Archives of Disease in Childhood

Background: Socioeconomic deprivation is associated with childhood morbidity, but nationwide evidence on critical illness and death in a health system with universal insurance coverage is scarce. We assessed the association between area-level deprivation and the population-level incidence of hospital admission, complex intensive care treatment (CICT), and CICT-related mortality in German children, and changes over time. Methods: Population-based analysis of complete German hospital discharge data, 2016 to 2023, covering all cases aged > 28 days to < 18 years. Cases were linked to the German Index of Socioeconomic Deprivation (GISD) via the municipality of residence and grouped into quintiles (Q1 least, Q5 most deprived). Incidence rates were calculated per 100,000 child years. Negative binomial regression adjusted for calendar year, with population as offset, yielded adjusted incidence rate ratios (aIRR) per one-quintile increase in deprivation; sensitivity analyses additionally adjusted for age group. Excess cases were estimated by applying Q1 incidence rates to Q2 to Q5. Results: Of 8,890,103 pediatric cases, 140,509 (1.6 %) received CICT and 3,386 (2.40 %) of these died. Incidence rose with deprivation from Q1 to Q5: admissions 6,191 to 9,255 per 100,000 child years, CICT 97 to 128, mortality 2.54 to 2.96. Each one-quintile increase was associated with higher risk of admission (aIRR 1.10, 95 % CI 1.10-1.11), CICT (1.07, 1.05-1.08), and mortality (1.04, 1.01-1.06); estimates were unchanged after age adjustment. Relative to Q1 rates, Q2 to Q5 accounted for 1,295,896 excess admissions (20.8 %), 11,254 excess CICT cases (12.6 %), and 194 excess deaths (8.7 %). Case fatality among CICT cases was lower in more deprived quintiles (2.35 % in Q5 versus 2.64 % in Q1), as were organ dysfunction and chronic conditions. Disparities in admission and CICT narrowed over time, whereas the mortality gradient persisted. Conclusions: Universal health insurance did not eliminate socioeconomic inequalities in pediatric critical illness. Deprivation increased the population burden of admission, intensive care, and death, but did not worsen outcomes once intensive care had begun, indicating that inequalities arise before pediatric intensive care and that prevention upstream in the care continuum is the primary target.

Importance: Preschool children in care are at high risk for psychosocial health concerns. Population-based evidence is limited. Objective: Estimate prevalence of psychosocial health concerns in children in care and not in care, and assess care-status differences stratified by deprivation. Design: Population-based cross-sectional study using 27-30 Month Health Review data from April 2013 to March 2023. Setting: Universal health review program in Scotland. Participants: 7887 children in care and 445 547 children not in care. Exposures: Care status at review, classified as in care or not. Main Outcomes and Measures: Four outcome categories (emotional, behavioral, and/or attentional; personal and/or social; speech, language, and/or communication; and other developmental concerns) plus an aggregate indicator of any of the four. We estimated adjusted odds ratios between children in care and not in care, including variation with deprivation. Models adjusted for sex, age, ethnicity, and deprivation. Results: Psychosocial health concerns were more common in children in care (2290; 29.0%) than children not in care (77 836; 17.5%; relative risk 1.66). Concerns were more common in children in care across all outcomes. The adjusted odds ratio comparing children in care with children not in care for any recorded concern was 1.86 (95% CI, 1.77-1.96). Adjusted odds ratios varied by outcome from 1.57 (95% CI, 1.49-1.66) for speech, language, and/or communication concerns to 2.49 (95% CI, 2.34-2.66) for emotional, behavioral, and/or attentional concerns. Relative inequities between children in care and not in care decreased with increasing deprivation from aOR of 1.58 (95% CI, 1.45-1.72) in the most deprived fifth of areas to 2.61 (95% CI, 2.25-3.03) in the least deprived fifth. Prevalence of any recorded concern increased with deprivation in both care groups. The relative risk comparing the most deprived with least deprived fifth of areas was 1.46 (95% CI, 1.29-1.66) among children in care and higher at 2.34 (95% CI, 2.29-2.40) among children not in care. Conclusions and Relevance: Psychosocial health inequities are evident at an early age between children in care and not in care, and vary with deprivation. Support for children in care and children living in more deprived areas should be prioritized.

