DNA methylation (DNAm) is a developmentally dynamic epigenetic process; yet, most epigenome-wide association studies (EWAS) have examined DNAm at only one timepoint or without systematic comparisons between timepoints. Thus, it is unclear whether DNAm alterations during certain developmental periods are more informative than others for health outcomes, how persistent epigenetic signals are across time, and whether epigenetic timing effects differ by outcome. We applied longitudinal meta-regression models to published meta-analyses from the PACE consortium that examined DNAm at two timepoints—prospectively at birth and cross-sectionally in childhood—in relation to the same child outcome (ADHD symptoms, general psychopathology, sleep duration, BMI, asthma). These models allowed systematic comparisons of effect sizes and statistical significance between timepoints. Furthermore, we tested correlations between DNAm regression coefficients to assess the consistency of epigenetic signals across time and outcomes. Finally, we performed robustness checks, estimated between-study heterogeneity, and tested pathway enrichment. Our findings reveal three new insights: (i) across outcomes, DNAm effect sizes are consistently larger in childhood cross-sectional analyses compared to prospective analyses at birth; (ii) higher effect sizes do not necessarily translate into more significant findings, as associations also become noisier in childhood for most outcomes (showing larger standard errors in cross-sectional vs prospective analyses); and (iii) DNAm signals are highly time-specific, while also showing evidence of shared associations across health outcomes (ADHD symptoms, general psychopathology, and asthma). Notably, these observations could not be explained by sample size differences and only partly to differential study-heterogeneity. DNAm sites changing associations were enriched for neural pathways. Our results highlight developmentally-specific associations between DNAm and child health outcomes, when assessing DNAm at birth vs childhood. This implies that EWAS results from one timepoint are unlikely to generalize to another. Longitudinal studies with repeated epigenetic assessments are direly needed to shed light on the dynamic relationship between DNAm, development and health, as well as to enable the creation of more reliable and generalizable epigenetic biomarkers. More broadly, this study underscores the importance of considering the time-varying nature of DNAm in epigenetic research and supports the potential existence of epigenetic “timing effects” on child health.

Born in Bradford (BiB): Age of Wonder is a seven-year research programme documenting the experiences of adolescents growing up in a large, multi-ethnic city in the UK. It is an extension of the Born in Bradford birth cohort study (Wright et al. , 2013; McEachan et al. , 2024) and aims to expand the cohort to include all young people attending secondary schools in the Bradford local authority. Participants are recruited through their secondary school each year, where a range of measures are taken (Shire et al. , 2024). Each September/October, data from the previous academic year is processed, collated with data from earlier academic years, and released. This data note is updated with each release and describes the data contained therein. Firstly, we outline the full recruitment process, highlighting junctures where potential participants are lost. Secondly, we give a brief overview of the questionnaire and health measure data. Thirdly, cross-sectional profiles of measures collected for each academic year are provided. Finally, we present a longitudinal view of the data by cohort, detailing how many repeat measures have been obtained.

OBJECTIVES:To describe the epidemiology of common pathogens and risk factors among pregnant women and their children. METHODS:In three European population-based birth cohorts, we examined 2213 mother-child pairs, contributing 5036 blood samples from pregnancy to 12 years of age. We measured serum immunoglobulin G levels against polyomaviruses (BKPyV, JCPyV, KIPyV, WUPyV, MCPyV), herpesviruses (Epstein-Barr virus [EBV], cytomegalovirus [CMV], varicella-zoster virus), adenovirus 36, Helicobacter pylori, and Toxoplasma gondii with multiplex serology. RESULTS:Among pregnant women, seroprevalence ranged from 18.7% (H. pylori) to 95.7% (EBV); among 4-6-year-old children, seroprevalence ranged from 3.6% (H. pylori) to 88.4% (BKPyV). Although most primary infections occurred in the first 4 years of life, some children had primary infections at later ages. Seropositive mothers were more likely to have seropositive children, but an intergenerational decrease in seroprevalence was evident for herpesviruses and H. pylori. There were sizeable differences between countries for H. pylori and T. gondii. Non-western ethnicity mothers and their children were more likely to be infected. Female sex (WUPyV, MCPyV, CMV), breastfeeding (CMV), early daycare attendance (CMV, H. pylori), and obesity (JCPyV, EBV, Adv-36) were associated with child's seroprevalence. CONCLUSIONS:European children acquire common pathogens but often experience first exposure beyond early childhood. Differences are expected between and within countries and across generations.

