Date: July 24, 2009 (Friday)
Time: 12:30 – 14:00 (sandwich lunch from 12:30 –12:45; seminar begins at 12:45)
Venue: Seminar Room 6, LG-1/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong

Abstract:

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 micro-nutrient balance, iv) maternal endocrine status. Mechanisms through which these maternal influences alter fetal development include i) a mis-match between fetal nutrient demands and the materno-placental capacity to meet this demand, ii) alterations in the fetal endocrine milieu, iii) changes in placental vascular impedance, which impact on fetal cardiovascular loading, and iv) 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, Professor Godfrey’s ongoing research in the Southampton Women's Survey (SWS) is characterizing 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 characterized before pregnancy and detailed pre- and post-natal measurements have been made on the 3,150 women who subsequently become pregnant and delivered in Southampton. Post-natal measurements include assessments of the offspring’s nutrition, body composition, respiratory health and cardiovascular structure and function from birth to age 8 years. The SWS shows that women with few educational qualifications eat a poor quality diet, affecting their health and their offspring’s development. The Survey is the only population-based study in the developed world of a large and representative group of women who were characterized before pregnancy and had longitudinal measurements of fetal growth rates during pregnancy. 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.

Bio-sketch:

Professor Keith Godfrey BM, PhD, FRCP is Professor of Epidemiology & Human Development at the University of Southampton and Honorary Consultant, Southampton University Hospitals NHS Trust. His research is defining measures to improve the early growth and development of children, thereby improving their lifelong health.

Professor Godfrey's other appointments include Trustee of the UK registered charity the International Society for the Developmental Origins of Health and Disease, Deputy Director of the Centre for Developmental Origins of Health & Disease and Deputy Director of the Southampton Nutrition Biomedical Research Unit.

Presentation file