MRC Epidemiology Resouce Centre
Centre profile from the MRC Network publication issued November/December 2008
Ron Farr, 82, is a retired personnel director from Hitchin in Hertfordshire. He is married, has three children and enjoys painting. Ron is also a ‘Hertfordshire baby’ – a member of the Hertfordshire Study Cohort (HSC), a large group of county residents who are helping scientists to understand more about how our early life can affect our health in adulthood and the ageing process.
The HSC is just one of several large-scale epidemiological studies that are run by the MRC Epidemiology Resource Centre (ERC) in Southampton. Founded in 2003 under the direction of Professor Cyrus Cooper, the ERC is a centre of excellence in epidemiology; addressing the causes and prevention of common chronic disorders such as heart disease, osteoporosis, diabetes and obesity. The unit supports linked research programmes on the epidemiology of bone disease; occupation and health; and developmental origins of health and disease in India, as well as developing and managing long-term cohort studies like the one Ron belongs to.
Cyrus says: “The work of our unit fits in with key MRC health priorities such as musculoskeletal diseases, life-course studies of ageing, translational public health research and clinical medicine.”
The ERC occupies a purpose-built block on the campus of Southampton General Hospital and has around 60 staff, including many scientists who hold clinical appointments. The walls of the building are lined with stunning black and white photographs of the Southampton and Indian cohorts.
Developmental origins of adult disease
The ERC started out in 1979 as the MRC Environmental Epidemiology Unit (EEU), with a remit to investigate the occupational and environmental causes of disease within the UK. However, in the mid- 1980s the unit’s focus shifted to the developmental origins of adult disease; looking at how growth and development in foetal life, infancy and childhood can influence the risk of coronary heart disease, stroke, type 2 diabetes and osteoporosis in later life.
Cyrus explains: “For many years we have known that birth weight and weight in infancy predict the future risk of several chronic disorders including osteoporosis and heart disease. These observations were initially made in studies such as the HSC and have been widely confirmed around the world. Birth weight is a general indicator of the environmental circumstances of a mother prior to and during pregnancy. The findings led to the hypothesis that poor conditions in utero (such as under-nutrition) cause the developing foetus to make physiological and metabolic adaptations that persist into adult life and predispose him or her to later disease.”
Hertfordshire Study Cohort
So how do Ron and the three thousand other Hertfordshire babies fit in with this hypothesis and the unit’s research programmes? To study the developmental origins of disease you need to study a person closely from conception to adulthood. Hertfordshire residents were chosen for the cohort as their birth details were included in comprehensive midwife and health visitor records kept in the county. Measurements taken before, during and after birth could be compared to health assessments made by ERC scientists of the ‘babies’ in adulthood; for example medical histories, exercise patterns, strength tests, DNA and blood tests.
The HSC data have provided a basis for a wide variety of investigations into the associations between early development and clinical outcomes such as osteoporotic fracture.
Dr Elaine Dennison, a rheumatologist at the unit, says; “This unique cohort has allowed us to relate an individual’s early life experience, their genetic makeup and their adult lifestyle to their adult bone health. We now hope to follow these individuals to see if the factors identified are also associated with their risk of fracture.”
The HSC is closely linked to the ERC’s bone and joint programme. Professor Avan Aihie Sayer, an MRC clinical scientist and Honorary Chair in Geriatric Medicine at the University of Southampton, uses birth cohorts to study the causes, consequences and prevention of sarcopenia (degenerative loss of skeletal muscle mass and strength associated with ageing) and frailty in older people.
She says: “We can learn so much about the ageing process from studying cohort members. By assessing the decline in physical function which accompanies ageing and performing detailed physiological studies (such as examining specimens of muscle) we can delineate precisely the mechanism for sarcopenia and aim to develop strategies which improve the physical capacity of our ageing population.”
Southampton Women’s Survey
While the HSC has shown the importance of development in utero and in early life in determining the risk of chronic diseases later in life, the Southampton Women’s Survey (SWS) uses cohorts to explore how maternal influences might initiate developmental adaptations and have long-term consequences for a baby’s health.
Between 1998 and 2002, around 12,500 nonpregnant Southampton women aged 20-34 were interviewed about their diet, physical activity, lifestyle and social circumstances; their body composition was measured, blood and samples from the cheek inside the mouth were taken. Of these women, more than 3,000 have delivered babies and these babies are now being monitored as they grow up to find out how maternal nutrition affects foetal, neonatal and childhood development.
So what has the SWS revealed so far? Professor Hazel Inskip, who runs the survey, says: “The survey has led to a focus on the health and nutrition of young women. A woman’s diet before she becomes pregnant influences the development of the foetus and the child. For example, the mother’s diet before pregnancy is associated with the level of blood flow to the foetal liver. We also found that lower levels of bone mineral density are found in children born to mothers with lower levels of vitamin D during pregnancy. We are now developing interventions to improve diets in women and their families, and to educate teenagers in schools about their health and, in due course, that of their children.”
Data from the SWS also support additional studies on depression, placental function and bone development.
