Evidence for central hypercortisolism and elevated blood pressure in adolescent offspring of mothers with pre-eclampsia.

Abstract

Maternal total and free cortisol concentrations are reduced in pre-eclampsia (PE) and gestational hypertension (GH). However, the effect of this on the hypothalamic-pituitary-adrenal (HPA) axis function in the offspring is unknown. We examined the basal HPA axis activity in adolescent offspring of mothers with pre-pregnancy hypertension/GH/PE. A total of 1182 participants (mean age 17·1 years) recruited from the Western Australian Pregnancy Cohort (Raine) Study provided fasting morning blood samples for basal HPA axis and concomitant clinical assessments, including blood pressure. Plasma ACTH, total cortisol, corticosteroid-binding globulin (CBG) and free cortisol calculated by Coolens' equation were measured from the blood samples collected at home before 10:00 am. Total plasma cortisol (689 ± 153 nmol/l vs 583 ± 172 nmol/l, P = 0·024), ACTH (15·5 ± 13 pmol/l vs 10·8 ± 5·1 pmol/l, P = 0·040) and calculated free cortisol (52 ± 21 nmol/l vs 42 ± 22 nmol/l, P = 0·052) were higher in the PE offspring than in controls. The pre-pregnancy hypertension group had evidence of a lower ACTH/plasma free cortisol ratio (0·22 vs 0·33 P = 0·020) and lower CBG (713 nmol/l vs 821 nmol/l, P = 0·004) compared with controls. Systolic blood pressure was elevated in the GH/PE group compared with controls (120 mmHg vs 116 mmHg, P = 0·006). Hypothalamic-pituitary-adrenal axis activity is increased in the adolescent offspring of mothers with pre-eclampsia. This may be an adaptation resulting from the reduced maternal cortisol during foetal life. The resulting mild hypercortisolism may have implications for long-term health outcomes and warrants further investigation.