Cardiovascular disease remains the leading cause of death worldwide. It is well established that low birthweight is linked to later cardiovascular disease but underlying mechanisms are poorly understood. My research has shown that activation of stress hormones is a key mechanism linking early development with health and disease over the life-span. The findings have major implications for disease prediction and ultimately may indicate new ways to prevent disease with intervention in pregnancy or early childhood. The early life environment is a key determinant of later health and disease, a concept known as developmental ‘programming’.Low birthweight, a crude marker of an adverse intra-uterine environment, is associated with increased risk of a range of diseases including diabetes, hypertension and cardiovascular disease. I am one of the few investigators world-wide dissecting potential mechanisms underlying this association. My focus is the role of glucocorticoids as both mediators and targets of early life programming. Key research areas include a) the hypothalamic-pituitary-adrenal (HPA) axis as a mediator of programming: I have shown that low birthweight is associated with activation of the HPA axis and that HPA axis activation is also associated with cardiovascular risk factors. b) HPA axis regulation: I have dissected potential mechanisms underlying the HPA axis activation in detailed human physiological studies and designed novel tests to investigate HPA axis regulation. I have used cutting-edge techniques surrounding the highly topical issue of epigenetic modifications as a consequence of adverse effects in utero. c) HPA axis and cardiometabolic/cognitive outcomes: I have explored the links between glucocorticoids and cardiovascular and cognitive end-points in cohorts of men and women with established disease in a MRC-funded 4-year follow-up study of 1000 people with diabetes, the Edinburgh Type 2 Diabetes Study.Since the 2008 award of the Edinburgh Tommy’s Centre for Maternal and Fetal Health I have been extending my studies on early life programming to investigate the consequences of maternal obesity on offspring health. This is particularly relevant with the rising world-wide epidemic of obesity. In an on-going longitudinal study of obese and lean pregnant women I am exploring the consequences of overnutrition on offspring disease and am carrying out detailed studies of energy balance and glucocorticoid action in obese pregnancy. I am a key investigator in a multi-centre randomised controlled trial investigating the role of metformin in preventing pregnancy complications (EMPOWAR). In collaboration with colleagues in Edinburgh I am using novel magnetic resonance imaging techniques to study the influence of glucocorticoids on fetal brain growth in utero. In collaboration with colleagues at the University of Aberdeen I have demonstrated, for the first time, a link between maternal obesity in pregnancy and offspring all-cause mortality.