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中华实验和临床感染病杂志(电子版)

中华实验和临床感染病杂志(电子版) ›› 2021, Vol. 15 ›› Issue (05) : 311 -316. doi: 10.3877/cma.j.issn.1674-1358.2021.05.004

论著

足月胎膜早破孕妇羊水中β人绒毛膜促性腺激素、基质金属蛋白酶9及核苷酸结合寡聚化结构域受体2水平变化及与羊膜感染的相关性
牛丽佳1, 夏义欣1,†(), 宋琪1, 张晓莉1   
  1. 1. 100039　北京，解放军总医院第三医学中心妇产科
  • 收稿日期:2020-11-02 出版日期:2021-10-15
  • 通信作者: 夏义欣

Correlations of changes of β-human chorionic gonadotropin, matrix metalloproteinase 9, and nucleotide-binding oligomerization domain receptor 2 levels in the amniotic fluid with amniotic membrane infection of pregnant women with term premature rupture of membranes

Lijia Niu1, Yixin Xia1,†(), Qi Song1, Xiaoli Zhang1   

  1. 1. Department of Obstetrics and Gynecology, Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China
  • Received:2020-11-02 Published:2021-10-15
  • Corresponding author: Yixin Xia
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引用本文：

牛丽佳, 夏义欣, 宋琪, 张晓莉. 足月胎膜早破孕妇羊水中β人绒毛膜促性腺激素、基质金属蛋白酶9及核苷酸结合寡聚化结构域受体2水平变化及与羊膜感染的相关性[J]. 中华实验和临床感染病杂志(电子版), 2021, 15(05): 311-316.

Lijia Niu, Yixin Xia, Qi Song, Xiaoli Zhang. Correlations of changes of β-human chorionic gonadotropin, matrix metalloproteinase 9, and nucleotide-binding oligomerization domain receptor 2 levels in the amniotic fluid with amniotic membrane infection of pregnant women with term premature rupture of membranes[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2021, 15(05): 311-316.

目的

探讨足月胎膜早破（TPROM）孕妇羊水中β人绒毛膜促性腺激素（β-HCG）、基质金属蛋白酶9（MMP-9）和核苷酸结合寡聚化结构域受体2（NOD2）水平变化及其与羊膜感染的相关性。

方法

选取2018年1月至2020年1月解放军总医院第三医学中心妇产科收治的106例TPROM孕妇为观察组，另选取同时期于本院行剖宫产的100例正常分娩孕妇为对照组。根据羊膜感染程度分别将两组孕妇分为Ⅰ期组、Ⅱ期组和Ⅲ期组。比较观察组和对照组孕妇感染率和羊水中β-HCG、MMP-9和NOD2水平，并比较不同羊膜感染程度孕妇羊水中β-HCG、MMP-9和NOD2水平。采用Pearson相关性分析羊水中β-HCG、MMP-9及NOD2水平的相关性。采用受试者工作特征曲线（ROC）判断β-HCG、MMP-9和NOD2对羊膜感染的诊断效能。

结果

与对照组比较，观察组孕妇羊膜感染率显著升高（χ2 = 154.805，P < 0.001）；观察组孕妇羊水中β-HCG、MMP-9和NOD2水平显著升高，差异均有统计学意义（t =-13.225、18.151、15.441，P均< 0.001）。观察组不同羊膜感染程度孕妇羊水中β-HCG、MMP-9和NOD2水平差异有统计学意义（F = 56.480、91.888、76.958，P均< 0.001）。Ⅲ期组羊膜感染孕妇羊水中β-HCG、MMP-9及NOD2水平显著高于Ⅰ期组、Ⅱ期组（β-HCG：t = 9.694、11.751，MMP-9：t = 11.617、4.713，NOD2：5.441、5.512；P均< 0.001），Ⅱ期组羊膜感染孕妇羊水中β-HCG、MMP-9及NOD2水平显著高于Ⅰ期组（t = 6.541、8.988、7.402，P均< 0.001）。Pearson相关性分析显示，观察组孕妇羊水中β-HCG与MMP-9、NOD2水平呈正相关（r = 0.803、0.791，P均< 0.001），MMP-9与NOD2水平呈正相关（r = 0.840、P < 0.001）。ROC曲线下面积（AUC）显示，羊水中β-HCG + MMP-9 + NOD2水平联合诊断（AUC = 0.913，95%CI：0.866~0.948）羊膜感染诊断价值均高于β-HCG（AUC = 0.772，95%CI：0.708~0.828）、MMP-9（AUC = 0.754，95%CI：0.688~0.812）和NOD2（AUC = 0.768，95%CI：0.704~0.825）单独诊断（Z = 5.583、5.231、5.491，P均< 0.001）。

结论

TPROM孕妇羊水中β-HCG、MMP-9和NOD2水平显著升高，与羊膜感染程度严重程度相关，以上指标联合检测可有效预测TPROM孕妇羊膜感染风险。

关键词: 足月胎膜早破, 羊膜感染, β-绒毛膜促性腺激素, 基质金属蛋白酶9, 核苷酸结合寡聚化结构域受体2
Objective

To investigate the correlations of changes of β-human chorionic gonadotropin (β-HCG), matrix metalloproteinase-9 (MMP-9) and nucleotide-binding oligomerization domain receptor 2 (NOD2) levels with amniotic membrane infection in amniotic fluid of pregnant women with term premature rupture of membranes (TPROM).

Methods

Total of 106 pregnant women with TPROM admitted to the Department of Obstetrics and Gynecology, Third Medical Center of the PLA General Hospital from January 2018 to January 2020 were selected as observation group, while 100 normal delivered pregnant women who underwent cesarean section in our hospital during the same period were selected as control group. The two groups were divided into stage Ⅰ, Ⅱ and Ⅲ groups according to the degree of amniotic membrane infection. The infection rates and levels of β-HCG, MMP-9 and NOD2 in amniotic fluid of pregnant women in observation group and control group were compared, respectively. The levels of β-HCG, MMP-9 and NOD2 in the amniotic fluid of pregnant women with different degrees of amniotic membrane infection were also compared, respectively. The correlations between β-HCG, MMP-9 and NOD2 levels in amniotic fluid were analyzed by Pearson correlation analysis. The diagnostic efficacy of β-HCG, MMP-9 and NOD2 for amniotic membrane infection were determined by receiver operating characteristic (ROC).

Results

The rate of amniotic membrane infection was significantly higher of cases in observation group compared to that of control group (χ2 = 154.805, P < 0.001). The levels of β-HCG, MMP-9 and NOD2 in amniotic fluid were significantly higher of cases in observation group compared to those of control group (t =-13.225, 18.151, 15.441, all P < 0.001).The levels of β-HCG, MMP-9 and NOD2 in amniotic fluid of pregnant women with different degrees of amniotic infection in observation group were significantly different (F = 56.480, 91.888, 76.958, all P < 0.001). The levels of β-HCG, MMP-9 and NOD2 in amniotic fluid of pregnant women with amniotic membrane infection were significantly higher of cases in stage Ⅲ group than those of stage Ⅰ group and stage Ⅱ group (β-HCG: t = 9.694, 11.751; MMP-9: t = 11.617, 4.713; NOD: t = 25.441, 5.512; all P < 0.001), and the levels of β-HCG, MMP-9 and NOD2 in amniotic fluid of pregnant women with amniotic membrane infection were significantly higher in stage Ⅱ group than in stage Ⅰ group (t = 6.541, 8.988, 7.402, all P < 0.001). Pearson correlation analysis showed that β-HCG in amniotic fluid were positively correlated with MMP-9 and NOD2 levels in observation group (r = 0.803, 0.791; all P < 0.001) and MMP-9 was positively correlated with NOD2 levels (r = 0.840, P < 0.001). The area under ROC curve (AUC) showed that β-HCG + MMP-9 + NOD2 in amniotic fluid was significantly higher for amniotic membrane infection diagnosis (AUC = 0.913, 95%CI: 0.866-0.948) than single index of β-HCG (AUC = 0.772, 95%CI: 0.708-0.828), MMP-9 (AUC = 0.754, 95%CI: 0.688-0.812) and NOD2 (AUC = 0.768, 95%CI: 0.704-0.825), with significant differences (Z = 5.583, 5.231, 5.491; P < 0.001).

Conclusions

The levels of β-HCG, MMP-9 and NOD2 in amniotic fluid of pregnant women with TPROM were significantly elevated and correlated with the severity of amniotic membrane infection; the combined detection of these indexes could effectively predict the risk of amniotic infection in pregnant women with TPROM.

Key words: Term premature rupture of membranes, Amniotic membrane infection, β-human chorionic gonadotropin, Matrix metalloproteinase 9, Nucleotide binding oligomerization domain receptor 2
表1 两组孕妇的一般资料
组别 例数 平均年龄（±s，岁） 平均孕周（±s，周） 初产/经产（例） 自然分娩/剖宫产（例）
观察组 106 26.57 ± 2.74 38.26 ± 1.13 66/40 65/35
对照组 100 26.72 ± 2.88 38.37 ± 1.24 72/34 76/24
统计量   t = 0.383 t = 0.666 χ2 = 0.747 χ2 = 2.909
P值   0.351 0.253 0.387 0.088
表2 两组孕妇羊水中β-HCG、MMP-9及NOD2水平（±s）
组别 例数 β-HCG（ng/ml） MMP-9（pg/ml） NOD2（pg/ml）
观察组 106 4.08 ± 0.59 734.45 ± 237.97 0.47 ± 0.14
对照组 100 1.13 ± 0.66 288.07 ± 83.98 0.23 ± 0.08
t值   -13.225 18.151 15.441
P值   < 0.001 < 0.001 < 0.001
表3 观察组不同羊膜感染程度孕妇羊水中β-HCG、MMP-9及NOD2水平（±s）
羊膜感染程度 例数 β-HCG（ng/ml） MMP-9（pg/ml） NOD2（pg/ml）
Ⅰ期 49 3.67 ± 0.64 618.78 ± 130.18 0.42 ± 0.07
Ⅱ期 30 4.62 ± 0.61 870.74 ± 103.79 0.53 ± 0.07
Ⅲ期 16 5.72 ± 0.64 1072.72 ± 146.16 0.66 ± 0.09
F值   56.480 91.888 76.958
P值   < 0.001 < 0.001 < 0.001
tⅠ期vs. Ⅱ期   6.541 8.988 7.402
PⅠ期vs. Ⅱ期   < 0.001 < 0.001 < 0.001
tⅠ期vs. Ⅲ期   9.694 11.751 11.617
PⅠ期vs. Ⅲ期   < 0.001 < 0.001 < 0.001
tⅡ期vs. Ⅲ期   4.713 5.441 5.512
PⅡ期vs. Ⅲ期   < 0.001 < 0.001 < 0.001
图1 观察组羊水中β-HCG、MMP-9及NOD2水平的相关性图注：A：β-HCG与MMP-9水平的相关性；B：β-HCG与NOD2水平的相关性；C：MMP-9与NOD2水平的相关性
表4 羊水中β-HCG、MMP-9及NOD2水平对羊膜感染的诊断效能
指标 AUC 95%CI Youden指数 Cut-off值 敏感度（%） 特异度（%）
β-HCG 0.755 0.691~0.812 0.377 > 2.52 ng/ml 71.70 66.00
MMP-9 0.775 0.711~0.830 0.482 > 461.93 pg/ml 64.15 84.00
NOD2 0.757 0.692~0.813 0.426 > 0.34 pg/ml 72.64 70.00
联合检测 0.918 0.872~0.952 0.646 — 89.62 75.00
图2 羊水中β-HCG、MMP-9及NOD2水平诊断羊膜感染的ROC曲线
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