Research into the developmental origins of, and lifecourse influences on, health and disease has a significant gap: infections. Clinical and subclinical infections are nearly universal in early life and can induce structural and functional changes in developing organ systems with life-long consequences. Emerging evidence links common childhood infections—such as Epstein–Barr virus, Cytomegalovirus and Helicobacter pylori—to so-called non-communicable diseases ranging from respiratory to neurodevelopmental and cardiometabolic diseases. Identifying infectious determinants of non-communicable diseases offers substantial opportunities for prevention and early intervention. We describe a newly developed infectious data resource within the EU Child Cohort Network, designed to enable triangulation of evidence on the impact of early life infections on children’s health and long-term trajectories of disease. The network established in 2017, currently brings together 37 pregnancy and childhood cohorts from 16 predominantly European countries and follows over 300,000 children and their families from pregnancy through childhood and, in many cohorts, into adulthood. Cohorts include a comprehensive set of harmonized variables covering health and disease phenotypes (cardiometabolic, respiratory, and mental) that are also well-established early indicators of later-life non-communicable disease risk. Building upon this, we present here the extensive infections data available in the cohorts ranging from questionnaires and registries to serological measurements for more than 20 pathogens. Harmonizing and integrating infection data within the EU Child Cohort Network supports a shift from viewing infections solely as causes of acute disease towards recognising them as integral components of the early-life exposome and potential determinants of lifelong health trajectories.

Introduction Improving the number of children who achieve a good level of development (GLD) on the Early Years Foundation Stage Profile (EYFSP) at the end of their first school year (aged five), and reducing the equity gap in this outcome was made a national priority in England in 2025. Children in England also receive a developmental assessment - the Ages and Stages Questionnaire-3 (ASQ-3) aged two. No study to date has explored the association between the ASQ-3 and EYFSP assessments. The aim of this study is to explore whether a GLD on the ASQ-3 is predictive of a GLD on the EYFSP using a longitudinal sample of children. Methods Longitudinal pseudonymised data from the Connected Bradford dataset was used to undertake multiple regression analyses. Results From September 2013 to May 2025, 47,046 children had an ASQ-3 record, of whom 6,021 (13%) had a linked EYFSP record. Boys and children living in the lowest quintiles of the Index of Multiple Deprivation were less likely to achieve a GLD on both the ASQ-3 and the EYFSP. Children from South Asian ethnic groups were least likely to achieve a GLD on the ASQ-3, whilst White Other children were least likely to achieve a GLD on the EYFSP. Achieving a GLD on the ASQ-3 was predictive of a GLD on the EYFSP, with children who achieved a GLD on the ASQ-3 having more than three-times the odds of achieving a GLD on the EYFSP (OR 3.18, 95% CI 2.70 to 3.75). Conclusion This study highlights the potential value of using the ASQ-3 results to intervene early and support more children to become school ready. These findings also show that many children have fallen behind by the age of two, thus emphasising the importance of intervening from the earliest possible moment to reduce inequities in child development. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This is independent research funded by a Wellcome Trust Discovery Award (BiBBS Achieve, 310017/Z/24/Z ) and the National Institute for Health and Care Research (NIHR) - YX, RS and HH are supported by NIHR Bradford Health Determinants Research Collaboration (HDRC); JD, MMW & JW are supported by the NIHR Yorkshire and Humber Applied Research Collaboration (ARC-YH; Ref: NIHR200166, see https://www.arc-yh.nihr.ac.uk); JD is further funded by a Population Health Career Scientist Award, NIHR302938 for this research project. The views in this publication are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study is based on data from Connected Yorkshire which has ethical approval to use data for research purposes (NHS REC 18/YH/0200 & 22/EM/0127). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data used in this study is a part of the Connected Bradford dataset. Data can be accessed at: https://bradfordresearch.nhs.uk/connected-bradford/governance-and-ethics/

