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中华妇幼临床医学杂志(电子版) ›› 2022, Vol. 18 ›› Issue (01) : 111 -119. doi: 10.3877/cma.j.issn.1673-5250.2022.01.015

论著

子宫动脉血流参数及血清学指标分别对早期先兆流产孕妇的预测价值
魏瑗, 罗红†()   
  • 收稿日期:2021-07-08 修回日期:2022-01-10 出版日期:2022-02-01
  • 通信作者: 罗红

Predictive value of uterine artery blood flow parameters and serological indexes in pregnant women with early threatened abortion

Yuan Wei, Hong Luo†()   

  • Received:2021-07-08 Revised:2022-01-10 Published:2022-02-01
  • Corresponding author: Hong Luo
  • Supported by:
    National Key Research and Development Project of China(2016YFC1000100)
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引用本文：

魏瑗, 罗红. 子宫动脉血流参数及血清学指标分别对早期先兆流产孕妇的预测价值[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(01): 111-119.

Yuan Wei, Hong Luo. Predictive value of uterine artery blood flow parameters and serological indexes in pregnant women with early threatened abortion[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2022, 18(01): 111-119.

目的

探讨同时进行子宫动脉血流参数及血清学指标检测(以下简称为"同时检测")，分别对早期先兆流产(ETA)孕妇的预测价值。

方法

选择2019年5月至2021年5月，于四川大学华西第二医院6~10孕周时进行腹部或阴道超声检查被确诊为ETA的90例孕妇为研究对象。确诊后，均对其采取阿司匹林等进行保胎治疗。采取回顾性分析法，根据妊娠结局，将其分为研究组[n＝27，早期自然流产(ESA)孕妇]和对照组(n＝63，≥12孕周持续妊娠孕妇)。对2组孕妇年龄、子宫动脉血流参数、血清学指标、妊娠方式、流产次数、产次、阴道流血率、同时检测时孕龄，采用成组t检验、Mann-Whitney U检验与χ2检验比较。对可能影响ETA孕妇发生ESA的因素进行多因素非条件logistic回归分析。绘制血清雌二醇水平预测ETA孕妇ESA的受试者工作特征(ROC)曲线，计算曲线下面积(AUC)，根据约登指数最大原则，确定最佳临界值，并计算其预测ETA孕妇发生ESA的敏感度和特异度。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求，并且通过四川大学华西第二医院医学伦理委员会审查、批准[审批文号：2021年审(167)号]。

结果

①研究组孕妇年龄显著大于对照组，同时检测时孕龄，血清β-人绒毛膜促性腺激素(hCG)、孕酮和雌二醇水平，均显著低于对照组，并且差异均有统计学意义(P<0.05)。2组孕妇妊娠方式构成比、流产次数、产次、阴道流血率，以及双侧子宫动脉收缩期峰值血流速度(SPV)与舒张末期血流速度(DEV)及其比值(S/D)、搏动指数(PI)与阻力指数(RI)分别比较，差异均无统计学意义(P>0.05)。②根据已有研究结果及临床经验，将ETA孕妇ESA影响因素的单因素分析结果中有统计学意义因素及双侧子宫动脉PI进行多因素非条件logistic回归分析结果显示，血清雌二醇水平是ETA孕妇ESA的独立影响因素(OR＝0.997，95%CI：0.995~1.000，P＝0.044)。③血清雌二醇水平预测ETA孕妇ESA的AUC为0.933(95%CI：0.849~1.000，P<0.001)。血清雌二醇水平预测ETA孕妇ESA的最佳临界值为567.5 pg/mL，敏感度为96.8%，特异度为88.5%。

结论

血清学指标中雌二醇水平，对ETA孕妇ESA具有较高预测价值，可早期评估ESA发生风险，可为及时干预提供参考。子宫动脉血流参数对ETA孕妇ESA无预测作用。

关键词: 流产，先兆, 流产，自然, 子宫动脉, 血流动力学, 雌二醇, 母体血清学筛查, 妊娠初期, 妊娠结局, 孕妇
Objective

To explore predictive values of simultaneous detection of uterine artery blood flow parameters and serological indexes (hereinafter referred to as " simultaneous detection" ) in pregnant women with early threatened abortion (ETA), respectively.

Methods

A total of 90 pregnant women with 6-10 gestational weeks who were diagnosed as ETA by abdominal or vaginal ultrasound examination in West China Second University Hospital, Sichuan University from May 2019 to May 2021 were admitted as research subjects. They were treated with drugs such as aspirin to prevent miscarriages after diagnosis of ETA. According to different pregnancy outcomes, they were divided into study group [n=27, early spontaneous abortion (ESA) pregnant women] and control group (n=63, women with pregnancy duration ≥12 gestational weeks) by retrospective analysis method. Maternal age, uterine artery blood flow parameters, serological indexes, fertilization method, abortion time, parity, vaginal bleeding rate and gestational age at the time of simultaneous detection between two groups were compared by independent-samples t test, Mann-Whitney U test and chi-square test. Multivariate unconditional logistic regression analysis was conducted to analyze influencing factors of ESA in ETA pregnant women. Receiver operating characteristic (ROC) curve of serum estradiol level predicting ESA in ETA pregnant women was drawn, and area under ROC curve (AUC) was calculated. The best cutoff value was determined according to the maximum principle of Youden index, and its sensitivity and specificity were calculated. The procedures followed in this study were in line with the requirements of newly revised World Medical Association Declaration of Helsinki in 2013, and were reviewed and approved by the Medical Ethics Committee of West China Second University Hospital, Sichuan University [Approval No. 167-2021].