Background Respiratory infections remain the leading infectious cause of death among children and adolescents, yet the share of these deaths that could be averted with currently feasible care is not routinely quantified. Existing amenable-mortality frameworks rely on cause lists and population-level mortality benchmarks and do not exploit information on how many episodes occur. We propose an episode-fatality-ratio (EFR) frontier approach and apply it to lower respiratory infections (LRI), whooping cough (pertussis) and upper respiratory infections (URI) in 204 countries, 1990-2023. Methods For each cause, country and year we computed EFR = deaths/incident episodes using Global Burden of Disease (GBD) 2023 estimates for ages 0-19 years. The frontier was defined as the 10th-percentile country EFR within each GBD super-region, cause and year; avoidable deaths = max(0, deaths - episodes x frontier EFR). Primary estimates are deterministic; 95% uncertainty intervals (UIs) come from 2,000 Monte Carlo draws. Sensitivity analyses varied the frontier percentile, applied an aspirational global frontier, constructed pertussis counterfactuals, and recomputed all estimates within the single under-5 age band. Results In 2023, 333,803 childhood deaths from lower respiratory infections (95% UI 289,123-417,460; 46.9% of LRI deaths) were avoidable. Summing the three causes deterministically gives 391,034 avoidable deaths (46.5% of 840,444); the combined figure is a deterministic sum, and a UI is available for the LRI component only. The pertussis (43,958; 39.0%) and URI (13,273; 81.0%) estimates are secondary: their deterministic point values fall below their own Monte Carlo intervals and the underlying death estimates carry very wide uncertainty (global pertussis UI 12,545-321,874). Avoidable deaths fell from 1,050,468 (44.9%) in 1990, but between 2019 and 2023 the avoidable share for LRI+URI barely moved (48.7% to 47.7%) while absolute avoidable deaths fell 14.5%, a pattern consistent with stalled convergence to the frontier. Sub-Saharan Africa plus South Asia held 73.1% of avoidable deaths in 2023 versus 41.8% in 1990; ten countries accounted for 59.1%. Conclusion Nearly half of childhood respiratory-infection deaths remain avoidable relative to within-region best practice, and the residual burden is increasingly concentrated in low-income settings. In the pertussis counterfactual, most countries kept pace with their regional frontier, so further gains require advancing the frontier itself through quality-of-care improvements.

Purpose: Outcome consequences of critically ill children treated outside of pediatric intensive care units (PICU) are unknown. We assessed case fatality of children receiving complex intensive care treatment (CICT) by treating department in Germany and explored reasons for admission to adult intensive care units (AICU). Methods: Retrospective study using the German nationwide hospital discharge dataset 2016 to 2023. Cases aged [&ge;] 28 days and < 18 years receiving CICT were classified as PICU, AICU, or interdisciplinary by department codes. Odds ratios (OR) for in-hospital case fatality were estimated in generalized linear mixed models with the hospital as random effect, adjusted for age, acute organ dysfunction, and chronic conditions. Excess deaths were estimated and a survey among pediatric and adult intensivists was analyzed qualitatively. Results: Of 143,034 cases, 67.8 % were treated in PICUs, 14.0 % in AICUs, and 18.2 % were interdisciplinary. The crude OR for death in PICUs versus AICUs was 1.14 (95 % CI 1.03 to 1.26), reversing to 0.73 (0.63 to 0.84) after adjustment. For PICU and interdisciplinary cases combined versus AICU, the fully adjusted OR was 0.61 (0.54 to 0.70). Estimated excess deaths across the study period were 100, rising to 191 when interdisciplinary cases counted as pediatric. Capacity constraints, organizational factors, and clinical expertise were the main domains underlying AICU admissions. Conclusions: Children treated outside of PICUs had higher risk-adjusted case fatality, while crude figures pointed in the opposite direction. The findings support treating critically ill children in settings with routine pediatric intensive care experience.

BACKGROUND: We used anthropometric data from electronic health records (EHRs) of Swiss childrens hospitals to evaluate growth references and estimate centile curves. METHODS: We received EHRs extracted from seven Swiss childrens hospitals and analysed two samples: all children with a height, weight, body mass index (BMI), or head circumference recording, and a subsample restricted to children without diseases potentially affecting growth, weighted to represent the general population. We calculated mean z-scores based on the World Health Organization growth references adopted for Switzerland in 2011 (CH-WHO 2011) and current Swiss growth references (Swiss 2026). We estimated sex-specific centile curves in the subsample using generalised additive models for location, scale, and shape. RESULTS: We included 213,868 children with height, 448,002 with weight, 209,244 with BMI, and 67,397 with head circumference recordings. Mean z-scores in the all children sample were (CH-WHO 2011; Swiss 2026): height (0.10; -0.19), weight (0.16; -0.09), BMI (0.04; -0.07), head circumference (-0.28, -0.28); and in the subsample: height (0.34; 0.00), weight (0.27; 0.01), BMI (0.18; 0.05), and head circumference (0.04; 0.01). The 50th height, weight, BMI, and head circumference centiles of girls and boys in the subsample closely followed those of Swiss 2026, with slightly wider 3rd and 97th centiles in infancy and adolescence. CONCLUSION: Height, weight, BMI, and head circumference centiles aligned well with the Swiss 2026 growth references in Switzerland, demonstrating that hospital EHRs could contribute to future growth references.

