Maternal serum glucocorticoid levels and maternal cortisol/cortisone ratio in healthy pregnancy, preeclampsia and intrauterine growth restriction

Objective:

Glucocorticoids play an essential role in pregnancy. The right proportion between maternal and fetal bioactive cortisol (F) and inactive cortisone (E) is responsible for proper embryonic implantation and normal fetal intrauterine development. The placental 11ß-dehydroxysteroiddehydrogenase (11ß-HSD2) acts as a barrier by converting F to E and protecting the fetus against excessive exposure to F. The reduced activity of 11ß-HSD2 is linked with prematurity and small birth weight. The aim of the study was to calculate F/E ratio to estimate the overall activity of 11ß-HSD2 throughout healthy pregnancy and in pregnancies complicated by preeclampsia (PE) and IUGR. We here hypothesize that disturbed placental function reflected by intrauterine growth restriction rather than a maternal hypertensive disorder is characterized by decreased placental 11ßHSD2 activity as reflected by maternal serum F/E ratio.

Methods:

A total of 188 maternal serum samples were analyzed for F and E by Gas chromatography-mass spectrometry (GC-MS). Study Group A: In a longitudinal set 33 healthy pregnant women were analyzed at three different time points throughout gestation and post partum. Study Group B: A total of 56 patients were enrolled in a cross-sectional study. We compared patients with PE (N = 14) and IUGR (N = 14) with gestational age matched healthy controls (N = 28). Statistics: Kruskal-Wallis test and Mann-Whitney.

Results:

Group A: F concentrations increased from first to second trimester followed by a drop post partum (group effect p < 0.0001). E concentrations increased from first to second trimester. A further increase to third trimester has been observed followed by a drop poast partum (group effect p < 0.0001). F/E ratio significantly increased from first to second trimester (p = 0.458) and then droped significantly to ratios recorded at first trimester (p = 0.009). Group B: Maternal serum E levels were significantly lower in IUGR (P value < 0.05). The F/E Ratio was significantly lower in PE (P value < 0.05).

Conclusion:

The rising levels of F and E during a healthy pregnancy are in association with increasing levels of corticosteroid-binding globulin and resetting of hypothalamic-pituitary-adrenal axis. The decreased plasma F/E ratios with advancing gestation observed in normal pregnancy may reflect increase in placental 11β-HSD2 activity with gestation. In IUGR a significant lower maternal serum E concentration is rather an effect of lack of substrate than 11ß-HSD2 activity since F/E ratio is not different to controls. However, in PE lower F/E Ratio points to more intensive F metabolism. Low maternal F/E Ratio in PE reflects not only changes in placental 11ß-HSD2 activity. We suggest that overall activity of 11ß-HSD2 in maternal tissue (kidney, salivary glands, colon and sweat glands) is exaggerated in preeclampsia pregnancy supported by recent findings of others.