 0.003), persistence of the processus vaginalis on the initially operated side (aOR = 5.94, 95% CI 2.44-14.48; p < 0.001) and prematurity (aOR = 6.38, 95% CI 1.75-23.25; p = 0.005). CONCLUSION: The overall incidence of metachronous cryptorchidism in patients with unilateral disease was 15%. A higher incidence was observed among patients with acquired cryptorchidism than among those with congenital cryptorchidism, although this difference did not reach statistical significance. These findings suggest that periodic follow-up until adolescence may be warranted in patients with unilateral cryptorchidism, particularly in those with acquired forms. Patients with congenital cryptorchidism require periodic follow-up until adolescence, while those with acquired unilateral cryptorchidism should be carefully monitored before surgery to detect bilateral involvement and allow simultaneous treatment. WHAT IS KNOWN: • Cryptorchidism affects 1-4% of full-term newborns, with long-term consequences for fertility and testicular cancer risk. Acquired cryptorchidism, the ascent of a previously descended testis, accounts for more than half of all cases. • The risk factors for metachronous contralateral cryptorchidism after unilateral disease remain poorly characterized, and no consensus exists on the appropriate follow-up strategy for these patients. WHAT IS NEW: • Metachronous contralateral cryptorchidism occurred in 15% of patients. The incidence was higher in patients with acquired cryptorchidism than in those with congenital cryptorchidism althouh the difference was not statistically significant. Persistence of the processus vaginalis at the time of surgery on the first side, and prematurity were other associated factors. • Prospective studies are needed to validate these associated factors and to determine whether active observation before surgery enables earlier detection of bilateral disease and synchronous orchidopexy.
Prevalence of underlying organic causes in infants presenting with excessive crying: a 2-year follow-up study.
de Graaf K, Vlieger AM, Corvers SAVM … +3 more , Groenendijk R, Benninga MA, de Kruijff I
Eur J Pediatr · 2026 Jun · PMID 42274798 · Publisher ↗
UNLABELLED: The objective of this study is to assess the proportion of infants referred for excessive crying (EC) who were diagnosed with an underlying condition likely related to EC within 2 years of follow-up. A retros...
UNLABELLED: The objective of this study is to assess the proportion of infants referred for excessive crying (EC) who were diagnosed with an underlying condition likely related to EC within 2 years of follow-up. A retrospective study reviewing the records of infants younger than 5 months with EC as the primary reason for referral. Infants with fever at presentation, acute illness, gestational age < 32 weeks, birth weight < 1500 g, perinatal asphyxia, or previously diagnosed congenital disorders were excluded. Of 1123 screened infants, 530 presenting with EC were included (53% male; mean age, 2 months). Underlying organic conditions were identified in 52 infants (9.8%). Of these, 39 (7.4%) had cow's milk allergy (CMA) confirmed by food challenge and 15 (2.8%) had other organic conditions, including developmental delay or genetic disorders (n = 9) and urinary tract infection (n = 2); two infants were diagnosed with both CMA and another condition. Clinical signs prompting early diagnosis included painful hip examination, feeding difficulties with choking, paroxysmal pain with rectal bleeding, progressive vomiting, and fever during follow-up. Later diagnoses emerged in the context of developmental delay or persistent EC, sleep or feeding problems. Initial physical examinations were normal in all infants. CONCLUSION: In infants referred for EC, approximately 1 in 10 are diagnosed with an underlying organic condition, most commonly CMA. Although EC is often benign, persistent symptoms or emerging developmental concerns warrant careful evaluation and structured follow-up rather than reassurance alone. Future prospective studies should identify early clinical predictors distinguishing benign EC from pathology and improve timely recognition. WHAT IS KNOWN: • Excessive crying in early infancy is a common parental concern, usually without an underlying organic condition. • Its nonspecific presentation complicates distinguishing normal behavior from rare organic conditions, challenging clinicians and often prolonging parental distress. WHAT IS NEW: • This 2-year follow-up of 530 infants referred for excessive crying confirms that underlying organic conditions are uncommon. • Cow's milk allergy accounted for the majority of identified organic diagnoses, whereas other organic conditions were rare and typically identified later, underscoring the need for structured follow-up in infants with persistent crying, regulatory problems, or developmental concerns.
Topical application of emollients to maintain skin integrity in preterm neonates: a systematic review and meta-analysis.
