Development of endogenous glucocorticoids, mineralocorticoids and progestins in the human fetal and perinatal period

Summary

Corticosteroids (CS) are known to be essential for fetal organ maturation and seem to play an important role in both the initiation of parturition and the postnatal adaptation of the human neonate. Pharmacologically, CS are widely used for enhancing fetal lung maturation prior to premature delivery. However, knowledge of endogenous CS and precursor levels throughout fetal and perinatal life and their response to exogenous CS is limited. Therefore, using automated liquid column chromatography plus specific radioimmunoassays, unconjugated aldosterone (Aldo), corticosterone (B), 11-deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol (F) and cortisone (E) were simultaneously followed in 70 amniotic fluid (AF) control samples throughout pregnancy, and in cord and neonatal plasma longitudinally during the first week of life. From 14 to 38 weeks, AF levels of all measured steroids except E rose by 2 to 12-fold on the average (allP<0.001) but declined at term. E increased until 31–35 weeks (P<0.01), then remained almost constant until term. Cord levels of all steroids were substantially higher than those found in AF at term. While levels of the placentally derived steroids P, 17-OHP, DOC and E dropped sharply after birth by several orders of magnitude (P≪0.01) showing typical disappearance curves, the biologically most potent CS Aldo and F rose even further immediately after birth. Whereas Aldo levels declined from maxima about 100 times above normal adult levels at 6 h by almost 3-fold until day 7 (P<0.01), F (and also B) fluctuated considerably resembling a damped oscillation and, by day 7, reached mean levels less than half of those seen in later childhood. After betamethasone treatment of the mother, neonatal levels of Aldo and F were suppressed to 24–69% of normal until day 9, whereas those of the other steroids (except E) returned to normal during the first hours of life. Phenobarbital (PB) therapy of the mother led to decreased steroid levels in maternal and umbilical venous plasma at term, while umbilical arterial CS levels, notably those of Aldo and F (P<0.02), were increased when compared with untreated controls, indicating a stimulation of the most potent CS in the fetus after PB. The significance of the findings in view of fetoplacental function and fetal organ maturation is briefly discussed.