Background. Designing high-quality Objective Structured Clinical Examination (OSCE) stations is a time-consuming process. Generative artificial intelligence (AI) represents a promising path to accelerate content creation by automating the generation of scenarios. A growing number of AI tools is now available for this purpose. Objective. To assess the variability between generative AI models in their ability to produce OSCE stations in the field of paediatrics. Methods. A structured prompt was developed based on the French national OSCE guidelines for medical education. Five distinct AI models were provided with this prompt, alongside the neonatal jaundice chapter from the French pediatric reference textbook, to generate 6 complete OSCE stations. Results. Prompt compliance was high for ChatGPT 5.1, ChatGPT 5.2, Gemini 3.0 Pro, and Claude Opus 4.5, while it was lower for Grok 4.1. Expert-rated quality was generally high, with few factual errors or missing information across models. However usability differed significantly between models. This was also true for several quality dimensions such as checklist clarity, embedding of checklist answers within vignettes, and ease of standardized patient formation. ChatGPT 5.1 required the most revisions and Gemini most often rated usable as is. Significant inter-model differences were observed in diagnostics, only with ChatGPT 5.1 sampling all three neonatal jaundice categories. Contextual variables showed systematic narrowing across models. Clinical grid density was consistent (10-12 items per station), but thematic distribution differed markedly. Soft skills coverage varied significantly across models (p=0.002), none of them consistently representing all communication competency domains. Conclusion. Large language models can generate structurally compliant OSCE stations, but surface compliance conceals substantive inter-model differences in diagnostic coverage, contextual diversity, and soft skills representation, that compromise content validity. No model currently meets the criteria for unsupervised deployment in a summative assessment bank. The choice of model carries pedagogical implications and expert curation remains essential before integration into high-stakes assessment workflows.

Background: Exclusive breastfeeding may protect infants against common infections and support healthy growth and development. Working mothers may face constraints on exclusive breastfeeding arising from work schedules, separation from their infants, and inadequate breastfeeding support. National evidence on the individual, healthcare-related, and contextual factors associated with exclusive breastfeeding among working Ghanaian mothers appears to remain limited. Design: Cross-sectional secondary analysis. Setting: Nationally representative survey covering urban and rural communities across all 16 administrative regions of Ghana. Participants: The analysis included 620 currently working mothers whose youngest living infants were aged 0-5 completed months and lived with them. The complete-case multivariable analysis included 619 mother-infant pairs. Primary outcome measure: Current exclusive breastfeeding, defined using the standard 24-hour infant-feeding indicator. Infants were classified as exclusively breastfed when they received breast milk without water, formula, animal milk, other liquids, or solid or semi-solid foods during the preceding day or night. Oral rehydration solution, vitamins, minerals and prescribed medicines were permitted. Aim: To estimate the prevalence of exclusive breastfeeding and examine its individual, healthcare-related and contextual correlates among working mothers of infants aged 0-5 months in Ghana. Methods: Birth Recode data from the 2022 Ghana Demographic and Health Survey were analysed. Unweighted frequencies and survey-weighted percentages described the study population. Design-adjusted Wald tests assessed bivariate associations. Survey-weighted binary logistic regression estimated adjusted odds ratios (AORs) and 95% confidence intervals (CIs), accounting for sampling weights, primary sampling units, and strata. Results: The survey-weighted prevalence of exclusive breastfeeding was 54.3% (95% CI: 49.2-59.3). Ethnicity, mode of delivery, region, and community poverty appeared to be statistically significant in the bivariate analyses. In the adjusted model, region was jointly associated with exclusive breastfeeding (p = 0.004). Mothers in the Northern (AOR = 4.93; 95% CI: 1.5-16.17) and Savannah (AOR = 4.22; 95% CI: 1.08-16.41) regions had higher odds than mothers in the Western Region. Mothers in low-education communities had lower odds than those in high-education communities (AOR = 0.54; 95% CI: 0.30-0.98). Although Guan mothers had higher odds than Akan mothers, the overall association with ethnicity was non-significant, and the estimate appeared imprecise. Maternal age, individual education, religion, parity, wealth, infant sex, antenatal care, postnatal care, and residence were not independently associated with exclusive breastfeeding. Conclusion: The prevalence estimate suggests that slightly more than half of working mothers exclusively breastfed their infants. Regional and community differences appeared more pronounced than those associated with most measured individual characteristics. Regionally responsive breastfeeding support and practical community education may contribute to improved coverage. Workplace recommendations require further evidence because employment conditions were not measured directly. Keywords: Exclusive breastfeeding; working mothers; infant feeding; maternal employment; regional inequalities; community education; Ghana; 2022 Ghana Demographic and Health Survey; survey-weighted analysis.

