Objective To evaluate the diagnostic performances of plasma placental extracellular vesicles(pcEV)and their clearance protein(Lactadherin)in predicting adverse pregnancy outcomes in patients with severe preeclampsia(sPE).Methods This is a retrospective case-control study.60 patients aged 32(29,36)years diagnosed with sPE at 27-37 weeks of pregnancy,who underwent prenatal examinations and delivered between January 31th,2018 and January 31th,2019,were recruited.According to the occurrence of endpoint events(fetal distress and/or fetal growth restriction),sPE patients were further divided into an event group of 34 cases and a non event group of 26 cases.33 healthy pregnant women of the same gestational age were selected as the control group,aged 31(29,36)years old.25 non pregnant healthy women were selected as the healthy control group,aged 26(25,38)years old.Flow cytometry was used to detect placental alkaline phosphatase antibody positivity as pcEV,while membrane surface expression of phosphatidylserine,i.e.membrane associated protein V(AV)positivity as AV+pcEV.ELISA kits were used to detect the level of Lactadherin.Logistic regression was used to perform multiple correlation analysis.The performances of pcEV and Lactadherin in predicting adverse pregnancy outcomes were evaluated by the receiver operating characteristic(ROC)curve.Survival analyses were performed by the Kaplan Meier curve.The hazard ratios(HR)was calculated by the Cox proportional risk regression model.Results The plasma AV+pcEV levels in sPE patients were 8 260(4 991,16 751)/μl,which were higher than 1 088(784,1 871)/µl of healthy pregnant women and 206(116,256)/μl of healthy controls(H=94.490,P＜0.05).The plasma AV+pcEV levels in sPE patients with endpoint events were 11 225(7 496,20 599)/μl,which were higher than 5 199(2 914,8 347)/μl of patients without endpoint events(U=178,P＜0.05).The plasma levels of Lactadherin in sPE patients were 2 635(1876,3 137)pg/ml,which were higher than 1 597(1 287,1 818)pg/ml in healthy pregnant woman and 1 123(749,1 405)pg/ml in healthy controls(H=54.307,P＜0.05).ROC showed that the critical value of AV+pcEV predicting fetal distress and/or fetal growth restriction events within 77 days in sPE patients was 6 524/μl and area under the curve(AUC)was 0.799(95％CI 0.680-0.917).The critical value of Lactadherin was 2 336.5 pg/ml and AUC was 0.702(95％CI 0.564-0.841).Logistic regression analysis showed that there was a significant correlation between AV+pcEV levels in sPE patients and 24-hour urine protein quantification(OR=9.288,95％CI 1.993-43.293),as well as the need for combined antihypertensive therapy(OR=18.690,95％CI 1.919-182.077)(P＜0.05).Survival analysis showed that the cumulative probability of fetal distress and/or fetal growth restriction events within 77 days were significantly increased in sPE patients with AV+pcEV levels above the critical value(Log-rank x2=21.430,P＜0.05).The Cox proportional regression model showed that the levels of AV+pcEV can independently identify fetal distress and/or fetal growth restriction events(HR=7.983,P＜0.05).Conclusions The changes of pcEV in plasma of pregnant women in late pregnancy were related to the development of PE.High concentrations of pcEV suggested an increased risk of fetal distress and fetal growth restriction,and pcEV could serve as an effective marker for early warning of adverse pregnancy outcomes.
万方数据
维普
