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Reduced maternal glucocorticoid clearance is associated with higher serum cortisol and reduced offspring birthweight

Presented at the Neonatal Society Spring Meeting 2019.

Authors: Stoye DQ1, Andrew R1, Boardman JP1, Buss C2, Entringer S2, Wadhwa PD2,  Keenan-Devlin L3, Borders A3, Reynolds RM1

Institution(s)
1University of Edinburgh, UK  2University of California, Irvine, USA  3University of Chicago, USA

Introduction
Glucocorticoids play a critical role in directing fetal maturation. High levels of maternal cortisol, measured in serum or saliva, are associated with offspring growth restriction and adverse neurodevelopment1. After release from the adrenal gland most cortisol is metabolised and excreted in urine. We hypothesised that variation in this peripheral metabolism and excretion influences maternal serum cortisol levels, and fetal growth.

Methods
151 women with mean age 30.5 ± SD 5.0 years and BMI 27.6 ±.7.1 kg/m2, performed 24 hour urine collections in the 2nd and 3rd trimesters at gestational age (GA) 17.3 ± 2.4 and 33.9 ± 1.2 weeks, respectively. Maternal serum was sampled at GA 16.7 ± 2.4 and 33.3 ± 1.1 weeks. 24 hour-total urinary glucocorticoid metabolites (TUG) were measured by gas chromatography triple quadrupole mass spectrometry (GC-MS/MS). Associations of log-transformed TUG with serum cortisol and birthweight Z-score were tested with Pearson’s correlation and linear regression adjusting for potential confounders. Study approval was provided by the Institutional Review Boards of each of the Measurement of Maternal Stress (MOMS) study’s 4 sites.

Results

During the 3rd trimester there was a negative correlation between TUG and serum cortisol (r=-0.179, p=0.029). 2ndtrimester, 3rd trimester and mean TUG were all positively associated with offspring birthweight Z-score in adjusted and unadjusted models (Table 1).

During the 3rd trimester there was a negative correlation between TUG and serum cortisol (r=-0.179, p=0.029).  2ndtrimester, 3rd trimester and mean TUG were all positively associated with offspring birthweight Z-score in adjusted and unadjusted models (Table 1).

Table 1. 1 p≤ 0.05, 2 p≤ 0.01 Adjusted model variables: Gestation urine samples collected, ethnicity, smoking, maternal age, pre-eclampsia, hypertension, diabetes, maternal BMI, parity

Conclusions
Reduced maternal urinary glucocorticoid excretion was associated with both increased serum cortisol levels and reduced offspring birthweight. Variation in peripheral metabolism and clearance of cortisol from maternal peripheral tissues may serve as a novel mechanism influencing fetal glucocorticoid exposure and somatic growth.

References

  1. Duthie L, Reynolds RM. Changes in the maternal hypothalamic-pituitary-adrenal axis in pregnancy and postpartum: influences on maternal and fetal outcomes. Neuroendocrinology. 2013;98(2):106-15.

Senior author supporting presentation on day of meeting: Professor James Boardman

Corresponding author e-mail address: david.stoye@ed.ac.uk

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