Background The historic decline in childhood pneumonia mortality was driven substantially by single-pathogen vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Yet the pathogen spectrum underlying child pneumonia deaths is diversifying: the effective number of pathogens rose from 5.57 in 1990 to 9.94 in 2023, and the residual burden is shifting toward opportunistic and hospital-associated pathogens for which no licensed childhood vaccines exist. This paper asks how resources should be sequenced between single-pathogen interventions and platform investments as this transition proceeds. Methods We analyzed Global Burden of Disease Study 2023 deaths from 29 pathogens in ages 0-19 years by super-region, combined with WHO/UNICEF Estimates of National Immunization Coverage (WUENIC) for PCV3 and Hib3. We quantified the spectrum transition under two denominators (26- and 29-pathogen calibers), constructed a share-by-intervenability matrix assigning each pathogen to a dominant intervention channel (vaccine-reachable, mixed, platform-sensitive) under explicit classification rules, compared platform-sensitive deaths with a transparently computed scenario of residual vaccine-preventable deaths, and cross-classified pathogens by age tropism and poverty lock. We anchored platform interventions to verified published evidence. Results The vaccine-preventable group share fell from 54.0% to 40.2% while the opportunistic/hospital group rose from 18.1% to 23.1% (29-pathogen caliber, 1990-2023). Super-region vaccine coverage showed no significant association with pathogen-share change (PCV3 Spearman rho = 0.108, p = 0.818; Hib3 rho = -0.036, p = 0.939), a null result we report as evidence that simple coverage-burden correlations do not hold at the regional level, not as evidence against vaccine value. In 2023, vaccine-reachable pathogens accounted for 441,410 deaths (45.7%, channel including COVID-19), mixed for 126,926 (13.1%), and platform-sensitive pathogens for 396,995 (41.1%). Platform-sensitive deaths were 2.9-5.1 times the scenario estimate of residual vaccine-preventable deaths (52,435-77,512). Nine of 14 classifiable pathogens fell into the poverty-locked, infant-tropic cell (480,922 deaths; Fisher OR = 9.0, p = 0.1758). Conclusions The marginal value of single-pathogen strategies declines as the spectrum diversifies and residual deaths concentrate in platform-sensitive, poverty-locked, infant-tropic pathogens. Vaccine scale-up remains a certain and sizeable opportunity; the next increment of marginal resources should increasingly fund platform capabilities (oxygen systems, antimicrobial access and stewardship, infection prevention and control, referral, and nutrition) delivered as a package to the populations where the residual burden is locked.

Background Obtaining uncontaminated urine samples from children can be difficult. Clean catch urine (CCU) is non-invasive but may be slow and lead to a contaminated sample, whereas transurethral bladder catheterisation (TUBC) and suprapubic aspiration (SPA) are invasive. We assessed the feasibility of randomising children to a definitive trial. Methods FROG was a multicentre, randomised feasibility trial with a mixed-methods perspectives study, health-economic analysis and stakeholder consensus meeting. Children under 16 years requiring urine testing for suspected urinary tract infection (UTI) who could not provide a midstream sample were eligible for the feasibility trial. Parents, children and healthcare professionals were eligible for the perspectives study and consensus meeting. Results Of 703 children screened, 170 were offered the study and 99 were recruited. Overall, 64/170 (37.6%) consented to randomisation, exceeding the feasibility threshold (33%); 32 were allocated to CCU and 32 to TUBC. The allocated method was received by 46/64 (71.9%); delays, unsuccessful collection and distress contributed to non-receipt. Among participants with available cultures, contamination occurred in 2/12 (16.7%) allocated CCU and 0/6 allocated TUBC. No participants consented to randomisation involving SPA. The perspectives study included 14 parent interviews, 89 parent questionnaires and 28 staff across 5 focus groups and 1 interview. CCU and TUBC were considered acceptable, although participants balanced speed and accuracy against pain and distress. SPA availability and acceptability were limited. A total of 19 stakeholders attended the consensus meeting; 94% supported recruiting children aged under 18 months and 100% supported comparing CCU with TUBC, without SPA. Accuracy was the highest-ranked outcome. Conclusions A definitive trial comparing CCU-first with TUBC-first in children aged under 18 months is feasible. Its primary outcomes should reflect diagnostic accuracy and clinical consequences of contamination, with successful collection, collection time, pain and distress assessed as key secondary outcomes.

