Archives of Disease in Childhood
● BMJ
Preprints posted in the last 90 days, ranked by how well they match Archives of Disease in Childhood's content profile, based on 16 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.
John, A.; Pike, C.; Olga, L.; Sovio, U.; Wong, H. S.; Smith, G. C.; Aiken, C.
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Background: Children born prematurely (before 37 weeks) or admitted to the neonatal unit (NNU) are at increased risk of adverse long-term physical health outcomes. It is also recognised that there is an association with later academic performance and special educational needs, however it is not clear whether these broad risk factors could be used as stand-alone heuristics to identify children who may benefit from additional support in educational settings. We aimed to examine the associations between neonatal unit (NNU) admission and educational attainment in mid-childhood. Methods and Findings: Pregnancy data from a prospective birth cohort (Pregnancy Outcome Prediction Study, Cambridge, United Kingdom, 2008-2012) were linked to national educational outcomes (Department for Education, United Kingdom). Multivariable regression models adjusted for maternal, child, and socioeconomic factors were used to evaluate associations between (i) all NNU admissions, (ii) at term NNU admissions >48 hours, (iii) preterm birth without ongoing physical health needs, and educational outcomes at ages 5-11 years. Children who required any NNU care were more likely not to meet expected educational standards across multiple ages and domains in early and mid-childhood: age 5 early year foundation (aOR 1.64, 95% CI 1.19-2.27, p=0.003), phonics at age 6 (aOR 2.43, 95% CI 1.72-3.57, p<0.001), and at age 7 (here assessments were divided into multiple domains): reading (aOR 1.67, 95% CI 1.18-2.38, p=0.004), writing (aOR 1.72, 95% CI 1.25-2.38, p<0.001), mathematics (aOR 1.56, 95% CI 1.09-2.22, p=0.020), and science (aOR 1.85, 95% CI 1.22-2.78, p=0.003). Similar patterns were observed among both at term-born infants who stayed >48hrs in NNU (phonics assessment at age 6 aOR 2.26, 95% CI 1.51-3.36, p<0.001) and in children born preterm without long-term physical health sequelae (phonics assessment at age 6 aOR 3.07, 95% CI 1.96-4.81, p<0.001). These associations were robust to adjustment for demographic, perinatal, and socio-economic factors. By age 11, differences in academic attainment were attenuated and no longer clearly distinguishable across all exposure groups. However, there was an increased likelihood of special educational needs (SEN) at age 11 associated with any NNU admission (aOR 1.78, 95% CI 1.15-2.73, p=0.009), at term NNU admission for >48hrs (aOR 1.88, 95% CI 1.19-3.00, p=0.007), and children born preterm without long-term physical health sequelae (aOR 1.50, 95% CI 1.00-2.25, p=0.049). Predictive performance of any NNU admission for SEN at age 11 was moderate (AUC 0.70, 95% CI: 1.14-2.65, p=0.010), with balanced sensitivity and specificity and high negative predictive value. Conclusions: NNU admission, for both term and preterm infants, is associated with poorer educational outcomes and an increased likelihood of special educational needs in mid-childhood.
Hojeij, R.; Oenning, C.; Ravichandrajah, H.; Haertel, C.; Dohna-Schwake, C.; Felderhoff-Mueser, U.; Bruns, N.
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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.
Bradford, D. R. R.; Abou Saab, Y.; McMahon, A. D.; Leyland, A. H.; Allik, M.; Brown, D.
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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.
Hansas, J. B.; Csonka, P.; Karunadasa-Visama, M.; Vartiainen, P.; Vuorinen, A.-L.
