Frontiers in Pediatrics

Congenital heart disease contributes substantially to chronic morbidity, growth impairment, and repeated healthcare utilization among children. Evidence regarding nutritional burden and outpatient healthcare patterns among pediatric patients with congenital heart disease in Indonesia remains limited. This study aimed to evaluate clinical characteristics, nutritional status, healthcare utilization, and factors associated with malnutrition among pediatric outpatients with congenital heart disease at Adam Malik General Hospital, Indonesia. A retrospective observational study was conducted using medical records of pediatric outpatients treated between January and December 2024. Demographic characteristics, cardiac diagnoses, nutritional status, complications, and outpatient visit history were analyzed. Logistic regression analysis was performed to identify factors associated with malnutrition. A total of 606 pediatric outpatients were included. Non cyanotic congenital heart disease predominated the cohort, with ventricular septal defect representing the most common diagnosis followed by patent ductus arteriosus and atrial septal defect. Nearly half of all patients demonstrated underweight or severe underweight nutritional status, while pulmonary hypertension emerged as the most frequent complication. Younger pediatric age groups and higher cumulative clinical burden independently increased the odds of malnutrition. Children with congenital heart disease at this tertiary referral center carried a substantial nutritional and clinical burden. Early nutritional surveillance and integrated long term outpatient management may improve growth outcomes and reduce chronic disease burden in resource limited settings.

ObjectiveTo examine associations of BMI-related polygenic scores (PGSs) with BMI-for-age z-score (BMIz), height-for-age z-score (HAZ), and weight; assess sex-specific effects; and test PGS-by-diet interactions in youth experiencing the double burden of malnutrition. MethodsIn this cross-sectional study of Filipino youth aged 6-19 years, we analyzed genome-wide genotype, anthropometric, and dietary data from two 24-hour recalls. Four ancestry-standardized BMI PGSs were evaluated using linear regression adjusted for age, sex, and ancestry principal components, with platform-specific estimates combined by fixed-effects meta-analysis. ResultsAll four PGSs were positively associated with BMIz ({beta} range: 0.119 - 0.320). The strongest association was observed for the multi-ancestry score PGS005202 ({beta} = 0.320; P = 2.39 x 10-9; {Delta}R2 = 4.98%). No PGS was associated with HAZ. PGS005202 and PGS005279 were associated with higher weight independent of HAZ. A significant PGS000716-by-sex interaction was observed for BMIz (q = 0.034), with an association in boys ({beta} = 0.253; P = 0.002) but not in girls ({beta} = -0.007; P = 0.93). No PGS-by-diet interaction remained significant after multiple-testing correction. ConclusionsBMI-related PGSs were associated with adiposity-related traits, but not linear growth, in Filipino youth. Findings support sex-stratified analyses and further evaluation of ancestry-inclusive PGSs in similar pediatric settings.

Purpose: To assess maternal knowledge of preterm infant care in Gaza and identify clinically actionable education priorities in a resource-constrained neonatal setting. Methods: A cross-sectional survey was conducted among 170 mothers of premature infants admitted to neonatal departments in four government hospitals. A 30-item interviewer-administered questionnaire assessed knowledge across thermoregulation, feeding, phototherapy, and infection and skin care. Bivariate analyses, ordinal logistic regression, adjusted predicted probabilities, and exploratory clinical-priority gap analyses were conducted. Results: Overall knowledge was moderate, with a mean score of 64.1% (SD 22.3). Knowledge was classified as poor in 53 mothers (31.2%), good in 41 (24.1%), and excellent in 76 (44.7%). Knowledge differed across domains (p<0.001), with feeding weakest (53.6%) and infection and skin care strongest (73.8%). Not receiving specialist premature-care antenatal follow-up was independently associated with lower odds of higher knowledge (adjusted OR 0.34, 95% CI 0.15-0.80, p=0.013). Mothers without specialist follow-up also had a higher adjusted probability of poor knowledge than those who received it (37.4% vs 18.1%) and more clinical-priority gaps (IRR 1.28, 95% CI 1.04-1.57, p=0.019). Among the 10 lowest-scoring items, 110 mothers (64.7%) had five or more gaps. Conclusion: Maternal knowledge was uneven, with clinically important gaps in practical care domains. Domain-specific education checklists may strengthen antenatal counselling, bedside teaching, and discharge preparation in similar constrained neonatal settings.

