Increased fetal exposure to glucocorticoids is a key mechanism thought to underlie the early life programming of later life disease. There is substantial experimental data in animal models in support of this hypothesis. Emerging evidence suggests glucocorticoid programming may also occur in humans with some studies now linking maternal endogenous cortisol levels with size at birth and gestation at delivery. The dramatic changes to the maternal hypothalamic-pituitary-adrenal axis during pregnancy mean that large scale studies in humans are challenging to conduct. One of the key regulators of fetal glucocorticoid exposure is the activity of placental ‘barrier’ enzyme 11ß-hydroxysteroid dehydrogenase type 2 (HSD2) which converts active cortisol to inactive cortisone. In animal models this enzyme is down regulated by various influences including maternal malnutrition, inflammation or stress but it is not known whether this is a major factor in regulation of human fetal glucocorticoid exposure. More studies are needed to understand the mechanisms whereby altered fetal glucocorticoid exposure may alter fetal growth trajectories and whether changes in the maternal hypothalamic-pituitary-adrenal axis in pregnancy could be suitable as a biomarker to identify those pregnancies most at risk.
- glucocorticoids; birthweight