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Abstract Importance Acute otitis media is the most common infection in children and a major reason for antibiotic prescriptions, up to one third of which may be unnecessary. Sector of care may influence AOM management through differences in access to care, specialist involvement, parental expectations and financial foundation. Objective The objective is to examine differences in antibiotic prescribing practices between healthcare sectors. Design This is a nationwide register-based study comparing data from different healthcare sectors. Setting Finnish primary and secondary healthcare, covering both public- and private-sector visits. Prescriptions and sociodemographic information were linked from nationwide registers. Participants We included children under 18 years old who received a diagnosis of acute otitis media, defined by ICD-10 codes H65-H67, between January 1, 2017 and December 31, 2022. Exposures The exposure is the sector of care (public sector vs. private sector). Main Outcomes and Measures Primary outcomes were antibiotic prescribing, guideline adherence of the prescribed antibiotics, and rates of management failure. Secondary outcomes included antibiotic selection and guideline-adherent eligibility for tympanostomy tube placement. Associations were estimated using adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results The study included 295 064 children with 596 634 acute otitis media index visits, of which 77.6% resulted in an antibiotic prescription. Private-sector visits were associated with higher odds of antibiotic being prescribed (adjusted odds ratio [aOR]: 1.45; 95% CI: 1.41-1.49). Overall, 87.3% of antibiotic prescriptions were guideline adherent, but private-sector care was associated with lower odds of guideline-adherent prescribing (aOR: 0.64; 95% CI: 0.60-0.69). Compared with amoxicillin, the private sector showed higher odds of prescribing amoxicillin-clavulanic acid (32.8% vs. 8.3%; aOR: 3.00; 95% CI: 2.91-3.10). Management failure occurred in 7.0% of episodes and was more common in the private sector (aOR:1.52; 95% CI: 1.48-1.56). Only 48.7% of all tympanostomy tube insertions met the eligibility criteria. Conclusions and Relevance In this study overall adherence to guideline-recommended antibiotic treatment for AOM was high in Finland. Nevertheless, observed clinically meaningful sectoral differences in antibiotic selection, treatment failure, and tympanostomy eligibility adherence indicate a need for targeted antimicrobial stewardship and quality-improvement efforts, especially in the private sector.
Li, D.; Xie, J.; Xue, J.; Chen, H.; Wang, X.; Shen, C.
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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.
Nambooze, R.; Pitua, I.; Bongomin, F.; Walakira, E. J.; Hove, G. V.; Schauwer, E. D.
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Objective. This systematic review and meta-analysis synthesised the global prevalence of overweight and obesity in people with Down syndrome (DS) across the lifespan, characterised determinants of excess adiposity, and examined associations with adverse cardiometabolic outcomes. Methods. Six databases were searched without date or language restriction. Two independent reviewers screened studies, extracted data, and assessed quality using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. Prevalence was pooled using a random-effects logit model. A pre-specified subgroup analysis by age band was conducted. Publication bias was assessed with Egger's test and certainty of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results. Twenty-six studies (7,840 individuals; 14 countries) were included. The pooled prevalence was 18% (95% CI 15-22%) in children and adolescents, 36% (95% CI 26-47%) in adults, and 30% (95% CI 20-43%) in mixed-age cohorts; the test for subgroup differences was significant. The overall pooled prevalence was 22% (95% CI 18-26%; prediction interval 7-53%; I^2 = 95.3%). No publication bias was detected (Egger's t = 0.39, p = 0.6964). DS-specific growth charts yielded estimates 14-37 percentage points lower than general-population references applied to the same cohorts. Obesity more than doubled obstructive sleep apnea risk (RR 2.4; 95% CI 1.34-4.34) and non-alcoholic fatty liver disease was present in 82% of obese versus 45% of non-obese children with DS. GRADE certainty was Moderate for prevalence estimates. Conclusions. Overweight and obesity in DS are highly prevalent, age-progressive, and substantially exceed general-population rates at every life stage. Roughly one in five people with DS is affected overall, rising to more than one in three adults. The reference chart applied is the single largest source of heterogeneity in reported estimates. Cardiometabolic surveillance, adapted lifestyle interventions, and primary prevalence research from low- and middle-income countries are the highest-priority gaps.
Bruns, N.; Wessel, A.; Biedermann, R.; Fiedler, K. M.; Goretzki, S. C.; Greve, S.; Hannes, T.; Felderhoff-Mueser, U.; Heimann, K.; Mand, N.; Masjosthusmann, K.; Merker, M.; Soler Wenglein, J.; van den Heuvel, I. A.; Westhoff, J. H.; Tsaka, S.; Lieftuechter, V.; Haertel, C.; Dohna-Schwake, C.; Hojeij, R.
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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 [≥] 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.
Leuenberger, L. M.; Shoman, Y.; Romero, F.; Sasaki, M.; Deligianni, X.; Goebel, N.; Mozun, R.; Bielicki, J. A.; Burckhardt, M.-A.; Saner, C.; Schwitzgebel, V.; Hauschild, M.; Righini Grunder, F.; Mueller, P.; Schlapbach, L. J.; Jenni, O.; Spycher, B. D.; Kuehni, C. E.; Belle, F. N.; SwissPedHealth consotrium,
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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.
