European Journal Of Pediatrics[JOURNAL]
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200 papers
Holocarboxylase synthetase deficiency: pathogenesis, clinical features, diagnosis, treatment, and research prospects.
ZeZhao J, Ablimit A
Eur J Pediatr · 2026 Jun · PMID 42324336 · Publisher ↗
Holocarboxylase Synthetase Deficiency (HLCSD) is a rare autosomal recessive inborn error of metabolism caused by biallelic mutations in the HLCS gene. The encoded enzyme, holocarboxylase synthetase (HLCS), plays a critic...
Holocarboxylase Synthetase Deficiency (HLCSD) is a rare autosomal recessive inborn error of metabolism caused by biallelic mutations in the HLCS gene. The encoded enzyme, holocarboxylase synthetase (HLCS), plays a critical role in biotin metabolism by activating five essential carboxylases, including pyruvate carboxylase (PC) and propionyl-CoA carboxylase (PCC), thereby regulating key processes such as gluconeogenesis, fatty acid synthesis, and branched-chain amino acid catabolism [1, 14]. HLCS dysfunction leads to the accumulation of toxic metabolites (e.g., 3-hydroxyisovaleric acid, methylcitric acid), resulting in severe manifestations like metabolic acidosis and hyperammonemia [6]. This review systematically consolidates current knowledge on the molecular mechanisms, clinical spectrum, diagnostic approaches, and therapeutic strategies for HLCSD. It critically addresses core controversies, including genotype-phenotype correlations and variability in biotin treatment response, and proposes a multidimensional "gene-enzyme activity-metabolic phenotype-treatment response" framework. Studies confirm that early diagnosis via newborn screening, coupled with standardized biotin supplementation, achieves biochemical normalization and clinical symptom resolution in over 85% of patients and reduces the risk of neurological sequelae [10, 33, 35]. However, biotin-unresponsive cases and rare phenotypes present ongoing diagnostic and therapeutic challenges, necessitating further exploration of novel interventions to advance the precision medicine approach for HLCSD. What is Known: • Holocarboxylase synthetase defi ciency (HLCSD) is a rare autosomal recessive metabolic disorder caused by HLCSbiallelic mutations, and biotin supplementation is the mainstream treatment for most patients. • Distinct population-specifi c HLCS mutation hotspots exist, and residual enzyme activity is closely correlated with disease severity and age of onset. What is New: • A multidimensional framework of gene-enzyme activity-metabolic phenotype-treatment response was proposed tointerpret phenotypic heterogeneity and variable biotin responsiveness in HLCSD. • This review systematically summarized rare clinical phenotypes, diagnostic pitfalls, emerging detection technologies and novel therapeutic directions including gene therapy and epigenetic intervention.
Identification and characteristics of children with complex chronic diseases in the paediatric ward of a tertiary hospital: a prospective study.
García-Miralles L, Ortega-Macías M, Agüera-MartÍn C … +4 more , López-González L, Del Villar Guerra P, Ortiz SanRomán LB, Cano A
Eur J Pediatr · 2026 Jun · PMID 42322441 · Publisher ↗
UNLABELLED: Children with chronic and complex conditions (CCCC) are a population with a growing impact on healthcare. Several methods for their identification have been developed, but their performance requires further r...
UNLABELLED: Children with chronic and complex conditions (CCCC) are a population with a growing impact on healthcare. Several methods for their identification have been developed, but their performance requires further research. Our objective was to characterize hospitalizations due to CCCC and to compare two methods for identifying these patients on a hospital ward: one that requires a direct interview with the parents/caregivers (PedCom scale), and another based on clinical records (Parente algorithm). A prospective study was conducted over one year, including all children hospitalized > 24 h in a pediatric ward of a Spanish tertiary hospital. Children with special health needs (CSHN) were identified using a specific tool, the Children with Special Health Care Needs Screener, and among them, CCCC were identified by expert consensus. The performance and agreement of PedCom scale and Parente algorithm for identifying CCCC were compared. CSHN were identified in 22.7% of hospitalizations, and 23.3% of them were CCCC. CCCC accounted for 9.0% of all hospitalizations, and 13.3% of total hospital days. CCCC required longer hospital stays, more diagnostic and therapeutic procedures, and were more frequently transferred to other centers with a higher level of care, compared to CSHN no-CCCC. For the identification of CCCC, PedCom showed greater sensitivity (84.6%; 95%CI: 66.5-93.9) than Parente (34.6%; 95%CI: 19.4-53.8), with high specificity for both tools: 95.8% (95%CI: 88.3-98.6) and 100% (95%CI: 94.9-100.0), respectively. Agreement between PedCom and Parente was low-to-moderate (kappa 0.455; 95% CI: 0.211-0.699). CONCLUSIONS: A high proportion of pediatric hospitalizations correspond to CCCC, with a greater consumption of healthcare resources. The PedCom scale performs much better in identifying CCCC than Parente's algorithm. WHAT IS KNOWN: • The increasing prevalence of children with chronic and complex conditions (CCCC) poses a challenge to healthcare systems. Identifying these children is a key step in organizing health services. WHAT IS NEW: • The PedCom scale has suitable characteristics for identifying hospitalized CCCC, and has a superior performance to the Parente algorithm.
Subtypes in developmental coordination disorder: what do we know so far? A systematic review.
Verbecque E, Lust JM, Smits-Engelsman B
Eur J Pediatr · 2026 Jun · PMID 42322424 · Publisher ↗
UNLABELLED: Developmental coordination disorder (DCD) is a highly heterogeneous disorder. This systematic review examined whether statistically derived clusters can effectively distinguish subgroups of children with DCD....