Basu S, Singh P, Priyadarshi M … +2 more , Chaurasia S, Basu S
Eur J Pediatr · 2026 Jun · PMID 42268439 · Publisher ↗
UNLABELLED: This systematic review and meta-analysis compared the efficacy and safety of topical emollient application in preterm neonates for maintaining skin integrity. The available evidence related to the effects of...
UNLABELLED: This systematic review and meta-analysis compared the efficacy and safety of topical emollient application in preterm neonates for maintaining skin integrity. The available evidence related to the effects of topical emollients vs. routine skin care was identified, appraised, and synthesized. The outcome measures were assessment of skin integrity, objectively defined by a skin condition score (SCS), incidence of culture-positive neonatal sepsis, mortality, trans-epidermal water loss, skin colonization, and adverse events. Data were pooled using RevMan Web. Certainty of evidence (CoE) was analyzed by GRADE. Nineteen trials comprising 5586 neonates were included for meta-analysis. A significant decrease in SCS was observed, favoring topical emollients [SMD (95% CI), - 1.11 (- 1.57, - 0.65), I = 85%, 6 studies, n = 2807, high RoB, low CoE]. Although there was no overall difference in the incidence of culture-positive neonatal sepsis with topical emollients [RR (95% CI), 0.82 (0.61, 1.09), I = 56%, 15 studies, n = 5297, high RoB, low CoE], a sensitivity analysis including studies comparing topical oil vs. routine care showed significant benefits favoring topical oil [RR (95% CI) 0.66 (0.47, 0.92), I = 30%, 8 studies, n = 3392], whereas pooled data from studies including topical ointment/cream vs. routine care did not show any benefit [RR (95% CI) 1.03 (0.72, 1.48), I = 26%, 8 studies, n = 2046]. There was no difference in mortality, and no major adverse events were reported. Data for other outcomes could not be pooled. CONCLUSION: Low-CoE evidence suggested better skin integrity with topical emollients, and a lower incidence of culture-positive neonatal sepsis with topical oil application. High heterogeneity limits the generalizability of results. WHAT IS KNOWN: • Compared to routine skin care, application of topical oils may reduce the incidence of sepsis in preterm infants. • There is no difference in mortality with the use of topical emollients. WHAT IS NEW: • Low-certainty evidence documented an improvement in skin integrity with the use of topical emollients and a reduction in the incidence of culture-positive neonatal sepsis with topical oil application. • No major adverse effects of topical emollients were observed.
Correction to: 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 Jun · PMID 42268417 · Publisher ↗
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School-age neurodevelopmental outcomes after non-emergency red blood cell transfusions in preterm infants: a propensity score-matched study from the Epipage 2 cohort.
Coignard M, Marchand-Martin L, Kermorvant-Duchemin E … +5 more , Cambonie G, Tosello B, Ancel PY, Torchin H, Guellec I
Eur J Pediatr · 2026 Jun · PMID 42262600 · Publisher ↗
UNLABELLED: The objective of this study is to evaluate whether non-emergency red blood cell transfusions (RBCT) is associated with neurologic outcomes in preterm infants born at 27-31 weeks of gestation. This analysis us...
UNLABELLED: The objective of this study is to evaluate whether non-emergency red blood cell transfusions (RBCT) is associated with neurologic outcomes in preterm infants born at 27-31 weeks of gestation. This analysis used data from the Etude Epidémiologique sur les Petits Ages Gestationnels (EPIPAGE-2), a French nationwide prospective cohort. Infants born at 27-31 weeks and surviving to 5½ years were included, excluding those with emergency RBCT indications. Neurologic outcomes, defined as moderate or severe disabilities, a composite of motor, neurosensory, and cognitive disabilities, were assessed at 5½ years with standardized scales. Behavioral difficulties were evaluated using parental questionnaires. Transfused and non-transfused infants were matched 1:1 using propensity scores. Statistical analyses included odds ratios (ORs) and mean differences. Of the 2182 infants included (656 transfused, 1526 non-transfused), 1062 were matched (531 per group). In the unmatched cohort, RBCT exposure was significantly associated with the composite outcome of moderate to severe neurological disabilities (OR, 1.40; 95%CI, 1.04-1.87). Cognitive impairment and developmental coordination disorders were significantly increased with RBCT (OR, 1.40; 95%CI, 1.07-1.81 and OR, 1.44; 95%CI, 1.06-1.96), respectively. After adjustment using the propensity score, RBCTs were not significantly associated with any individual outcome: cerebral palsy, overall cognitive deficiency, coordination disorders, behavioral difficulties, or moderate-to-severe neurological disabilities. Only the association with cognitive performance relating to working memory persisted (mean difference, - 2.3; 95%CI, - 4.2 to - 0.5). CONCLUSION: After controlling for potential confounders, non-emergency RBCTs in preterm infants born at 27-31 weeks were not significantly associated with long-term neurologic outcomes but reduced working memory warrants further investigation. TRIAL REGISTRATION: NCT03078439. WHAT IS KNOWN: • Red blood cell transfusions (RBCTs) are frequently administered to preterm infants and have been associated with adverse neonatal outcomes in observational studies. • The long-term neurodevelopmental consequences of RBCT exposure remain uncertain because transfused infants are generally sicker and more immature, making confounding difficult to address. WHAT IS NEW: • In a large nationwide cohort of preterm infants born at 27-31 weeks' gestation, non-emergency RBCT exposure was associated with poorer neurodevelopmental outcomes in unadjusted analyses but not after propensity score matching.A modest reduction in working memory performance persisted after adjustment, suggesting a potential domain-specific effect that warrants further investigation.
