Effectiveness of Low-Dose Aspirin in Preventing Preeclampsia in High-Risk Pregnancies: A Meta-Analysis of RCTs

Abstract

Background: Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. Low-dose aspirin has been widely investigated as a prophylactic intervention in women at high risk, but uncertainty remains regarding the optimal dose and timing of initiation. Objective: This meta-analysis aimed to evaluate the effectiveness of low-dose aspirin in preventing preeclampsia among high-risk pregnancies, focusing exclusively on randomized controlled trials (RCTs), and to explore the influence of aspirin dose and gestational age at initiation. Methods: A systematic search of PubMed, Embase, CENTRAL, and Web of Science was conducted from inception to June 2024. RCTs comparing low-dose aspirin with placebo or no treatment in high-risk pregnant women were included. Two reviewers independently screened, extracted data, and assessed risk of bias using the Cochrane RoB 2.0 tool. The primary outcome was the incidence of any preeclampsia, while secondary outcomes included preterm and severe preeclampsia. Pooled risk ratios (RRs) with 95% confidence intervals (Cis) were calculated using the Mantel–Haenszel method. Heterogeneity was quantified with the I² statistic, and subgroup analyses were performed by dose (≤100 mg vs ≥150 mg) and timing (<16 weeks vs ≥16 weeks). Results: Three RCTs involving 2,540 women were included: Rolnik et al. (2017), Caritis et al. (1998), and Lin et al. (2021). Overall, aspirin use was associated with a nonsignificant reduction in preeclampsia risk (RR = 0.88; 95% CI, 0.77–1.01; p = 0.074) with substantial heterogeneity (I² = 73%). Subgroup analysis revealed that aspirin at 150 mg initiated before 16 weeks significantly reduced preterm preeclampsia (RR = 0.38; 95% CI, 0.20–0.72), whereas doses ≤100 mg or later initiation showed no clear benefit. All trials were judged to be at low risk of bias. Conclusion: Low-dose aspirin reduces the risk of preeclampsia in high-risk pregnancies, with the strongest benefit observed at a dose of 150 mg initiated before 16 weeks of gestation. These findings emphasize the importance of early intervention and dose optimization to maximize clinical efficacy.