Levels of placental extracellular vesicles predicts fetal growth restriction and fetal distress in established severe pre-eclampsia.

To evaluate whether plasma levels of placental extracellular vesicles (pcEVs), the EV-scavenging factor lactadherin, and prothrombotic markers predict fetal growth restriction (FGR) and/or fetal distress (FD) in established severe pre-eclampsia (sPE). We recruited 80 sPE patients, 41 normal pregnancies, and 27 non-pregnant women. SPE patients were further dichotomized into event and non-event groups based on the occurrence of FGR/FD during a follow-up period of 77 days. Plasma levels of pcEVs, lactadherin, von Willebrand factor (VWF), antithrombin (AT), and tissue plasminogen activator-plasminogen activator inhibitor complex (tPAI-C) were analyzed for predicting FGR and FD. Plasma levels of pcEVs, lactadherin, VWF, and tPAI-C were progressively increased from non-pregnant women, women with normal pregnancies, and patients with sPE, whereas levels of AT were decreased. Subgroup analyses further showed that pcEVs, lactadherin, and tPAI-C were 2.7, 1.5, and 1.5 times higher in sPE patients with FGR/FD than those without FGR/FD. In contrast, levels of AT were decreased by 10%. The receiver operating characteristic (ROC) analysis found pcEVs to be 84.4% sensitive and 71.4% specific for predicting FGR/FD. Logistic regression analysis indicated that levels of pcEVs were associated with heavy proteinuria (OR = 4.657) and combined antihypertensive therapy (OR = 6.972) in sPE patients. Patients with pcEVs exceeding 6524/μL had an elevated cumulative risk of FGR/FD (log-rank χ2 = 25.964, P = 0.000) and predicted FGR/FD in sPE patients, with a hazard ratio of 6.940. Plasma pcEVs may serve as an independent predictive biomarker for FGR/FD in sPE patients.