BACKGROUND:Socioeconomic inequalities in children's emotional and behavioural problems are already present at school entry. We examined associations between early-life socioeconomic conditions and children's externalising and internalising problems and assessed whether early-life risk factors mediated these associations. METHODS:We analysed harmonised individual participant data from eight birth cohorts within the EU Child Cohort Network. Maternal educational level during pregnancy was used as an indicator of early-life socioeconomic conditions (SECs). Scores of children's externalising and internalising problems around school entry age were used as the outcome variables. Inequalities were quantified using the Slope Index of Inequality which captures the difference in prevalence of problems between children from highest and lowest SECs. Mediation analysis was used to assess the mediating role of five early-life risk factors: maternal smoking during pregnancy, gestational age, small for gestational age, postpartum depression and breastfeeding. RESULTS:Inequalities in externalising and internalising problems by SECs were consistent across cohorts: Children of mothers with low educational level had on average a 12 and 11 percentage point increased prevalence of externalising and internalising problems respectively. Early-life factors explained around 8% (DNBC, Denmark) to 54% (INMA, Spain) of the inequality in externalising problems and 7% (ELFE, France) to 25% (ALSPAC, UK) in internalising problems. CONCLUSIONS:Children from lower SECs consistently had a higher prevalence of both externalising and internalising problems around school entry age. These inequalities were partly mediated by early-life factors. Public health interventions in pregnancy and the preschool period are critical to address the early emergence of inequalities in children's mental health.

Genes & Health (G&H) is a biomedical study of adult British Pakistani and Bangladeshi research volunteers enriched for autozygosity. Here we performed whole-exome sequencing in 44,028 G&H participants, establishing a large publicly available South Asian exome resource linked to longitudinal electronic health records. We performed exome-wide association analyses for 645 electronic health record-derived traits under additive and recessive models, and meta-analyses of 33 cardiometabolic traits with UK Biobank, finding more than 100 novel gene-phenotype associations. We identified 2,991 genes with rare biallelic predicted loss-of-function ('knockout') genotypes, 546 of which had not been previously reported. We show that drugs targeting genes with knockouts in adults are associated with a 2.2-fold higher likelihood of progressing beyond phase 1 clinical trials. We further illustrate how phenotypic profiles associated with knockout genotypes can enhance efficacy and safety assessment of drug targets and aid in the interpretation of variants with ambiguous clinical significance in autosomal recessive disease genes.

The prevalence of childhood obesity has quadrupled globally over the last 30 years highlighting the urgency for robust research on modifiable risk factors. This study investigates the association between prenatal and early-life (0–24 months) antibiotic use and obesity at 4–5 years within the Born in Bradford (BiB) cohort, and whether this differs by ethnicity or by sex. BiB is a large, multi-ethnic birth cohort of 13 858 children in Bradford, UK. Data for children and their mothers were obtained from a baseline questionnaire, linked electronic health records (including maternity records and general practitioner prescriptions), and anthropometric measurements at school. Logistic regression models were employed to estimate the associations between antibiotic exposure in pregnancy and early-life and the outcome, having obesity at age 4–5 years, adjusting for several confounders. In this population, nearly a tenth of children had obesity, just over a third were exposed to antibiotics in pregnancy, and nearly three quarters were exposed in the first two years of life. The adjusted analysis revealed no clear evidence of an association between prenatal antibiotic use and having obesity at 4–5 years (aOR 1.09; 95

Background/Objectives : Ethnic disparities in cardiometabolic risk emerge early in life. Because body mass index (BMI) underestimates adiposity in South Asian populations, universal BMI thresholds may fail to identify clinical risk compared to White European children. Subjects/Methods : We conducted a cross-sectional analysis of White European and South Asian aged 7-11 years from the Born in Bradford birth cohort, including 6 971 children with blood pressure measurements and 2 013 with blood-based cardiometabolic markers. Multivariable linear regression with multiple imputation was used to examine associations between age- and sex-standardised BMI z-score and cardiometabolic risk factors (blood pressure, HbA1c, non-HDL cholesterol, triglycerides). We estimated the BMI z-scores at which South Asian children reached the equivalent cardiometabolic risk of White European children at the UK90 ‘overweight’ threshold (BMI z-score = 1.036). Results : Higher BMI was associated with adverse cardiometabolic profiles in both ethnic groups. However, South Asian children exhibited higher HbA1c across the BMI distribution and a steeper increase with BMI (interaction p=0.032). Notably, South Asian children classified as healthy weight had higher predicted HbA1c than White European children with obesity. South Asian children also had consistently higher diastolic blood pressure across all BMI levels. Equivalent-risk analyses showed that South Asian children reached comparable cardiometabolic risk at lower BMI z-scores: 0.97 (95% CI: 0.65, 1.30) for systolic blood pressure and -0.55 (95% CI: -1.06, -0.03) for diastolic blood pressure. For HbA1c, equivalent glycaemic risk was not observed within the plausible BMI range. Conclusions : Universal BMI thresholds may underestimate cardiometabolic risk in South Asian children. Because adverse metabolic profiles occur at BMI levels currently classified as healthy, ethnicity-specific approaches to paediatric risk assessment and early prevention should be considered.

