MR341 - Environmental Factors in Early Life and Ischaemic Heart Disease

The University of Bristol requires access to mortality, cancer registration, and demographics for the purpose of the Boyd Orr cohort.

Boyd Orr is an historical cohort study based on the long-term follow-up of 4,999 children who were surveyed in the Carnegie United Kingdom Trusts study of Family Diet and Health in Pre-War Britain (1937-1939). The cohort was established in 1988 by Professors George Davey Smith and Stephen Frankel who retrieved the original research records of the pre-war survey from the Rowett Research Institute, in Aberdeen, Scotland. The initial aim was to investigate the long-term impact of environmental factors in early life on adult coronary heart disease mortality. Since 1989, the scope of the research has widened to chronic disease outcomes and studies on the cohort to date have investigated a range of disease endpoints, particularly coronary heart disease and cancer, in relation to infant and childhood diet, the socio-economic conditions experienced by the children and markers of childhood nutritional status (body mass index, leg length and height).

The names, ages and addresses at the time of the survey of the children in the study, obtained from the archived material were used to trace individuals who took part in the original survey using the National Health Service Central Register. Of the 4,999 original participants, 88% have been traced and flagged.

Cox's proportional hazards and logistic regression analyses are undertaken to investigate associations of early factors with chronic disease risk outcomes. Since the NHS CR was established in 1948, analyses are restricted to subjects who were alive and resident in Britain on 1 January 1948; deaths occurring before this date are excluded from analyses. In Cox regression models, follow-up starts from 1 January 1948 and ended on the date of death embarkation or end of follow-up. Robust standard errors are calculated in all models to allow for clustering effects in children from the same household. Only fully anonymised data are available for statistical analysis. Only aggregated data are published. Further details of the study and results are summarised in Martin R et al International J Epidemiology 2005; 34: 742–749.

The possible impact of early-life factors, such as poor childhood nutrition, on adult health have been the subject of research and policy interest for many years, but recently interest has intensified as epidemiological studies (such as the Boyd Orr cohort) have shown important associations. This study, funded by grants from the Medical Research Council (UK), the World Cancer Research Fund, Research into Ageing, UK Survivors, the Economic and Social Research Council, the Wellcome Trust and the British Heart Foundation, has and (with continued support from DARS) will continue to provide high quality evidence that has informed nutritional and other guidelines and policies related to early-life factors.

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Data held and processed under this agreement were as follows - MRIS - Cause of Death Report; MRIS – Cohort Event Notification Report; MRIS – Members and Postings Report.

No further data will flow under this version of the agreement.

Between 2009 and 2013 the University of Bristol received digital data extracts from the Office of National Statistics relating to cause of death and cancer registrations, and listed separately for individuals residing in Scotland and England. Prior to this, the same data were shared in hard copy (beginning in 1988/89) with these data subsequently being entered into University of Bristol's database.

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No processing or analysis of these data has taken place. The files were retained in the secure location at the University of Bristol.

With this application the applicant seeks permission to hold the data received previously for the three-year period covered by the agreement.

In 2022, the NHSCR confirmed that further approvals were not needed to continue to hold the Scottish data provided by NHSCR via NHS Digital. They stated that only if an update of data were required would approval from the Public Benefit and Privacy Panel for Health and Social Care (HSC-PBPP) need to be sought.

The main outcomes of the study are the impact of early-life factors, such as poor childhood nutrition, on adult health. it was anticipated that research will focus on investigating links between aspects of childhood diet, nutritional status, dentition, body size and socioeconomic circumstances and later cancer incidence, all cause and cause specific mortality. MREC approval is in place for possible future genetic studies using stored specimens taken in the 2002/2003.

The expected outputs to health arise from the unique nature of the material collected in the Boyd Orr cohort. Detailed measures of childhood diet on all cohort members; most research in this field uses proxy measures of pre-natal and childhood nutrition (e.g. birthweight, height).