Background: 48,XXYY syndrome is a rare sex chromosome aneuploidy (SCA) characterized by neurodevelopmental deficits and medical comorbidities. The limited information available in the literature is almost exclusively limited to postnatally diagnosed cases. This study aims to describe the early medical and developmental features of prenatally identified 48,XXYY infants, with comparisons to 47,XYY, 47,XXY cohorts, and typical populations, as well as previously reported postnatally diagnosed 48,XXYY cases. Methods: The eXtraordinarY Babies Study prospectively follows children prenatally identified to be at high risk for SCA with annual medical and neurodevelopmental evaluations. Data presented herein include the prevalence of medical conditions, developmental milestones, developmental and adaptive functioning assessment scores, and therapy utilization in participants confirmed to have 48,XXYY. Comparisons were made between this cohort and the typical population, infants with 47,XYY and 47,XXY also enrolled in the eXtraordinarY Babies Study, and a 2008 cohort of individuals postnatally identified 48,XXYY. Results: Infants with 48,XXYY exhibited a range of early medical features, including high rates of feeding and GI disorders (breastfeeding difficulties, gastroesophageal reflux, and eosinophilic esophagitis), allergic disorders (food allergies and environmental allergies), and hypotonia. Developmental and adaptive functioning scores indicated delays in motor, communication, and social domains, with nearly all infants receiving speech therapy, physical and/or occupational therapy. Comparisons with the 47,XYY and 47,XXY cohorts revealed more medical and developmental challenges in the 48,XXYY group, however there was variability and some overlap with both the general population and sex chromosome trisomy conditions. Additionally, comparison to the 2008 postnatally identified 48,XXYY cohort indicated that while prenatal diagnosis allowed for earlier intervention, developmental outcomes in the first years of life were similar between the two groups. Conclusions: 48,XXYY diagnosed prenatally facilitates early monitoring, anticipatory guidance, and proactive referrals for medical evaluations and intervention, given developmental delays and medical challenges are more common in infancy and early childhood compared to the general population and trisomy SCAs. These findings provide valuable insights for genetic counselors and healthcare providers, emphasizing the spectrum of medical and developmental findings and importance of early and proactive care to support individual outcomes. Prospective study of this prenatally identified cohort will provide important natural history and phenotypic variability in XXYY, as well as identification of predictors of health and developmental outcomes.

Background: Apnoea of prematurity is common and may cause desaturation and/or bradycardia. There is marked variability in infants cardiorespiratory responses to apnoea, despite standardised clinical thresholds. Factors influencing apnoea-related cardiorespiratory instability and whether instability can be predicted warrant investigation. Methods: 181,511 apnoeas >5 seconds were identified from continuous physiological recordings from 146 preterm infants <37 weeks postmenstrual age. Cardiorespiratory instability was defined as bradycardia (>30% heart rate reduction) and/or oxygen desaturation (<85%). Mixed-effects models assessed clinical, demographic and dynamic modulators of the relationship between apnoea duration and cardiorespiratory instability. Machine learning (XGBoost) was used to train models to predict apnoea-related cardiorespiratory instability. Results: Longer duration apnoeas were associated with increased instability, although variability was substantial and 3.6% of apnoeas <10 seconds were associated with cardiorespiratory instability, while 61.2% of apnoeas [&ge;]20 seconds were not. Multiple clinical/demographic (postmenstrual and gestational age, sex, weight z-score, and ventilation mode) and dynamic (baseline heart rate, oxygen saturation, and recent apnoea clustering) factors were associated with increased instability risk. Apnoea-related cardiorespiratory instability could be predicted with a balanced test accuracy of 75.8% when incorporating all features, while a model using only clinical/demographic features achieved 66.0%. Conclusions: Multiple factors influence cardiorespiratory responses to apnoea. Predictive modelling may enable personalised apnoea definitions, improving individualised care.