Background Ambient air pollution, particularly black carbon (BC), is associated with adverse pregnancy outcomes, but the molecular pathways linking in utero particle exposure to fetal programming remain incompletely understood. We examined whether cord-blood BC particle burden relates to small extracellular vesicle (sEV)-associated microRNA (miRNA) profiles and enriched developmental pathways. Methods Cord blood was collected from newborns in the Born in Bradford's Better Start (BiBBS) cohort. Plasma sEVs were isolated and miRNA was profiled by small RNA sequencing. BC particle load in whole cord blood was quantified by femtosecond pulsed-laser microscopy. After quality control and complete-case restriction, 68 newborns were included in the analysis. Candidate miRNAs were prioritised using elastic-net regression, and associations with log10-transformed BC particle burden were estimated using linear mixed-effects models with covariate adjustment and Benjamini---Hochberg false discovery rate (BH-FDR) control. Results Five of the ten candidate miRNAs were associated with BC at BH-FDR ≤0.10: hsa-miR-25-3p and hsa-miR-433-3p (positive associations) and hsa-miR-518a-3p, hsa-miR-519a-3p/519b-3p, and hsa-miR-520g-3p/520h (negative associations). Three of the five negatively associated miRNAs belong to the placenta-specific chromosome 19 miRNA cluster (C19MC). All five signals were robust in 100 × 20% holdout resampling. Validated target pathway analysis revealed enrichment for developmental and specifically neurodevelopmental processes, including axon guidance and neurotrophin signaling. Conclusions These findings link cord-blood BC particle burden to a placenta-linked C19MC miRNA signature in newborn sEVs and developmental pathway enrichment, providing molecular evidence consistent with particle-associated fetal programming at birth.

Importance: Infants born small or large for gestational age exhibit different growth patterns compared with appropriate-for-gestational age counterparts. Evidence is lacking on how birth weight centiles beyond conventional thresholds predict early life growth. Objective: Quantify association of birth weight centile range with infant and child growth. Design: Prospective cohort study. Setting: France, Netherlands, Portugal, Singapore, United Kingdom, United States. Participants: Singletons from seven birth cohort studies with repeated growth measurements from age one week to 10 years. Five European cohorts were used for discovery analysis, and remaining cohorts for replication. Exposures: Birth weight centiles standardised for sex and gestational age using the INTERGROWTH-21st standards and classified into deciles. Main Outcomes and Measures: Infant height (cm/month) and weight (g/month) velocity at 1, 6, 12, 24 months, body mass index (BMI: kg/m2) and age (months or years) at infancy BMI peak and childhood BMI rebound, and overweight/obesity at age 10 years. Results: The discovery analysis included 36,018 children (48% girls, birth years: 1991-2011). Growth velocity, peak BMI (mean: 17.7 vs. 17.3 kg/m2), age at peak BMI (10.2 vs. 10.4 months), rebound BMI (15.6 vs. 15.5 kg/m2), age at rebound BMI (5.3 vs. 5.0 years), and overweight/obesity prevalence were broadly similar in boys and girls. Compared with lowest birth weight decile (<10th centile), all higher decile groups had an initially lower height velocity that reversed by 24 months, an increasingly higher weight velocity through infancy, a higher and earlier peak BMI, higher rebound BMI, and a higher probability of overweight/obesity at age 10 years. For example, mean differences in BMI and age at peak BMI, and probability of overweight/obesity at age 10 years for the 7th (vs. 1st) birth weight decile were 0.77 kg/m2 (0.72 to 0.82), -0.58 months (-0.69 to -0.46), and 34% (18 to 49). Birth weight was not associated with age at rebound BMI. Replication analyses (n=2,517) supported findings. Associations were typically linear and consistent for boys and girls. Deciles provided only modest predictive gains over conventional categories. Conclusions and Relevance: Birth weight centiles may identify high-risk children missed by traditional thresholds, although predictive benefit over conventional groups was modest. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The research leading to these results has received funding from the European Research Council under grant agreement No 101021566 (ART-HEALTH), the EU Horizon 2020 research and innovation program under grant agreements 733206 (LifeCycle) and 874739 (LongITools), the UK Medical Research Council (MC\_UU\_00032/2, MC\_UU\_00032/5, MC\_UU\_00011/6, UKRI481), and University of Bristol Elizabeth Blackwell Institute for Health Research Institutional Strategic Support Fund. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All studies had ethical approval from their local or national ethics committees and study participants gave informed consent/assent to participate in respective cohorts and secondary analyses. Approval for ABCD was obtained from the Central Committee on Research involving Human Subjects in the Netherlands, the Medical Ethical Committees of the participating hospitals, and from the Registration Committee of the Municipality of Amsterdam. Written informed consent was obtained from all participating mothers. Ethical approval for ALSPAC was obtained from the ALSPAC Law and Ethics committee and local research ethics committees. Informed consent for use of questionnaire and clinic data was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time. BiB had ethical approval from Bradford Research Ethics Committee. All BiB participants provided informed consent or assent to participate in the study and secondary data analyses. The EDEN study received approval from the ethics committee (CCPPRB) of Kremlin Bicetre on 12 December 2002 and from CNIL (Commission Nationale Informatique et Liberte), the French data privacy institution. The University of Porto Medical School/S. Joao Hospital Centre Ethics Committee approved the study protocols. Generation XXI complies with the Ethical Principles expressed in the Helsinki Declaration and with the national legislation and was registered with the Portuguese Authority for Data Protection. In all evaluations, Generation XXI participants were informed about the purposes and design of the study, as well as the potential discomfort caused by participation. The institutional review board of Harvard Pilgrim Health Care approved this Project Viva project in line with ethical standards established by Declaration of Helsinki. GUSTO study protocols following the principles of the Declaration of Helsinki and were approved by the respective ethics committees for two hospitals: National Healthcare Group Domain Specific Review Board (NUH) and SingHealth Centralized Institutional Review Board (KKH). All participants in this study provided informed consent to participate and contribute their data to publications. The GUSTO study is registered under study ID: [NCT01174875][1] (clinicaltrials.gov) which broadly covers investigations of parental and gestational influences on child health. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data used in this study can be accessed by making an application to each individual cohort study. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01174875&atom=%2Fmedrxiv%2Fearly%2F2026%2F01%2F13%2F2026.01.10.26343435.atom