The data provide both clinical and policy relevant data on the roles of breastfeeding, socioeconomic factors in early-life, childhood growth and obesity, and intakes in childhood of energy, foods and nutrients, in the development of cardiovascular disease and cancer, the main causes of premature mortality in the UK.

To date, research on the cohort has resulted in over 50 peer-reviewed research publications. Boyd Orr was the first cohort study to demonstrate protective associations between childhood fruit and vegetable intake and adult cancer risk (Maynard et al JECH 2003, 10.1136/jech.57.3.218) and the adverse impact of high calorie intake on cancer (Frankel et al BMJ 1998, 10.1136/bmj.316.7130.499). Research based on Boyd Orr data has shown that breast feeding promotes childhood growth (Martin et al Arch Dis Childhood 2002, 10.1136/fn.87.3.F193) and the adverse impact of childhood overweight on adult mortality (Gunnell et al Am J Clin Nut 1998, 10.1093/ajcn/67.6.1111). Most of our studies have investigated life course influences on adult health, all-cause mortality, cancer and cardiovascular disease risk. When the study approachs the stage where all original participants have died, such analyses will be maximally powered, with all health events across each individual’s life course having been captured.

Research will be presented at academic conferences and published in peer reviewed academic journals. The Applicant will liaise with our Public Advisory Group to develop a strategy for dissemination to the general public.

The expected benefits from retaining these data include the ability to recommence data flows when additional funding has been secured to add contemporary cancer registrations, deaths and changes to NHS registration status for this cohort. Further publications based on the long term follow up of this cohort will be disseminated widely providing clinical and policy relevant data to inform policies and practice (see also yielded benefits). Given the unique nature of the material collected on this and their age now these data have great importance speaking to the impact of early-life family diet and health in Pre-War Britain (1937-1939) on development and health over the life course. As the cohort continues to age (the average age of study members is 95 years) it provides an opportunity to investigate early life influences on adult overall- and cause-specific mortality. The presence of such rich phenotypic data across the life course (recorded at the time and not reliant on participant recall) is rare.

Boyd Orr study has provided high quality evidence that has informed nutritional and other guidelines and policies related to early-life factors. For example, analyses of these records have provided evidence on the roles of breastfeeding, socioeconomic factors in early-life, childhood growth and obesity, and intakes in childhood of energy, foods and nutrients, in the development of cardiovascular disease and cancer, the main causes of premature mortality in the UK. Such observations, directly or indirectly, inform important national and international guidelines, such as the World Health Organisation (2007) and Centers for Disease Control and Prevention (2007) reports on the long-term effects of breastfeeding; the World Cancer Research Fund Cancer Prevention Report (2007) and policies aimed at maximising child development and reducing socioeconomic inequalities (e.g. the Marmott Review, 2010).

Following a period of relative inactivity due to resource constraints, over the past 18 months considerable effort has been put into developing the policies and procedures to support the use of the Boyd Orr data by researchers. The study is one of several legacy cohort studies (i.e., studies with no ongoing participant involvement) maintained by the MRC Integrative Epidemiology Unit (MRC IEU) at the University of Bristol. A formal process is now in place for researchers to apply for access to data, including review of applications by a Data Access Committee. Oversight of the study is provided by a Steering Committee and a Public Advisory Group feeds into the maintenance, development and promotion of the study.

Within the next REC review period (up to 2029) the applicant hopes to move the Speedwell data into the UK Longitudinal Linkage Collaboration (LLC), a trusted research environment (TRE), that will further enable Boyd Orr data to contribute to meta-analyses with other UK cohort studies. The applicant has been approached by researchers who are interested in analysing Boyd Orr data when they can facilitate access to updated data either locally (for University of Bristol researchers) or via the TRE.

Therefore, whilst the yielded benefits have been minimal in the period since our last application renewal, gaining approval to maintain our current data is vital to secure this resource for the long term. Furthermore, with the future addition of new outcome data from NHS-England it will have followed up almost the whole cohort to death which is very unusual in most studies. These data provide a window into the health of a population from the earlier part of the twentieth century and will enable comparisons with more modern cohorts.