Evidence for fetal glucocorticoid excess as a cause of adult cardiovascular disease

Purpose of reviewAnimal experiments demonstrating associations between birth weight and postnatal phenotypes that may increase the risk of cardiovascular disease, such as hypertension, obesity, anxiety, and increased glucocorticoid activity, support the human epidemiologic findings of an association between reduced size at birth and adult cardiovascular disease. Here we review the evidence for exposure of the fetus to excess glucocorticoid as the key underlying mechanism. Recent findingsAdministration of synthetic glucocorticoids to, and undernutrition of, pregnant animals both results in reduced birth weight and the relevant postnatal phenotypes. However, in the latter paradigm direct evidence of fetal exposure to excess endogenous glucocorticoids of often lacking. Thirty-year-old offspring of pregnant women given glucocorticoids for threatened preterm labour have minimal evidence of increased cardiovascular risk factors. SummaryExposure of the fetus to inappropriate amounts of glucocorticoids can result in a postnatal phenotype that may predispose to cardiovascular disease, although the fact that surrogate endpoints are often studied in animal experiments must be borne in mind. However, assumptions that effects of other interventions, such as maternal undernutrition, are mediated via exposure of the fetus to excess glucocorticoids are often not supported by direct evidence. The value of available human data should not be overlooked.