UNLABELLED: Developmental coordination disorder (DCD) is a highly heterogeneous disorder. This systematic review examined whether statistically derived clusters can effectively distinguish subgroups of children with DCD. Web of Science, Scopus, PubMed, Embase, and PsycInfo were systematically searched (CRD420251237685) using controlled terminology and free-text terms. Studies were eligible if they included children (aged 0-18 years) with DCD with(out) comorbidities and employed statistical clustering to identify subtypes. Methodological quality was assessed using an adapted version of the Critical Appraisal Skills Programme and certainty of the evidence with the Grading of Recommendations Assessment, Development and Evaluation. Ten of the 1719 search results were included, three of which included both children with DCD and typical development. Two studies explored clusters unidimensionally (motor-only and mental health-only). Eight studies included multiple domains of functioning: motor (n = 8), sensory functions (n = 5), fitness (n = 3), cognitive functions (n = 3), executive functions (n = 2), mental health (n = 1), and participation (n = 1). Studies identified between four (n = 4) and six (n = 1) subtypes, which primarily reflected gradients of severity rather than distinct domain-specific profiles. The overall certainty of evidence for distinct subtypes in DCD was rated low to very low. CONCLUSION: Evidence suggests that DCD is better conceptualized as a spectrum of pervasiveness rather than discrete subtypes. Existing findings lack consistency across studies due to methodological shortcomings and variable measurement domains. Although evidence-based clinical subtypes cannot yet be recommended, future research should prioritize subtyping studies focused on primary symptoms to better identify potential phenotypes within the DCD population. WHAT IS KNOWN: • DCD is a heterogeneous condition, and identifying discrete subtypes is a long-standing research goal to improve clinical support. • Researchers have proposed various motor and non-motor profiles, but no consensus exists on a definitive subtyping model. WHAT IS NEW: • This review found no consistent discrete subtypes, suggesting DCD is better viewed as a spectrum of pervasiveness rather than categories. • Future research should focus on subtyping primary motor symptoms to determine whether distinct, stable subgroups exist within the broader DCD population.
Self-reported vaccine hesitancy and refusal among parents of children with autism spectrum disorder and other developmental delays: a cross-sectional study.
Kara-Aksay A, Özyurt G, Emir B … +2 more , Özgül-Katırcıoğlu D, Erten-Almak T
Eur J Pediatr · 2026 Jun · PMID 42319500 · Publisher ↗
UNLABELLED: Due to the spread of misinformation that some vaccines cause autism spectrum disorder (ASD), many parents report changes in their vaccination behavior following a diagnosis of ASD, putting their children at i...
UNLABELLED: Due to the spread of misinformation that some vaccines cause autism spectrum disorder (ASD), many parents report changes in their vaccination behavior following a diagnosis of ASD, putting their children at increased risk for preventable diseases. Our study aimed to determine the rate of vaccination-related concerns and refusal behaviors in parents of children with ASD and non-autistic developmental delays (non-ASD-DD) and to examine factors potentially associated with vaccine hesitancy and refusal. In our study, a questionnaire was distributed to all parents of children diagnosed with ASD and non-ASD-DD who attended outpatient check-ups over 3 months at the Child Psychiatry Clinic of the two large hospitals. Participants completed a structured questionnaire assessing self-reported vaccination behaviors before and after diagnosis, as well as separate Likert-scale items evaluating vaccine-related beliefs and attitudes. No parents declined participation, and all 154 eligible parents were included in the study. Among the respondents, 87.7% were mothers. The most common diagnoses were intellectual disability (41.6%) and ASD (31.2%). Reported vaccine refusal increased from 3.9% before diagnosis to 9.7% after diagnosis (p = 0.012). The main reason cited for hesitancy or refusal was the belief that vaccines had caused their child's neurodevelopmental condition. No independent associations were found between post-diagnosis vaccine hesitancy/refusal and parental education, income, source of vaccine information, or depression/anxiety scores. However, 88.3% of participants disagreed or strongly disagreed with the statement that vaccines cause ASD or developmental disorders. CONCLUSIONS: Parental concerns about vaccines persist after a diagnosis of neurodevelopmental disorders. Tailored education and communication strategies are essential to support informed vaccine decision-making in these families and to prevent refusal for both diagnosed children and their siblings. WHAT'S KNOWN: • Persistent misinformation linking childhood vaccines-particularly the MMR vaccine-to autism spectrum disorder continues to influence parental attitudes toward vaccination. • Parents of children with ASD have been shown to exhibit higher rates of vaccine hesitancy, especially regarding vaccination of younger siblings. WHAT IS NEW: • Vaccine hesitancy and refusal were more frequently reported after the diagnosis of not only autism spectrum disorder but also other developmental delays, including intellectual disability and speech delay. • Although concerns about vaccines causing developmental disorders were common, vaccine refusal remained relatively uncommon and no independent predictors of post-diagnosis hesitancy or refusal were identified, highlighting the complex nature of parental vaccination decisions.
Distinct clinical phenotypes and outcomes in pediatric chronic eosinophilic pneumonia: a 12- year retrospective cohort study.
Li C, Zhu L, Yu G … +6 more , Su M, Lin L, Wen S, Dong L, Zhang H, Li H
Eur J Pediatr · 2026 Jun · PMID 42319480 · Full text
UNLABELLED: Chronic eosinophilic pneumonia (CEP) is a rare interstitial lung disease. Although CEP has been partially characterized in adults, pediatric data remain scarce, which often leads to diagnostic delays and mana...
UNLABELLED: Chronic eosinophilic pneumonia (CEP) is a rare interstitial lung disease. Although CEP has been partially characterized in adults, pediatric data remain scarce, which often leads to diagnostic delays and management uncertainty. This retrospective cohort study analyzed demographic, clinical, laboratory, imaging, bronchoalveolar lavage fluid (BALF), and treatment data from children with CEP between 2014 and 2025. Patients were stratified into 'Cured' (complete resolution) and 'Protracted' (persistent symptoms or imaging abnormalities > 3 months) groups for exploratory comparison. Thirteen patients (median age 2.92 years; 61.5% male) were included, with 84.6% having allergic comorbidities. The most common symptoms were productive cough (92.3%) and wheeze (61.5%). Chest CT displayed interlobular septal thickening and ground-glass opacities (each 92.3%). BALF revealed marked eosinophilia (median 46%). After a median follow-up of 35.4 months, 8 patients (61.5%) achieved cure, while 5 (38.5%) had a protracted course. Compared with the Cured group, the Protracted group tended to be younger at onset, displayed more extensive radiographic involvement (100% bilateral, 40% lobar consolidation), received a lower initial corticosteroid dose (0.42 vs. 0.82 mg/kg/day) for a shorter duration (7 vs. 34 days), and exhibited a distinct biomarker profile (lower neutrophil-to-lymphocyte ratio, CRP, and LDH but higher platelet count), along with lower BALF neutrophils (5.0 vs. 24.0%) and higher lymphocytes (13.0 vs. 7.0%). CONCLUSION: Pediatric CEP is strongly associated with atopy. The protracted phenotype may be associated with younger age, more extensive radiographic involvement, a platelet-predominant and low-acute-phase biomarker profile, lymphocyte-skewed BALF, and lower initial corticosteroid exposure. Early recognition and adequate initial corticosteroid therapy appear crucial for optimizing outcomes. WHAT IS KNOWN: • CEP is a rare interstitial lung disease that classically affects middle-aged women and is frequently associated with asthma or allergy. • Diagnosis relies on demonstrating pulmonary eosinophilia, and prolonged systemic corticosteroid therapy remains the standard treatment. WHAT IS NEW: • This pediatric cohort reveals that CEP often presents with early onset and male predominance, with outcomes following either a 'Cured' or 'Protracted' course. • The Protracted phenotype may be associated with younger age, specific radiologic findings, lower initial corticosteroid dosing, and elevated platelet counts with lower acute-phase reactants.
