Professor Keith Godfrey
Bm, PhD, FRCP
Professor of Epidemiology and Human Development
After studying medicine at the University of Southampton , I undertook specialist clinical training in dermatology and joined the MRC Environmental Epidemiology Unit in 1990. As MRC Clinical Scientist & Honorary Consultant in Southampton University Hospitals NHS Trust, I developed the MRC Environmental Epidemiology Unit Maternal Nutrition programme with the aim of improving the health of women and their offspring. In 2003, I was appointed Deputy Director of the University of Southampton Centre for the Developmental Origins of Health and Disease, followed by appointment as Professor of Epidemiology and Human Development at the University of Southampton in 2005.
Our work has established that people who were small at birth and had poor growth in infancy have an increased risk of adult coronary heart disease and type 2 diabetes, particularly if this is followed by increased childhood weight gain. Impaired early growth is also linked with later osteoporosis and obstructive airways disease including asthma. The relations between smaller infant size and ill-health in adulthood extend across the normal range of infant size in a graded manner. The associations do not simply reflect genetic influences, rather our findings show that interactions between the early life environment and genetic influences determine disease susceptibility.
The observations have led to the hypothesis that cardiovascular disease, type 2 diabetes, osteoporosis and obstructive airways disease originate through developmental plastic responses made by the fetus and infant as part of a prediction of the subsequent environment to which it anticipates that it will be exposed. Critical periods in development result in irreversible changes; if the environment in childhood and adult life differs from that predicted during fetal life and infancy, the developmental responses may increase the risk of adult disease. Evolutionary considerations and experimental findings strongly support the existence of major developmental effects on health and disease in adulthood.
Our research has linked raised adult blood pressure and altered glucose-insulin metabolism and stress responsiveness to specific maternal influences, notably i) the mothers own birthweight, ii) maternal body composition, including fat and lean mass, iii) dietary macro- and micronutrient balance, iv) maternal endocrine status. Mechanisms through which these maternal influences alter fetal development include a) a mis-match between fetal nutrient demands and the materno-placental capacity to meet this demand, b) alterations in the fetal endocrine milieu, c) changes in placental vascular impedance, which impact on fetal cardiovascular loading, and d) epigenetic processes, including altered DNA methylation, which change gene expression.
There is evidence that the consequences of developmental plastic responses can be modified during infancy, and that their effects can be amplified by high childhood weight gain and perhaps by low levels of habitual physical activity, increasing vulnerability to adverse lifestyle influences during adulthood. Within the MRC Epidemiology Resource Centre, my ongoing research in the Southampton Women’s Survey (SWS) is characterising these effects and integrating this understanding with parent/offspring genetic information, including epigenetic modification of fetal and placental genes. In the SWS, 12,500 women aged 20 to 34 years have been characterised before pregnancy and detailed pre- and postnatal measurements have been made on the 3,050 women who subsequently become pregnant and delivered in Southampton.
The SWS is the only population-based study in the developed world of a large and representative group of women who were characterised before pregnancy and had longitudinal measurements of fetal growth rates during pregnancy. Support for assessments of the offspring’s nutrition and body composition from birth to age 4 has come from the Arthritis Research Campaign, MRC and the Food Standards Agency. The Food Standards Agency and British Lung Foundation have funded respiratory assessment at age 6, and a programme grant from the British Heart Foundation is funding detailed measurement of cardiovascular structure and function at age 8. Epidemiological observations are combined with detailed clinical studies of mechanisms through research with the Centre for the Developmental Origins of Health and Disease in Southampton. Our epigenetic studies are supported through Epigen, a consortium founded in 2006 between MRC Technology, the University of Southampton, the University of Auckland, and AgResearch New Zealand.
The SWS shows that women with few educational qualifications eat a poor quality diet, affecting their health and their offspring’s development. We have formed an alliance of researchers to explore barriers to healthy eating in women with lower levels of educational attainment, and to define a complex nutritional intervention to improve the health of young women and their offspring. This alliance, the Southampton Initiative for Health, bridges public health nutrition, clinical epidemiology, psychology and public health medicine. The work forms part of the Southampton Nutrition Biomedical Research Unit, funded in 2008 by the National Institute for Health Research, and will enable us to define preventive measures to optimise early growth and minimise the long-term consequences of impaired early development on later health.