Cheptoo, J.; Shisanya, M. S.; Mukthar, V.; Morema, E. N.
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Abstract Background. Low-birth-weight (LBW) neonates carry a disproportionate burden of morbidity and mortality in resource-limited newborn units, yet facility-level evidence on the determinants of severe in-hospital outcomes at county referral level in Kenya is limited. We determined the maternal, neonatal and care-related determinants of severe adverse outcomes among LBW neonates admitted to Kericho County Referral Hospital (KCRH) and used healthcare-provider perspectives to explain the quantitative findings. Methods. We conducted a facility-based, convergent mixed-methods cross-sectional study. Quantitative data were obtained from 169 LBW neonate-mother pairs through structured maternal interviews and clinical-record abstraction; qualitative data came from nine key informant interviews with newborn-unit healthcare workers. A severe adverse outcome was defined as the occurrence of at least one of respiratory distress, sepsis, hypothermia, hypoglycaemia, prolonged neonatal unit stay ([≥]7 days) or neonatal death. Associations were examined using bivariate tests and a multivariable binary logistic regression model entering 13 candidate predictors simultaneously, with multicollinearity, calibration and discrimination diagnostics. Interviews were analysed thematically and integrated with the quantitative results in a joint display. Results. A severe adverse outcome occurred in 136 of 169 neonates (80.5%); respiratory distress was the most common single complication (69.8%), and neonates experienced a mean of 2.46 (SD 1.31) adverse outcomes. In the adjusted model (omnibus {chi}{superscript 2}(13) = 57.70, p < 0.001; Nagelkerke R{superscript 2} = 0.46; area under the receiver-operating-characteristic curve = 0.879), three factors independently predicted severe adverse outcome: lower birth weight (adjusted odds ratio [AOR] 0.997 per gram, 95% CI 0.995-0.999, p = 0.012), maternal pregnancy-induced hypertension (AOR 18.49, 95% CI 1.87-182.47, p = 0.013) and warm-chain care (AOR 10.94, 95% CI 1.40-85.41, p = 0.023; a direction consistent with confounding by indication). Providers emphasised the fragile first hour of stabilisation, staffing and workload, warm-chain maintenance, infection prevention, commodity availability and referral coordination. Conclusions. Severe adverse outcomes were near-universal among LBW neonates at KCRH and were driven by neonatal biological vulnerability, maternal hypertensive disease and the readiness of newborn-unit care. Improving outcomes requires early, birth-weight-based risk stratification of the smallest neonates alongside strengthening of antenatal detection of hypertension and reliable, timely newborn-unit care processes.
Clarke, M. J.; Paleologos, K.; Kelly, N. R.; Bailey, S. M.; Joseph, M.; Kupchik, G. S.; Lumba, R.; Ganesh, J. J.; Stroustrup, A.; Orsini, J.; Goldenberg, A. J.; Wasserstein, M. P.
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ScreenPlus is a consented pilot program that aims to screen 100,000 babies for a panel of rare disorders. Given its size, ScreenPlus provides a unique opportunity to learn about optimal recruitment practices. ScreenPlus recruitment strategy includes recruiter-initiated Active and Hybrid modes and parent-initiated Independent mode. Active recruitment occurs in-person at the postpartum bedside, whereas Hybrid recruitment includes other attempt types. In Independent recruitment, parents access online educational and e-consent forms. Analysis of 47,642 completed recruitment profiles from May 2021 through April 2025 showed that Active recruitment was used in 72.2% and had the highest percentage of parents consenting (65.5%) in an average of 1.2 days. Hybrid recruitment was used in 27.1% of profiles and resulted in a 44.5% consent rate in an average of 8.6 days, with electronic medical record messaging being the attempt type most likely to lead to a consent. Independent recruitment was used in less than 1% of profiles. In Active and Hybrid Recruitment, non-English speakers were more likely to consent compared with English speakers. Collectively, these findings emphasize that although optimal pilot NBS recruitment is multi-modal, direct communication between parents and study team has the highest consent yield.
Joseph-Delaffon, K.; Desgrouas, M.; Catanese, S.; Lejeune, J.; Nait-Kaci, J.; Piver, E.; Breteau, I.; Leducq, S.; Gatault, P.; Khanna, R. K.; Angoulvant, D.; Vallet, N.
