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胎盘生长因子、可溶性fms样酪氨酸激酶1和孕酮作为异位妊娠和稽留流产的诊断生物标志物。

Placental growth factor, soluble fms-like tyrosine kinase 1 and progesterone as diagnostic biomarkers for ectopic pregnancy and missed abortion.

作者信息

Martínez-Ruiz Ana, Sarabia-Meseguer María Desamparados, Pérez-Fornieles Joaquín, Vílchez Juan Antonio, Tovar-Zapata Isabel, Noguera-Velasco Jose Antonio

机构信息

Clinical Analysis Department, Virgen de la Arrixaca University Hospital, Murcia, Spain.

Clinical Analysis Department, Virgen de la Arrixaca University Hospital, Murcia, Spain.

出版信息

Clin Biochem. 2014 Jun;47(9):844-7. doi: 10.1016/j.clinbiochem.2014.03.013. Epub 2014 Mar 31.

Abstract

OBJECTIVE

The aim of this study is to investigate if progesterone, placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt1) serum levels are useful markers to differentiate between ectopic pregnancy (EP), missed abortion (MA) and viable intrauterine implantation pregnancy (IUP).

METHODS

We designed a retrospective case-control study which included 100 pregnant women (50 EP and 50 MA) at 6-8 weeks of gestation with βhCG serum levels between 800 and 3500 UI/L and a viable IUP group. Progesterone, PlGF and sFlt-1 levels were measured with an electrochemiluminescence assay (Roche Diagnostics, Manheim, Alemania). A non parametric test was used to compare the markers in the different groups and we used receiver operating characteristic (ROC) curve analysis to calculate the area under the curve (AUC).

RESULTS

When we compared the EP group with the MA group, we didn't find significant differences for PlGF (15.1[13.2-17.4]/16.7[12.8-18.7] pg/mL) (p=0.275). We only obtained significant differences for progesterone (9.1[3.1-16.8]/2.6[1.3-6.1] ng/mL) (p<0.001) and sFlt-1 (84[65-96]/126[94-256] pg/mL) (p<0.001). The AUC for progesterone was 0.756 and the cutoff point with better sensitivity and lower false positive rate was 6 ng/mL (sensitivity=60%, specificity=72.7%). The AUC for sFlt-1 was 0.842 and the cutoff point was 93 pg/mL (sensitivity=84.5%, specificity=86.3%). The combination of both markers allowed us to increase the AUC to 0.910.

CONCLUSIONS

In conclusion, the present study suggests that sFlt-1 could be a useful marker to differentiate between an EP or a MA when βhCG levels are similar in both groups. The combination of sFlt-1 with progesterone helps to increase the diagnostic performance.

摘要

目的

本研究旨在探讨血清孕酮、胎盘生长因子(PlGF)和可溶性fms样酪氨酸激酶-1(sFlt1)水平是否有助于鉴别异位妊娠(EP)、稽留流产(MA)和宫内活胎妊娠(IUP)。

方法

我们设计了一项回顾性病例对照研究,纳入了100例妊娠6-8周、血清βhCG水平在800至3500 UI/L之间的孕妇(50例EP和50例MA)以及一个宫内活胎妊娠组。采用电化学发光法(罗氏诊断公司,德国曼海姆)检测孕酮、PlGF和sFlt-1水平。使用非参数检验比较不同组间的标志物,并采用受试者工作特征(ROC)曲线分析计算曲线下面积(AUC)。

结果

当我们将EP组与MA组进行比较时,发现PlGF(15.1[13.2-17.4]/16.7[12.8-18.7] pg/mL)无显著差异(p=0.275)。仅孕酮(9.1[3.1-16.8]/2.6[1.3-6.1] ng/mL)(p<0.001)和sFlt-1(84[65-96]/126[94-256] pg/mL)(p<0.001)有显著差异。孕酮的AUC为0.756,具有较好敏感性和较低假阳性率的截断点为6 ng/mL(敏感性=60%,特异性=72.7%)。sFlt-1的AUC为0.842,截断点为93 pg/mL(敏感性=84.5%,特异性=86.3%)。两种标志物联合使用可使AUC提高至0.910。

结论

总之,本研究表明,当两组βhCG水平相似时,sFlt-1可能是鉴别EP与MA的有用标志物。sFlt-1与孕酮联合使用有助于提高诊断性能。

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