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

doi:10.3877/cma.j.issn.1674-1358.2021.05.004

Abstract

Abstract:

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

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.

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References 26

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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

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

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

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

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

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