Cervicovaginal Fluid Acetate: A Metabolite Marker of Preterm Birth in Symptomatic Pregnant Women.
Cervicovaginal Fluid Acetate: A Metabolite Marker of Preterm Birth in Symptomatic Pregnant Women.
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DOI：
10.3389/fmed.2016.00048
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发表时间：
2016
影响因子：
3.9
通讯作者：
Anumba DO
中科院分区：
文献类型：
--
作者：
Amabebe E;Reynolds S;Stern V;Stafford G;Paley M;Anumba DO
与早产（PTB）相关的阴道微生物群的变化会留下特定的代谢物指纹，可以使用代谢组学技术在宫颈阴道液（CVF）中检测到。在这项研究中，我们表征和验证的CVF代谢产物的孕妇表现出先兆早产（PTL）的症状，1H-核磁共振光谱（NMR）和酶为基础的分光光度法。我们还确定了其预测PTB的能力，单独和组合，与目前的临床筛查工具-宫颈阴道胎儿纤维连接蛋白（FFN）和超声宫颈长度（CL）。CVF是从82名妊娠24 - 36周的胎膜完整的孕妇的高阴道拭子中获得的，这些孕妇有先兆PTL的症状，但未建立PTL。用400 MHz NMR光谱仪扫描溶解的CVF样品。在NMR光谱中鉴别乙酸盐和其他代谢物，对峰面积进行积分，并归一化为总光谱积分。为了确认和验证我们的观察结果，还使用乙酸测定试剂盒通过NADH的分光光度吸收从相同样品的随机选择的子集（n = 57）确定乙酸盐浓度（AceConc）。还确定了CVF FFN水平、经阴道超声CL和阴道pH。早产妇女的醋酸盐标准化积分和AceConc显著高于足月妊娠妇女（分别为P = 0.002和P = 0.006）。1H-NMR衍生的乙酸酯积分与分光光度法估计的AceConc强相关（r = 0.69; P < 0.0001）。两种方法对PTB <37周的预测力相同（醋酸盐积分：AUC = 0.75，95% CI = 0.60-0.91; AceConc：AUC = 0.74，95% CI = 0.57-0.90，最佳预测临界值>0.53 g/l），以及在指数评估的2周内分娩（醋酸盐积分：AUC = 0.77，95%CI = 0.58-0.96; AceConc：AUC = 0.68，95%CI = 0.5-0.9）。CVF醋酸盐的预测准确性与CL和FFN相似。在二元逻辑回归模型中，与单独的三种标志物相比，CVF醋酸盐、FFN和超声CL的组合改善了PTB的预测，但CVF醋酸盐与超声CL联合CVF FFN相比没有提供预测性改善。在有PTL症状的女性中，醋酸CVF升高似乎预示着早产，以及在发病后2周内分娩。CVF中乙酸盐的测定可证明用于预测PTB的临床实用性。
Changes in vaginal microbiota that is associated with preterm birth (PTB) leave specific metabolite fingerprints that can be detected in the cervicovaginal fluid (CVF) using metabolomics techniques. In this study, we characterize and validate the CVF metabolite profile of pregnant women presenting with symptoms of threatened preterm labor (PTL) by both 1H-nuclear magnetic resonance spectroscopy (NMR) and enzyme-based spectrophotometry. We also determine their predictive capacity for PTB, singly, and in combination, with current clinical screening tools – cervicovaginal fetal fibronectin (FFN) and ultrasound cervical length (CL). CVF was obtained by high-vaginal swabs from 82 pregnant women with intact fetal membranes presenting between 24 and 36 weeks gestation with symptoms of threatened, but not established, PTL. Dissolved CVF samples were scanned with a 400 MHz NMR spectrometer. Acetate and other metabolites were identified in the NMR spectrum, integrated for peak area, and normalized to the total spectrum integral. To confirm and validate our observations, acetate concentrations (AceConc) were also determined from a randomly-selected subset of the same samples (n = 57), by spectrophotometric absorption of NADH using an acetic acid assay kit. CVF FFN level, transvaginal ultrasound CL, and vaginal pH were also ascertained. Acetate normalized integral and AceConc were significantly higher in the women who delivered preterm compared to their term counterparts (P = 0.002 and P = 0.006, respectively). The 1H-NMR-derived acetate integrals were strongly correlated with the AceConc estimated by spectrophotometry (r = 0.69; P < 0.0001). Both methods were equally predictive of PTB <37 weeks (acetate integral: AUC = 0.75, 95% CI = 0.60–0.91; AceConc: AUC = 0.74, 95% CI = 0.57–0.90, optimal predictive cutoff of >0.53 g/l), and of delivery within 2 weeks of the index assessment (acetate integral: AUC = 0.77, 95% CI = 0.58–0.96; AceConc: AUC = 0.68, 95% CI = 0.5–0.9). The predictive accuracy of CVF acetate was similar to CL and FFN. The combination of CVF acetate, FFN, and ultrasound CL in a binary logistic regression model improved the prediction of PTB compared to the three markers individually, but CVF acetate offered no predictive improvement over ultrasound CL combined with CVF FFN. Elevated CVF acetate in women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation. An assay of acetate in CVF may prove of clinical utility for predicting PTB.