Muñoz-Hernández Rocío, Medrano-Campillo Pablo, Miranda Maria L, Macher Hada C, Praena-Fernández Jose Manuel, Vallejo-Vaz Antonio J, Dominguez-Simeon María J, Moreno-Luna Rafael, Stiefel Pablo
Laboratorio de Hipertensión Arterial e Hipercolesterolemia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Laboratorio de Investigación clínica y traslacional en enfermedades hepáticas y digestivas. Instituto de Biomedicina de Sevilla (IBiS). Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Am J Hypertens. 2017 Jul 1;30(7):673-682. doi: 10.1093/ajh/hpx024.
Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by hypertension and proteinuria. The HELLP syndrome is the most severe form of PE. The aim of the present study was to determine different potential biomarkers that may help us perform an early diagnosis of the disease, assess on the severity of the disease, and/or predict maternal or fetal adverse outcomes.
We measured serum levels of total and fetal circulating cell-free DNA (cfDNA), soluble endoglin, soluble form of vascular endothelial growth factor receptor, and placental growth factor in a healthy control group of pregnant women (n = 26), patients with mild (n = 37) and severe PE (n = 25), and patients with HELLP syndrome (n = 16).
We observed a gradual and strong relationship between all the biomarkers mentioned and the range of severity of PE, with the highest levels in patients with HELLP syndrome. Nevertheless, only the values of total cfDNA were able to significantly differentiate severe PE and HELLP syndrome (20957 ± 2784 vs. 43184 ± 8647 GE/ml, P = 0.01). Receiver operating characteristic (ROC) curves were constructed (i) for the healthy group with respect to the groups with PE and (ii) for patients with PE with respect to the group with HELLP syndrome; sensitivity and specificity values at different cutoff levels were calculated in each case. The maximum ROC area under the curve value for PE and HELLP syndrome (with respect to controls) was 0.91 (P < 0.001).
The measured biomarkers of cell damage, angiogenesis, and antiangiogenesis may reflect the severity of PE, with higher levels in patients who develop HELLP syndrome. In addition, these biomarkers may also help predict adverse fetal and maternal outcomes.
子痫前期(PE)是一种妊娠期高血压疾病,其特征为高血压和蛋白尿。HELLP综合征是PE最严重的形式。本研究的目的是确定不同的潜在生物标志物,这些标志物可能有助于我们对该疾病进行早期诊断、评估疾病的严重程度和/或预测母婴不良结局。
我们测量了26名健康孕妇对照组、37名轻度PE患者、25名重度PE患者和16名HELLP综合征患者血清中的总循环游离DNA(cfDNA)、胎儿循环cfDNA、可溶性内皮糖蛋白、血管内皮生长因子受体可溶性形式和胎盘生长因子水平。
我们观察到上述所有生物标志物与PE严重程度范围之间存在逐渐增强的关系,HELLP综合征患者的水平最高。然而,只有总cfDNA值能够显著区分重度PE和HELLP综合征(20957±2784 vs. 43184±8647 GE/ml,P = 0.01)。构建了(i)健康组相对于PE组的受试者工作特征(ROC)曲线,以及(ii)PE患者相对于HELLP综合征组的ROC曲线;在每种情况下计算了不同临界值水平下的敏感性和特异性值。PE和HELLP综合征(相对于对照组)的最大曲线下ROC面积值为0.91(P < 0.001)。
所测量的细胞损伤、血管生成和抗血管生成生物标志物可能反映PE的严重程度,HELLP综合征患者的水平更高。此外,这些生物标志物还可能有助于预测不良的胎儿和母亲结局。