Bone and joint research
The ERC has studied the epidemiology of bone disease, specifically osteoporosis, since 1985. Osteoporosis, characterised by low bone mass and the breakdown of bone tissue, leaves people more vulnerable to fracture and affects 50 per cent of women and 20 per cent of men over the age of 50 in the UK. This in turn places a huge burden on NHS resources, making it a vital area for research.
There has already been research into the extent to which the disease might be linked to environmental influences before and just after birth. Using data from the SWS, ERC researchers have observed that a baby’s ability to accrue bone mineral is at a peak during intrauterine and early post-natal life. Therefore, environmental changes during this important period in development may profoundly affect the risk of osteoporosis in later life.
Cyrus, who leads the bone and joint programme, says: “We’re aiming to gain a greater understanding of interactions between genetic markers for osteoporosis, the intrauterine/early post-natal environment and adult lifestyle as determinants of bone strength, propensity to skeletal trauma and fracture risk. The ultimate goal is to create a platform of intervention studies in young women that will optimise skeletal health in their offspring.”
He adds: “This has led to the planning and funding of a large randomised control led trial in which mothers insufficient in vitamin D take dietary supplements with a view to enhancing the bone development of their offspring.”
India
Professor Caroline Fall coordinates a programme of research involving five study centres in India (Mumbai, Pune, New Delhi, Mysore and Vellore). In India, cardiovascular disease (CVD) has become the most common cause of early death, and type 2 diabetes has been predicted to affect 80 million Indians by 2030. Caroline’s research has shown that factors in early life, including poor maternal nutritional status during pregnancy, small new-born size, and poor weight gain in infancy, are risk factors for these adult disorders.
Caroline explains: “South Asians have an increased risk of metabolic syndrome (impaired glucose tolerance, high blood pressure and insulin resistance). This condition is linked to a characteristic body composition called the thin-fat phenotype (low muscle mass combined with high percentage body fat), which means they are more susceptible to CVD and diabetes. While increasing affluence and urbanisation are an important part of this phenomenon, we think the problem is exacerbated by under-nutrition in early life, which impairs the development of the body’s mechanisms for maintaining metabolic homeostasis.”
She adds: “Improving the nutritional status of women before and during pregnancy, and optimising the growth of the very young child, are as important for the prevention of cardiovascular disease and type 2 diabetes as improving adult lifestyles.”
The research programme has, until now, been based mainly on observational studies of large birth cohorts, such as the New Delhi Birth Cohort Study and Pune Maternal Nutrition Study. However, the emphasis of Caroline and her team’s research is now changing to interventional studies that will attempt to improve adult health by improving foetal and childhood nutrition. Caroline says: “The first of these is the Mumbai Maternal Nutrition Project, in which the aim is to increase the diet quality of women living in slums, from before conception and throughout pregnancy, and in turn to improve the long-term health of the offspring. In a rapidly changing society, where there are as many problems arising from overweight and obesity as from under-nutrition, other studies will seek to find ways of enabling adolescent and young women to adopt healthy diets in preparation for if and when they become mothers.”
Occupation and environment
Some of the ERC’s research continues within its original remit to investigate occupational and environmental causes of disease. This programme of work is being led by Professor David Coggon and Professor Keith Palmer.
Now that the causes of most of the serious occupational hazards of our modern world have been identified and addressed, attention has shifted to non-fatal work-related disorders that give rise to widespread illness and disability and put financial pressure on employers and healthcare services. Important among these are musculoskeletal disorders of the spine, upper limbs and large joints. Back pain alone costs the NHS an estimated £690m each year.
At the same time, increased public awareness of the potential dangers of workplace hazards, including using mobile phones, could also pose important unrecognised risks to health.
Keith, an Honorary Professor of Occupational Medicine at the University of Southampton and Consultant Occupational Physician, explains: “Evidence is showing us that conditions such as repetitive strain injury and lower back pain do not always occur simply through over-exposure to a hazardous agent or activity. Rather, the risk of symptoms and disability appears to be importantly modified by individual psychology and by societal beliefs and expectations.”
He adds: “Understanding the contribution of these non-occupational influences is crucial to tackling the problem. For example, efforts to prevent back pain through restrictions on lifting might have unintended adverse consequences if they reinforce workers’ expectations of injury.”
Both scientists, and their colleagues, contribute widely to the public debate on the risk factors and clinical management of occupational health. David has been involved in investigations into Gulf War illnesses, mobile phone-related issues, chronic fatigue syndrome/ME and multi-chemical allergies. Keith chairs the Industrial Injuries Advisory Council, a government body that advises ministers on occupational causes of illness and their compensation.
Future directions
The ERC has created a formidable body of research findings in a wide variety of health-related areas. The unit’s findings and subsequent interventions may one day directly inform and affect the health of ageing populations across the world. Where does Cyrus think the unit will go next? “The future evolution of our research programme will see an emphasis in two directions. Firstly, translation to effect public health interventions before and during pregnancy which improve one’s health status many decades later; secondly, to move towards a more profound understanding of the molecular and cellular mechanisms for this developmental component of disease risk.”
For more information on the Epidemiology Resource Centre, go to www.mrc.soton.ac.uk