Gastrointestinal (GI) conditions are common among children with neurodevelopmental disabilities (NDDs), and are associated with functional impairment, behavioral symptoms, and increased health care utilization. A unique relationship between autism and GI dysfunction has been proposed, leading to a focus on autism in GI research, management guidelines, and clinical tool development. Leveraging >20 years of electronic health record data and a cohort of 42,204 cases with attention-deficit/hyperactivity disorder, autism, cerebral palsy, epilepsy, or intellectual disability and 297,402 controls without NDDs, we quantified associations between NDDs and GI conditions in children. GI conditions were more common in cases than controls across all individual NDDs; intellectual disability and cerebral palsy were most strongly associated with having a GI condition. In this work, clinically recognized GI morbidity was elevated across all NDDs and not unique to autism, suggesting that a broader, transdiagnostic approach to GI dysfunction in children with NDDs is warranted.

Abstract Objective To describe variation in hospital costs among children with different combinations of health conditions, special educational needs or disability (SEND) and children social care (CSC) indicators. Study Setting and Design This cross-sectional study used regression analysis to test whether two-way and three-way interactions of cross-public sector service use (health, education and social care) are associated with higher hospital costs in England. Data Sources and Analytic Sample Hospital care costs between April 2022 and March 2023 for the 8.9 million children aged 5-18 years were obtained from linked administrative hospital, education or social care data in the ECHILD database. Children were classified into eight categories based on combinations of indicators of chronic health conditions, SEND or CSC. Principal Findings Over one-third (35.4%) of children had some hospital costs during the year. Average costs were 317GBP for all children and 895GBP for children with non-zero hospital costs. By age 18, few children had no indicator in any sector (35.1% of boys, 43.7% of girls) and indicators in all three sectors were not rare (7.1% of boys, 6.2% of girls). At age 5, children with indicators recorded in all three sectors had the highest hospital costs (2,952GBP for boys and 3,674GBP for girls). At age 18, males and females with indicators in all three sectors accounted for 21% and 23% of hospital costs, respectively. SEND and social care indicators without chronic health conditions were associated with only slightly higher hospital costs. Hospital costs were much higher for children with SEND if they also had a chronic health condition. Hospital costs were only higher for children with social care if they also had both a chronic health condition and SEND. Conclusions. Taking account of additional support from non-health sectors is important for understanding health sector costs. The compounding associations between use of other public sectors on health sector costs indicates scope for targeting of integrated care.

Background Agenda-setting is a fundamental patient-centered communication practice in which a clinician works with a patient to elicit, propose, and organize topics for discussion during a clinical encounter. Various agenda-setting interventions have been developed, including patient-facing tools and clinician training, but their effects have not been systematically evaluated. We aimed to determine the effects of these interventions on encounter, patient, care partner, and clinician outcomes. Methods We searched grey literature and seven databases, including PubMed, from inception through July 2025 for randomized and non-randomized comparative studies of interventions designed to promote or improve clinical visit agenda-setting. Two reviewers independently screened articles and extracted data, with a third reviewer resolving conflicts. We assessed risk of bias using RoB 2 for randomized studies and ROBINS-I for non-randomized studies. We conducted random effects meta-analyses when outcomes were sufficiently comparable, assessed heterogeneity using I2, and rated certainty of evidence using GRADE. Post hoc exploratory subgroup analyses examined study design, adjustment status, and intervention structure. Results Twenty-nine articles describing 22 unique studies met the inclusion criteria, including 13 randomized and nine non-randomized studies. Agenda-setting interventions increased the occurrence of agenda-setting (risk ratio 5.43, 95% confidence interval (CI) 2.06 to 14.28, I2=34.6%) and favored the intervention for concerns addressed when measured as a continuous outcome (standardized mean difference (SMD) 0.37, 95% CI 0.16 to 0.57, I2=65.3%) and overall clinician satisfaction (SMD 0.50, 95% CI 0.23 to 0.78, I2=0.0%). There were no clear differences in the number of concerns raised (mean difference (MD) 0.21, 95% CI -0.19 to 0.61, I2=59.6%), visit duration (MD 0.64 minutes, 95% CI -0.83 to 2.12, I2=51.4%), or overall patient satisfaction (SMD 0.05, 95% CI -0.05 to 0.15, I2=47.0%). Potentially important heterogeneity was present for four of these six outcomes. Post hoc exploratory subgroup analyses did not provide clear evidence that effects varied by study design, adjustment status, or intervention structure. Risk of bias was often high, serious, or critical, and certainty of evidence was low or very low for all pooled outcomes. Conclusions To our knowledge, this is the first comprehensive synthesis of clinical visit agenda-setting interventions. Such interventions may increase the occurrence of agenda-setting and the extent to which patient concerns are addressed without increasing visit length. However, the certainty of evidence was low or very low, and the available evidence does not establish a superior intervention structure.