Social media is a central part of the lives of adolescents in 2025. The recent rise of short-form content and gamification features has coincided with an increasing prevalence of mental health problems among this age group. Many policy makers are considering restrictions to the amount of time under-16s spend on social media. Despite this, there is limited contemporary evidence about the extent of their social media use, nor meaningful estimates of the effect a reduction may have on their mental health. Here, we estimate daily social media usage for adolescents in the culturally and ethnically diverse city of Bradford, England, plus its association with their mental health. We did a cross-sectional analysis of data from Born in Bradford: Age of Wonder 2023-24, a school-based survey of students aged 12–15 (n = 8,466). We weighted the sample to be representative of the city-wide population of 12–15-year-olds and report the median daily screen time spent on social media apps by age, sex, and ethnicity. We used a log-linear model to estimate the effect of daily social media screen time on anxiety and depression symptoms (RCADS-25), adjusting for age, sex, ethnicity, free school meal eligibility, special educational needs, deprivation, and season of survey completion. Predictions from this model were used to estimate the change in prevalence of clinical threshold symptomatology associated with a range of daily screen time limits. The median time spent using social media apps was 3.36 h per day (IQR 1.88–5.44). Longer durations of social media use were associated with greater mental health symptoms after adjustment for potential confounders. In a scenario where this association is causal, capping social media use at a maximum of 3 h per day would lead to a 1.25ppt (95

BACKGROUND:There is growing evidence for an association between air pollution exposure and cardiometabolic morbidity and mortality. However, research on the association between air pollution exposure and metabolic syndrome (MetS) risk during childhood is scarce. OBJECTIVE:To investigate the associations between childhood air pollution exposure in various microenvironments (home, school, commute) and their cardiometabolic risk score. METHODS:This population-based observational cohort study utilized data from the Human Early Life Exposome (HELIX) study, based in six European countries. A total of 1147 children aged 6-11 years were included. Land-use regression models (LUR) were used to estimate PM2.5 and NO2 concentrations in different microenvironments, one year before the outcome assessment. A composite MetS risk score was calculated using z-scores of waist circumference, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and insulin levels. Multiple linear regression models were used to determine the association between air pollution exposure in each microenvironment and MetS risk score. RESULTS:Children had an average MetS risk score of -0.05 (SD = 2.29). When adjusting for all covariates, an IQR increase of both pollutants at home (IQR PM2.5: 3.15 μg/m3; NO2: 18.65 μg/m3) and at school (IQR: PM2.5: 3.02 μg/m3; NO2: 17.41 μg/m3) was significantly associated with an increase in the MetS risk score (home: PM2.5 β = 0.29; 95% CI, 0.03 to 0.55, NO2 β = 0.42; 95% CI, 0.05 to 0.79; school: PM2.5 β = 0.36; 95% CI, 0.08 to 0.65, NO2 β = 0.60; 95% CI, 0.21 to 0.99). Air pollution during commuting was not statistically significantly associated with MetS. CONCLUSIONS:This multi-country cohort study indicates that childhood exposure to air pollution-both at home and at school-is associated with an increased risk of metabolic syndrome. Given the widespread nature of outdoor air pollution globally and the long-term health impacts of metabolic syndrome, these findings have significant public health implications.

