European Journal of Pediatrics最新文献

Children diagnosed with leukemia often undergo prolonged hospitalization for chemotherapy, during which treatment-related fears may adversely affect both their immediate treatment response and long-term psychological development. This study aims to deeply explore the nature and dynamics of medical fears in children with leukemia during chemotherapy. This study was conducted under a qualitative research design, employing a phenomenological approach. Semi-structured interviews centered around four core questions regarding the medical fear experiences of children with leukemia were carried out with 12 child-caregiver dyads. The data were analyzed using Colaizzi's seven-step phenomenological analysis method to identify and describe the medical fears of these children and their influencing factors. Four main themes were identified: (i) pain-centered fear experience; (ii) fear of death and its variations; (iii) fear of lumbar puncture and bone marrow aspiration and its variations; and (iv) transmission of fear by caregivers. Pain remained the central factor influencing medical fear. Children's fears predominantly concerned death and invasive procedures, with intensity varying across treatment phases. Caregivers' fears also changed over time and mutually influenced the children's emotional states.Conclusion: The findings highlight the complexity of medical fears in children with leukemia and underscore the influential role of caregivers-as the closest emotional bonds-in shaping these fears. Understanding the dynamics of children's fears and the role of caregivers is essential for providing effective family-centered support. What is Known • Medical fears can negatively affect children's engagement with healthcare. • The treatment experience of children with leukemia may impair their social adaptation. What is New • Medical fears in children with leukemia focus on death and invasive procedures, with distinct causes across treatment stages. • Caregivers also experience medical fears, and their emotional linkage significantly affects the child's fear. Dynamic assessment of both child and caregiver fears is essential to deliver timely family-oriented support.

Coffin-Siris Syndrome (CSS) is a neurodevelopmental disorder caused by variants in genes encoding BRG1- and BRM-associated factor (BAF) chromatin-remodeling complex. ARID1B gene variants are the most common cause of CSS. This study aimed to identify novel pathogenic ARID1B variants in patients clinically diagnosed with CSS and to explore their pathogenic role. In this study, eight patients clinically diagnosed with CSS were enrolled, and whole exome sequencing (WES) was performed to identify potential pathogenic variants. Heterozygous variants in the ARID1B gene were identified in six patients, including one previously reported pathogenic nonsense variant and five novel pathogenic truncating variants. The combined annotation-dependent depletion (CADD) scores of the five novel variants were significantly above the mutation significance cutoff (MSC), suggesting their potential pathogenicity. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), these five novel variants were classified as pathogenic.

Conclusions: Our findings add five novel variants to the list of known pathogenic variants of the ARID1B gene. This study further clarifies an enhanced connection between ARID1B gene variants and CSS and expands the variant spectrum of CSS.

What is known: • Coffin-Siris syndrome (CSS) is a rare neurodevelopmental disorder characterized by developmental delay, intellectual disability, and hypoplasia of the fifth digits or nails. • Pathogenic variants in genes encoding subunits of the BAF chromatin-remodeling complex are the major genetic causes of CSS, with ARID1B being the most frequently mutated gene, and most variants of which are truncating and lead to haploinsuffucuency.

What is new: • Five novel heterozygous truncating variants in ARID1B were identified in eight patients clinically diagnosed with Coffin-Siris syndrome. • All novel variants showed high CADD scores and were classified as pathogenic according to ACMG guidelines.

While early-life growth patterns are thought to be pivotal for long-term cardiovascular health, their specific links to adolescent blood pressure (BP) and potential mediators remain unclear. We aimed to examine the associations of growth trajectories from birth to age two with systolic and diastolic BP in adolescence, and to quantify the proportion mediated by concurrent adolescent BMI. In a prospective birth cohort in rural China, we repeatedly measured infant weight and length at birth and at 1, 3, 6, 9, 12, 18, and 24 months of age. Adolescent BP was measured and converted into percentiles. We used group-based trajectory modeling to identify early-life weight-, length-, BMI- and weight-for-length z-score trajectories and examined their associations with adolescent BP. A general causal mediation estimated the natural indirect effects and corresponding proportions mediated through adolescent BMI. Among the 1388 infants enrolled, 741 (60.9% male; mean age, 11.26 (SD, 0.57) years old) were followed at adolescence. Greater and rapid BMI and weight-for-length growth trajectories were statistically associated with elevated adolescent BP and BP percentiles, with adjusted mean differences ranging from 2.32 to 5.29 mmHg. Adolescent BMI mediated a substantial portion (up to 85%) of the association with systolic BP, but it showed no significant mediating effect for diastolic BP.Conclusion: Rapid adiposity growth in infancy predicts elevated adolescent BP. Since adolescent BMI did not fully explain this association, especially for diastolic BP, preventive interventions within the first 1000 days may be critical for lifelong cardiovascular health beyond managing later childhood weight. Trial registration: ISRCTN08850194, retrospectively registered December 14, 2006. https://www.isrctn.com/ISRCTN08850194?q=ISRCTN08850194&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10 . What is Known • Childhood body mass index (BMI) is positively associated with blood pressure at later life. What is New • This study identifies distinct weight, length, BMI, and weight-for-length growth trajectories from birth to two years of age and links rapid weight-related growth trajectories to elevated blood pressure in early adolescence. • Using causal mediation analysis, it shows adolescent BMI largely mediates the association for systolic, but not diastolic, blood pressure, highlighting interventions within the first 1000 day for lifelong cardiovascular health beyond managing later childhood weight.