Automated pupillometry for the prediction of neurologic outcomes in children requiring extracorporeal membrane oxygenation (ECMO).
McGetrick M, Diaz N, Li X … +6 more , Terrill T, Powers K, Said R, Sirsi D, Raman L, Miles D
Eur J Pediatr · 2026 Jun · PMID 42262594 · Full text
UNLABELLED: Neurologic injury is a significant cause of morbidity and mortality in pediatric extracorporeal membrane oxygenation (ECMO). Noninvasive neurologic monitoring is important for early detection and management o...
UNLABELLED: Neurologic injury is a significant cause of morbidity and mortality in pediatric extracorporeal membrane oxygenation (ECMO). Noninvasive neurologic monitoring is important for early detection and management of neurologic injury. Automated infrared pupillometry (AP) provides accurate and repeatable bedside quantitative measurements of pupil reactivity via the Neurological Pupil Index (NPi®). We evaluated if any abnormal NPi (defined as an NPi < 3) during the first 72 h of ECMO support could identify patients at risk for death or disability at discharge. An observational cohort of pediatric patients who required ECMO support was analyzed. NPis were measured during the first 72 h after ECMO cannulation using the NPi®-200 automated pupillometer, and the lowest value (NPi-min) was identified. The primary outcome was death prior to hospital discharge. The secondary outcome was discharge Functional Status Scale (FSS) score > 10, indicating at least moderate disability. A total of 75 patients were included in the study, of whom 26 (35%) died and 49 (65%) survived. Seventeen patients had an NPi-min < 3 during the first 72 h of their ECMO course. Patients who died had significantly lower median NPi-min values compared with patients who survived (2.6 vs. 4.3, p = 0.0008). An NPi-min < 3 was associated with increased mortality; in adjusted analysis, higher NPi-min was associated with lower odds of death (OR 0.57 per 0.5-unit increase, 95% CI 0.40-0.81, p = 0.0015); independent of age category (neonate versus non-neonate); ECMO type (venoarterial (VA), versus venovenous (VV)); electroencephalogram (EEG) severity; and pre-ECMO Pediatric Sequential Organ Failure Assessment (pSOFA) score. This model had a good discriminatory capacity for death with an area under the receiver operating curve (AUROC) of 0.82. In contrast, NPi-min was not significantly associated with at least moderate disability (FSS > 10) in adjusted analysis (OR 0.83 per 0.5-unit increase, 95% CI 0.60-1.15, p = 0.26; AUROC 0.70). CONCLUSION: In children undergoing ECMO support, any NPi measurement of less than 3 during the first 72 h of ECMO initiation is associated with hospital mortality, but associations with at least moderate discharge disability are less clear. Automated pupillometry can be a useful tool for the early prognostication of pediatric patients requiring ECMO. WHAT IS KNOWN: • Children supported on extracorporeal membrane oxygenation are at a disproprotionally higher risk for death and neurological morbidity compared with the broader critically ill pediatric population. • Automated pupillometry provides objective bedside assessment of pupillary reactivity, but its prognostic value in pediatric ECMO remains poorly defined. WHAT IS NEW: • In this single-center study of pediatric patients supported on extracorporeal membrane oxygenation, a minimum Neurological Pupil Index less than 3 within the first 72 hours of ECMO support was independently associated with in hospital mortality, but its association with discharge functional disability was less consistent.