Navigating fluoride hesitancy: mapping the evidence base for fluoride-free toothpaste alternatives.
Wong AJ, Donnell CC
Eur J Pediatr · 2026 Jun · PMID 42315717 · Full text
UNLABELLED: This study aims to synthesise and interpret evidence relating to fluoride-free toothpaste alternatives for caries prevention, examining how these products have been studied, the outcomes used to evaluate them...
UNLABELLED: This study aims to synthesise and interpret evidence relating to fluoride-free toothpaste alternatives for caries prevention, examining how these products have been studied, the outcomes used to evaluate them, and how this evidence may inform discussions with children and families. A scoping review was undertaken. Electronic searches of major bibliographic databases identified peer-reviewed studies published between January 2020 and March 2026 evaluating fluoride-free toothpaste formulations. Data were extracted on intervention type, study design, outcome measures, and population characteristics and synthesised narratively with emphasis on patterns of evidence generation rather than comparative effectiveness. A total of 122 studies were included, comprising predominantly laboratory and mechanistic investigations, with only 20 studies providing direct paediatric evidence. Fluoride-free formulations were associated with antimicrobial activity, biofilm modulation, and surrogate remineralisation outcomes. Direct assessment of clinical caries outcomes was uncommon, and substantial heterogeneity was observed in formulation composition, study design, and outcome selection. CONCLUSION: Fluoride-free toothpaste formulations demonstrate measurable biological effects, but evidence is dominated by surrogate outcomes and short-term study designs. While hydroxyapatite-based products have the most consistent evidence base, no fluoride-free category currently has evidence comparable to fluoride for long-term caries prevention in children. WHAT IS KNOWN: • Fluoride toothpaste has strong evidence for long-term caries prevention. • Fluoride-free alternatives are increasingly used, but existing evidence is largely based on surrogate or short-term outcomes. WHAT IS NEW: • Across formulations, observed effects are driven more by study design, delivery context, and outcome selection than by specific ingredients. • No fluoride-free category shows equivalent clinical evidence to fluoride for long-term caries prevention, although hydroxyapatite demonstrates relatively more consistent, yet still limited data.
SREBP gene polymorphisms and ambulatory blood pressure parameters in Chinese adolescents: a cross-sectional study.
Zhang J, Baker JS, Zeng Y … +7 more , Mao B, Jiang Y, Li S, Xia S, Zhang J, Hong XQ, Yang YD
Eur J Pediatr · 2026 Jun · PMID 42301492 · Publisher ↗
UNLABELLED: The purpose of this study was to investigate the association between SREBP gene polymorphisms and ambulatory blood pressure phenotypes. In the present study, 514 college students from a university in China we...
UNLABELLED: The purpose of this study was to investigate the association between SREBP gene polymorphisms and ambulatory blood pressure phenotypes. In the present study, 514 college students from a university in China were recruited. Questionnaire surveys, physical examinations, ambulatory blood pressure monitoring, and blood samples were collected. The relationship between SREBP gene polymorphisms and ambulatory blood pressure parameters in college students was analyzed using a multivariable linear regression model. A total of 510 students with complete data were included in the final analysis. After adjustment for sex, age, weight status, ethnicity, monthly household income per capita, salt intake habits, fruit intake frequency, vegetable intake frequency, smoking, alcohol consumption, history of hypertension, and waist circumference, SREBP1/rs11868035 was associated with 24-h SBP levels in college students under the additive and recessive genetic models (additive: β = 1.39, P = 0.045; recessive: β = 1.75, P = 0.027), but results were not significant after Bonferroni correction (P > 0.0167). Under the recessive genetic model, SREBP1/rs11868035 was associated with daytime SBP levels (β = 1.97, P = 0.026), and SREBP2/rs2228314 was positively associated with daytime DBP levels in college students (β = 2.44, P = 0.033), but neither remained significant after Bonferroni correction (P > 0.0167). CONCLUSION: SREBP gene polymorphisms exhibited suggestive associations with ambulatory blood pressure in Chinese adolescents. Although the associations were not significant after multiple testing correction, these findings suggest potential genetic influences on blood pressure regulation in youth and may inform future research on genetically informed approaches to hypertension prevention. WHAT IS KNOWN: • Accumulating evidence has demonstrated associations between SREBP gene polymorphisms and cardiometabolic phenotypes. • To date, no studies have investigated the association between SREBP gene polymorphisms and ambulatory blood pressure phenotypes. WHAT IS NEW: • In this exploratory analysis, we identified an association between the rs11868035 polymorphism in the SREBP1 gene and ambulatory blood pressure phenotypes, including 24-h and daytime systolic blood pressure, among Chinese adolescents. • The SREBP1/rs11868035 polymorphism appears to be associated with higher 24-h and daytime systolic blood pressure, whereas the SREBP2/rs2228314 polymorphism was positively associated with daytime diastolic blood pressure.
Evaluation of FABP1 as a biomarker of diabetic kidney disease in children with type 1 diabetes.
Aboelenin HM, ElTaher H, Elzehery R … +2 more , Nosir SM, Al-Haggar M
Eur J Pediatr · 2026 Jun · PMID 42298045 · Full text
Diabetic kidney disease (DKD) is a chronic microvascular complication of diabetes mellitus and a leading cause of chronic kidney disease worldwide. Microalbuminuria remains the current gold standard for the diagnosis and...