Exclusive breastfeeding (EBF) for the first six months is a critical protective practice, yet determinants beyond knowledge among young mothers in peri-urban sub-Saharan Africa remain insufficiently understood. This facility-based cross-sectional study assessed factors associated with EBF among 413 mothers aged 15-29 attending postnatal services at two public facilities in Lusaka, Zambia (Aug-Oct, 2025). Data from structured interviewer-administered questionnaires covered demographic, socioeconomic, cultural, mental health, peer support, and neonatal care knowledge factors. Logistic regression produced adjusted odds ratios (AOR) with 95% confidence intervals (CI). Although 99.5% reported receiving neonatal care education, 71.6% practiced EBF. Mothers aged 25-29 had lower odds of EBF than those aged 15-19 (AOR = 0.17, 95% CI: 0.03-0.99). Married mothers were more likely to exclusively breastfeed (AOR = 4.83, 95% CI: 1.59-14.65). Separated mothers also showed higher odds (AOR = 13.66, 95% CI: 1.89-98.71), although the wide confidence interval indicates substantial uncertainty and its based on a small subgroup (n=13). Formal employment was positively associated with EBF (AOR = 3.94, 95% CI: 1.12-13.85). Avoidance of specific traditional neonatal practices (AOR = 0.14, 95% CI: 0.04-0.53) and not consulting traditional healers (AOR = 0.06, 95% CI: 0.02-0.18) were also independently associated with EBF. Postnatal anxiety showed a strong inverse association (AOR = 0.14, 95% CI: 0.03-0.76). Parity, income, education, neonatal care awareness, and receipt of health education were not independently associated. These findings suggest that EBF in peri-urban Lusaka is shaped more by social, cultural, and psychological influences than knowledge alone, underscoring the need to integrate mental health screening, culturally sensitive counselling, and family-centred support within postnatal services to improve EBF uptake among young mothers in similar settings.

Background: Improved survival of adolescents with congenital heart disease has shifted the focus to examine health-related quality of life and address challenges in transition to adult care. We aim to describe how congenital heart disease complexity, gender, number of interventions, and Fontan circulation may affect the health-related quality of life and transition readiness of adolescents with congenital heart disease. Methods: We conducted a single-center cross-sectional study involving 536 patients aged 14 to 18 years old who attended a nurse-led, pediatric to adult care cardiac transition clinic, from 2020 to 2024. health-related quality of life was evaluated using the PedsQLTM 4.0 Generic Core Scales and the PedsQLTM 3.0 Cardiac Module. Patients were screened for anxiety and depression using the PHQ-9 and GAD-7. Transition readiness was assessed using the Transition-Q score. Results: The median age of patients was 16 years old and 44% self-identified as female. PedsQLTM 4.0 Generic had a median overall score of 77 (IQR 67?87), with no significant difference according to congenital heart disease severity. Female patients had significantly lower overall PedsQLTM 4.0 score (p=0.028) and lower physical and emotional functioning scores (p=0.005, p<0.001, respectively) when compared to males. Physical functioning scores were lower amongst patients with Fontan circulation compared to non-Fontan patients (p=0.003), although overall PedsQLTM 4.0 score and transition readiness scores were similar to those with complex biventricular congenital heart disease. Number of previous interventions were inversely associated with overall PedsQLTM 4.0 score (p=0.036). Moderate to severe symptoms of depression or anxiety were reported in 30% of screened patients and were associated with 2 significantly lower PedsQLTM 4.0 scores (p<0.001). Transition readiness was significantly lower in patients with moderate and complex compared to those with simple congenital heart disease (p<0.001). Transition readiness improved with repeat transition clinic visits (p=0.004) whereas PedsQLTM 4.0 score did not change significantly. Conclusion: In this large cohort of adolescents with congenital heart disease, health-related quality of life was lower than population norms. Female gender, higher interventional burden, and anxiety or depressive symptoms are associated with lower health-related quality of life scores rather than anatomical severity or Fontan physiology. Transition readiness was lower in complex disease; it has improved with a structured, nurse-led transition clinic, demonstrating modifiability. Consequently, adolescent congenital heart disease care requires a multidisciplinary approach including psychosocial screening, especially for high-risk groups, and structured transition planning to improve long-term outcomes.

