重新审视胎盘时钟：复发性早产中促肾上腺皮质素释放激素的早期升高。
Revisiting the placental clock: Early corticotrophin-releasing hormone rise in recurrent preterm birth.
机构信息
Department of Obstetrics & Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
出版信息
PLoS One. 2021 Sep 16;16(9):e0257422. doi: 10.1371/journal.pone.0257422. eCollection 2021.
OBJECTIVE
To determine if maternal plasma CRH and preterm birth history were associated with recurrent preterm birth risk in a high-risk cohort.
STUDY DESIGN
Secondary analysis of pregnant women with a prior preterm birth ≤35 weeks receiving 17-alpha hydroxyprogesterone caproate for the prevention of recurrent spontaneous preterm birth. All women with a 24-week blood sample were included. Maternal plasma CRH level at 24- and 32-weeks' gestation was measured using both enzyme-linked immunosorbent assay (ELISA) and extracted radioimmunoassay (RIA) technologies. The primary outcome was spontaneous preterm birth <37 weeks. The association of CRH, prior preterm birth history, and the two combined was assessed in relation to recurrent preterm birth risk.
RESULTS
Recurrent preterm birth in this cohort of 169 women was 24.9%. Comparing women who subsequently delivered <37 versus ≥37 weeks, mean levels of CRH measured by RIA were significantly different at 24 weeks (111.1±87.5 vs. 66.1±45.4 pg/mL, P = .002) and 32 weeks (440.9±275.6 vs. 280.2±214.5 pg/mL, P = .003). The area under the receiver operating curve (AUC) at 24 and 32 weeks for (1) CRH level was 0.68 (95% CI 0.59-0.78) and 0.70 (95% CI 0.59-0.81), (2) prior preterm birth history was 0.75 (95% CI 0.67-0.83) and 0.78 (95% CI 0.69-0.87), and (3) combined was 0.81 (95% CI 0.73-0.88, P = .001) and 0.81 (95% CI 0.72-0.90, P = .01) respectively for delivery <37 weeks. CRH measured by ELISA failed to correlate with gestational age or other clinical parameters.
CONCLUSION
In women with a prior preterm birth, CRH levels were higher and had an earlier rise in women who experienced recurrent preterm birth. Second trimester CRH may be useful in identifying a sub-group of women with preterm birth due to early activation of the placenta-fetal adrenal axis. Assay methodology is a variable that contributes to difficulties in reproducibility of CRH levels in the obstetric literature.
目的
确定母体血浆 CRH 和早产史是否与高危队列中复发性早产风险相关。
研究设计
对接受 17-α 羟孕酮己酸酯预防复发性自发性早产的既往早产≤35 周的孕妇进行二次分析。所有在 24 周时进行血液样本检测的孕妇均纳入研究。采用酶联免疫吸附试验（ELISA）和提取放射免疫分析（RIA）技术检测孕妇 24 周和 32 周时的血浆 CRH 水平。主要结局为自发性早产<37 周。评估 CRH、既往早产史以及两者联合与复发性早产风险的关系。
结果
在 169 名孕妇的队列中，复发性早产的发生率为 24.9%。与随后分娩<37 周和≥37 周的孕妇相比，RIA 检测的 CRH 水平在 24 周时（111.1±87.5 比 66.1±45.4 pg/ml，P=.002）和 32 周时（440.9±275.6 比 280.2±214.5 pg/ml，P=.003）存在显著差异。24 周和 32 周时，（1）CRH 水平的受试者工作特征曲线下面积（AUC）分别为 0.68（95%CI 0.59-0.78）和 0.70（95%CI 0.59-0.81），（2）既往早产史的 AUC 分别为 0.75（95%CI 0.67-0.83）和 0.78（95%CI 0.69-0.87），（3）两者联合的 AUC 分别为 0.81（95%CI 0.73-0.88，P=.001）和 0.81（95%CI 0.72-0.90，P=.01）。ELISA 法检测的 CRH 与孕龄或其他临床参数无相关性。
结论
在既往有早产史的孕妇中，发生复发性早产的孕妇的 CRH 水平更高，且上升更早。孕中期 CRH 可能有助于识别胎盘-胎儿肾上腺轴早期激活导致的早产亚组。检测方法的差异是导致产科文献中 CRH 水平重复性差的一个因素。
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