Diabetic kidney disease (DKD) is a chronic microvascular complication of diabetes mellitus and a leading cause of chronic kidney disease worldwide. Microalbuminuria remains the current gold standard for the diagnosis and staging of DKD; however, it often reflects established renal injury rather than early pathological changes. Fatty acid-binding protein 1 (FABP1), a cytoplasmic protein abundantly expressed in the renal proximal tubules, is released into the urine in response to tubular damage. FABP1 plays an essential role in intracellular fatty acid transport and metabolism and may serve as a potential biomarker for tubular involvement in pediatric diabetic kidney disease. A case-control study was performed on 90 children (30 T1DM with DKD, 30 T1DM without DKD [non-DKD], and 30 controls). Albumin-creatinine ratio (ACR) and serum FABP1 were ELISA measured. FABP1 was significantly higher in the DKD group versus non-DKD (p = 0.026) and controls (p = 0.009). FABP1 positively correlated with ACR (r = 0.25, p = 0.018), total cholesterol (r = 0.25, p = 0.019), and LDL-C (r = 0.25, p = 0.017). A cutoff > 189 ng/L discriminated DKD from non-DKD (AUC = 0.67, sensitivity 63%, specificity 73%).Conclusion: Serum FABP1 may represent a complementary biomarker of tubular involvement in pediatric diabetic kidney disease.
Live viral measles-mumps-rubella revaccination and varicella vaccination in children and adolescents with juvenile idiopathic arthritis: a systematic review.
Dipasquale RF, Sinopoli P, Mendicino A … +1 more , Gallizzi R
Eur J Pediatr · 2026 Jun · PMID 42297949 · Full text
UNLABELLED: The purpose of this systematic review is to synthesize the available evidence on the immunogenicity and safety of live viral measles-mumps-rubella (MMR) booster/revaccination and varicella vaccination in chil...
UNLABELLED: The purpose of this systematic review is to synthesize the available evidence on the immunogenicity and safety of live viral measles-mumps-rubella (MMR) booster/revaccination and varicella vaccination in children and adolescents with juvenile idiopathic arthritis. PubMed, Scopus, and Web of Science were systematically searched from inception to October 1, 2025, for studies including patients with juvenile idiopathic arthritis who had received live viral MMR or varicella vaccination and reporting immunogenicity, adverse events, vaccine-strain infection, breakthrough infection, or post-vaccination disease activity. Nine studies comprising 743 patients with juvenile idiopathic arthritis were included: five retrospective studies, three prospective cohort studies, and one open-label randomized controlled trial. Seven studies assessed MMR booster or revaccination, whereas two small prospective cohorts assessed varicella vaccination. MMR booster/revaccination was generally immunogenic and clinically safe in the short term, with no consistent increase in disease activity and no serious vaccine-related complications reported. However, 5-year seroprotection after MMR booster was lower among children receiving biologic disease-modifying antirheumatic drugs (DMARDs) at vaccination than among non-bDMARD users for measles (60% vs 86%), mumps (80% vs 94%), and rubella (60% vs 83%). Varicella vaccination induced protective antibodies in 82-83% of patients after two doses, but antibody levels were lower than those in healthy controls; VZV-specific cellular immunity was detectable in 72% in the larger cohort and appeared to persist longer than humoral immunity. No vaccine-strain varicella infection was reported, although mild breakthrough varicella occurred in some vaccinated patients. CONCLUSION: In clinically stable children with juvenile idiopathic arthritis, the available evidence supports the cautious use of MMR booster/revaccination and varicella vaccination under specialist supervision. The main residual concern is not a consistent safety signal but incomplete or less durable protection in selected biologic-treated patients, particularly for measles and rubella 5 years after MMR booster and for varicella in low responders. These findings support individualized vaccine timing and consideration of post-vaccination serology in selected higher-risk children. WHAT IS KNOWN: • Live viral vaccines in children with juvenile idiopathic arthritis are used cautiously because of concerns about attenuated-virus-related adverse events, disease flare, and reduced immunogenicity during immunosuppressive therapy. • The evidence base is stronger for MMR booster/revaccination than for varicella vaccination, because MMR data include one randomized trial and several larger cohorts, whereas varicella data come from two small prospective cohorts. WHAT IS NEW: • MMR booster/revaccination and varicella vaccination appeared generally safe in clinically stable children with juvenile idiopathic arthritis, with no serious vaccine-related complications or vaccine-strain infections reported in the included cohorts. • Five-year seroprotection after MMR booster was lower in biologic-treated children for measles, mumps, and rubella, supporting individualized vaccine timing and selected post-vaccination serologic monitoring.
Health-related quality of life and caregiver burden in Chinese families with disorders of sex development: a person-centered analysis.
Zheng Z, Guan L, Gao M … +8 more , Tian H, Ye L, Wei X, Chen X, Ademuwagun T, Zhang K, Tang D, Bai G
Eur J Pediatr · 2026 Jun · PMID 42295517 · Publisher ↗
UNLABELLED: This study aimed to describe HRQoL of both children and parents in a Chinese DSD cohort, evaluate caregiver burden, and employ the latent profile analysis (LPA) to identify distinct parental HRQoL profiles an...
UNLABELLED: This study aimed to describe HRQoL of both children and parents in a Chinese DSD cohort, evaluate caregiver burden, and employ the latent profile analysis (LPA) to identify distinct parental HRQoL profiles and their associated determinants. This study included 147 parents of children with DSD and 519 parents of healthy controls. Group differences in HRQoL were analyzed using t-tests or one-way analysis of variance (ANOVA). Multivariate regression identified predictors of parental HRQoL, and LPA classified parental HRQoL profiles with multinomial logistic regression used to assess their associated factors. Children with DSD had similar HRQoL scores to healthy controls (p > 0.05), but their caregivers showed significant impairments across all domains (p < 0.05). In multivariate analysis, caregiver burden and child HRQoL were significantly associated with parental HRQoL (p < 0.05), with caregiver burden mediating 60.8% of the effect of child HRQoL on parental HRQoL. Latent profile analysis identified three parental HRQoL profiles: "Poor" (24.5%), "Moderate" (35.4%), and "Good" (40.1%). Higher caregiver burden increased the odds of "Poor" and "Moderate" profiles (OR = 1.52 and 1.26, both p < 0.001), while better child HRQoL protected against "Poor" profile membership (OR = 0.91, p = 0.002). CONCLUSIONS: This study reveals that HRQoL of children with DSD is comparable to the healthy controls, while their parents experience significant impairments in HRQoL, primarily determined by caregiver burden and the child's HRQoL. As caregiver burden mediates the impact of child HRQoL on parental HRQoL, clinical care must adopt a family-centered approach focusing on burden alleviation. WHAT IS KNOWN: • Children with DSD face complex medical and psychosocial challenges that may affect HRQoL in both patients and their families. • Their caregivers often experience significant psychological burden, which can negatively impact their own well-being. WHAT IS NEW: • In a Chinese DSD cohort, children's HRQoL was comparable to healthy controls, whereas their parents exhibited significant and heterogeneous HRQoL impairments across all domains, with three distinct parental HRQoL profiles identified via latent profile analysis. • Caregiver burden mediated 60.8% of the effect of child HRQoL on parental HRQoL, highlighting burden alleviation as a priority target in family-centered clinical care for DSD.