Background Adolescence is a critical period of development which paves the way for longer term health trajectories and lifestyles. Understanding the variety of factors which influence adolescent health is crucial to developing interventions and services which have the potential to influence health across the life-course. Collecting representative, longitudinal data with adolescents at scale is difficult. Secondary school settings offer an excellent opportunity to collect such data with adolescents, however, there are inherent challenges in working with these settings. The Born in Bradford Age of Wonder (AoW) study aims to capture the health and wellbeing trajectories of up to 30,000 adolescents living in the diverse and multi-ethnic city of Bradford, UK. Methods This paper presents key challenges and associated lessons from the first three years of implementing the AoW programme across Bradford secondary schools. Challenges and lessons are described across seven thematic areas, with illustrative examples of how these learnings subsequently fed back into the programme design. These reflections later inform key recommendations to help guide future researchers. Results Notable challenges in implementing the research programme included collecting data for opt-in measures, providing tailored approaches for individual schools with differing facilities and needs, fitting data collection within school timings, and returning tangible value to schools and students in a responsive way. Key lessons included engaging schools as partners, enacting rigorous ethical processes and balancing flexibility with programme fidelity. Co-production and regular stakeholder engagement (including parents, teachers, students) ensured alignment between the programme delivery and local needs and priorities. Our recommendations describe successful implementation as a three-phased iterative process of preparation, implementation, and sustained engagement. Conclusions Conducting longitudinal health research in secondary schools is a highly dynamic and complex process. By embracing co-production, operational flexibility, and cohesive working practices, AoW offers a model for conducting large-scale research in UK secondary schools.

Background:Environmental factors play a role in the pathogenesis of complex traits including atopic eczema (AE) and a greater understanding of gene-environment interactions (G*E) is needed to define pathomechanisms for disease prevention. We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors. We tested for replication using a further 10 studies and in vitro modelling to independently assess findings. Results:The discovery analysis showed suggestive evidence for interaction (p<0.05) between 7 environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking and washing practices) and at least one established variant for AE, 14 interactions in total (maxN=25,339). In replication analysis (maxN=252,040) dog exposure*rs10214237 (on chromosome 5p13.2 near IL7R) was nominally significant (ORinteraction=0.91 [0.83-0.99] P=0.025), with a risk effect of the T allele observed only in those not exposed to dogs. A similar interaction with rs10214237 was observed for siblings in the discovery analysis (ORinteraction=0.84[0.75-0.94] P=0.003), but replication analysis was under-powered ORinteraction=1.09[0.82-1.46]). Rs10214237 homozygous risk genotype is associated with lower IL-7R expression in human keratinocytes, and dog exposure modelled in vitro showed a differential response according to rs10214237 genotype. Conclusions:Interaction analysis and functional assessment provide evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via IL7R, supporting observational epidemiology showing a protective effect for dog ownership. The lack of evidence for other G*E studied here implies that only weak effects are likely to occur.

Objective MIREDA aims to provide a harmonized UK-wide resource of restructured, routinely collected anonymised data from multiple birth cohorts using the OMOP Common Data Model (CDM). It will enable analyses across sites without sharing sensitive data and produce real-world evidence to support interventions and policies that improve maternal and infant outcomes. Methods MIREDA harmonizes data from five UK birth cohorts by identifying and compiling common data within each Trusted Research Environment (TRE). The data is cleaned and assessed using summary reports before being mapped to a common format through a mix of automated and manual steps. Transformation rules are applied to standardize the data while ensuring privacy, as no raw data leaves the TREs. Analyses are conducted separately within each TRE using the same methods, with strict checks and validations before securely federating the results. Results Preliminary findings reveal significant regional variations in preterm birth rates and school attainment, alongside differing exposure risks such as smoking rates, maternal age, ethnicity, and multimorbidity. By stratifying populations with similar exposure risks but residing in different regions, the dataset enables natural experiment methods to evaluate the impact of local policies and interventions. Early results demonstrate how harmonized data can reveal disparities in crude versus standardized prevalence rates and provide case studies highlighting the effectiveness of local interventions in improving maternal and child outcomes. Conclusion The OMOP CDM provides a scalable, internationally accepted framework for data harmonisation. MIREDA will expand this to include non-healthcare data, such as education and health visitor records, and foster international collaborations. This initiative will help policymakers identify effective interventions to improve maternal and infant outcomes across the UK and beyond.