Background: Vitamin K prophylaxis is universally recommended for newborns to prevent life threatening vitamin K deficiency bleeding. Although not on the immunization schedule, vitamin K prophylaxis is often coadministered with hepatitis B birth dose and erythromycin ophthalmic ointment, and rising hesitancy around vaccines/preventive care may spill over into vitamin K administration. Methods: We conducted a retrospective cohort study using Truveta electronic health record data with linked mother-child dyads. Live births to mothers aged 15-49 from January 1, 2019 through June 30, 2026 were included. Vitamin K administration was defined as documentation on the birth date or following day. Logistic regression assessed sociodemographic predictors of non-receipt, and interrupted time series analysis evaluated changes after January 2026. Results: Among 1,026,375 infants, 995,628 (96.97%) had documented vitamin K administration. Non-receipt increased from an average of 2.1% during 2019-2022 to 4.3% in 2025 and 6.1% in 2026, reaching 8.10% in June 2026. Older maternal age, non-Hispanic or Latino ethnicity, Medicaid or unknown insurance, and year of delivery were associated with greater odds of non-receipt. After January 2026, there was no immediate step change, but the odds of vitamin K receipt declined an additional 10% per month (OR: 0.90; 95% CI, 0.88-0.91). Conclusions: Vitamin K non-receipt increased over the study period and accelerated after January 2026. Because vitamin K recommendations were not changed by the January vaccine schedule, this association may reflect broader impacts to confidence in newborn preventive care. Future studies should examine causal mechanisms, parental decision-making, and associated clinical outcomes.

Obesity is a significant public health concern. Early-onset obesity in the context of rare disease can reflect genetically-mediated pathology or elevated susceptibility through indirect mechanisms. Mapping the diverse characteristics and needs of young people with obesity in the rare disease population is a first step toward mechanistic and translational research. We carried out a retrospective comparative analysis of demographic, genotypic, phenotypic and health service utilisation data for young people with obesity (cases: n=500) and without obesity (controls: n=11,444) from the UK 100,000 Genomes Project rare disease cohort. Cases and controls were recruited prior to genomic diagnosis, across clinical disorder categories. We observed significant association between socioeconomic deprivation and obesity risk. Young people with obesity had significantly higher utilisations of acute care and mental health services, indicating an overall higher health burden. A curated panel of 519 candidate obesity-associated genes demonstrated aggregate association with obesity, although no single gene reached significance. Phenotypic comparison between cases and controls highlighted increased multi-organ and neurological system involvement, highlighting the overlap between neurodevelopmental and obesity risks. Within the case group, we conducted cluster analysis to identify early-onset obesity groups with different phenotypic profiles, potentially arising from different causal pathways - this identified six obesity subgroups of interest, with differing involvement of neurodevelopmental and other systems. Our study confirms that obesity co-occurs with a wide range of factors within the rare disease population, and is associated with significant physical and mental health needs, requiring holistic lifelong care.