Is it a Reliable Guide or a Source to be Approached with Caution? GenAI in Parents' Information Search Processes Regarding Their Children.
Erol M, Erol A
Eur J Pediatr · 2026 Jun · PMID 42295482 · Full text
Generative artificial intelligence (GenAI) is increasingly used by parents to get information on child care and learning. This study examines how parents use GenAI in their information-seeking process related to their ch...
Generative artificial intelligence (GenAI) is increasingly used by parents to get information on child care and learning. This study examines how parents use GenAI in their information-seeking process related to their children's care and learning. It looks at how this shapes decision-making and how parents emotionally interpret these experiences. Thirty parents of children aged 0-3 participated. Researchers collected data with open-ended qualitative questionnaires and analyzed it through inductive content analysis. Findings showed that parents used generative AI for quick information and guidance during periods of uncertainty, emergencies, or developmental questions. They viewed AI as a helpful resource for health, care, behavior, development, and planning activities. Parents did not always use AI suggestions directly; instead, they evaluated them by considering their experiences, their children's needs, and professional advice. Emotionally, some felt relief, a sense of security, or a sense of being in control, while others felt insecurity, anxiety, or caution. Conclusions: Parents view generative AI as a helpful, easy-to-access resource for child care and learning. They use it most when needing immediate answers or guidance. At the same time, they treat their information with caution by combining it with their own experiences and expert advice. Generative AI now works as a supporting tool for parents, not as a replacement for human judgment or expert help.
Surfactant administration in late preterm and term neonates: is LISA ready for routine use?
Kamwana D, Vardhelli V, Dumpa V … +4 more , Anne RP, Hoque N, Khalil MY, Chedid F
Eur J Pediatr · 2026 Jun · PMID 42295455 · Publisher ↗
UNLABELLED: Minimally invasive surfactant administration, including less invasive surfactant administration (LISA) and minimally invasive surfactant therapy (MIST), is increasingly preferred in very preterm infants recei...
UNLABELLED: Minimally invasive surfactant administration, including less invasive surfactant administration (LISA) and minimally invasive surfactant therapy (MIST), is increasingly preferred in very preterm infants receiving non-invasive ventilation despite unresolved physiological and methodological questions regarding its benefits. Furthermore, evidence supporting its use in late preterm (LPT) and term neonates remains limited. This narrative review summarises physiological and clinical aspects and evidence on current surfactant administration methods in LPT and term infants based on relevant original studies, reviews, and international guidelines. Compared to very preterm infants, these relatively more mature infants differ significantly in respiratory pathophysiology, surfactant requirement, and procedural tolerance and are at limited risk of prematurity-related complications such as bronchopulmonary dysplasia and intraventricular haemorrhage. Potential risks of LISA/MIST in this population include procedural instability, need for sedation, surfactant reflux, airway obstruction, and uncertain surfactant distribution. Current evidence remains insufficient to support routine use of LISA/MIST in LPT and term neonates. CONCLUSION: Until adequately powered randomised controlled trials are available, surfactant administration should be individualised and should be selected based on clinical context, infant stability, and available expertise. WHAT IS KNOWN: • Minimally invasive surfactant administration techniques are often preferred in preterm neonates although physiological, methodological, and outcome-related uncertainties remain. WHAT IS NEW: • Evidence for the use of appropriate surfactant replacement technique in late preterm and term neonates is sparse. Adequately powered randomised controlled trials are needed to determine the efficacy, safety, and patient selection criteria in this population.
Time-dependent pattern of liver injury biomarkers in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia.
Warlop J, Borloo N, Muniraman H … +11 more , Michniewicz B, Kovacs K, Annaert P, Kayki G, Clarke P, Szpecht D, Szabo M, Fieuws S, Yalcin N, Smits A, Allegaert K
Eur J Pediatr · 2026 Jun · PMID 42295422 · Full text
UNLABELLED: Hypoxic-ischemic encephalopathy (HIE) often results in multi-organ damage. Liver injury following HIE is typically characterized by time-dependent altered patterns of alanine aminotransferase (ALT), aspartate...
UNLABELLED: Hypoxic-ischemic encephalopathy (HIE) often results in multi-organ damage. Liver injury following HIE is typically characterized by time-dependent altered patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin (TB) concentrations. This study aims to describe age-dependent patterns of liver injury biomarkers during and after therapeutic hypothermia (TH). Liver injury biomarkers (ALT, AST, TB) over the first 10 days of postnatal age (PNA) from six cohorts, including 428 neonates with moderate-to-severe HIE treated with TH were pooled. Statistical modelling with linear mixed models and quantile regression was applied to assess trends and correlations with HIE severity, gestational age, and birth weight. ALT and AST concentrations were highest on PNA day 1 (median [IQR]: 37.5 [18.75-85.50] U/L), and 154 [79-345 U/L], respectively) and declined thereafter. ALT and AST values were both associated with HIE severity (p < 0.001). The AST/ALT (De Ritis) ratio remained > 3.0 throughout PNA days 1-10. CONCLUSION: We characterize age-dependent reference values of liver-injury biomarkers in HIE neonates treated with TH. Along with PNA, HIE severity has a strong association with liver biomarkers, while the De Ritis ratio reflects ischemic hepatic injury throughout PNA (day 1-10). These age-dependent reference values can be used to assess intra- and interpatient variability, or to explore other causes of hepatic toxicity like drug-induced liver injury, preferably following external validation. WHAT IS KNOWN: • Moderate to severe hypoxic-ischemic encephalopathy in neonates undergoing therapeutic hypothermia is often associated with multi-organ damage, including liver injury. • Except for acid/base parameters, laboratory values are inconsistently collected and reported in this specific population, so that reference values are warranted. WHAT IS NEW: • We report time-dependent reference values of liver injury biomarkers during and after therapeutic hypothermia. • These reference values can be used to assess intra- or interpatient variability and patterns in this specific population.