Abstract Background Maternal BMI and gestational glycaemia are associated with higher offspring adiposity, but it remains unclear whether these associations differ by ethnicity and fat distribution. We examined longitudinal associations of maternal BMI and fasting glucose with offspring total, central, and peripheral adiposity from birth to mid-childhood in White British and Pakistani children. Methods We analysed data from 8,857 mother–child pairs in the Born in Bradford cohort. Offspring adiposity was assessed using repeated measures of weight, BMI, subscapular skinfold thickness (SSF), and triceps skinfold thickness (TSF) from birth to ages 7–8 years; BMI was assessed from ages 4–8 years only. Linear mixed-effects models were used to estimate adiposity trajectories in relation to maternal BMI and fasting glucose, including interactions by ethnicity and age. Results Higher maternal BMI was associated with greater offspring adiposity across childhood in both ethnic groups, although patterns differed by adiposity measure. At age 7.5 years, maternal BMI of 30 kg/m 2 compared with 20 kg/m 2 was associated with higher predicted BMI z-score in both White British and Pakistani children, with differences of approximately 0.30–0.37 SD. For central adiposity, larger differences were observed in Pakistani children. At age 7.5, the predicted difference in SSF z-score comparing maternal BMI 30 kg/m 2 with 20 kg/m 2 was approximately +0.32 SD in Pakistani children and +0.27 SD in White British children. Higher maternal fasting glucose was associated with greater offspring adiposity, particularly for skinfold thickness, although ethnic differences in predicted contrasts varied by age and outcome. Formal statistical evidence for interaction by ethnicity was limited. Conclusions Maternal BMI and glycaemia were associated with offspring adiposity trajectories from early life, with larger differences for central adiposity. BMI alone may underestimate ethnic differences in adiposity development.

BACKGROUND:Childhood obesity is a global public health crisis. Endocrine-disrupting chemicals (EDCs) - widespread pollutants that interfere with hormonal and metabolic systems - may contribute to excessive adiposity. The combined, long-term, and mechanistic effects of multi-class EDC mixtures remain unexplored. METHODS:We analyzed 1301 mother-child pairs from the Human Early Life Exposome (HELIX) project, spanning six European cohorts. Prenatal and childhood exposures to 45 EDCs across nine chemical classes were measured in maternal and child biospecimens. Thirty-six plasma proteins were quantified in childhood using targeted proteomic panels. Adiposity outcomes in childhood (6-11 years) and adolescence (12-18 years) included BMI z-scores, waist circumference, and body fat percentage. We applied penalized Lasso-type Bayesian Weighted Quantile Sum Regression to assess mixtures, a signed iterative random forest for interactions, and mediation analyses for biological pathways. RESULTS:Prenatal metal and organochlorine pesticide mixtures were associated with higher BMI z-scores in childhood and adolescence and 47-48 % higher odds of overweight. Prenatal PFAS exposure was associated with higher body-fat percentage in both periods. Childhood phenol and high-molecular-weight phthalate exposures were associated with higher adolescent zBMI, whereas parabens and persistent compounds showed inverse associations. Childhood metal exposures were associated with higher body-fat percentage and overweight odds. An inflammatory-metabolic protein pattern mediated ∼ 30 % of the prenatal metal-adolescent zBMI association. CONCLUSIONS:Early-life exposure to EDC mixtures may reprogram metabolic and inflammatory pathways, predisposing children to obesity that persists into adolescence. These findings provide mechanistic evidence linking chemical exposures to the global obesity epidemic and underscore the urgent need for policies preventing EDC exposure during critical developmental periods.

