The effects of low-dose aspirin on preterm birth: a systematic review and meta-analysis of randomized controlled trials

Aim To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the efficacy of low-dose aspirin (LDA, <= 160 mg/day) on preventing preterm birth (PB). Methods Five databases were screened from inception until June 25, 2023. The RCTs were assessed for quality according to Cochrane's risk of bias tool. The endpoints were summarized as risk ratio (RR) with 95% confidence interval (CI). Results Overall, 40 RCTs were analyzed. LDA significantly decreased the risk of PB < 37 weeks (RR: 0.91, 95% CI 0.87, 0.96, p < 0.001, moderate certainty of evidence) with low between-study heterogeneity (I2 = 23.2%, p = 0.11), and PB < 34 weeks (RR: 0.78, 95% CI 0.61, 0.99, p = 0.04, low certainty of evidence) with high between-study heterogeneity (I2 = 58.3%, p = 0.01). There were no significant differences between both groups regarding the risk of spontaneous (RR: 0.94, 95% CI 0.83, 1.07, p = 0.37) and medically indicated (RR: 1.28, 95% CI 0.87, 1.88, p = 0.21) BP < 37 weeks. Sensitivity analysis revealed robustness for all outcomes, except for the risk of PB < 34 weeks. For PB < 37 weeks and PB < 34 weeks, publication bias was detected based on visual inspection of funnel plots for asymmetry and statistical significance for Egger's test (p = 0.009 and p = 0.0012, respectively). Conclusion LDA can significantly reduce the risk of PB < 37 and < 34 weeks. Nevertheless, further high-quality RCTs conducted in diverse populations, while accounting for potential confounding factors, are imperative to elucidate the optimal aspirin dosage, timing of initiation, and treatment duration for preventing preterm birth and to arrive at definitive conclusions.