Changes in the Maternal Hypothalamic-Pituitary-Adrenal Axis in Pregnancy and Postpartum: Influences on Maternal and Fetal Outcomes

Abstract

Overexposure of the developing fetus to glucocorticoids is hypothesised to be one of the key mechanisms linking early life development with later life disease. The maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes dramatic changes during pregnancy and postpartum. Although cortisol levels rise threefold by the third trimester, the fetus is partially protected from high cortisol by activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2). Maternal HPA axis activity and activity of HSD11B2 may be modified by maternal stress and disease allowing greater transfer of glucocorticoids from mother to fetus. Here we review emerging data from human studies linking dysregulation of the maternal HPA axis to outcomes in both the mother and her offspring. For the offspring, greater glucocorticoid exposure is associated with lower birth weight and shorter gestation at delivery. In addition, evidence supports longer term consequences for the offspring including re-setting of the HPA axis and susceptibility to neurodevelopmental problems and cardiometabolic disease. For the mother, the changes in the HPA axis, particularly in the postpartum period, may increase vulnerability to mood disturbances. Further understanding of the changes in the HPA axis during pregnancy and the impact of these changes may ultimately allow early identification of those most at risk of future disease.