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血管生成标志物预测子痫前期的妊娠并发症和延长:连续值与截断值。

Angiogenic Markers Predict Pregnancy Complications and Prolongation in Preeclampsia: Continuous Versus Cutoff Values.

机构信息

From the Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (L.S., A.H.v.d.M., A.H.J.D., W.V.), Division Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynecology (L.S., E.A.P.S., W.V.), Department of Public Health, Centre for Medical Decision Sciences (Y.V.), and Department of Clinical Chemistry (H.R.), Erasmus MC, Rotterdam, The Netherlands; Department of Internal Medicine, Ikazia Ziekenhuis, Rotterdam, The Netherlands (K.V.); Department of Obstetrics and Gynecology, Reinier de Graaf Hospital, Delft, The Netherlands (H.A.B.); and Department of Obstetrics and Gynecology, Maasstad Hospital, Rotterdam, The Netherlands (H.J.V.).

出版信息

Hypertension. 2017 Nov;70(5):1025-1033. doi: 10.1161/HYPERTENSIONAHA.117.09913. Epub 2017 Aug 28.

Abstract

To assess the incremental value of a single determination of the serum levels of sFlt-1 (soluble Fms-like tyrosine kinase 1) and PlGF (placental growth factor) or their ratio, without using cutoff values, for the prediction of maternal and fetal/neonatal complications and pregnancy prolongation, 620 women with suspected/confirmed preeclampsia, aged 18 to 48 years, were included in a prospective, multicenter, observational cohort study. Women had singleton pregnancies and a median pregnancy duration of 34 (range, 20-41) weeks. Complications occurred in 118 women and 248 fetuses. The median duration between admission and delivery was 12 days. To predict prolongation, PlGF showed the highest incremental value (=0.72) on top of traditional predictors (gestational age at inclusion, diastolic blood pressure, proteinuria, creatinine, uric acid, alanine transaminase, lactate dehydrogenase, and platelets) compared with =0.53 for the traditional predictors only. sFlt-1 showed the highest value to discriminate women with and without maternal complications (C-index=0.83 versus 0.72 for the traditional predictors only), and the sFlt-1/PlGF ratio showed the highest value to discriminate fetal/neonatal complications (C-index=0.86 versus 0.78 for the traditional predictors only). Applying previously suggested cutoff values for the sFlt-1/PlGF ratio yielded lower incremental values than applying continuous values. In conclusion, sFlt-1 and PlGF are strong and independent predictors for days until delivery along with maternal and fetal/neonatal complications on top of the traditional criteria. Their use as continuous variables (instead of applying cutoff values for different gestational ages) should now be tested in a prospective manner, making use of an algorithm calculating the risk of an individual woman with suspected/confirmed preeclampsia to develop complications.

摘要

为了评估在不使用截断值的情况下,单次检测血清可溶性 fms 样酪氨酸激酶 1(sFlt-1)和胎盘生长因子(PlGF)水平或其比值对预测母体和胎儿/新生儿并发症及妊娠延长的增量价值,我们纳入了 620 例疑似/确诊子痫前期的 18-48 岁的女性进行前瞻性、多中心、观察性队列研究。这些女性的单胎妊娠中位孕期为 34 周(范围 20-41 周)。共有 118 例女性和 248 例胎儿发生并发症。入院至分娩的中位时间为 12 天。为了预测延长,与仅使用传统预测因素(纳入时的孕龄、舒张压、蛋白尿、肌酐、尿酸、丙氨酸转氨酶、乳酸脱氢酶和血小板)相比,PlGF 在预测方面的增量价值最高(=0.72),而仅使用传统预测因素时的增量价值为=0.53。sFlt-1 对区分有或无母体并发症的女性具有最高价值(C 指数=0.83 与仅使用传统预测因素的 C 指数=0.72),而 sFlt-1/PlGF 比值对区分胎儿/新生儿并发症具有最高价值(C 指数=0.86 与仅使用传统预测因素的 C 指数=0.78)。应用之前建议的 sFlt-1/PlGF 比值截断值比应用连续值的增量值低。总之,sFlt-1 和 PlGF 是除传统标准外预测分娩天数及母体和胎儿/新生儿并发症的有力且独立的预测因素。它们应作为连续变量(而不是应用不同孕龄的截断值)进行前瞻性测试,利用一种算法计算疑似/确诊子痫前期女性个体发生并发症的风险。

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