Factors predicting the severity of gastrointestinal involvement in children with IgA vasculitis? A Turkish multicenter cohort study.
Belder N, Acun B, Öztürk D … +53 more , Kaya Yıldırım N, Öksel B, Atamyıldız Uçar S, Erkan MO, Kutlar Tanıdır M, Sönmez AB, Kurt T, Karakaş HD, Cevizbaş S, Kılıç Sağlam M, Tığrak SN, Baba Ö, Kısaoğlu H, Dizman EN, Demir F, Çakan M, Girgeç A, Köker O, Yüksel S, Doğantan Ş, Küçükali B, Karaçayır N, Gündoğdu T, Adıgüzel Dündar H, Doğan Kuzuca T, Sezer M, Şener S, Sümer G, Demirkan FG, Taşkın SN, Bozkaya Yücel B, Yıldız Ç, Ekici Tekin Z, Albayrak SE, Şahin N, Tunce E, Sağ E, Ertem Ş, Gürgöze MK, Sönmez HE, Sözeri B, Bilginer Y, Özkayın EN, Ünsal E, Ergüven M, Türkuçar S, Öztürk K, Balat A, Elmas S, Demir S, Dönmez O, Gezgin Yıldırım D, Bakkaloğlu SA
Eur J Pediatr · 2026 Jun · PMID 42289526 · Publisher ↗
Gastrointestinal (GI) involvement of IgA vasculitis (IgAV) has various clinical presentations from isolated abdominal pain to severe gastrointestinal bleeding. The aim of this study is to determine the incidence of GI in...
Gastrointestinal (GI) involvement of IgA vasculitis (IgAV) has various clinical presentations from isolated abdominal pain to severe gastrointestinal bleeding. The aim of this study is to determine the incidence of GI involvement in children with IgAV and identify the predictors of severe GI involvement. Medical records of IgAV patients with GI involvement from 30 centers in Türkiye between 2014 and 2024 were retrospectively reviewed. Patients were classified into two groups according to the severity of GI presentations: Group 1 consisted of mild GI involvement, while Group 2 had severe GI involvement. Severe GI involvement was observed in 476 (42%) out of 1131 patients. A significant postpandemic (after March 2020) increase in GI involvement was observed (p < 0.001). Abdominal pain as an initial symptom, vomiting, purpuric rash on upper extremities and trunk, and kidney involvement were more frequent in Group 2 than in Group 1 (all p < 0.01). Leukocytosis, neutrophilia, thrombocytosis, increased C-reactive protein (CRP) level and neutrophil-to-lymphocyte ratio (NLR), and decreased serum total protein and albumin levels were detected more frequently in Group 2 (all p < 0.01). In multivariate regression analysis, thrombocytosis, elevated NLR and CRP, hypoalbuminemia, abdominal pain preceding rash, vomiting, and upper extremity rash were associated with severe GI involvement (all p < 0.05). ROC analyses identified the following optimal cut-off values for predicting severe GI involvement: WBC > 12.90 10^3/µL, ANS > 7.81 10/µL, NLR > 3.09, PLT > 404 103/µL, CRP > 20 mg/L, plasma albumin ≤ 4 g/dL.Conclusion: Abdominal pain preceding rash, purpuric rash on upper extremities, vomiting, thrombocytosis, hypoalbuminemia, increased NLR, and high CRP may predict severe GI involvement in children with IgAV.
Mortality differences between immigrant and native children and youths in Denmark: a nationwide cohort study focusing on refugees and family-reunified immigrants.
Wang Y, Jacobsen R, Petersen JH … +1 more , Nørredam M
Eur J Pediatr · 2026 Jun · PMID 42287440 · Full text
UNLABELLED: Immigrant children and youths represent a growing population in Europe, yet studies on their health are scarce. Mortality is an indicator of both morbidity and healthcare access. This national register-based...
UNLABELLED: Immigrant children and youths represent a growing population in Europe, yet studies on their health are scarce. Mortality is an indicator of both morbidity and healthcare access. This national register-based study aimed to compare all-cause and cause-specific mortality between natives and immigrants under 25 in Denmark. Using the Danish Migrant Cohort, we followed 82,461 immigrant and 473,244 native children and youths from 1993 to 2015 and from 2020 to 2022. Incidence rate (IR) was used to describe mortality by sex and age (in both groups) and by region of origin, migrant status, and length of stay (among immigrants). We used sex-stratified, age-adjusted Cox proportional hazard ratios (HR) to compare all-cause and cause-specific mortality between natives and immigrants overall and by region of origin and migrant status. We identified 156 deaths (IR = 3.20 per 10,000 person-years) and 815 deaths (IR = 2.49 per 10,000 person-years) among immigrant and native children and youths, respectively. Immigrants had higher overall mortality risk (HR 1.27, 95% CI 1.07-1.51). Group analyses showed elevated mortality in (i) males originating from Sub-Saharan Africa, (ii) male asylum seekers, and (iii) quota refugees of both sexes. Cause-specific mortality analyses showed higher suicide mortality in females from North Africa and Middle East and higher neurological disorder mortality in female quota refugees. With longer residence, mortality rates among immigrants decreased. CONCLUSIONS: Immigrant children and youths in Denmark face excess mortality risks that diminish with longer stay. More research is needed to understand these differences and to reduce mortality among young immigrants. WHAT IS KNOWN: • Adult immigrants often show an overall mortality advantage compared with natives, but evidence on mortality for immigrant children and youths is limited and inconsistent. WHAT IS NEW: • This nationwide Danish register-based cohort study shows that immigrant children and youths have higher all-cause mortality than natives.
Performance of artificial intelligence chatbots in providing feeding management and oral health guidance for children with cleft lip and palate: ChatGPT 5.2 vs Gemini 3 Pro.