Background Sierra Leones neonatal mortality rate is among the highest in the world. Koidu Government Hospital opened a Special Care Baby Unit (SCBU) in 2020. To increase knowledge of the SCBU health care providers (HCPs), a neonatal curriculum was implemented to facilitate HCP education on management of neonatal conditions. The aim of this study was to understand the effect of the curriculum on knowledge acquisition and the perception of the teaching methodologies among participating HCPs. Methods US-based mentors facilitated a two-phase, flipped classroom, virtual neonatal medicine curriculum between October 2024 and April 2025, followed by one-week in-person education sessions with SCBU HCPs. With each phase, participants completed pre- and post-test educational assessments. At the end of the curriculum, they completed a subjective assessment to capture perceptions related to the quality of teaching methodologies integrated within the curriculum. Wilcoxon signed rank test was used to assess pre- versus post-test change. Descriptive statistics were used to analyse the subjective assessment. Results Thirty-eight participants completed the educational assessments, 30 (79%) took all four pre- and post-tests; 25/38 (65.8%) were female, 27 (71.1%) were nurses. Median correct answers for both phases increased from the pre- to post-test for individual learners [Phase 1, pre-test 14/27 (51.9%), post-test 23/27 (85.2%), p<0.001], [Phase 2, pre-test 14/25 (56.0%), post-test 23/25 (92.0%), p <0.001]. Thirty-one participants completed the subjective assessment, of whom 96.8% (30/31) rated the curriculum to be "very effective." All 31 participants indicated that the in-person instruction was "very helpful." Through open text responses, they offered valuable insight into challenges, strengths, and next steps. Conclusion This neonatal curriculum resulted in significantly increased knowledge and was well regarded. Adapting this curriculum or similar curricula show promise to improve the quality of care for small and/or sick neonates in low resource settings.

Abstract Background: Pediatric respiratory infections are a leading cause of morbidity and mortality globally, representing a major health challenge in children. Research Gap: Despite extensive studies on epidemiology, clinical management, and specific pathogens, no bibliometric analysis has systematically evaluated the most influential research in this field. Objectives: This study aimed to evaluate the characteristics of the top 50 most-cited articles on pediatric respiratory infections and to identify emerging research trends. Methods: The Web of Science database was searched without publication year restrictions. Independent reviewers screened studies based on predefined inclusion and exclusion criteria. Data were extracted using a standardized form, including study details. Results: The 50 most-cited articles ranged from 34 to 384 citations and showed a right-skewed distribution with a sharp drop after the top ten. Publication years ranged from 1978 to 2021, with over half published in the 2010s. Articles appeared in 31 journals, with Pediatrics contributing five. Leading countries were the United States (18%), China (12%), and Canada (10%), with research largely concentrated in high-income regions and limited multicenter collaboration. Cohort studies dominated (66%), while randomized trials (12%) and reviews/meta-analyses (16%) were less common. Research clustered around three themes: clinical outcomes (e.g., pneumonia, bronchiolitis); viral etiology/diagnostics (e.g., RSV, SARS-CoV-2); and antimicrobial stewardship. Conclusion: Over the past decades, pediatric respiratory infection research has developed but remains unbalanced, relying heavily on observational evidence from high-income countries, with limited randomized trials, systematic reviews, multicenter collaborations, and LMIC-led studies. These findings provide insights that may direct researchers to identify potential focal points and guide future research in the field.

