The objective of this study was to identify predictable maternal serum signatures of cortisol metabolism during the first trimester of women who are expected to deliver small-for-gestational-age (SGA) neonates. This prospective cohort study included 112 pregnant women (with and without SGA, n = 56 each). Maternal serum samples were collected at 10–14 gestational weeks to quantify the levels of cortisol and its precursors and metabolites by liquid chromatography-mass spectrometry. Increased maternal serum levels of tetrahydrocortisol (11.82 ± 8.16 ng/mL vs. 7.51 ± 2.90 ng/mL, P < 0.005) and decreased 21-deoxycortisol (2.98 ± 1.36 ng/mL vs. 4.33 ± 2.06 ng/mL, P < 0.0001) were observed in pregnant women carrying SGA fetus. In conjunction with individual steroid levels, metabolic ratios corresponding to the activity of related enzymes were calculated. In addition to increased tetrahydrocortisol/cortisol ratio (P < 0.006), the SGA group showed a significant increase in the two metabolic ratios including cortisol/11-deoxycortisol (P < 0.03) and cortisol/21-deoxycortisol (P < 0.0003). The receiver operating characteristic (ROC) curve generated in combination with three variables of 21-deoxycortisol concentration and two metabolic ratios of cortisol/21-deoxycortisol and tetrahydrocortisol/cortisol resulted in an area under the ROC curve = 0.824 (95% confidence interval, 0.713–0.918). A significant decrease in maternal serum levels of 21-deoxycortisol and an increase in two metabolic ratios of cortisol/21-deoxycortisol and tetrahydrocortisol/cortisol, indicating cortisol biosynthetic rate, represent potential biomarkers for the prediction of SGA in the first trimester.
Bibliographical noteFunding Information:
This study was supported by a grant from the Korea Institute of Science and Technology Institutional Program (Project No. 2E30480), and the Bio & Medical Technology Development Programs (NRF-2016M3A9B6902059) through the Ministry of Science and ICT, and sponsored by the Seoul National University Hospital research fund (03–2018-0400).
© 2021, Society for Reproductive Investigation.
- Cortisol biosynthesis
- Steroid hydroxylase
ASJC Scopus subject areas
- Obstetrics and Gynaecology