Does Aspirin Affect Extracellular Vesicles Involved in the Pathogenesis of Preeclampsia? A Systematic Review and Meta-Analysis

BACKGROUND: Preeclampsia is a challenging pregnancy disorder to treat, and current preventive measures are not always effective. Aspirin is prescribed as a preventive agent for pregnant women who are at high risk of developing preeclampsia although there is no definitive conclusion for its mechanism of action or efficacy. Extracellular vesicles (EVs) provide a picture of the physiological state of the cells from which they originate and have been implicated in both normal and pathological pregnancies. This study reviewed the potential effects of aspirin on EVs when prescribed for prevention of preeclampsia. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to identify published studies from the CENTRAL, The Cochrane Library (Cochrane Central Register of Controlled Trials), MEDLINE (Medical Literature Analysis and Retrieval System online) on PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Science, and Embase (Excerpta Medica Database) from inception to March 2024. RESULTS: Sixty-three studies met the inclusion criteria and were grouped as studies on aspirin-mediated prevention of preeclampsia (n=31), studies on EVs in the pathogenesis of preeclampsia (n=28), and studies on the effects of aspirin on EVs in preeclampsia (n=4). Meta-analysis of randomized control trials showed that the odds of preeclampsia occurrence is 36% less likely in the aspirin treatment group (odds ratio, 0.64 [95% CI, 0.47-0.87]; P<0.01). EVs are involved in the pathogenesis of preeclampsia, and aspirin effectively reduced the negative effects of EVs in both in vitro and in vivo studies. CONCLUSIONS: Aspirin has an inhibitory effect on EVs in preeclampsia. However, further studies are needed to understand and confirm the mechanisms involved.