Background National childhood respiratory pathogen spectra are diversifying nearly everywhere - within-country diversity rose in 203 of 204 countries between 1990 and 2023 - yet whether countries are diversifying toward a common spectrum or along divergent paths is unknown. We quantified between-country compositional distance of national pathogen spectra over the same period. Methods We built national pathogen share vectors from Global Burden of Disease Study 2023 lower respiratory infection etiologic attributions (26 pathogens, 204 countries, ages 0-19 years) at five timepoints spanning 1990-2023. Between-country distance was measured as all pairwise Jensen-Shannon divergences (JSD; primary) and Bray-Curtis dissimilarities, with Baselga and Jaccard decompositions; robustness was assessed across metrics, pathogen panels, low-count thresholds and a balanced panel of 107 countries. Results Mean pairwise JSD rose from 0.0084 in 1990 to 0.0283 in 2023 (+238%; trend p = 0.030), peaking in 2021 (+283%) with a partial 2023 pullback. Bray-Curtis dissimilarity rose +120% and the balanced panel +423%. Divergence was entirely balanced variation (share reallocation), with spectrum richness rising from 18.5 to 21.1 of 26 pathogens. Dispersion rose fastest for influenza (coefficient of variation 0.03 to 0.55) and respiratory syncytial virus (0.08 to 0.48). Within-region distance rose in every computable GBD super-region (five of seven): divergence occurs within regions, not between blocs. Conclusions National spectra are re-sorting along country-specific axes as vaccine-preventable dominance recedes at different speeds. Diversification is universal, but convergence is absent: the transition at the etiologic-spectrum level is asynchronous and path-dependent, with implications for empirical treatment policy and pathogen surveillance.

Background: Risk adjustment for disease severity in pediatric intensive care research commonly relies on clinical organ dysfunction scores requiring detailed clinical and laboratory information, which is often unavailable in administrative healthcare datasets. We therefore evaluated the feasibility of a coding-based Pediatric Organ Dysfunction Index (PODI) derived from International Classification of Diseases (ICD-10) and Operation and Procedure System (OPS) codes, for approximating sepsis-related organ dysfunction and adjusting for disease severity, using the pediatric Sequential Organ Failure Assessment (pSOFA) score as a reference standard. Methods: In this retrospective single-center cohort study, pediatric sepsis episodes treated between November 2011 and November 2021 were identified. Discrimination for in-hospital mortality and calibration were assessed. Agreement between PODI and pSOFA was quantified using Spearman's rank correlation, and organ-specific agreement using sensitivity, specificity, and predictive values. An expanded PODI incorporating additional ICD-10 and OPS codes was evaluated in sensitivity analyses. Results: A total of 488 pediatric sepsis episodes were included, with an in-hospital mortality of 14.1%. The PODI showed good discrimination for in-hospital mortality (AUC 0.85, 95% CI 0.80-0.89), comparable to the maximum pSOFA (pSOFAmax) (AUC 0.78, 95% CI 0.72-0.83) and superior to pSOFA at sepsis onset (pSOFAonset) (AUC 0.73, 95% CI 0.67-0.80). Agreement between PODI and pSOFA organ-specific components varied considerably across organ systems, with the highest sensitivity to detect pulmonary dysfunction. Correlation between both scores was moderate (0.54 for pSOFAonset and 0.60 for pSOFAmax), indicating that comparable predictive performance does not render the scores interchangeable. The expanded PODI improved organ-level sensitivity for selected components but did not meaningfully improve mortality discrimination. Conclusions: The standard PODI may represent a practical approach to adjust for organ dysfunction and therapy intensity in administrative datasets with ICD-10 coding where clinical and laboratory information is unavailable. Given only moderate agreement with the pSOFA, the PODI should be understood as a covariate for risk adjustment at the group level rather than as a substitute for clinical organ dysfunction scores in individual patients. Further validation and refinement in non-sepsis cohorts are required before broader implementation in large-scale administrative research can be recommended.

Background: Chronic pain affects approximately 20% of children and youth worldwide and is associated with mental and physical health impacts. Canada-specific data on the prevalence of chronic pain in children and youth are limited, highlighting the need for current high-quality population-based estimates Aims: The aim of this study is to provide national estimates of self-reported chronic pain among Canadian children and youth by pain type (headache stomach ache, backache), sex (female, male), age group (5-11, 12-17 years) and province or territory. Methods: Publicly available data were used from the 2019 Canadian Health Survey on Children and Youth (CHSCY), a population-based survey conducted by Statistics Canada using a nationally representative sample of Canadian children and youth Results: Overall, headaches were the most commonly reported pain type (15.4%), followed by stomach aches (12.5%), and backaches (11.1%). Prevalence was consistently higher among females than males and among youth than children, with youth girls reporting the highest prevalence across all pain types. Prevalence also varied geographically, with some of the highest estimates observed in the Atlantic Provinces. Conclusions: Chronic pain affects substantial proportions of Canadian children and youth with disparities observed by pain type, sex, age, and geography. These findings under score pediatric chronic pain as an important public health issue and highlight the need for equity-oriented approaches that address the needs of populations experiencing the greatest burden.