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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.
Farr, I.; James, J.; Howcroft, T.; Yap, M. H.; Reeves, N. D.; Pappachan, J. M.; Chandrabalan, V. V.
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Aim: Inequalities in diabetic foot ulcer (DFU) outcomes are driven by several factors including sociodemographic factors. This study examined the intersectional risks of ethnicity, sex, and deprivation on DFU progression, which prior research often evaluated in isolation. Methods: A retrospective cohort study (2009 - 2024) of 2,125 patients at Lancashire Teaching Hospitals Trust utilized flexible parametric survival modelling. Models assessed DFU onset, overall mortality, and post-clinic prognostic survival, adjusting for demographics and comorbidities. Results: The most deprived patients presented significantly younger (median 64 vs. 73 years). Male sex accelerated DFU onset (HR: 1.24) and increased overall mortality risk (HR: 1.14). Black patients presented older with higher comorbidity burdens but paradoxically exhibited lower overall mortality risk (HR: 0.49). Deprivation heavily impacted life expectancy as the most deprived group showed higher mortality rates (HR: 0.73) and reduced 5-year prognostic survival (48.7% vs. 59.1%). Presence of comorbidities linearly increased overall mortality risk. Furthermore, severe deprivation caused greater overall life-years lost in men (4.0) than women (2.5). Conclusions: Patient outcomes with DFU are heavily influenced by cumulative demographic and socioeconomic factors. Effective management requires accessible, holistic care that actively accommodates these complex biosocial-economic realities.
Vartiainen, P.; Haapaniemi, H.; Lee, Y.; Magnus, M. C.; Hartonen, T.; Detrois, K.; Viippola, E.; Ferro, M.; Laitinen, T.; FinnGen, ; Madsen, M. A.; Ostrowski, S. R.; Pedersen, O. B.; Soerensen, E.; Erikstrup, C.; Gong, T.; Rhedin, S.; Lundholm, C.; Dallagiacoma, G.; Almqvist, C.; Egeskov-Cavling, A. M.; Fischer, T. K.; Pasanen, A.; Ramet, M.; Vuorinen, A.-L.; Hiekkalinna, T.; Haberg, S. E.; Magnus, P.; Perola, M.; Jugessur, A.; Ganna, A.; Heinonen, S.
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Background Early-life respiratory syncytial virus (RSV) infection is associated with childhood recurrent wheeze or asthma (RW/A), but causality and shared genetic liability remain unclear. Methods We combined Finnish nationwide registries and Nordic genetic cohorts. First, in 965 312 Finnish children born between 1998 and 2014, we defined severe RSV as RSV hospitalisation before age 1 year, and recurrent wheezing or asthma (RW/A) as inhaled medication reimbursement between ages 1 and 7 years, and compared medication and eosinophil trajectories by RSV history. Second, we assessed familial confounding in 527 776 full siblings and 15 667 RW/A-discordant pairs. Third, we performed a genome-wide association study (GWAS) of RSV susceptibility with meta-analysis across six Nordic cohorts (3 107 cases, 92 031 controls) and two-sample Mendelian randomisation (2SMR) using 155 asthma-associated variants. Findings RSV-associated RW/A showed higher inhaled medication use at ages 1-2 years but lower use after age 4, and lower mean blood eosinophils (0.34 vs 0.39*10e9/L; p=0.003) than RW/A without RSV hospitalisation. In RW/A-discordant sibling pairs, RSV hospitalisation was associated with RW/A (OR 2.8; 95% CI 2.4-3.2), while unaffected siblings also had elevated RW/A prevalence. GWAS identified an RSV association at APBB1IP (rs787036; beta=0.209; p=8.80*10e-9). 2SMR provided no evidence that asthma genetic liability influenced RSV susceptibility. Interpretation The RSV-asthma association is unlikely to be explained by shared genetic or environmental factors, and RSV-associated RW/A shows a distinct trajectory. These findings help prioritise long-term outcomes for RSV prevention trials and monitoring. Funding: Paivikki and Sakari Sohlberg Foundation, Foundation for Pediatric Research, Sigrid Juselius Foundation, Orion Research Foundation, the Research Council of Norway.
Siddiq, A. I.; Saafu, I.; Borkor, E. T.; Vondee, E.; Sampana, F. T.; Okine, B.
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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.