Purpose Urban environments are a key determinant of health and health inequality. We explore the impact of multiple spatial inequalities on primary healthcare use in a prospective multi-ethnic urban cohort of children. Method Primary-care consultations and prescription data for 4949 children were collected from birth to 10 years. Environmental exposure scores for air-pollution, road-traffic, green-space, and proximity to fast-food outlets were calculated longitudinally using home-addresses. The top 20% of addresses were classified as hazardous; environmental risk was calculated using the count of exposures above this threshold (range 0-4). Health impacts were assessed using negative binomial regression models adjusting for ethnicity; sex; age; birth outcomes; family financial status; area-level deprivation; maternal education and maternal health behaviours. Interaction terms were included for financial status and ethnicity. Results Half of Pakistani heritage and one-third of Other ethnic minority children experienced multiple environmental risks, compared to 7% of white British children. Rates of annual consultations and prescriptions increased for ethnic minority children as environment risks accumulated (consultations: no risks- Pakistani: 3·97 (95% CI: 3·79-4·15); Other: 3·37 (95% CI: 3·13-3·61); 4 risks- Pakistani: 4·23 (95% CI: 3·95-4·52); Other: 4·14 (95% CI: 3·55-4·72). Prescriptions (no risks- Pakistani: 6·14 (95% CI: 5·69-6·58; Other: 6·20 (95% CI: 5·53-6·87); 4 risks- Pakistani: 8·32 (95% CI: 7·41-9·22); Other: 6·54 (95% CI: 5·09-7·99). The reverse was found for white British children. Conclusions Ethnic minority children are disproportionately exposed to multiple environmental risks and are more vulnerable to their harmful effects. Improvements to multi-ethnic urban neighbourhoods may mitigate health inequalities.

Purpose The Human Early Life Exposome (HELIX) cohort was established to assess a wide range of environmental exposures (the exposome) during early life and study the effects of the early life exposome on child and adolescent health outcomes and molecular omics signatures. Here, we describe the second follow-up of the HELIX cohort during adolescence, including measurements available and population characteristics.Participants HELIX is a collaborative study across six established and ongoing population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the United Kingdom). The cohort includes 1663 mother-child pairs recruited during pregnancy from 2003 to 2009 and followed up during childhood at 6–12 years from 2013 to 2016. This update summarises the most recent follow-up during adolescence (12–18 years) which took place from 2020 to 2022 and included 864 participants.Findings to date HELIX data have been used extensively in more than 100 publications, specifically pioneering the implementation of exposome approaches to address questions around the occurrence and effects of multiple exposures to real-life pollutant mixtures. These findings have improved our understanding of how multiple exposures co-exist and which exposures are driving the early-life exposome. Further, HELIX data have been used in exposome-wide discovery analyses to examine child health outcomes and used high-throughput omics techniques to characterise the internal exposome.Future plans Although no additional follow-up visits are currently planned, HELIX will remain an active exposome research resource for years to come. The cohort will leverage its comprehensive database and extensive biobank to investigate complex exposure-omics-health relationships and measure additional biological markers.

Purpose: Whole system approaches to public health challenges such as low physical activity levels have the potential to create sustained behaviour change at a population level and tackle health inequalities. However, there is currently little evidence of the nature or effectiveness of adopting whole system approaches. This study evaluated whether a whole system physical activity intervention (JU:MP) was effective at improving physical activity in five- to eleven-year-olds. Methods: A before and after controlled study with two-arms (JU:MP intervention and control), was conducted in Bradford, United Kingdom with data collected at baseline and 24-months follow-up. Habitual physical activity was measured via accelerometry. The primary outcome was difference in moderate-to-vigorous intensity physical activity (MVPA) between groups at 24-months. Secondary outcomes included: sedentary time (ST), counts per minute (CPM), BMI z-score, waist circumference, social, emotional, and behavioural health, and quality-of-life. An exploratory analysis compared intervention effects between sub-groups. Results: 1,453 children were recruited. 330 children with valid wear-time at baseline and 24-months (JU:MP group n = 175, control group n = 155) were included in the final analysis of physical activity outcomes. The JU:MP group improved levels of MVPA (+4.99 minutes/day, confidence interval (CI) = 1.01, 8.96, standardised mean difference (SMD) = 0.29), ST (–8.69 minutes/day, CI = –16.76, –0.61, SMD = –0.20), and CPM (+32.72, CI = 5.93, 59.53, SMD = 0.28) compared to controls. There were minor differences between groups in all secondary outcomes, favouring the JU:MP group. Exploratory sub-group analysis revealed that MVPA improved for boys (+7.34 minutes/day, CI = 0.70, 13.99, SMD = 0.36) and South Asian heritage children (+7.20 minutes/day, CI = 1.67, 12.72, SMD = 0.52) in the JU:MP group compared to the control group. Conclusions: Whole system approaches hold considerable promise for addressing children’s levels of physical activity at scale, whilst also tackling inequalities. Support/Funding Source: This study was supported by Sport England’s Local Delivery Pilot – Bradford; weblink: https://www.sportengland.org/campaigns-and-our-work/local-delivery. Sport England is a non-departmental public body under the Department for Digital, Culture, Media and Sport. Keywords: Physical activity, whole system, children, inequalities, before and after trial