Novelties in the pragmatic management of anaphylaxis in pediatric age.
Marseglia GL, Tosca MA, Miraglia Del Giudice M … +3 more , Manti S, Ciprandi G, Licari A
Eur J Pediatr · 2026 Jun · PMID 42262574 · Full text
UNLABELLED: Anaphylaxis is a time-critical, potentially fatal systemic hypersensitivity reaction. This narrative review summarizes recent advances in the diagnosis and management of anaphylaxis in children and adolescent...
UNLABELLED: Anaphylaxis is a time-critical, potentially fatal systemic hypersensitivity reaction. This narrative review summarizes recent advances in the diagnosis and management of anaphylaxis in children and adolescents, with emphasis on new diagnostic frameworks, improved self-management strategies, intranasal adrenaline, and disease-modifying therapies. A narrative review was conducted using PubMed and MEDLINE, focusing on articles and guidelines published between January 2020 and March 2026. Search terms included "anaphylaxis", "pediatric anaphylaxis", "adrenaline", "epinephrine", "autoinjector", "intranasal adrenaline", "food anaphylaxis", "omalizumab", and "oral immunotherapy". International guidelines, consensus documents, systematic reviews, pharmacokinetic studies, and pediatric studies were prioritized. Food remains the leading trigger in children, but drug, Hymenoptera venom, cofactor-dependent, and non-IgE-mediated mechanisms must be systematically considered. Adrenaline is underused in community settings despite being the only life-saving drug. Intranasal adrenaline represents the most visible delivery innovation: it may reduce needle-related barriers and simplify administration, but current evidence is largely based on pharmacokinetic/pharmacodynamic studies and limited pediatric clinical data. Omalizumab and oral immunotherapy are reshaping long-term risk reduction in food allergy but do not remove the need for emergency adrenaline. CONCLUSION: The pragmatic management of anaphylaxis in children and adolescents entails self-management and hospital-based care. Intramuscular adrenaline is the first-line treatment when anaphylaxis is ongoing or recurrent, whereas adjunctive therapies should be considered on clinical grounds. Discharge recommendations should be individualized and include structured education, risk assessment, emergency planning and specialist follow-up. Intranasal adrenaline is a promising innovation, but its introduction requires clinical positioning, pharmacovigilance, cost-effectiveness evaluation, and continued emphasis on early treatment. WHAT IS KNOWN: • Intramuscular adrenaline is the first-line treatment for anaphylaxis and should not be delayed. • Food is the leading trigger in children, while drugs, venom, and cofactors become more relevant with age. WHAT IS NEW: • Intranasal adrenaline is a promising needle-free option, but pediatric evidence remains limited. • Omalizumab and oral immunotherapy may reduce risk but do not replace emergency preparedness.
Trends in unplanned non-surgical paediatric oncology admissions to paediatric intensive care units in England between 2008 and 2022.
Ward RA, Solomons MR, Chatterjee A … +6 more , Barton JC, Mallah M, Nowak AM, Allen-Tejerina AM, Corrigan AE, Round JEC
Eur J Pediatr · 2026 Jun · PMID 42260247 · Publisher ↗
UNLABELLED: Children with cancer requiring PICU admission have a relatively high mortality. This study reports trends in management and outcomes for a large cohort of unplanned PICU admissions for children with underlyin...