Guerra Buezo, B.; Sasaki, M.; Leuenberger, L. M.; Glick, S.; Gaillard, E. A.; Moeller, A.; Regamey, N.; Sutter, O.; Goutaki, M.; Kuehni, C. E.
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Background: Clinical guidelines recommend objective tests to diagnose asthma in school-age children, but their availability and use in routine practice remain uncertain. We evaluated asthma diagnostic practices in Switzerland, focusing on first-line tests (spirometry, bronchodilator reversibility testing, and fractional exhaled nitric oxide [FeNO]). Methods: Cross-sectional, nationwide online survey of primary care paediatricians (PCPs) and respiratory specialists. We assessed access to and use of diagnostic tests, focusing on first-line tests, and examined reasons for non-use, referral practices, and guideline consultation. We used multivariable logistic regression to identified factors associated with spirometry access among PCPs. Results: Of 1,055 respondents, 625 diagnosed asthma in children, including 419 PCPs. Among PCPs, 50% (95% confidence interval [CI] 45-55) reported no access to spirometry and 95% (95% CI 92-97) no access to FeNO, whereas all paediatric respiratory specialists and almost all adult respiratory specialists had access to both tests. Barriers to first-line testing among PCPs included economic constraints and difficulties interpreting test results. Spirometry access was lower in French- and Italian-speaking regions than in German-speaking regions (adjusted odds ratio [aOR] 0.09, 95% CI 0.05-0.15), but higher among PCPs working full-time (aOR 2.04, 95% CI 1.11-3.82) and those using Swiss asthma guidelines (aOR 1.71, 95% CI 1.01-2.92). PCPs without spirometry access more frequently referred children to specialists for diagnostic confirmation (89% versus 80%; p=0.019). Conclusion: Many PCPs in Switzerland lack access to guideline-recommended tests. Improving access, reimbursement, and training in test interpretation may help reduce the gap between guidelines and clinical practice.
Li, D.; Chen, H.; Xie, J.; Li, J.; Wang, X.; Shen, C.
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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.
Richards, M.; McDonald, H.; Ramanjam, V.; Lawrence, E.; Donald, K.
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Background Persistence with stimulant medication is poor in children and adolescents with ADHD, and the evidence base is derived predominantly from high-income countries. We describe methylphenidate utilisation patterns and predictors of 12-month retention across 14 years in a large South African public health service. Methods Retrospective cohort study using routine pharmacy data from the Western Cape provincial health service (2011-2024). Children aged 5-18 at first prescription were included. Treatment episodes were defined as continuous prescription sequences with no gap exceeding 90 days and classified as initiations or restarts. Logistic regression modelled 12-month retention against early visit frequency and formulation type as pre-specified exposures. Findings 421,925 prescription events for 23,243 children across 115 facilities generated 65,885 treatment episodes. Median age at first prescription was 10 years (IQR 8-12); 77.6% were male. Kaplan-Meier 12-month survival was 28.2% for initiations and 15.4% for restarts, substantially below high-income country comparators. A quarter of all initiating prescriptions were not followed by a subsequent dispensing event; nearly 40% of patients had three or more treatment episodes. Early visit frequency was the strongest predictor of 12-month retention (high vs low: OR 2.85, 95% CI 2.65-3.06). The sustained-release formulation effect was present but attenuated on multivariable adjustment. Treatment re-initiations showed a marked seasonal pattern consistent with the South African school calendar. Interpretation Twelve-month retention was markedly lower than high-income country rates. Against a backdrop of high attrition, both early visit frequency and sustained-release formulation access predicted persistence; clinical engagement and reducing structural barriers to access are modifiable factors in this setting. Funding None.
Waterfield, T.; Taylor Miller, P.; McDowell, C.; Agus, A.; Murphy, L.; Sanders, C.; Kearney, A.; Sherrett, F.; Wyche, J.; Hartshorn, S.; Bandi, S.; Blackwood, B.; Williams, N.; Roland, D.; Ferris, K.; Marshall, A.; Clarke, M.; Sutcliffe, A.; Woolfall, K.
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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.
Savatt, J. M.; Nixon, M. P.; Berry, A. S. F.; Johns, A.; Walsh, L. K.; Martin, C. L.; Ledbetter, D. H.; Challman, T. D.; Myers, S. M.
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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.
Lau, Y.-S.; Gilbert, R. E.; Parra, G. P.; Sutton, M.
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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.