BACKGROUND:Multiple environmental and genetic factors play a role in the pathogenesis of atopic eczema (AE). We aimed to investigate gene-environment interactions (G × E) to improve understanding of the pathophysiology. METHODS:We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors. We tested for replication using a further 10 studies and in vitro modeling to independently assess findings. RESULTS:The discovery analysis (including 25,339 individuals) showed suggestive evidence for interaction (p < 0.05) between seven environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking and washing practices) and at least one established variant for AE, 14 interactions in total. In the replication analysis (254,532 individuals) dog exposure × rs10214237 (on chromosome 5p13.2 near IL7R) was nominally significant (ORinteraction = 0.91 [0.83-0.99] p = 0.025), with a risk effect of the T allele observed only in those not exposed to dogs. A similar interaction with rs10214237 was observed for siblings in the discovery analysis (ORinteraction = 0.84 [0.75-0.94] p = 0.003), but replication analysis was under-powered (ORinteraction = 1.09 [0.82-1.46]). rs10214237 homozygous risk genotype is associated with lower IL-7R expression in human keratinocytes, and dog exposure modelled in vitro showed a differential response according to rs10214237 genotype. CONCLUSION:Interaction analysis and functional assessment provide preliminary evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via IL7R, supporting observational epidemiology showing a protective effect for dog ownership. The lack of evidence for other G × E studied here implies only weak effects are likely to occur.

Objective To assess, evaluate and determine the most appropriate data model for implementation by the BaBi Network, which will collaborate to create a meta-cohort with a standardised dataset. A common data model serves as a blueprint for the standardisation of data across multiple sites and organisations. Methods BaBi is an evolving multi-site cohort study which involves recruiting pregnant women and their babies with the focus on linking together routine data across organisations. Online resources were consulted including attendance at a webinar on an established common data model (the Observational Medical Outcomes Partnership (OMOP) model) to explore the practical applications of a common data model in research contexts. Discussions were conducted with BaBi sites to assess their skills, capacity, and infrastructure, providing a deeper understanding of how to implement a data model that would be feasible for all parties while also meeting the brief. Results Despite significant advantages offered by the OMOP model, including data standardisation, this model was found to be unsuitable for standardising datasets for the BaBi meta-cohort. It was determined that OMOP may introduce unnecessary complexity especially where BaBi sites are in their early stages. BaBi sites have varying technical skills and capabilities, and we want to avoid imposing excessive technical demands at this stage. Since sites join our cohort at different times, not all will initially have a dedicated data specialist, though they are expected to hire one as they expand. Therefore, we recommend the implementation of a bespoke common data model given that it can be tailored to the project's specific needs while accounting for variations in skills and capacity across the network. Conclusion Opting for a bespoke common data model would benefit all BaBi sites including those who lack resources, skills and capabilities. However, this doesn’t rule out migrating the bespoke BaBi common data model into OMOP at a future date, if this is deemed beneficial for future data collaboration and sharing.

Birth cohort studies involve repeated surveys of large numbers of individuals from birth and throughout their lives. They collect information useful for a wide range of life course research domains, and biological samples which can be used to derive data from an increasing collection of omic technologies. This rich source of longitudinal data, when combined with genomic data, offers the scientific community valuable insights ranging from population genetics to applications across the social sciences. Here we present quality-controlled whole exome sequencing data from three UK birth cohorts: the Avon Longitudinal Study of Parents and Children (8,436 children and 3,215 parents), the Millenium Cohort Study (7,667 children and 6,925 parents) and Born in Bradford (8,784 children and 2,875 parents). The overall objective of this coordinated effort is to make the resulting high-quality data widely accessible to the global research community in a timely manner. We describe how the datasets were generated and subjected to quality control at the sample, variant and genotype level. We then present some preliminary analyses to illustrate the quality of the datasets and probe potential sources of bias. We introduce measures of ultra-rare variant burden to the variables available for researchers working on these cohorts, and show that the exome-wide burden of deleterious protein-truncating variants, S het burden, is associated with educational attainment and cognitive test scores. The whole exome sequence data from these birth cohorts (CRAM & VCF files) are available through the European Genome-Phenome Archive, and here we provide guidance for their use.

