Programming Effects of Glucocorticoids

Fetal glucocorticoid overexposure is a key potential mechanism underlying the link between low birthweight and later life diseases. The fetus is protected from high maternal glucocorticoid levels by the placental enzyme 11-hydroxysteroid dehydrogenase type 2. Antenatal glucocorticoid administration to women at threat of preterm labor, and high endogenous maternal glucocorticoid levels during pregnancy associate with lower birthweight. Long-term consequences for offspring include hypothalamic-pituitary-adrenal axis activation, increased metabolic and cardiovascular disorders, and neurodevelopmental sequelae. Strategies are needed to limit antenatal glucocorticoid use to those most at risk of preterm labor and to identify those most at risk of future disease.