Maternal Glucocorticoid Metabolism Across Pregnancy: A Potential Mechanism Underlying Fetal Glucocorticoid Exposure

David Q. Stoye, Ruth Andrew, William A. Grobman, Emma K. Adam, Pathik D. Wadhwa, Claudia Buss, Sonja Entringer, Gregory E. Miller, James P. Boardman, Jonathan R. Seckl, Lauren S. Keenan-Devlin, Ann E.B. Borders, Rebecca M. Reynolds*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Context: Across pregnancy, maternal serum cortisol levels increase up to 3-fold. It is not known whether maternal peripheral cortisol metabolism and clearance change across pregnancy or influence fetal cortisol exposure and development. Objectives: The primary study objective was to compare maternal urinary glucocorticoid metabolites, as markers of cortisol metabolism and clearance, between the second and third trimester of pregnancy. Secondary objectives were to test associations of total maternal urinary glucocorticoid excretion, with maternal serum cortisol levels and offspring birth weight z score. Design, Participants, and Setting: A total of 151 women with singleton pregnancies, recruited from prenatal clinic at the Pittsburgh site of the Measurement of Maternal Stress (MOMS) study, had 24-hour urine collections during both the second and third trimesters. Results: Between the second and third trimester, total urinary glucocorticoid excretion increased (ratio of geometric means [RGM] 1.37, 95% CI 1.22-1.52, P <. 001), and there was an increase in calculated 5β-reductase compared to 5α-reductase activity (RGM 3.41, 95% CI 3.04-3.83, P <. 001). During the third trimester total urinary glucocorticoid excretion and serum cortisol were negatively correlated (r = -0.179, P =. 029). Mean total urinary glucocorticoid excretion across both trimesters and offspring birth weight z score were positively associated (β = 0.314, P =. 001). Conclusions: The estimated activity of maternal enzymes responsible for cortisol metabolism change between the second and third trimester of pregnancy. Additionally, maternal peripheral metabolism and clearance of cortisol may serve as a novel mechanism affecting fetal cortisol exposure and growth.

Original languageEnglish (US)
Article numberdgz313
JournalJournal of clinical endocrinology and metabolism
Issue number3
StatePublished - Jan 8 2020


  • HPA
  • birth weight
  • cortisol
  • glucocorticoid
  • metabolism
  • pregnancy

ASJC Scopus subject areas

  • Biochemistry, medical
  • Endocrinology
  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism


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