Search

Summary: Over the last 15 years, there has been growing evidence that poor nutrition during gestation plays an important role in the development of coronary heart disease. This hypothesis, commonly known as the ‘fetal origins of adult disease’ has now gained widespread acceptance in the scientific community. In this review, we discuss the evidence for this theory and analyse the patho-physiological mechanisms underlying the relationship between altered fetal growth and coronary heart disease. Finally, the potential relevance of the theory to cardiac surgical practice will be evaluated. [Copyright &y& Elsevier]

It is widely accepted that the likelihood of offspring developing heart disease, stroke, or diabetes in later life, is influenced by the their in utero environment and maternal nutrition. There is increasing epidemiological evidence that osteoporosis in the offspring may also be influenced by the mother's nutrition during pregnancy. This review provides evidence from a range of animal models that supports the epidemiological data; suggesting that lifelong bone development and growth in offspring is determined during gestation.

Epidemiological studies have led to the hypothesis that a major component of the risk of diseases such as hypertension, coronary heart disease and non-insulin-dependent diabetes (the 'metabolic syndrome') is established before birth. Although the underlying mechanisms of this 'programming' of disease have not yet been conclusively determined, a reduced fetal nutrient supply as a consequence of poor placental function or unbalanced maternal nutrition is strongly implicated. It has been proposed that one outcome of suboptimal nutrition is exposure of the fetus to excess glucocorticoids, which restrict fetal growth and programme permanent alterations in its cardiovascular, endocrine and metabolic systems. This review focuses on the effects of endogenous and exogenous glucocorticoid exposure in utero on postnatal hypothalamo-pituitary-adrenal (HPA) axis activity, both in humans and experimental animals. The physiological consequences and proposed underlying molecular and cellular mechanisms are discussed. Current data indicate that key targets for programming may include not only the HPA axis but also glucocorticoid receptor gene and 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) gene expression in a range of tissues.