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预测宫颈机能不全孕妇紧急环扎术结局:羊水中的炎症、血管生成和细胞外基质相关蛋白的作用。

Prediction of emergency cerclage outcomes in women with cervical insufficiency: The role of inflammatory, angiogenic, and extracellular matrix-related proteins in amniotic fluid.

机构信息

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

出版信息

PLoS One. 2022 May 10;17(5):e0268291. doi: 10.1371/journal.pone.0268291. eCollection 2022.

Abstract

OBJECTIVE

We aimed to determine whether various novel inflammatory, angiogenic, and extracellular matrix-related mediators in amniotic fluid (AF) can independently predict emergency cerclage outcomes in women with acute cervical insufficiency (CI).

METHODS

This was a retrospective cohort study conducted among 50 singleton pregnant women (18-25 weeks) who underwent emergency cerclage for CI and were subjected to amniocentesis. The AF samples were assayed for endoglin, endostatin, haptoglobin, insulin-like growth factor-binding protein (IGFBP)-3, -4, kallistatin, lumican, macrophage colony-stimulating factor (M-CSF), pentraxin 3, p-selectin, receptor for advanced glycation end products (RAGE), resistin, transforming growth factor beta-induced (TGFBI), and vitamin D-binding protein (VDBP) levels. Interleukin (IL)-6 levels in the AF were also measured for comparison with potential biomarkers assessed in this study. The primary endpoint was spontaneous preterm delivery (SPTD) at <34 weeks following emergency cerclage.

RESULTS

The AF levels of pentraxin 3, RAGE, and resistin were significantly higher in women who had SPTD at <34 weeks after cerclage placement (pentraxin-3: P = 0.003; RAGE: P = 0.041; and resistin; P = 0.002). In multivariate analysis, elevated AF levels of pentraxin 3 (P = 0.007) and resistin (P = 0.006), but not those of RAGE (P = 0.069), were independently associated with the occurrence of SPTD at <34 weeks after cerclage, following adjustment for baseline clinical variables (e.g., cervical dilation). The area under the curve (AUC) values of AF pentraxin 3, RAGE, and resistin for the prediction of SPTD at <34 weeks were 0.749, 0.669, and 0.770, respectively, which were similar to those of AF IL-6. However, in univariate analyses, no differences in the AF levels of endoglin, endostatin, haptoglobin, IGFBP-3, IGFBP-4, kallistatin, lumican, p-selectin, TGFBI, and VDBP were found to be associated with SPTD at <34 weeks after cerclage placement.

CONCLUSIONS

In women with acute CI, the AF levels of pentraxin 3, RAGE, and resistin could be useful novel biomarkers for predicting SPTD following emergency cerclage. However, the clinical utility of these new biomarkers should be validated in larger multicenter studies.

摘要

目的

我们旨在确定羊水中(AF)各种新型炎症、血管生成和细胞外基质相关介质是否可以独立预测急性宫颈机能不全(CI)患者急诊宫颈环扎术的结局。

方法

这是一项回顾性队列研究,共纳入 50 名单胎妊娠妇女(18-25 周),因 CI 接受急诊宫颈环扎术,并进行羊膜穿刺术。检测 AF 样本中的内胚层蛋白、内皮抑素、结合珠蛋白、胰岛素样生长因子结合蛋白(IGFBP)-3、-4、卡利斯坦、亮氨酸氨基肽酶、巨噬细胞集落刺激因子(M-CSF)、五聚素 3、p-选择素、晚期糖基化终产物受体(RAGE)、抵抗素、转化生长因子β诱导(TGFBI)和维生素 D 结合蛋白(VDBP)水平。还测量了 AF 中的白细胞介素(IL)-6 水平,以便与本研究评估的潜在生物标志物进行比较。主要终点是急诊宫颈环扎术后 <34 周时自发性早产(SPTD)。

结果

在接受宫颈环扎术 <34 周后发生 SPTD 的女性中,AF 中的五聚素 3、RAGE 和抵抗素水平明显更高(五聚素 3:P=0.003;RAGE:P=0.041;抵抗素;P=0.002)。多变量分析显示,AF 中五聚素 3(P=0.007)和抵抗素(P=0.006)水平升高与宫颈环扎术后 <34 周时 SPTD 的发生独立相关,调整基线临床变量(例如,宫颈扩张)后。AF 五聚素 3、RAGE 和抵抗素预测 <34 周 SPTD 的曲线下面积(AUC)值分别为 0.749、0.669 和 0.770,与 AFIL-6 相似。然而,在单变量分析中,AF 中内胚层蛋白、内皮抑素、结合珠蛋白、IGFBP-3、IGFBP-4、卡利斯坦、亮氨酸氨基肽酶、p-选择素、TGFBI 和 VDBP 水平与宫颈环扎术后 <34 周时 SPTD 无差异。

结论

在急性 CI 妇女中,AF 中五聚素 3、RAGE 和抵抗素水平可能是预测急诊宫颈环扎术后 SPTD 的有用新型生物标志物。然而,这些新生物标志物的临床应用价值应在更大的多中心研究中得到验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e8/9089878/4ba1144372d8/pone.0268291.g001.jpg

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