妊娠晚期血浆雌三醇-16-葡萄糖醛酸苷、17-羟基孕酮与分娩启动的关系研究

Study on the Relationship Between Plasma Estriol-16-Glucuronide,17-Hydroxyprogesterone and Labor Onset During Third Trimester of Pregnancy

目的应用液相色谱-串联质谱法(liquid chromatography tandem-mass spectrometry,LC-MS/MS)同时定量检测妊娠晚期孕妇临产前后血浆中雌三醇-16-葡萄糖醛酸苷(estriol-16-glucuronide,E3-16-G)、17-羟基孕酮(17-hydroxyprogesterone,17-OHP)的浓度,并探究其与分娩启动的关系及对分娩启动的预测价值。方法以2020年11月至2022年2月于华中科技大学同济医学院附属同济医院就诊的117名孕妇为研究对象,以其血浆样本作为检测标本。根据采血时是否足月及临产情况分为4组,早产未临产组(10例)、早产临产组(10例)、足月未临产组(57例)、足月临产组(40例)。应用前期建立的LC-MS/MS法同批检测所有的血浆标本中E3-16-G及17-OHP浓度;收集孕妇的基本资料,对纳入的研究对象进行倾向评分配对(propensity score matching,PSM),比较临产前后孕妇血浆中E3-16-G、17-OHP的浓度差异,并对测定结果进行Pearson相关分析、单因素Logistic回归分析及受试者工作特征(receiver operating characteristic,ROC)曲线等统计学分析。结果受试孕妇妊娠晚期临产前血浆中E3-16-G的中位数浓度为47.22 ng/mL,95%置信区间(confidence interval,CI)浓度范围为46.44~64.32 ng/mL;17-OHP的中位数浓度为8.42 ng/mL,95%CI浓度范围为8.13~9.93 ng/mL。妊娠晚期临产后血浆中E3-16-G的中位数浓度为76.86 ng/mL,95%CI浓度范围为71.73~104.53 ng/mL;17-OHP的中位数浓度为8.09 ng/mL,95%CI浓度范围为7.37~9.36 ng/mL。足月孕妇临产前后血浆E3-16-G/17-OHP比值的差异有统计学意义(P<0.05),早产孕妇临产前后血浆中E3-16-G/17-OHP比值的差异无统计学意义(P>0.05)。受试孕妇血浆中E3-16-G与17-OHP水平为弱正相关关系(r=0.225,P<0.05),17-OHP水平与妊娠天数为弱负相关关系(r=-0.219,P<0.05)。Logistic回归分析结果显示,E3-16-G/17-OHP是足月分娩启动的独立影响因素。血浆中E3-16-G/17-OHP比值增加可提示分娩启动风险增加。ROC曲线分析结果表明,E3-16-G/17-OHP比值的曲线下面积(area under the curve,AUC)为0.69,E3-16-G/17-OHP比值为8.68时,正确指数最大,此时敏感度为62.50%,特异度为79.17%。结论血浆E3-16-G/17-OHP比值与足月分娩启动有关,E3-16-G/17-OHP比值对预测足月分娩启动具有临床价值。

Objective In this study,the liquid chromatography-tandem mass spectrometry(liquid chromatography tandem-mass spectrometry,LC-MS/MS)method will be used to simultaneously quantitatively detect the concentrations of plasma estriol-16-glucuronide(E3-16-G)and 17-hydroxyprogesterone(17-OHP)during the third trimester,and explore their relationship with labor onset and the prediction value of it.Methods A total of 117 pregnant women who visited Tongji Hospital in Wuhan from November 2020 to February 2022 were enrolled in this study,and their plasma samples were collected.The patients were divided into 4 groups according to gestational ages and state of labor at the time of blood collection:preterm labor group(10 cases),preterm non-labor group(10 cases),term non-labor group(57 cases),term labor group(40 cases).All plasma samples were detected in the same batch by using LC-MS/MS method.The basic information of pregnant women was collected,and propensity score matching(PSM)was performed among the study subjects.The differences between the concentrations of E3-16-G and 17-OHP before and after labor onset were compared.The Pearson correlation analysis,univariate logistic regression analysis,and receiver operating characteristic(receiver operating characteristic,ROC)curve were carried out on the measured results.Results The median concentration of E3-16-G in plasma before labor onset in the third trimester was 47.22 ng/mL,and the 95%CI was 46.44-64.32 ng/mL;the median concentration of 17-OHP was 8.42 ng/mL,and the 95%CI was 8.13-9.93 ng/mL.The median concentration of E3-16-G in plasma after labor onset in the third trimester was 76.86 ng/mL,and the 95%CI was 71.73-104.53 ng/mL;the median concentration of 17-OHP was 8.09 ng/mL,95%CI was 7.37-9.36 ng/mL.There was a statistically significant difference in the plasma E3-16-G/17-OHP ratio between full-term pregnant women before and after labor onset(P<0.05).Difference between plasma E3-16-G/17-OHP ratio before and after labor onset was not significant(P>0.05).There was a weak positive correlation between E3-16-G and 17-OHP levels in plasma(r=0.225,P<0.05),and a weak negative correlation between 17-OHP levels and days of gestational(r=-0.219,P<0.05).Logistic regression analysis showed that the E3-16-G/17-OHP ratio was a independent influencing factor for full-term labor onset.An increased E3-16-G/17-OHP ratio in plasma suggested an increased risk of labor onset.The ROC curve analysis showed that the area under the curve(AUC)of the E3-16-G/17-OHP ratio was 0.69,and the correct index was the largest when the E3-16-G/17-OHP ratio was 8.68.At this point,the sensitivity was 62.50%and the specificity was 79.19%.Conclusion The plasma E3-16-G/17-OHP ratio is associated with full-term labor onset,which has a predictive value in clinical practice.