Beşparmak A, Beşparmak TM
Eur J Pediatr · 2026 Jun · PMID 42287436 · Publisher ↗
UNLABELLED: This study aims to comparatively evaluate the quality, reliability, and readability of responses generated by ChatGPT 5.2 and Gemini 3 Pro regarding feeding management and oral health guidance for children wi...
UNLABELLED: This study aims to comparatively evaluate the quality, reliability, and readability of responses generated by ChatGPT 5.2 and Gemini 3 Pro regarding feeding management and oral health guidance for children with cleft lip and palate (CLP). A cross-sectional design was used. Both models were asked 20 questions on feeding and oral-dental care in infants and children with CLP. Response quality was assessed using the Global Quality Score (GQS) and the CLEAR tool, reliability with the modified-DISCERN (m-DISCERN), and readability with the Flesch Reading Ease (FRES) and Flesch-Kincaid Grade Level (FKGL). The mean GQS was significantly higher for Gemini 3 Pro than for ChatGPT 5.2 (4.51 ± 0.29 vs. 3.76 ± 0.33; p < 0.001). The CLEAR tool score was likewise significantly higher in Gemini 3 Pro compared with ChatGPT 5.2 (22.95 ± 0.94 vs. 19.40 ± 1.47; p < 0.001), and the m-DISCERN scores were also significantly higher for Gemini 3 Pro (4.0 [4.0-4.0]) than for ChatGPT 5.2 (3.0 [2.0-3.0]; p < 0.001). The FRES values were significantly higher for Gemini 3 Pro compared with ChatGPT 5.2 (49.50 ± 10.33 vs. 23.60 ± 14.48; p < 0.001), whereas the FKGL values were significantly lower (9.77 ± 1.54 vs. 13.44 ± 2.81; p < 0.001). Correlation analysis revealed strong positive correlations between GQS and CLEAR (r = 0.753) and between GQS and m-DISCERN (r = 0.740), while FKGL showed significant negative correlations with all quality and reliability measures (-0.566≤ r ≤ -0.484; all p < 0.001). CONCLUSION: Gemini 3 Pro outperformed ChatGPT 5.2 across content quality, reliability, and readability. Although both models can support guidance in CLP care, AI chatbot outputs should be used as complementary tools alongside professional clinical guidance. WHAT IS KNOWN: • Large language model (LLM) chatbots are increasingly used as sources of health information for patients and families. • Existing studies on cleft lip and palate largely focus on single-model evaluations. WHAT IS NEW: • This study provides the first comparative analysis of ChatGPT 5.2 and Gemini 3 Pro for feeding management and oral-health guidance in CLP care. • Gemini 3 Pro demonstrated higher content quality, reliability, and readability than ChatGPT 5.2, indicating model-dependent variability in chatbot performance.
Impact of a multiplex respiratory PCR panel on antibiotic stewardship in hospitalized pediatric pneumonia: a randomized clinical trial.
Chen J, Wang J, Zhou Y … +13 more , Wang Z, Cao Q, Ren H, Teng T, Liang J, Wu F, Zhao R, Shen N, Xu Z, Mo X, Liu Y, Yin Y, Tao Y
Eur J Pediatr · 2026 Jun · PMID 42287352 · Publisher ↗
UNLABELLED: We aimed to evaluate whether the FILMARRAY® Pneumonia Panel (FAPP) added to standard care could effectively guide antibiotic prescriptions in hospitalized pediatric patients with infectious pneumonia. In this...
UNLABELLED: We aimed to evaluate whether the FILMARRAY® Pneumonia Panel (FAPP) added to standard care could effectively guide antibiotic prescriptions in hospitalized pediatric patients with infectious pneumonia. In this single-center, open-label, parallel-group randomized controlled clinical trial, we enrolled hospitalized children (28 days to 18 years old) diagnosed with infectious pneumonia. Participants were randomized to standard care only (control) or to added FAPP (intervention group). The primary outcome was the proportion of patients with antibiotic change within 72 h. Between December 8, 2021, and February 16, 2023, we enrolled 315 patients (157 in the intervention group and 158 in the control group). Pathogens were detected in 86.6% (32.7% bacterial, 56.5% viral, and 10.9% atypical) via FAPP, which may encompass colonizing organisms due to its enhanced sensitivity. The primary outcome was comparable between the intervention and control groups (51.6%, 81/157, versus 49.4%, 78/158; P = 0.693). However, key exploratory secondary outcomes demonstrated significant improvements in the intervention group: total frequency of changes in antibiotic and antiviral agents based on pathogen results (47.8%, 75/157, versus 25.3%, 40/158; P < 0.001) and proportion of patients with antibiotic de-escalation within 72 h (14.6%, 23/157, versus 1.9%, 3/158; P < 0.001). CONCLUSION: Integrating FILMARRAY® into pediatric pneumonia clinical management did not significantly boost initial overall antibiotic modification rates. However, exploratory analysis showed it improved targeted antimicrobial adjustments and facilitated antibiotic de-escalation, suggesting FILMARRAY® may add value to antibiotic stewardship. Subsequent trials could substantiate this theoretical proposition. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100047213, registered 11 June 2021-prospectively registered, https://www.chictr.org.cn/showproj.html?proj=128024 . WHAT IS KNOWN: • FILMARRAY® molecular techniques, via semiquantitative analysis to identify potential pathogens, may contribute to reduce antibiotic usage and facilitate more targeted and appropriate antibiotic therapy in adult patients with lower respiratory tract infections. WHAT IS NEW: • Integrating FILMARRAY® into pediatric pneumonia care did not notably raise initial overall antibiotic modification rates. However, exploratory analysis showed it improved targeted antimicrobial adjustments and promoted antibiotic de-escalation, suggesting potential value for antibiotic stewardship.
Integrating environmental exposure assessment into maternal and neonatal care: a practical mini-review.
Al-Saleh I
Eur J Pediatr · 2026 Jun · PMID 42286274 · Publisher ↗
Environmental exposure assessment remains under-integrated in maternal and neonatal care despite growing evidence that pregnancy, fetal development, and early neonatal life are highly sensitive periods during which envir...
