Mayne Gabriella B, DeWITT Peter E, Ringham Brandy, Warrener Anna G, Christians Uwe, Dabelea Dana, Hurt K Joseph
Department of Anthropology, University of Colorado, Denver, CO 80204, USA.
Department of Pediatrics Informatics and Data Science, University of Colorado School of Medicine, Aurora, CO 80045, USA.
J Endocr Soc. 2022 Nov 24;7(2):bvac179. doi: 10.1210/jendso/bvac179. eCollection 2022 Dec 15.
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.
We evaluated maternal serum ALLO, progesterone, cortisol, cortisone, pregnanolone, and epipregnanolone twice in gestation to evaluate associations with preterm birth.
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, χ, test, and linear and logistic regression as statistical tests.
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; < 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.
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.
慢性应激是早产的一个风险因素；然而，孕期应激的客观测量方法有限。母体应激生物标志物可能填补这一空白。类固醇激素和神经甾体，如别孕烯醇酮（ALLO），在应激生理学和维持妊娠中发挥重要作用，因此可能有望用于早产预测。
我们在孕期对母体血清中的ALLO、孕酮、皮质醇、可的松、孕烷醇酮和表孕烷醇酮进行了两次评估，以评估其与早产的关联。
我们使用来自“健康开端”产前队列的生物样本库中的空腹血清样本进行了一项巢式病例对照研究。我们纳入了单胎妊娠的健康女性，并将早产病例与足月对照进行匹配（1:1；每组N = 27）。我们使用一种新的高效液相色谱-串联质谱分析法来定量ALLO和五种相关类固醇。我们使用方差分析、Fisher精确检验、χ²检验以及线性和逻辑回归作为统计检验方法。
母体血清ALLO与早产无关，两组之间也无差异。早产组在孕早期（13周0天 - 18周0天）的平均皮质醇水平显著更高（P < 0.05），且孕早期较高的皮质醇与早产几率增加相关（在13周0天时；优势比，1.007；95%置信区间，1.0002 - 1.014）。孕酮、可的松、孕烷醇酮和表孕烷醇酮与早产无关。
我们的初步研究结果表明，皮质醇作为孕早期早产风险评估的母体血清生物标志物具有潜在效用。使用更大的队列以及对ALLO和其他分析物增加更多孕期时间点进行进一步评估可能会提供更多信息。
