Reduced maternal corticosteroid-binding globulin and cortisol levels in pre-eclampsia and gamete recipient pregnancies

Objective To measure and contrast maternal cortisol and corticosteroid-binding globulin (CBG) levels in pregnancies with normal outcomes, pre-eclampsia, intrauterine growth restriction (IUGR) and in gamete recipients. Study design Prospective study of 93 women at high risk of pre-eclampsia, including gamete recipients (n = 22) and 33 controls. Plasma total and free cortisol and CBG were measured every 2 weeks from 16 weeks' gestation until delivery. Results Forty-two per cent of the high-risk group had complications, including pre-eclampsia (n = 11), gestational hypertension (n = 16) and small-for-gestational-age (SGA) neonates (n = 12). There were no complications in the controls. In all groups, plasma CBG concentrations increased progressively across gestation (P < 0.05), in parallel to total cortisol, but fell significantly from 36 weeks' gestation onwards, with a corresponding rise in free cortisol concentrations. In pre-eclampsia and gestational hypertension, plasma CBG, and total and free cortisol concentrations were lower from 36 weeks onwards (P < 0.05). In IUGR, plasma CBG concentrations were suppressed from 28 weeks' gestation until delivery (P < 0.05), but with no significant difference in plasma total and free cortisol. Gamete recipients had significantly lower plasma CBG from 20 weeks' gestation onwards, and plasma total and free cortisol were reduced at 24 and 32 weeks onwards, respectively. Conclusions Maternal plasma CBG, total and free cortisol concentrations are reduced in pre-eclampsia/gestational hypertension, and markedly reduced in gamete recipients. Low CBG may be due to reduced synthesis or enhanced inflammation-driven degradation. Low maternal cortisol may be due to a lack of placental corticotropin-releasing hormone or reduced maternal ACTH, driving cortisol production. Low maternal cortisol may influence the foetal hypothalamic-pituitary-adrenal axis and disease patterns later in life following complicated pregnancy.