Abstract Background: Mean platelet volume (MPV) is a simple, low-cost biomarker that reflects platelet activation. Its prognostic value in septic shock remains controversial. We aimed to determine whether MPV at intensive care unit (ICU) admission is associated with hospital mortality in patients with septic shock. Methods: Retrospective cohort study of consecutive adults with septic shock (Sepsis-3 criteria) admitted to a single ICU. MPV, severity scores (SOFA, APACHE II, SAPS II), procalcitonin, and clinical data were collected. The primary outcome was in-hospital mortality. Spearman correlation, univariate and multivariate logistic regression (with Firth's correction), ROC curves, and subgroup analyses were performed. Results: Fifty-eight patients were included; mortality was 58.6%. MPV did not differ between non-survivors and survivors (13.09 {+/-} 1.37 vs. 12.66 {+/-} 1.45 fL, p = 0.259). MPV showed a weak correlation with procalcitonin ({rho} = 0.394, p = 0.002) but not with severity scores. In multivariate analysis adjusting for age, sex, SOFA and comorbidity count, MPV was not an independent predictor of mortality (OR 1.075, 95% CI 0.682-1.755, p = 0.749). The area under the ROC curve for MPV was 0.598 (95% CI 0.444-0.752), significantly lower than that of SOFA (0.837) and procalcitonin (0.836). Subgroup analyses showed no significant association between MPV and mortality in any stratum. Conclusions: In this cohort of septic shock patients, MPV at ICU admission was not associated with hospital mortality and had poor discriminative ability. Widely used severity scores and procalcitonin remain superior prognostic markers. MPV should not be used as a prognostic tool in septic shock. Keywords: Septic shock, Mean platelet volume, Mortality, SOFA, Procalcitonin, Biomarker

Background/Objectives: Children aged 6-24 months are highly vulnerable to malnutrition during conflict because they depend on breastfeeding, complementary feeding and functioning nutrition services. This study assessed nutritional status, socioeconomic correlates, maternal knowledge and primary health care centre (PHCC) nutrition service gaps in Gaza. Subjects/Methods: This cross-sectional study was conducted at Al-Daraj Martyrs Health Centre, one of the remaining functioning PHCCs in Gaza City during the study period, between late August and October 2025. Mother-child pairs were recruited by convenience sampling. Of 276 approached, 200 were included after non-response and exclusion of questionnaires with missing anthropometric data. Data came from structured interviews and medical records; haemoglobin results were available for 55 children. Results: Stunting affected 12.5% of children, underweight 20.1%, wasting 20.8%, and anaemia 63.6% of the haemoglobin-tested subsample. Underweight was associated with household food shortage (p=0.013) and previous malnutrition treatment (p=0.002), wasting with child age category (p=0.0024), and anaemia with paternal unemployment (p=0.020). Maternal knowledge and practice scores were positively correlated (r=0.177, p=0.012), but neither was independently associated with stunting or underweight in adjusted models. PHCC nutrition support was limited, with 71.0% of mothers reporting nurse-provided nutrition advice and 52.5% reporting growth-chart review. Conclusions: In this clinic-based sample from conflict-affected Gaza, malnutrition among children aged 6-24 months was substantial. The overall pattern suggests that nutritional risk was shaped more by structural deprivation and weakened PHCC support than by maternal knowledge alone. These findings underline the need to restore essential nutrition services and improve access to adequate food for young children.

Aim: To systematically evaluate evidence on the effects of post-discharge early developmental intervention programs (EI) on behavioral development, quality of life, participation, executive functioning, parent-child interaction, and use of medical services from infancy through adolescence in children born preterm. Method: Four bibliographic databases and one trial registry were systematically searched for randomized controlled trials up to April 23, 2024. Two reviewers independently screened studies and extracted data. In clinically and methodologically comparable studies, random-effects meta-analysis were performed. Risk of bias was assessed with the Cochrane RoB 2 tool, and certainty of evidence with the GRADE approach. Results: Twenty-six studies met inclusion criteria, eleven studies including 2,315 preterm born infants reported relevant outcomes, and seven contributed to meta-analyses. Most reported results showed some concerns or high risk of bias; certainty of evidence ranged from very low to moderate across outcomes. EI may offer small benefits for selective attention, behavioral problems and parent-child interaction. Little to no effect was found for special educational needs, language skills, executive functioning and the use of medical services. No included studies evaluated the effect of EI on ADHD, quality of life, or participation related to mobility or leisure activities. Interpretation: EI may improve problems typically seen in preterm children and should be offered especially to those with additional medical or social risk factors. High-quality, contemporary trials are needed to establish reliable clinical recommendations regarding EI strategies and complementary interventions throughout childhood.

