David Q Stoye1, Ruth Andrew2, William A Grobman3,4, Emma K Adam5, Pathik D Wadhwa6, Claudia Buss6,7, Sonja Entringer6,7, Gregory E Miller8, James P Boardman1, Jonathan R Seckl2, Lauren S Keenan-Devlin9, Ann E B Borders4,9, Rebecca M Reynolds1,2. 1. MRC Centre of Reproductive Health, University of Edinburgh, Edinburgh, UK. 2. Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK. 3. Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 4. Center for Healthcare Studies, Institute for Public Health and Medicine, Northwestern University, Chicago, Illinois. 5. School of Education and Social Policy, Institute for Policy Research, Northwestern University, Evanston, Illinois. 6. Development, Health and Disease Research Program, University of California, Irvine, California. 7. Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany. 8. Department of Psychology, Institute for Policy Research, Northwestern University, Evanston, Illinois. 9. Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, NorthShore University Health System, University of Chicago Pritzker School of Medicine, Chicago, Illinois.
Abstract
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. Published by Oxford University Press on behalf of the Endocrine Society 2020.
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. Published by Oxford University Press on behalf of the Endocrine Society 2020.
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