A Nested Case-Control Study of Allopregnanolone and Preterm Birth in the Healthy Start Cohort

Gabriella B Mayne; Peter E DeWITT; Brandy Ringham; Anna G Warrener; Uwe Christians; Dana Dabelea; K Joseph Hurt

doi:10.1210/jendso/bvac179

A Nested Case-Control Study of Allopregnanolone and Preterm Birth in the Healthy Start Cohort

J Endocr Soc. 2022 Nov 24;7(2):bvac179. doi: 10.1210/jendso/bvac179. eCollection 2022 Dec 15.

Authors

Gabriella B Mayne¹, Peter E DeWITT², Brandy Ringham³, Anna G Warrener¹, Uwe Christians⁴, Dana Dabelea³, K Joseph Hurt⁵

Affiliations

¹ Department of Anthropology, University of Colorado, Denver, CO 80204, USA.
² Department of Pediatrics Informatics and Data Science, University of Colorado School of Medicine, Aurora, CO 80045, USA.
³ Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
⁴ iC42 Clinical Research & Development, Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
⁵ Divisions of Maternal Fetal Medicine and Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.

Abstract

Context: Chronic stress is a risk factor for preterm birth; however, objective measures of stress in pregnancy are limited. Maternal stress biomarkers may fill this gap. Steroid hormones and neurosteroids such as allopregnanolone (ALLO) play important roles in stress physiology and pregnancy maintenance and therefore may be promising for preterm birth prediction.

Objective: We evaluated maternal serum ALLO, progesterone, cortisol, cortisone, pregnanolone, and epipregnanolone twice in gestation to evaluate associations with preterm birth.

Methods: We performed a nested case-control study using biobanked fasting serum samples from the Healthy Start prebirth cohort. We included healthy women with a singleton pregnancy and matched preterm cases with term controls (1:1; N = 27 per group). We used a new HPLC-tandem mass spectrometry assay to quantify ALLO and five related steroids. We used ANOVA, Fisher exact, χ², t test, and linear and logistic regression as statistical tests.

Results: Maternal serum ALLO did not associate with preterm birth nor differ between groups. Mean cortisol levels were significantly higher in the preterm group early in pregnancy (13w0d-18w0d; P < 0.05) and higher early pregnancy cortisol associated with increased odds of preterm birth (at 13w0d; odds ratio, 1.007; 95% CI, 1.0002-1.014). Progesterone, cortisone, pregnanolone, and epipregnanolone did not associate with preterm birth.

Conclusion: The findings from our pilot study suggest potential utility of cortisol as a maternal serum biomarker for preterm birth risk assessment in early pregnancy. Further evaluation using larger cohorts and additional gestational timepoints for ALLO and the other analytes may be informative.

Keywords: Cortisol; maternal stress; neuroactive steroids; neuroendocrine; neurosteroids; parturition.