Maternal Signatures of Cortisol in First Trimester Small-for-Gestational Age

Chaelin Lee, Seung Mi Lee, Dong Jun Byun, So Yeon Kim, Hugh I. Kim, Do Yup Lee, Young Mi Jung, Chan Wook Park, Joong Shin Park, Man Ho Choi

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1498-1505
Number of pages8
JournalReproductive Sciences
Issue number5
Publication statusPublished - 2022 May

Bibliographical note

Funding 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).

Publisher Copyright:
© 2021, Society for Reproductive Investigation.


  • 5-Reductase
  • Cortisol biosynthesis
  • SGA
  • Steroid hydroxylase

ASJC Scopus subject areas

  • Obstetrics and Gynaecology


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