Background It is crucial to find pragmatic design alternatives to randomised trials to evaluate early childhood parenting interventions in practice, which can suffer from potentially low uptake and disappointment bias. In the first study of its kind, we assess the feasibility of nesting a randomised Trial within a Cohort Study (TwiCS) to evaluate an early years parenting intervention delivered to parents of 1-2-year-old children living in inner-city Bradford, England. The study evaluated: (1) whether TwiCS methodology can be implemented to create control and intervention arms, whilst documenting any incidences of contamination; (2) whether satisfactory rates of intervention uptake are achieved; and (3) whether satisfactory rates of retention of participants are achieved. Methods A stratified random sample of 240 mother-child dyads were selected from an eligible population in the Born in Bradford’s Better Start cohort. Mother-child dyads were individually randomised 1:1 to the intervention or control, with stratification by child age (1 or 2 years old at the time of randomisation) and ethnicity (White British, South Asian, or other). A Red Amber Green (RAG) rating system supported the assessment of each objective: red (not achieved), amber (partly achieved), and green (achieved). Results TwiCS methodology created balanced control and intervention arms, and 73% of parents could be contacted about the intervention (green), though rates of contamination were higher than desired (2%, amber). Satisfactory rates of intervention uptake could not be achieved: 43% of parents consented to a referral (amber), and 14% of parents enrolled in IY-T (red). Satisfactory rates of retention in the intervention may be achievable, as 80% of enrolled parents participated (amber), and all participating parents completed the intervention (green). Conclusions It was feasible to use TwiCS methodology to randomly select, allocate, and contact parents, and document contamination in this setting. However, intervention uptake was low, and this would need improving for a future TwiCS evaluating this intervention to be feasible. This study suggests a TwiCS is not a viable approach to evaluating early years interventions delivered >12 months after cohort recruitment. Other pragmatic and implementable methods of evaluation may be more feasible, such as quasi-experimental designs, or target trials. Trial registration The study was prospectively registered on ISRCTN (ISRCTN16150114).

OBJECTIVE:To examine ethnic differences in the incidence and timing of recorded health conditions from birth to adolescence between White British and Pakistani British children. DESIGN:Longitudinal population-based birth cohort linked to primary care electronic health records. SETTING:Born in Bradford (BiB), a multiethnic UK birth cohort. PARTICIPANTS:13 282 children born between 2007 and 2011 with linked primary care records and ≥1-year follow-up, including 4818 White British and 5878 Pakistani British children in the primary comparison. MAIN OUTCOME MEASURES:Recorded diagnoses of atopic conditions, overweight/obesity, common mental health disorders and neurodevelopmental disorders. Incidence rates, Kaplan-Meier cumulative incidence and sex-adjusted Cox regression HRs were estimated. RESULTS:Atopic conditions emerged early and were more common among Pakistani British children, with higher hazards of eczema (HR 2.29, 95% CI 2.01 to 2.61), allergic rhinoconjunctivitis (HR 2.27, 2.00 to 2.58) and asthma (HR 1.35, 1.22 to 1.50). Overweight/obesity was recorded later and was also more frequent in Pakistani British children (HR 1.25, 1.16 to 1.35). In contrast, common mental health and neurodevelopmental diagnoses were more frequently recorded among White British children; Pakistani British children had lower hazards of neurodevelopmental diagnoses (HR 0.28, 0.23 to 0.35) and mental health disorders (HR 0.53, 0.41 to 0.70). CONCLUSIONS:Ethnic differences in recorded health conditions between White British and Pakistani British children were condition-specific and varied by age. These findings identify when recorded diagnoses diverge in Bradford and highlight the need to distinguish differences in morbidity from differences in recognition, access, assessment, and recording.