Background and ObjectivesChildren with Down syndrome (DS) have a high prevalence of obstructive sleep apnea (OSA) due to anatomic, neuromuscular, immunological and metabolic factors, yet the contribution of the tonsillar microbiome to airway obstruction in this population remains unexplored. We hypothesized that DS-associated OSA would be associated with a distinct tonsillar microbiome compared to non-DS OSA. MethodsTonsillar tissue from 22 DS and 18 NDS participants were analyzed by 16S rRNA sequencing. Alpha and beta diversity were assessed using Faiths phylogenetic diversity and UniFrac distances, respectively, and significantly different taxa were identified with ANCOM-BC and Mann-Whitney testing. ResultsAlthough overall microbial richness and community structure were similar between groups, overweight DS participants demonstrated increased phylogenetic diversity compared to normal-weight DS peers. Taxonomic profiling of the entire patient cohort revealed that in DS tonsils there were selective alterations in key genera with selective depletion of Haemophilus and enrichment of Staphylococcus, Rothia, and Lactobacillales. Haemophilus abundance correlated positively with tonsil weight in both cohorts. ConclusionsThese findings suggest that while global diversity is preserved, specific microbial shifts distinguish the DS tonsillar niche, potentially reflecting altered immune and metabolic environments associated with trisomy 21. Understanding these microbial differences may reveal mechanisms underlying the higher incidence and persistence of OSA in DS and inform targeted therapeutic strategies.

BackgroundPulmonary artery (PA) wave reflection is a key determinant of right ventricular (RV) afterload. RV function is the most important factor determining long-term prognosis in patients with surgically repaired tetralogy of Fallot (rTOF). This study aimed to evaluate PA wave reflection in rTOF using RV pressure phase plane (PPP) analysis, and to identify the clinical, morphological, and hemodynamic characteristics associated with increased PA wave reflection in patients with rTOF. MethodsAugmentation pressure (AugPr) during late systole was quantified using the inflection point of systolic dP/dt on the PPP. The ratio of AugPr to RV systolic pressure (RVSP) was defined as the AugPr index. The study included 87 patients with rTOF (mean age, 15.9 {+/-} 10.0 years), 17 control subjects (13.3 {+/-} 6.3 years), and seven patients with pulmonary arterial hypertension (PAH) (16.4 {+/-} 11.7 years). The rTOF cohort was categorized according to surgical procedure: pulmonary valve-sparing repair (PVS, n = 5), transannular patch repair (TAP, n = 34), and the Rastelli procedure (n = 48). ResultsThe prevalence of AugPr was 0% in the control group, 100% in the PAH group, and 26.4% in the rTOF group (p < 0.0001). Among the surgical subgroups, the prevalence was 0% in PVS, 14.7% in TAP, and 41.7% in the Rastelli group (p < 0.0027). AugPr and the AugPr index were significantly higher in the Rastelli group than in the other two groups (p = 0.0447 and 0.0433, respectively). In addition, AugPr showed significant correlations with RVSP, RV outflow tract obstruction, maximal dP/dt, and pulmonary regurgitation grade (all p < 0.05). ConclusionsPA wave reflection can be clearly visualized using PPP. The Rastelli group demonstrated a higher prevalence and magnitude of PA wave reflection, suggesting a greater increase in RV afterload compared with other surgical repair types.

Purpose: Obstructive sleep apnea (OSA) is a treatable chronic condition associated with significant health and societal consequences. Primary care providers (PCPs) often manage OSA with support from sleep specialists but face challenges navigating a complex system of care. By developing a Journey Map, we sought to identify factors influencing primary care OSA management and the associated PCPs' perspectives and emotions. Methods: Twenty-one Calgary-based PCPs were interviewed as part of a study evaluating a primary care management pathway for OSA. We used conventional content analysis, utilizing inductive coding to define journey phases and deductive coding via the Theoretical Domains Framework (TDF) to identify barriers and enablers. These were then mapped onto journey phases for OSA management to create a Journey Map. Results: The Journey Map included five phases of OSA care. PCPs described feeling neutral during the Learning phase and expressed neutral to positive emotions during the Patient Encounter and Diagnosing OSA phases. In contrast, the Initial Treatment and Ongoing Management phases were associated with neutral to negative emotional experiences. Barriers included limited OSA-related training and education, unclear roles among provider groups, and low patient engagement. Enablers included accessible knowledge resources, a shared key role in OSA screening, and availability of sleep testing. Opportunities to enhance primary care OSA management were identified at each step. Conclusion: This study identified several behavioural factors influencing PCP decision-making across the OSA care continuum. The Journey Map illustrates how high diagnostic confidence of PCPs shifts to escalating challenges and negative sentiment during treatment and long-term management of OSA. Keywords: obstructive sleep apnea; primary health care; health service delivery; process assessments; attitude of health personnel