AIM: To evaluate whether selective motor control quantified from spontaneous infant movement recordings provides diagnostic and prognostic information for cerebral palsy (CP) beyond established movement-based assessments. METHOD: This multicenter diagnostic and prognostic accuracy study included 302 infants (151 with CP) with spontaneous movement recordings obtained between 10 and 20 weeks corrected age from cohorts in Australia and the United States. All eligible infants with CP were included, and a comparison sample without CP was randomly selected. Recordings were scored using the Baby Observational Selective Control Appraisal (BabyOSCAR), Motor Optimality Score Revised (MOS-R), and General Movements Assessment (GMA). Outcomes at 2 years or older included CP diagnosis, Gross Motor Function Classification System (GMFCS) level, and motor distribution. RESULTS: BabyOSCAR discriminated CP diagnosis (area under the curve [AUC] 0.98), including children later classified in GMFCS level I. Among infants with CP, BabyOSCAR discriminated GMFCS levels I - II from III - V (AUC 0.89). BabyOSCAR absolute asymmetry also discriminated unilateral CP from all other infants (AUC 0.90). Diagnostic discrimination was also observed for MOS-R (AUC 0.94) and GMA (AUC 0.86). INTERPRETATION: Quantifying selective motor control from brief infant movement recordings may provide complementary early information about CP diagnosis, functional level, and motor distribution.

Background and Objectives: Preterm infants are commonly transfused, yet direct cardiorespiratory effects of red blood cell (RBC) transfusions remain poorly understood. We explored the feasibility of using multicentre electronic health data (EHD) to study such cardiorespiratory responses. Methods: Highly granular routine EHD were collected from preterm infants born <32 weeks gestational age at three European centres. Heart rate, oxygen saturation, and respiratory rate were evaluated 12 hours before and after the RBC transfusion. Results: A total of 321 transfusions in 164 infants were analysed. Overall, there was no significant change in the rate of bradycardia and apnoea following transfusion. Cardiorespiratory parameters varied substantially between infants; e.g. 20% of transfusions were associated with an unexpected, significant increase in heart rate. Respiratory rate and oxygen saturation exhibited similarly heterogenous patterns following transfusion. In sub-group analysis, the proportion of transfusions with increased heart rate was significantly higher within the first two weeks than later (32% vs 13%, p=0.0019). Conclusions: Multicentre EHD extraction allows to identify otherwise masked short-term effects of RBC transfusions on cardiorespiratory parameters, possibly indicating cardiac or pulmonary overload. Such effects may vary with adaptation to anaemia. Analysing EHD may ultimately enable personalized transfusion practice.

Background: High rates of young people who are not in education, employment or training (NEET) are a major societal concern in the UK. Whilst other studies have highlighted that adolescent health can predict NEET status in young adulthood, robust and recent longitudinal evidence remains limited. Methods: This study used data from the Millennium Cohort Study, a longitudinal study of people born in the UK in the early 2000s, to estimate the extent to which mental health conditions, physical health conditions and health behaviours during adolescence predict NEET status in early adulthood (median age: 23). Co-occurrence of exposures was also considered and population attributable fractions were calculated to account for differences in exposure prevalence. Results: Among 8,374 young people, 12.5% were NEET at age 23; approximately two thirds were seeking work and one third were economically inactive. Estimates adjusted for demographic factors indicated that multiple health exposures increased risk of being NEET at age 23, with mental health conditions predicting greater risk than physical health conditions and health behaviours. For instance, a longstanding mental health condition more than doubled the risk of being NEET (adjusted relative risk [aRR] = 2.39, 95% CIs = 1.85, 3.09), while autism (aRR = 3.60, 95% CIs = 2.69, 4.83) and ADHD (aRR = 3.25, 95% CIs = 2.38, 4.44) more than tripled the risk. A greater number of reported adolescent mental health conditions was associated with greater risk of being NEET in young adulthood. Obesity predicted being NEET at age 23 (aRR = 1.54, 95% CIs = 1.18, 2.01) and obesity accompanied by a mental health condition further increased risk (aRR = 2.01, 95% CIs = 1.38, 2.93). Follow-up analyses indicated that associations between adolescent mental health and young adult NEET status were more pronounced for females than males and for the economically inactive than those seeking work. Conclusions: Findings indicate that adolescent health, especially mental health, strongly predicts being NEET in early adulthood. Early, integrated health and education interventions may help reduce later educational and labour market disengagement.