The majority of pregnancy steroids originate in the fetal zone of the fetal adrenal (FZ). The data in the literature indicates that placental CRH directly stimulates the FZ. Despite the substantial alterations in the placental CRH production in late pregnancy, the predictivity of CRH for an estimation of term is poor. To sidetrack the expensive determination of unstable CRH, it may be expediential to use the FZ steroids. However, even these substances may not be optimal for prediction due to their rapid catabolism. Accordingly, we attempted to find the steroid catabolites, which are rapidly synthesized from the key FZ steroids and, having slower metabolic turnover, may be even better predictors for gestational age. Therefore, we have measure 69 steroids and steroid polar conjugates in maternal circulation at labor coming on from 28th to 41st week of gestation using GCMS. In contrast to the group of healthy women after the 38th week of gestation, all preterm births were induced by sudden unexpected complications in which the association with gradual changes in steroid metabolome was not the reason for the preterm birth. Beside the expected rise in conjugated δ-5 steroids, estrogens and their 16-α-hydroxy-metabolites, we have identified a number of further subordinate steroids like 4-ene-16α-hydroxy-metabolites, conjugated 3α-5α/β-androstane catabolites, and conjugated 7α/β-metabolites of δ-5 steroids showing excellent correlation with gestational age. Moreover, some of them and their ratios to the parent steroids showed exponential rise near term and appeared to be excellent predictors of ingoing labor.
The study was approved by the ethics committee of the Institute of Endocrinology in Prague, Czech Republic.
Supported by grant projects IGA NS/9834 and NS/9790.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology