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

Abstract Objective 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). Methods 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. Results 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 χ 2 = 25.964, P = 0.000) and predicted FGR/FD in sPE patients, with a hazard ratio of 6.940. Conclusion Plasma pcEVs may serve as an independent predictive biomarker for FGR/FD in sPE patients.