Vitamin K (VK) deficiency is a condition that puts newborn infants at increased risk of vitamin K deficiency bleeding (VKDB) during the first 6 months of life. In Switzerland, current prophylactic guidelines have been shown to prevent VKDB effectively in healthy infants. They were implemented in 2003 and prescribe oral administration of VK (2 mg oral Konakion® MM (mixt micellar) hour 4, day 4, and week 4). As prophylaxis parental refusal has been increasingly reported, we prospectively tested the Swiss VKDB prophylaxis validity using a nationwide surveillance program (Swiss Paediatric Surveillance Unit) designed to detect all hospitalized VKDB cases. During 6 years (September 1, 2018, until August 31, 2024), nine VKDB cases were reported for 505,708 live births (1.78/10⁵, 95% CI 0.81/10⁵-3.38/10⁵). All infants were exclusively breast fed and had VKDB risk factors such as parental VK refusal and/or cholestasis. Both Swiss VKDB 2018-2024 and 2005-2011 incidences were similar.

Conclusion:  The Swiss VKDB prophylactic guidelines are still valid and effective for healthy infants if applied appropriately.

What is known: • Infantile vitamin K deficiency bleeding (VKDB) can be prevented by either intramuscular or oral VK administration in healthy infants. • Parental VK prophylaxis refusal (reported as increasing in frequency) as well as unrecognized cholestasis are main risk factors for VKDB.

What is new: • Switzerland's 2003 VKDB prophylactic regimen (2 mg oral Konakion® MM (hour 4, day 4, and week 4) remains a valid recommendation for healthy infants. • Again, parental VK prophylaxis refusal and/or unrecognized cholestasis remain risk factors for VKDB.

Medical comorbidities are common in autistic children, yet patterns of co-occurrence at diagnosis-particularly in under-researched regions-remain poorly characterized. We examined the prevalence, distribution, temporal trends, and sex-specific clustering of medical comorbidities at ASD diagnosis in a large Chilean cohort. We performed a retrospective chart review of 544 children diagnosed with ASD between 2015 and 2023 at a specialized pediatric neurodevelopmental center. Comorbidities were identified through standardized caregiver interviews, clinical examination, anthropometric assessment, and clinician-verified medical record review. Analyses included prevalence estimates, temporal trends, and sex-stratified exploratory network analysis. At least one comorbidity was present in 90% of children. The most frequent were insomnia (61%), overweight (52%), allergic rhinitis/atopic dermatitis (28%), and constipation (27%). Underweight prevalence declined significantly over time (from 11% to 5%; p = 0.028), whereas other conditions remained stable. Exploratory network analysis showed high connectivity in both sexes, with denser clustering in girls. In boys, insomnia, overweight, constipation, and allergic disorders formed the main cluster; in girls, allergic disorders remained central, while underweight showed more limited connectivity within the network. Demographic characteristics did not differ between children with and without additional medical conditions.

Conclusion: Medical comorbidities are highly prevalent at the time of ASD diagnosis, with distinct sex-specific co-occurrence patterns that may guide early screening priorities. These findings support systematic, multidisciplinary assessment during the diagnostic process and highlight the need for longitudinal, multicenter studies to validate comorbidity clusters and clarify their developmental trajectories.

What is known: • Autistic children frequently have medical comorbidities such as sleep, nutritional, gastrointestinal, and allergic disorders. • The prevalence of individual comorbidities is documented, but patterns of co-occurrence at diagnosis-particularly in Latin American cohorts-remain understudied.

What is new: • In a large Chilean cohort of autistic children, 90% had ≥1 clinician-verified medical comorbidity at ASD diagnosis. • Sex-stratified exploratory network analysis showed a shared central cluster (insomnia, overweight, constipation, and ARAD), with higher overall connectivity in girls; underweight and epilepsy showed more limited connectivity at diagnosis.

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

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

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

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

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

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

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

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

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

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

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

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

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