Objective To examine ethnic differences in the incidence and age-related trajectories of childhood health conditions from birth to adolescence within a UK birth cohort. Design Longitudinal population-based birth cohort with linkage to primary care electronic health records. Setting Born in Bradford (BiB), a multi-ethnic birth cohort in Bradford, UK. Participants 13,282 children (36% White British, 44% Pakistani British, 20% other ethnicity) born 2007 to 2011 with linked primary care records and over 1 year follow-up. Main outcome measures Incident diagnoses of atopic conditions (asthma, eczema, allergic rhinoconjunctivitis), overweight/obesity, common mental health disorders (anxiety, depression), and neurodevelopmental disorders (including ADHD and autism). Incidence rates, Kaplan-Meier cumulative incidence, and Cox regression hazards ratios (HRs) were estimated. Results Atopic conditions emerged early (median onset 5 to 6 years) and were more common among Pakistani British children, with higher hazards of eczema (HR 2.29, 95% CI 2.01 to 2.61), allergic rhinoconjunctivitis (HR 2.27, 2.00 to 2.58), and asthma (HR 1.35, 1.22 to 1.50). Overweight/ obesity developed later (median 9 to 10 years) and were also more frequent in Pakistani British children (HR 1.25, 1.16 to 1.35). In contrast, common mental health disorders emerged predominantly in early adolescence (median around 13 years), and both mental health and neurodevelopmental diagnoses were more frequently recorded among White British children; Pakistani British children had lower hazards of neurodevelopmental diagnoses (HR 0.28, 0.23 to 0.35) and mental health disorders (HR 0.53, 0.41 to 0.70). Conclusions Ethnic differences in childhood health are condition-specific and vary by age of onset, emerging at distinct stages. These findings inform the timing of prevention, service planning, and research into underlying mechanism. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The Born in Bradford study presents independent research commissioned by the National Institute for Health Research Collaboration for Applied Health Research and Care (NIHR CLAHRC) and the Programme Grants for Applied Research funding scheme (RP-PG-0407-10044). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Born in Bradford study presents independent research commissioned by the National Institute for Health Research Collaboration for Applied Health Research and Care (NIHR CLAHRC) and the Programme Grants for Applied Research funding scheme (RP-PG-0407-10044). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Individual-level data from Born in Bradford study cannot be made publicly available due to ethical approvals and the need to protect participant confidentiality. Researchers may apply to access these data via the Born in Bradford Data Access process. Full details of the application process, eligibility criteria, and data access conditions are available at https://borninbradford.nhs.uk/our-data/how-to-access-data/. Applications are reviewed subject to appropriate scientific justification, governance approval, and completion of a data sharing agreement. Enquiries can be directed to the Born in Bradford research team (borninbradford{at}bthft.nhs.uk).

OBJECTIVES:This study aimed to evaluate the impact of a social prescribing intervention (the Central Locality Integrated Care Service (CLICS)) on unplanned hospital usage in the city of Bradford. DESIGN:A quasi-experimental study applying a dynamic staggered difference-in-differences (DID) analysis on a propensity matched cohort between 2019 and 2023, using data from the Connected Bradford dataset, a pseudonymised linked health dataset on the whole Bradford population. SETTING:CLICS was delivered within general practices in deprived and ethnically diverse inner-city areas of Bradford, Yorkshire, UK. PARTICIPANTS:In total, 1304 CLICS patients were matched to 5216 control patients on key characteristics including ethnicity, deprivation, age, gender and health conditions. INTERVENTIONS:A proactive social prescribing intervention that integrates clinical and non-clinical services, including an individualised approach to tailor support based on the patient's needs, both within primary care services and by linking them to appropriate community-based assets/services. PRIMARY AND SECONDARY OUTCOME MEASURES:The primary outcome was the rate of unplanned hospital admissions and the secondary outcome was unplanned accident and emergency (A&E) attendances. RESULTS:CLICS patients were 2.1% (95% CI -3.8% to -0.4%, p=0.013) less likely to have an unplanned hospital admission and 2.4% (95% CI -4.6% to -0.2%, p=0.03) less likely to have an unplanned A&E attendance compared with the matched control. The DID analysis demonstrated a gradual increase in the association over time. Subanalyses revealed heterogeneity by ethnicity, the reduction in unplanned hospital admissions was observed only in patients of the Pakistani group, whereas the reduction in A&E attendances was statistically significant only in the white British group. CONCLUSION:The CLICS intervention was associated with a reduction in unplanned hospital usage. Social prescribing may be a valuable component of strategies to reduce health inequalities in unplanned hospital usage.