Birth cohort studies involve repeated surveys of large numbers of individuals from birth and throughout their lives. They collect information useful for a wide range of life course research domains, and biological samples which can be used to derive data from an increasing collection of omic technologies. This rich source of longitudinal data, when combined with genomic data, offers the scientific community valuable insights ranging from population genetics to applications across the social sciences. Here we present quality-controlled whole exome sequencing data from three UK birth cohorts: the Avon Longitudinal Study of Parents and Children (8,436 children and 3,215 parents), the Millenium Cohort Study (7,667 children and 6,925 parents) and Born in Bradford (8,784 children and 2,875 parents). The overall objective of this coordinated effort is to make the resulting high-quality data widely accessible to the global research community in a timely manner. We describe how the datasets were generated and subjected to quality control at the sample, variant and genotype level. We then present some preliminary analyses to illustrate the quality of the datasets and probe potential sources of bias. We introduce measures of ultra-rare variant burden to the variables available for researchers working on these cohorts, and show that the exome-wide burden of deleterious protein-truncating variants, S het burden, is associated with educational attainment and cognitive test scores. The whole exome sequence data from these birth cohorts (CRAM & VCF files) are available through the European Genome-Phenome Archive, and here we provide guidance for their use.

IntroductionBirth cohorts are valuable resources for studying early life, the determinants of health, disease, and development. They are essential for studying life course. Dynamic longitudinal electronic cohorts use routinely collected data, are live, and can reduce selection bias specifically associated with direct recruitment in traditional birth cohorts. However, they are limited to health and administrative data and may lack contextual information. The MIREDA (Mother and Infant Research Electronic Data Analysis) partnership creates a UK-wide birth cohort by aligning existing electronic birth cohorts to have the same structure, content, and vocabularies, enabling UK-wide federated analyses. Objectives1) Create a core dynamic, live UK-wide electronic birth cohort with approximately 500,000 new births per year using a common data model (CDM). 2) Provide data linkage and automation for long-term follow up of births from the Clinical Practice Research Datalink (CPRD), MuM-PreDiCT and the `Born in' initiatives of Bradford, Wales, Scotland, and South London for comparable analyses. MethodsWe will establish core data content and collate linkable data. A suite of extraction, transformation, and load (ETL) tools will be used to transform data for each birth cohort into the CDM. Transformed datasets will remain within each cohort's trusted research environment (TRE). Metadata will be uploaded for the public to the Health Data Research (HDRUK) Innovation Gateway. We will develop a single online data access request for researchers. A cohort profile will be developed for researchers to reference the resource. EthicsEach cohort has approval from their TRE through compliance with their project application processes and information governance. DisseminationWe will engage with researchers in the field to promote our resource through partnership networking, publication, research collaborations, conferences, social media, and marketing communications strategies.

BACKGROUND:Helicobacter pylori is a prevalent infection that may complicate pregnancy, but evidence remains limited, controversial and may not apply to all pregnant women. OBJECTIVE:This study aims to evaluate whether Helicobacter pylori is a risk factor for adverse pregnancy outcomes and to identify vulnerable subpopulations. STUDY DESIGN:Multiplex serology was utilized to measure blood levels of immunoglobulin G against eight Helicobacter pylori antigens in 1372 pregnant women from three European birth cohorts: BiB (United Kingdom), Rhea (Greece) and INMA (Spain). Outcomes of interest included gestational diabetes mellitus, gestational hypertension, preeclampsia, preterm birth and small for gestational age neonates, as well as prenatal anxiety and depression. Adjusted logistic regression models were used to evaluate the association between Helicobacter pylori seropositivity (overall and by antigen) and antigen specific antibody levels with the outcomes. We examined effect modification of the associations by ethnicity. RESULTS:Helicobacter pylori seropositivity was detected in 18.8% (258/1372) of pregnant women. Preeclampsia was the least common outcome (26/830). Helicobacter pylori seropositivity was associated with the development of two or more adverse pregnancy outcomes (gestational hypertension, gestational diabetes, preterm birth, small gestational age and preeclampsia) [OR:1.32 (95% CI: 1.06-1.65), p-value: 0.01], especially in women with high antibody levels to OMP antigen [OR: 2.12 (95% CI: 1.62-2.76), p-value: 0.001]. Women with high antibody levels to Helicobacter pylori antigens GroEL and NapA were more likely to develop preeclampsia [OR: 2.34 (95% CI: 1.10-8.82), p-value: 0.03; OR: 4.09 (95% CI: 1.4-11.93), p-value 0.01)]. Helicobacter pylori seropositivity increased the odds of developing any hypertensive disorder during pregnancy among women of western ethnicity (948/1372) [OR:3.35 (95% CI: 1.29-8.74), p-value 0.03]. CONCLUSION:Our study suggests that Helicobacter pylori seropositivity is a risk factor for multiple adverse pregnancy outcomes and particularly in women of western origin for hypertensive disorders during pregnancy. Moreover, pathogen specific characteristics reflected in the antibody responses against OMP, GroEL and NapA seem to determine disease associations.