Background: Pediatric dilated cardiomyopathy (DCM) is a leading cause of heart failure and transplantation, with variable prognosis and high early mortality. This study developed and validated a nomogram predicting short-term mortality risk to guide clinical decisions. Methods: The data were sourced from the Pediatric Cardiomyopathy Database at Shandong Provincial Hospital. Cox regression analysis was conducted to determine outcome-associated factors, and a nomogram was developed to estimate 1, 3, and 5year mortality risks for children with DCM. Model effectiveness was assessed through the concordance index (C-index) and area under the receiver operating characteristic curve (AUC). Additionally, calibration curves and decision curve analysis (DCA) were employed to evaluate the model's predictive accuracy and clinical relevance. Results: A cohort of 106 children diagnosed with primary DCM and who underwent genetic analysis was studied, with a median diagnostic age of 10 months (ranging from 5 to 84 months), comprising 50 girls (47.2%). The rate of detecting genetic mutations was 28.3%, uncovering 14 gene variants linked to DCM, with TTN mutations being the most common. Both univariate and multivariate Cox regression analyses indicated that both sex and NT-proBNP levels had a significant impact on survival rates among pediatric DCM patients.The model exhibited strong discriminative performance, calibration, and clinical net benefit, as assessed by the C-index, calibration plots, and decision curve analysis (DCA). Conclusions: The prediction model created in this research shows strong accuracy in forecasting survival rates at 1, 3, and 5 years for children with DCM, highlighting its significant relevance in clinical settings.

Background: 39M children worldwide are overweight or have obesity, accelerating risk for adult non-communicable diseases. Presently, interventions to prevent obesity have had limited success due to poor timing and lack of personalisation. Objective: We aimed to identify early-life predictors of childhood obesity (ChOB) that could aid targeting specific population subsets for obesity prevention interventional studies. Methods: Data were from the Raine Study Gen2 participants (n=1494). Anthropometric and genetic predictors evaluated included birthweight (BW), early-life BMI (1-3 years), and three polygenic scores (PGS) [two BW-PGSs (BW-PGS2016 and BW-PGS2019) and a ChOB-PGS], developed from BW and ChOB genome-wide-association-studies, respectively. Multivariate analyses were performed to investigate associations between predictors and child-BMI (5-, 8-, 10-years). Results: BW-PGS2019 associate with child-BMI at 5-years. BW-PGS2016 was not associated with child-BMI. Remaining predictors positively associate with child-BMI at 5-, 8- and 10-years (p<0.001). Early-life BMI, ChOB-PGS and BW accounted for up to 38.7%, 5.8% and 3.4% of the variability in child-BMI, respectively. Conclusions: Our data suggest early-life BMI is a better predictor of child-BMI than ChOB-PGS, and BW, accounting for up to ten-fold more variance in child-BMI. Future interventional studies to mitigate obesity could target early-life BMI as a marker to identify children at the highest risk.