Results

①The age of pregnant women in study group was significantly older than that of control group, but gestational age at the time of simultaneous detection, levels of serum β-human chorionic gonadotropin (hCG), progesterone and estradiol in study group were significantly lower than those of control group, and all differences were statistically significant (P<0.05). Whereas the composition ratio of fertilization method, abortion time, parity, vaginal bleeding rate and bilateral uterine artery blood flow parameters, such as systolic peak velocity (SPV), diastolic end velocity (DEV), ratio of SPV and DEV (S/D), pulsatility index (PI), and resistance index (RI) were not significantly different between two groups (P>0.05). ②According to the existing research results and clinical experience, factors with statistical significance in univariate analysis results of influencing factors of ESA in ETA pregnant women and bilateral uterine artery PI were analyzed by multivariate unconditional logistic regression. Logistic regression analysis results showed that serum estradiol level was an independent protective factor affecting the occurrence of ESA in ETA pregnant women (OR=0.997, 95%CI: 0.995-1.000, P=0.044). ③AUC of serum estradiol level predicting ESA in ETA pregnant women was 0.933 (95%CI: 0.849-1.000, P<0.001). According to the maximum principle of Youden index, the best cutoff value for serum estradiol to predict the occurrence of ESA in ETA pregnant women was 567.5 pg/mL, with a sensitivity of 96.8% and specificity of 88.5%.

Conclusions

The estradiol level in serological indexes has a high predictive value for ETA pregnant women to develop ESA, which can provide reference for early clinical assessment of ESA risk and timely intervention. However, uterine artery blood flow parameters could not predict the occurrence of ESA in ETA pregnant women.