Background Adolescence and transition into adulthood are periods shaping life-long mental health, cardiometabolic risk, and inequalities. However, they are poorly studied and understood. By extending and expanding the Born in Bradford (BiB) cohort study through this period using innovative, co-produced approaches to collect and analyse data, we aim to understand better the interplay of factors that influence health and wellbeing, and inform/evaluate interventions to improve them and reduce inequalities. Protocol BiB Age of Wonder (AoW) is a large, whole city cohort that will capture the contemporary lived experience amongst multi-ethnic adolescents progressing into young adulthood. We will collect repeated data from existing BiB participants and their peers (N~30,000 adolescents). The protocol for the first phase of the quantitative methods, involving survey measurements and health assessments in mainstream secondary schools is described here. We describe the co-production behind these methods, and lessons learned from the first year of data collection.

Background Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear. Methods We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p < 4.9 x 10-10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations. Findings Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7,110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (-59 g, 95% CI: -106, -11) and phenylalanine (-25 g, 95% CI: -47, -4) lower offspring birthweight. These findings are supported by sensitivity analyses. Interpretation Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth.

Background Foetal and early childhood development contributes to the risk of adult non-communicable diseases such as hypertension and cardiovascular disease. We aimed to investigate whether kidney size at birth is associated with markers of kidney function at 7–11 years. Methods Foetal kidney dimensions were measured using ultrasound scans at 34 weeks gestation and used to derive kidney volume (cm 3 ) in 1802 participants in the Born in Bradford (BiB) birth cohort. Blood and urine samples were taken from those who participated in the BiB follow-up at 7–11 years (n = 630) and analysed for serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP). Estimated glomerular filtration rate (eGFR) was calculated using Schwartz creatinine only and combined with cystatin C, and cystatin C only Zappitelli and Filler equations. Linear regression was used to examine the association between foetal kidney volume and eGFR, ACR, PCR and blood pressure, unadjusted and adjusted for confounders. Results Kidney volume was positively associated in adjusted models with eGFR calculated using Schwartz combined (0.64 ml/min diff per unit increase in volume, 95% CI 0.25 to 1.02), Zappitelli (0.79, 95% CI 0.38 to 1.20) and Filler (2.84, 95% CI 1.40 to 4.28). There was an association with the presence of albuminuria but not with its level, or with other urinary markers or with blood pressure. Conclusion Foetal kidney volume was associated with small increases in eGFR in mid-childhood. Longitudinal follow-up to investigate the relationship between kidney volume and markers of kidney function as children go through puberty is required.

Background: Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in South Asians. Foetal kidney size was smaller in South Asians in the Born in Bradford (BiB) birth cohort. As part of BiB follow up, we aimed to investigate if there were ethnic differences in kidney function and blood pressure in early childhood and whether this was different by foetal kidney size. Methods: Serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP) were analysed in blood and urine samples from those who participated in the BiB follow-up at 7-11 years. Ethnicity was categorised by parental self-report as White European and South Asian. Estimated glomerular filtration rate (eGFR) was calculated using Schwartz, and cystatin C Zappitelli and Filler equations. Linear regression was used to examine the association between ethnicity and eGFR, PCR and blood pressure. Results: 1591 children provided blood (n=1403) or urine (n=625) samples. Mean eGFR was 92 ml/min/1.73m2 (standard deviation (SD) 9) using Schwartz (n=1156) and 94 (SD 11) using Zappitelli (n=1257). CKD prevalence was rare (1 with eGFR <60 ml/min/1.73m2, 14 (2.4%) had raised ACR (>2.5 mg/mmol in boys/3.5 mg/mmol in girls). Diastolic blood pressure was higher in South Asian children (difference 2.04 mmHg, 95% CI 0.99 to 3.10) but was not significant in adjusted analysis. There was no evidence of association in adjusted models between ethnicity and any eGFR or urinary measure at this age. Conclusions: There was no evidence of significant ethnic differences in kidney function at pre-pubertal age despite differences in kidney volume at birth. Longitudinal follow-up is required to track ethnic patterns in kidney function and blood pressure as children develop through puberty.