UNLABELLED: Children with cancer requiring PICU admission have a relatively high mortality. This study reports trends in management and outcomes for a large cohort of unplanned PICU admissions for children with underlying oncology diagnoses. A retrospective cohort study, analysing all unplanned oncology admissions for all English PICUs from 2008 to 2022, captured by PICANet, a quality-assured, prospectively collected national database. Unplanned oncology admissions to the PICU aged 1 month to 16 years were included. Patients with benign disease were excluded. A total of 4371 admissions from 3277 children underwent further analysis. Unplanned oncology admissions increased from 209 in 2008, peaking at 357 in 2020, representing 1.2 and 1.9%, respectively, of all PICU admissions in those years. Haematological malignancies had the largest rise. Presentations with infections also rose, making up over half of oncology admissions by 2022. The percentage invasively ventilated fell from 55.8 to 48.1%, but significant changes in the use of vasoactive agents, non-invasive ventilation and renal support were not seen. Mean PIM score (0.085 to 0.06) at admission fell, reflecting lower overall acuity. Mortality in unplanned oncology admissions fell from 16.7 to 12.2%. Survival, when banded for PIM risk group, showed no improvement except possibly in those with over 30% risk of death, where a downward trend in actual mortality was seen. CONCLUSIONS: Unplanned admissions of children with cancer to PICU remain at a relatively high risk of death. The cause of the improved overall percentage mortality is likely related to increased low-acuity admissions. WHAT IS KNOWN: • Significant improvements have been seen in mortality for unplanned oncology admissions to the PICU over the last few decades. • Studies have attempted to define these trends; however, heterogeneity between patient populations and outcome measures included makes it difficult to draw meaningful conclusions from them. WHAT IS NEW: • Overall mortality in all PICU admissions for children with oncological diagnoses in England decreased. • The improvement in PICU percentage mortality is likely due to a reduced admission threshold rather than specific improvements in clinical or oncological care for these patients.
Genomic testing in the neonatal intensive care unit: a 5-year retrospective single-centre study from a tertiary care hospital in Bengaluru, India.
Devaranavadagi RA, Nekkileru NK, Shetty M … +1 more , Nagesh K
Eur J Pediatr · 2026 Jun · PMID 42252336 · Publisher ↗
UNLABELLED: Genetic disorders contribute significantly to morbidity and mortality in neonatal intensive care units (NICUs), yet data from low- and middle-income settings remain limited. This study evaluated the diagnosti...
UNLABELLED: Genetic disorders contribute significantly to morbidity and mortality in neonatal intensive care units (NICUs), yet data from low- and middle-income settings remain limited. This study evaluated the diagnostic yield and clinical utility of genetic testing in a tertiary care NICU. This retrospective observational study included neonates and young infants who underwent genetic testing in a tertiary NICU in Bengaluru, India, over 67 months (January 2019-July 2024). Genetic variants were classified using American College of Medical Genetics and Genomics criteria. Diagnostic yield and its distribution across clinical phenotypes and inheritance patterns were analysed descriptively. Seventy infants underwent genetic evaluation, with an overall diagnostic yield of 24.3% (17/70). Variants of uncertain significance were identified in 35.7% of cases. Diagnostic yield varied by phenotype, with the highest yield in metabolic/endocrine presentations (50%) and the lowest in non-specific presentations (7.7%). Among confirmed diagnoses, autosomal recessive disorders predominated (47%), followed by autosomal dominant (29%) and X-linked (24%) inheritance. Genetic testing appeared to influence clinical management and family counselling in selected cases, including targeted therapy, treatment modification, and definitive interventions. One infant (1.4%) with an HRAS variant highlighted the evolving clinical relevance of variants of uncertain significance. CONCLUSION: Genetic testing may provide clinically meaningful diagnoses in a subset of NICU infants, particularly in well-defined clinical phenotypes. A phenotype-driven approach, along with cautious interpretation and follow-up, may help optimise the clinical utility of genomic testing in resource-limited settings. WHAT IS KNOWN: • Genetic disorders contribute substantially to morbidity and mortality in NICU infants. • Genomic testing can improve diagnostic yield, particularly in critically ill neonates with well-defined clinical phenotypes. WHAT IS NEW: • This study provides real-world data on genomic testing patterns, diagnostic yield, and clinical utility from a single Indian tertiary NICU. • A phenotype-driven approach showed the highest yield in metabolic/endocrine presentations and supported targeted management and family counselling.
Long-term effects of hematopoietic stem cell transplantation on endocrine function in childhood and adolescence: a single tertiary care center study.
Aziz S, AlGhamdi A, Heaphy E … +9 more , AlEysaye N, Elhadidi M, Shahzad MK, Ahmed A, Aboelghar H, Almahbosh A, Sobahi M, Bayoumy M, Ahmad N
Eur J Pediatr · 2026 Jun · PMID 42252329 · Publisher ↗
UNLABELLED: The purpose of this study is to evaluate long-term endocrine dysfunctions in pediatric hematopoietic stem cell transplantation (HSCT) survivors. This retrospective study analyzed 141 pediatric HSCT recipients...
