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 pre-birth 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 high-performance liquid chromatography-tandem mass spectrometry assay to quantify ALLO and five related steroids. We used ANOVA, Fisher Exact, Chi-square, 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, OR = 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.