A Lower Maternal Cortisol-to-Cortisone Ratio Precedes Clinical Diagnosis of Preterm and Term Preeclampsia by Many Weeks

Abstract

Context Previous studies have shown reduced placental levels of 11- β -hydroxysteroid dehydrogenase type 2 (11 β HSD2) in preeclampsia (PE). However, it is unknown if the maternal cortisol-to-cortisone ratio is predictive of placental complications of pregnancy. Objective To determine the relationship between the maternal serum cortisol-to-cortisone ratio at different stages of pregnancy and the risk of PE or fetal growth restriction (FGR). Design Women from the Pregnancy Outcome Prediction Study experiencing PE (n = 194) or FGR (n = 185), plus a random sample of healthy controls (n = 279), were studied. Steroids were measured at ∼12, ∼20, ∼28, and ∼36 weeks of gestational age (wkGA). Separate analyses were performed for outcomes with term or preterm delivery. Associations were modeled using logistic regression. Results At 28 wkGA, the cortisol-to-cortisone ratio was negatively associated (OR per 1 SD increase, 95% CI)] with preterm PE (OR 0.33, 95% CI 0.19 to 0.57), term PE (OR 0.61, 95% CI 0.49 to 0.76), and preterm FGR (OR 0.50, 95% CI 0.29 to 0.85). At 36 wkGA, the cortisol-to-cortisone ratio was negatively associated with term PE (OR 0.42, 95% CI 0.32 to 0.55) but not term FGR (OR 1.07, 95% CI 0.87 to 1.31). Associations were not materially affected by adjustment for maternal characteristics. Conclusions A lower maternal serum cortisol-to-cortisone ratio precedes clinical manifestation of PE and preterm FGR by many weeks, despite previous reports of reduced levels of placental 11 β HSD2 in these conditions. Our observations implicate enhanced maternal 11 β HSD2 activity or reduced 11 β HSD type 1 activity in the pathophysiology of PE.

Global 11 Beta-Hydroxysteroid Dehydrogenase Activity Assessed by the Circulating Cortisol to Cortisone Ratio is Associated with Features of Metabolic Syndrome

“…It is not clear how the 11HSD activity measured in serum samples would reflect the activity in 24-hour urine samples. Nevertheless, 24-hour urine collection is cumbersome and inadequate collection procedures may cause sampling error, and the serum cortisol:cortisone ratio has been utilized adequately for such purpose [19]. In addition, detailed assessments of glucose homeostasis and blood pressure control could not be practically performed in the current population-based cross-sectional study.…”

Cortisol metabolism in pregnancies with small for gestational age neonates

“…17 and Jayasuriya et al . 33 , and detail the glucocorticoids’ profile in pre-eclamptic pregnancy. The advantage of our study is that we included the two cohorts of pre-eclamptic women: those who gave birth to SGA (SGA-PE), and AGA neonates (AGA-PE).…”

“…The limitation of this assumption is a single measurement of total plasma F (morning sample); therefore, it needs verification in the future. Some authors noted the decreased plasma F in PE 33–35 , but one has never assessed this phenomenon in relation to the coexisting PE and SGA. Vasku et al .…”

“…Scarce literature data concern the systemic F metabolism in women with idiopathic IUGR. Idiopathic IUGR was characterized by normal values of serum F/E ratio 17,33 , plasma E/F ratio 10 , or serum levels of A-ring metabolites of F and E 17 . It complies with our findings from plasma and urine for the SGA-NT group with female fetuses.…”

“…It complies with our findings from plasma and urine for the SGA-NT group with female fetuses. None of the cited authors 10,17,33 analyzed glucocorticoid balance in idiopathic IUGR pregnancy concerning fetal sex. Our results indicate that it may be fetal-sex-specific: we revealed the trend towards increased function of renal 11β-HSD2 (Fig.…”