Mercury has high industrial utility and is present in many products, and environmental contamination and occupational exposure are widespread. There are numerous biological systems involved in the absorption, metabolism, and excretion of Hg, and it is possible that some systems may be impacted by genetic variation. If so, genotype may affect tissue concentrations of Hg and subsequent toxic effects. Genome-wide association testing was performed on blood Hg samples from pregnant women of the Avon Longitudinal Study of Parents and Children (n = 2893) and children of the Human Early Life Exposome (n = 1042). Directly-genotyped single-nucleotide polymorphisms (SNPs) were imputed to the Haplotype Reference Consortium r1.1 panel of whole genotypes and modelled againstlog-transformed Hg. Heritability was estimated using linkage disequilibrium score regression. The heritability of Hg was estimated as 24.0% (95% CI: 16.9% to 46.4%) in pregnant women, but could not be determined in children. There were 16 SNPs associated with Hg in pregnant women above a suggestive p-value threshold (p < 1 × 10−5), and 21 for children. However, no SNP passed this threshold in both studies, and none were genome-wide significant (p < 5 × 10−8). SNP-Hg associations were highly discordant between women and children, and this may reflect differences in metabolism, a gene–age interaction, or dose–response effects. Several suggestive variants had plausible links to Hg metabolism, such as rs146099921 in metal transporter SLC39A14, and two variants (rs28618224, rs7154700) in potassium voltage-gated channel genes. The findings would benefit from external validation, as suggestive results may contain both true associations and false positives.

The purpose of this study is to describe the burden of health care utilisation and early education outcomes of children with and without rare diseases. Using the Born in Bradford birth cohort and its linked routine health care and education data, we looked at cumulative primary care episodes, hospital admissions and medication prescriptions. We assessed education outcomes using Early Years Foundation Stage Profile and the National Curriculum Tests-Key Stage 1 results. Among analytical sample of 13,858, 1711 or 12.3

Background: The Born in Bradford’s Better Start (BiBBS) interventional birth cohort study was designed as an innovative cohort platform for efficient evaluation of early life interventions delivered through the Better Start Bradford programme. There are a growing number of interventional cohorts being implemented internationally. This paper provides an interim analysis of BiBBS in order to share learning about the feasibility and value of this method. Methods: Recruitment began in January 2016 and will complete in December 2023 with a target sample of 5,000 pregnancies. An interim analysis was completed for all pregnancies recruited between January 2016 and November 2019 with an expected due date between 1st April 2016 and 8th March 2020. Descriptive statistics were completed on the data. Results: Of 4,823 eligible pregnancies, 2,626 (54%) pregnancies were recruited, resulting in 2,392 mothers and 2,501 children. The sample are representative of the pregnant population (61% Pakistani heritage; 12% White British; 8% other South Asian and 6% Central and Eastern European ethnicity). The majority of participants (84%) live in the lowest decile of the Index of Multiple Deprivation, and many live in vulnerable circumstances. A high proportion (85%) of BiBBS families have engaged in one or more of the Better Start Bradford interventions. Levels of participation varied by the characteristics of the interventions, such as the requirement for active participation and the length of commitment to a programme. Conclusions: We have demonstrated the feasibility of recruiting an interventional cohort that includes seldom heard families from ethnic minority and deprived backgrounds. The high level of uptake of interventions is encouraging for the goal of evaluating the process and outcomes of multiple early life interventions using the innovative interventional cohort approach. BiBBS covers a period before, during and after the coronavirus disease 2019 (COVID-19) pandemic which adds scientific value to the cohort.