Perinatal growth failure: the road to obesity, insulin resistance and cardiovascular disease in adults

A continuum of increasing risk of adulthood diseases, such as cardiovascular disease, type 2 diabetes and hypertension, with decreasing size at birth is now well-reported and a number of different hypotheses have been proposed. Birthweight links with disease risk markers such as insulin resistance are apparent from childhood, particularly when low birthweight is followed by rapid postnatal weight gain and childhood obesity. Such growth patterns follow fetal growth restraint, associated with maternal-uterine factors such as primiparity, smoking, maternal genes or variations in maternal diet. The fetal metabolic and hormonal responses to intrauterine growth restraint and to rapid postnatal growth are likely to be key to the early pathogenesis of adulthood disease. Thrifty fetal genotypes may enhance these adaptations and improve perinatal survival but predispose to adulthood disease. Their historical selection could explain high prevalences of type 2 diabetes in some ethnic groups, and their identification could allow targeting of potential interventions.