BackgroundSickle cell disease (SCD) is the most common recessive genetic disorder, caused by pathogenic variants of the HBB gene. SCD is associated with a range of clinical manifestations, including vaso-occlusive crises, infections, and severe anaemia, which contribute to increased morbidity and mortality. The frequency of pathogenic alleles is high in Sub-Saharan African countries, with heterozygous carriers reaching up to 25% of the population. Several methods can be employed for molecular diagnostics, with HBB gene sequencing being the most precise. However, access to DNA analyses and sequencing in Low- and Middle-Income Countries (LMICs), where SCD prevalence is high, is limited. Understanding genetic profiles is crucial at both individual and population levels, as it can guide public health strategies and facilitate accurate genetic counselling. AimThis feasibility study aimed to demonstrate that a portable medical genetic laboratory (in suitcases) can be used to genotype individuals for the HBB A, S, and C alleles and their combinations within a few hours outside of a laboratory setting. Methods and resultsWe established a portable medical genetics laboratory capable of DNA extraction and isothermal DNA amplification using a commercially available kit for the A, S, and C alleles of the HBB gene. During one single study day, this portable lab was set up in a room where the Swiss Association of Patients with SCD was holding its annual meeting. We analysed the samples of 27 participants who were aware of their A, S, or C status. We collected buccal swabs and dried blood samples for genotyping. Genotype results for all participants were obtained within five hours after sample collection. In four cases, we observed discrepancies between the buccal swab and blood genotypes; three were resolved upon repeat testing, and one reflected donor chimerism following hematopoietic stem-cell transplantation. ConclusionsThis study demonstrates the feasibility and efficiency of using a portable medical genetics laboratory for rapid genotyping of HBB SCD alleles in community settings.This approach can improve access to molecular diagnostics in resource-limited environments. Such tools have the potential to significantly enhance local capabilities for genetic screening, counselling, and public health planning in regions heavily affected by SCD.

Background Migraine prevalence is higher among individuals with attention deficit hyperactivity disorder (ADHD). However, most research has focused on single-disease studies. This study used Global Burden of Disease (GBD) data to analyze co-occurrence patterns and related risk factors. Methods This study extracted the incidence and age-standardized incidence rate (ASIR) of migraine and ADHD among individuals across 204 countries and territories in GBD 2021, as well as exposure values for risk factors. To explore the co-occurrence patterns of migraine and ADHD and their spatial heterogeneity in global distribution, the incidence of both diseases was classified into quartiles, and countries and territories were categorized into three regional types: consistent regions, migraine-dominant regions, and ADHD-dominant regions. Global groupings by economy and risk factors were analyzed separately for co-occurrence patterns, and disease burden projections were made for 2050. Results In 2021, countries and regions were categorized into three distinct groups based on disease prevalence patterns: the majority exhibited an ADHD-dominant profile, predominantly found in high-SDI regions; a consistent pattern, where both diseases occurred at comparable levels, was primarily observed across South Africa and the Middle East, while a migraine-dominant pattern was identified in North Africa. Co-occurrence patterns were generally less prevalent in areas with lower socioeconomic development. Across all three patterns, high temperature exposure, iron deficiency, and metabolic risks emerged as the primary contributing factors. Looking ahead to 2050, the global burden of migraine was projected to stabilize, whereas the prevalence of ADHD was expected to experience a slight yet consistent increase. Conclusion This study systematically identifies the co-occurrence patterns of ADHD and migraine, along with their socioeconomic and environmental drivers, offering evidence-based insights for early prevention and targeted intervention in disease populations globally. Keywords GBD, migraine, ADHD, incidence, disease burden

ObjectiveRecurrent urinary tract infections (rUTIs) significantly decrease quality of life and antibiotics are becoming increasingly less effective due to antimicrobial resistance. Alternative effective treatment strategies are urgently needed for rUTIs. Prior studies have indicated that women can experience resolved or improved rUTI following electrofulguration (EF). To further investigate these findings, we report on the design and methodology behind a randomized trial examining two treatment arms: standard prolonged antibiotic treatment with nitrofurantoin (NF) alone or in combination with EF. Patients and MethodsThe aim of this randomized trial is to determine, at two institutions, the efficacy of two interventions for rUTI associated with early stages of chronic cystitis (stages 1 and 2): conventional 6 months low-dose (100mg) NF daily antibiotic suppression alone (NF) or conventional NF with EF (EF + NF). The study is also designed to analyze changes in the urinary microbiomes in the two different treatment arms and to determine the durability of clinical outcomes in both treatment arms at 2 years after the end of each intervention. The primary outcomes will be obtained from 6 to 18 months, as well as 18 - 30 months following completion of the original 6-month intervention. Failure is defined based on UTI symptoms documented by a validated questionnaire with a documented urine culture confirming a bacterial strain at each UTI episode following the end of the 6-month intervention. ConclusionsThis randomized trial is designed to examine the efficacy and durability of treating women with rUTIs using the standard of care of NF alone, or an EF procedure with NF.