Environmental exposure assessment remains under-integrated in maternal and neonatal care despite growing evidence that pregnancy, fetal development, and early neonatal life are highly sensitive periods during which environmental exposures may influence immediate and longer-term health. This narrative mini-review highlights the clinical relevance of environmental exposures in maternal and neonatal practice, outlines why exposure assessment remains underused in routine care, and proposes a pragmatic framework for integration. Key barriers include limited clinician training, unclear referral pathways, and the perception that environmental risks are difficult to assess and interpret in clinical settings. A targeted approach may be most appropriate in high-risk pregnancies, unexplained adverse outcomes, fetal growth restriction, preterm birth, and medically vulnerable neonates. A practical framework based on recognizing higher-risk situations, obtaining a focused exposure history, and acting through counseling, referral, or selective testing is proposed to help bring environmental health closer to routine maternal and neonatal care. What is Known? • Pregnancy, fetal development, and early neonatal life are highly sensitive periods during which environmental exposures may influence health and development. • Environmental exposure assessment remains underused in routine maternal and neonatal care because of limited clinician training, unclear referral pathways, and uncertainty about how to act on exposure concerns. What is New? • This narrative mini-review proposes a practical framework for integrating environmental exposure assessment intomaternal and neonatal care through focused history taking, counseling, referral, and selective testing when appropriate. • A practical screening table is provided with example exposure questions, red flags, and suggested clinical actions to support real-world clinical decision-making.
Universal saliva PCR screening for congenital cytomegalovirus identifies asymptomatic infections with neuroimaging abnormalities in a prospective neonatal cohort.
Vitaliti SM, Vassallo A, Vitaliti G … +4 more , Imparato S, Scimeca C, Destri NL, Di Berbardo F
Eur J Pediatr · 2026 Jun · PMID 42283916 · Publisher ↗
UNLABELLED: Congenital cytomegalovirus (cCMV) infection is the leading non-genetic cause of sensorineural hearing loss and an important cause of neurodevelopmental impairment [1-3, 6-14]. Targeted screening strategies fr...
UNLABELLED: Congenital cytomegalovirus (cCMV) infection is the leading non-genetic cause of sensorineural hearing loss and an important cause of neurodevelopmental impairment [1-3, 6-14]. Targeted screening strategies frequently fail to detect infected infants who are asymptomatic at birth but remain at risk for late sequelae [9]. This study aims to evaluate the diagnostic yield of universal saliva PCR screening compared with targeted screening strategies and to describe neuroimaging findings in identified cases. We conducted a prospective observational cohort study including 4000 neonates born at ARNAS Civico di Palermo, Italy, between July 2023 and September 2025. All neonates underwent saliva PCR screening on the second day of life. Positive results were confirmed by urine PCR. Infants with confirmed infection underwent cranial ultrasound, brain MRI, ophthalmologic examination, and audiological assessment. The prevalence of cCMV infection was 0.2% (8/4000). Using targeted screening criteria based on symptoms or failed hearing screening, only 62.5% (5/8) of infections would have been detected. Consequently, 37.5% (3/8) represented infections in asymptomatic infants who passed hearing screening. Neuroimaging abnormalities were observed in all confirmed cases. CONCLUSION: Universal screening improves diagnostic yield and identifies clinically asyntomatic infections with early neuroimaging abnormalities, supporting broader neonatal surveillance strategies. WHAT IS KNOWN: • cCMV infection is a leading non-genetic cause of childhood hearing loss and neurodevelopmental impairment. Only ~10% of infected neonates are symptomatic at birth; targeted screening often misses asymptomatic infants. Saliva PCR is a practical and accurate diagnostic tool for early detection. WHAT IS NEW: • Universal saliva PCR screening detected 37.5% more infections than targeted strategies. All infected infants, including asymptomatic cases, showed early neuroimaging abnormalities, highlighting neurological involvement.
Trends and regional disparities in hypoplastic left heart syndrome prevalence and mortality in the USA: a nationwide study.
Mantena J, Vidavalur R
Eur J Pediatr · 2026 Jun · PMID 42283907 · Publisher ↗
UNLABELLED: Hypoplastic left heart syndrome (HLHS) is a critical congenital heart that requires complex surgical and medical management. Despite recent clinical advances, population-level data on infant mortality trends...
UNLABELLED: Hypoplastic left heart syndrome (HLHS) is a critical congenital heart that requires complex surgical and medical management. Despite recent clinical advances, population-level data on infant mortality trends related to HLHS remain limited. This study examines temporal patterns in HLHS-related infant mortality rates (HLHS-IMR), timing of death, interstate variation, and demographic disparities, along with updated prevalence estimates. We analyzed U.S national data from 2007 to 2021 using CDC-WONDER linked births/deaths database. HLHS-related infant mortality rates (HLHS-IMR), identified using ICD-10 code Q23.4, were calculated per 100,000 live births. Bivariate analyses estimated relative risks (RR) by sex, race, gestational age (GA), and state. We used Joinpoint regression to estimate annual percent changes (APC) and average annual percent change (AAPC). We assessed recent state-level prevalence data from the National Birth Defects Prevention Network (NBDPN) for two 5-year periods: 2012-2016 and 2016-2020. Among 59,117,761 live births, 3566 (0.006%) HLHS-related infant deaths were recorded. HLHS-IMR declined by 43% (7.4 to 4.2 per 100,000), with an AAPC of - 3.2% (95% CI, - 5.1, - 1.6; p < .01). Mortality declined more steeply after 2016 (APC - 6.5%; 95% CI, - 21.0, - 3.2). Most deaths (57%) occurred in the neonatal period. Black infants had higher mortality risk (RR 1.15; 95% CI, 1.05, 1.26), while Asian infants had lower risk (RR 0.61; 95% CI, 0.51, 0.73). Recent HLHS prevalence was approximately 1 in 3653 live births. CONCLUSION: National HLHS-IMR has declined significantly, likely reflecting improvements in early diagnosis and critical clinical care. However, persistent racial and geographic disparities exist, warranting further investigation. WHAT IS KNOWN: • Hypoplastic left heart syndrome remains a major cause of infant cardiac mortality despite advances in surgical and neonatal care. • Prior studies have reported improving survival, but contemporary national data on mortality trends and geographic disparities remain limited. WHAT IS NEW: • This study demonstrates a sustained national decline in HLHS-related infant mortality in the USA over the past 15 years. • Persistent racial and interstate disparities in outcomes remain, with distinct state-level mortality patterns with varied burdens.
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