UNLABELLED: The purpose of this study is to evaluate long-term endocrine dysfunctions in pediatric hematopoietic stem cell transplantation (HSCT) survivors. This retrospective study analyzed 141 pediatric HSCT recipients (75 males, 66 females). Endocrine outcomes, including gonadal dysfunction, hypothyroidism, growth hormone deficiency, and adrenal insufficiency, were assessed through clinical evaluations and laboratory tests. Statistical analyses examined associations between conditioning regimens and endocrine complications. Endocrine dysfunction was diagnosed in 46.1% of patients, with a higher prevalence in females (72.7% vs. 22.7% in males). The most striking finding was gonadal dysfunction, which occurred exclusively in girls, and occurred in 72% of female patients, all of whom received myeloablative conditioning. Hypothyroidism was seen in approximately 20% of patients, while growth hormone deficiency and adrenal insufficiency occurred in 3% and 9% of patients respectively. CONCLUSION: The study highlights the gender-specific vulnerabilities in endocrine outcomes following HSCT, emphasizes the critical importance of long-term endocrine surveillance and early interventions to mitigate the burden of these complications, and stresses the necessity of optimizing guidelines for endocrine care in this vulnerable population, ultimately enhancing quality of life and long-term outcomes for HSCT survivors. WHAT IS KNOWN: • Hematopoietic stem cell transplantation (HSCT) is an important curative therapy for several debilitating and life-threatening conditions, but this is associated with many endocrine dysfunctions. • There is currently a lack of standardized screening guidelines based on timing, age, and gender for detecting endocrine disorders in children who survived HSCT. WHAT IS NEW: • Endocrine dysfunction was diagnosed in 46.1% of patients, with a higher prevalence in females (72.7% vs. 22.7% in males); the gonadal dysfunction with no pubertal onset and absent secondary sexual characteristics occurred exclusively in girls. • Reduced intensity conditioning regimens can reduce the endocrine dysfunction, while standard screening protocols can improve early diagnosis and management.
Genetic testing and analysis of 1024 children with global developmental delay or intellectual disability: a single-center cohort study.
Wang B, Ji X, Wu F … +9 more , Shen M, Zheng P, Feng S, Wu H, Li S, Liu A, Xie L, Zhang X, Chen Q
Eur J Pediatr · 2026 Jun · PMID 42250153 · Full text
UNLABELLED: Global developmental delay (GDD) and intellectual disability (ID) are common neurodevelopmental disorders with a strong genetic basis. However, comprehensive large-cohort analyses integrating genotype-phenoty...
UNLABELLED: Global developmental delay (GDD) and intellectual disability (ID) are common neurodevelopmental disorders with a strong genetic basis. However, comprehensive large-cohort analyses integrating genotype-phenotype correlations and functional mechanisms remain limited. This study aimed to systematically characterize the clinical and genetic spectrum of GDD/ID in a large single-center cohort and to explore the functional attributes of disease-causing genes. We retrospectively analyzed 1024 children diagnosed with GDD or ID who underwent genetic testing, including trio whole-exome sequencing (trio-WES), proband-only WES, and clinical exome sequencing. Clinical phenotypes were categorized, and functional enrichment analyses were conducted for genes associated with diagnostic and probable diagnostic results. A genetic diagnosis was achieved in 48.1% of patients, with trio-WES demonstrating a significantly higher diagnostic yield than proband-only approaches. Pathogenic variants mainly comprised single-nucleotide variants and copy number variants. Identified genes were predominantly involved in protein homeostasis, synaptic and ion channel function, epigenetic regulation, and key developmental signaling pathways. Distinct genotype-phenotype associations were observed among clinical subgroups, including enrichment of synaptic-related genes in epilepsy-associated GDD/ID and epigenetic regulatory genes in patients with facial dysmorphism. CONCLUSION: This study provides a comprehensive characterization of the genetic landscape of GDD/ID in a large single-center cohort and identifies distinct genotype-phenotype correlations and convergent molecular pathways underlying these disorders. WHAT IS KNOWN: • Global developmental delay (GDD) and intellectual disability (ID) are highly heterogeneous neurodevelopmental disorders with a strong genetic basis. WHAT IS NEW: • We report a large single-center cohort of 1024 children with GDD/ID, providing a comprehensive overview of the genetic landscape and diagnostic yield of different sequencing strategies. • Our study systematically integrates genotype-phenotype correlations with functional pathway analyses, highlighting key molecular mechanisms underlying GDD/ID and supporting refined molecular stratification.