Key words: Abortion, threatened, Abortion, spontaneous, Uterine artery, Hemodynamics, Estradiol, Maternal serum screening tests, Pregnancy trimester, first, Pregnancy outcome, Pregnant women
表1 2组ETA孕妇ESA影响因素的单因素分析结果比较
组别 例数 年龄[岁，M(P25~P75)] 孕龄[周，M(P25~P75)]a 流产次数[次，M(P25~P75)] 产次[次，M(P25~P75)] 妊娠方式[例数(%)] 阴道流血[例数(%)]
自然受孕 辅助生殖
研究组 27 32.7(29.0~35.0) 7.4(7.0~8.0) 1.4(1.0~2.0) 0.3(0.0~1.0) 24(88.9) 3(1.1) 10(37.0)
对照组 63 30.2(28.0~32.0) 8.1(7.0~9.0) 1.4(1.0~2.0) 0.2(0.0~0.0) 62(98.4) 1(1.6) 18(28.6)
检验值   Z＝-2.208 Z＝-2.280 Z＝-0.010 Z＝-0.336 χ2＝4.037 χ2＝0.632
P值   0.027 0.023 0.992 0.738 0.079 0.427
组别 例数 β-hCG[mIU/mL，M(P25~P75)] 孕酮(ng/mL，±s) 雌二醇[pg/mL，M(P25~P75)] SD[M(P25~P75)] PI
左侧 右侧 左侧[M(P25~P75)] 右侧(±s)
研究组 27 65 282.0(13 708.0~112 352.0) 22.6±15.6 383.1(110.0~509.0) 6.1(4.4~7.4) 6.2(4.2~7.3) 2.2(1.8~2.4) 2.2±0.6
对照组 63 160 047.0(133 316.0~200 000.0) 39.3±14.6 1 255.2(950.0~1 518.0) 7.0(4.6~8.1) 6.8(4.8~7.9) 2.4(1.9~2.7) 2.3±0.7
检验值   Z＝-5.654 t＝4.757 Z＝-6.494 Z＝-0.731 Z＝-0.929 Z＝-1.471 t＝1.125
P值   <0.001 <0.001 <0.001 0.465 0.353 0.141 0.266
组别 例数 RI[M(P25~P75)] SPV(m/s) DEV[m/s，M(P25~P75)]
左侧 右侧 左侧(±s) 右侧[M(P25~P75)] 左侧 右侧
研究组 27 0.8(0.8~0.9) 0.8(0.8~0.9) 57.2±20.1 57.7(37.3~67.5) 10.4(6.7~12.4) 9.8(7.2~13.2)
对照组 63 0.8(0.8~0.9) 0.8(0.8~0.9) 64.9±21.9 65.1(48.3~77.8) 10.9(7.1~20.8) 11.0(6.6~13.3)
检验值   Z＝-0.656 Z＝-1.094 t＝1.607 Z＝-1.391 Z＝-0.460 Z＝-0.260
P值   0.512 0.274 0.114 0.164 0.645 0.795
表2 研究亚组1和对照亚组1 ETA孕妇同时检测结果比较
组别 例数 β-hCG[mIU/mL，M(P25~P75)] 雌二醇[pg/mL，M(P25~P75)] SD PI
左侧(±s) 右侧[M(P25~P75)] 左侧[M(P25~P75)] 右侧(±s)
研究亚组1 13 40 557.6(9 358.0~71 067.5) 204.8(100.5~283.0) 6.2±1.7 6.0(4.6~7.4) 2.2(2.0~2.6) 2.3±0.6
对照亚组1 22 164 382.0(144 801.5~200 000.0) 1 174.2(960.5~1 404.8) 8.1±3.9 8.3(4.9~9.6) 2.6(2.0~2.9) 2.5±0.6
检验值   Z＝-4.689 Z＝-4.848 t＝-1.999 Z＝-0.990 Z＝-1.225 t＝0.994
P值   <0.001 <0.001 0.054 0.332 0.220 0.328
组别 例数 孕酮(ng/mL，±s) RI(±s) SPV(m/s，±s) DEV(m/s)
左侧 右侧 左侧 右侧 左侧[M(P25~P75)] 右侧(±s)
研究亚组1 13 24.6±13.1 0.8±0.1 0.8±0.1 62.4±22.3 60.1±25.0 10.8(6.4~16.0) 10.2±3.3
对照亚组1 22 43.2±13.7 0.8±0.1 0.8±0.1 65.3±22.3 59.8±20.1 9.5(6.2~10.8) 8.4±3.3
检验值   t＝3.948 t＝0.832 t＝1.001 t＝0.381 t＝0.772 Z＝-0.937 t＝-1.517
P值   <0.001 0.412 0.324 0.706 0.972 0.349 0.139
表3 研究亚组2和对照亚组2 ETA孕妇同时检测结果比较
组别 例数 β-hCG[mIU/mL，M(P25~P75)] 孕酮(ng/mL，±s)) 雌二醇[pg/mL，M(P25~P75)] SD PI
左侧(±s) 右侧[M(P25~P75)] 左侧(±s) 右侧[M(P25~P75)]
研究亚组2 14 88 241.6(19 672.5~152 184.5) 20.7±17.8 548.8(112.8~584.8) 6.0±1.9 6.3(4.2~6.7) 2.1±0.6 2.1(1.7~2.3)
对照亚组2 41 157 722.2(118 831.0~200 000.0) 37.2±14.8 1 298.6(927.5~1 594.5) 6.2±2.3 6.0(4.6~7.3) 2.3±0.6 2.3(1.9~2.8)
检验值   Z＝-3.208 t＝3.412 Z＝-4.174 t＝0.351 Z＝-0.725 t＝1.058 Z＝-0.850
P值   0.001 0.001 <0.001 0.727 0.469 0.295 0.395
组别 例数 RI[M(P25~P75)] SPV(m/s) DEV[m/s，M(P25~P75)]
左侧 右侧 左侧(±s) 右侧[M(P25~P75)] 左侧 右侧
研究亚组2 14 0.8(0.8~0.9) 0.8(0.8~0.9) 52.4±17.9 55.5(35.1~68.6) 10.0(6.6~10.8) 9.5(6.1~11.1)
对照亚组2 41 0.8(0.8~0.9) 0.8(0.8~0.9) 64.6±21.9 67.9(49.9~77.7) 11.7(8.3~15.5) 12.4(7.6~16.3)
检验值   Z＝-0.107 Z＝-0.881 t＝1.872 Z＝-1.575 Z＝-1.217 Z＝-1.159
P值   0.915 0.378 0.067 0.115 0.223 0.246
表4 ETA孕妇ESA影响因素的多因素非条件logistic回归分析结果
影响因素 B SE Wald值 P值 OR值 OR值95%CI
年龄 0.145 0.128 1.283 0.257 1.156 0.900~1.486
同时检测时孕龄 -0.697 0.372 3.506 0.061 0.498 0.240~1.033
血清β-hCG水平 -0.016 0.010 2.652 0.103 0.984 0.965~1.003
血清孕酮水平 -0.034 0.033 1.033 0.309 0.967 0.905~1.032
血清雌二醇水平 -0.003 0.001 4.062 0.044 0.997 0.995~1.000
右侧PI 0.008 0.685 0.000 0.991 1.008 0.263~3.862
左侧PI -1.241 0.876 2.007 0.157 0.289 0.052~1.609
常数项 7.799 5.255 2.203 0.138 2 438.091 —
图1 血清雌二醇水平预测ETA孕妇发生ESA的ROC曲线注：ETA为早期先兆流产，ESA为早期自然流产。ROC曲线为受试者工作特征曲线
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