Correction to: Structural lung assessment in children with primary ciliary dyskinesia: evaluation with the SPEC scoring system.
Dinç GA, Ertuna EY, Tabakçı SÖ … +11 more , Bilgiç I, Çakar MK, Ünlü A, Yetişgin H, Yıldırım Ç, Tural DA, Polat SE, Tuğcu GD, Keçeli AM, Sığırcı A, Cinel G
Eur J Pediatr · 2026 Jun · PMID 42250126 · Publisher ↗
Abstract loading — click title to view on PubMed.
Sleep-related breathing disorders beyond infancy following open spina bifida repair.
Lee D, Del Cid-Linares D, Van Speybroeck A … +5 more , Smith KA, Chmait RH, Keens TG, Ward SLD, Perez IA
Eur J Pediatr · 2026 Jun · PMID 42250124 · Full text
In patients with repaired open spina bifida, there are limited data on respiratory outcomes beyond the first year of life. We hypothesize that after 1 year of age there is 1) resolution of sleep-related breathing disorde...
In patients with repaired open spina bifida, there are limited data on respiratory outcomes beyond the first year of life. We hypothesize that after 1 year of age there is 1) resolution of sleep-related breathing disorders (SRBD), 2) improvement of oxygenation and 3) no difference in SRBD between prenatally vs. postnatally repaired groups. We reviewed 67 patients with repaired open spina bifida and polysomnography (PSG) after age 1 year seen at Children's Hospital Los Angeles between 2015-2025. Demographics, neural tube defect location, surgery type, PSG results, and respiratory support data were collected. There were 34/67 subjects with PSG before and after 1 year of age. Before 1 year of age, 19/34 had central sleep apnea (CSA), 33/34 had obstructive sleep apnea (OSA) and 30/34 required supplemental oxygen. At age 12 to 35 months, the prevalence of OSA (p < .001) and supplemental oxygen requirement (p = .006) decreased, however CSA persisted. There were no differences in SRBD between those with prenatal repair and postnatal repair of open spina bifida. There were 33/67 subjects with PSG after age 1 year only. In children ages 3 to 17 years, up to 92% had OSA, 11% had CSA, and 44% required supplemental oxygen.Conclusion: In patients with repaired open spina bifida, OSA and supplemental oxygen requirement improved after 1 year of age, however, the majority still had SRBD without difference between those prenatally vs. postnatally repaired. Our findings highlight the importance of continued surveillance with PSG in this population. What is Known: • Infants with prenatally or postnatally repaired open spina bifida have sleep-related breathing disorders • Current guidelines do not require formal evaluation with polysomnography as standard of care What is New: • After age 1 year, obstructive sleep apnea prevalence decreased, but persisted in the majority of patients • Oxygen supplementation requirement prevalence decreased.
Has discomfort during neonatal transfers improved over time?
Timings-Thompson A, Courtney S, Harrison C
Eur J Pediatr · 2026 Jun · PMID 42249980 · Publisher ↗
The aim of this study was to evaluate neonatal pain during neonatal transfer. Comparison with previous published data was carried out to assess if the increase in neonatal pain scores seen during transport was mitigated...
The aim of this study was to evaluate neonatal pain during neonatal transfer. Comparison with previous published data was carried out to assess if the increase in neonatal pain scores seen during transport was mitigated by developments in the transport process and equipment. This is a prospective cohort study on all infants transported by Embrace, Yorkshire and Humber Infant and Children's Transport Service over a 12-month period. The Premature Infant Pain Profile (PIPP) was used to measure stress and discomfort at five specified times during transport. The score before any interventions/transport at the referring unit was used as the baseline. A total of 113 babies had complete data and were included in final analysis. PIPP scores from our 2024 data showed a similar pattern to 2009, with the PIPP scores increasing during the transport process and peaking on arrival at the receiving unit. When compared to baseline scores, PIPP score data from this study was higher than the 2009 data. Conclusion: Infants continue to demonstrate high levels of discomfort during the transport process. Despite advances in transport equipment, our current cohort showed higher levels of discomfort compared to 2009 when against their respective baseline scores. What is Known: • Discomfort and pain have been studied in the NICU setting but data is limited in the transport environment. What is New: • This study shows that neonatal pain scores increase during the transport process. Despite efforts to mitigate this, current PIPP scores are higher than our previous cohort. • Further considerations need to be made to reduce neonatal pain during transport.
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