Low-dose aspirin for the prevention of preterm birth in nulliparous women: systematic review and meta-analysis

Objective The objective was to assess the efficacy and safety of low-dose aspirin for the prevention of preterm birth in nulliparous women. Data sources We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to June 2022. Study eligibility criteria Randomized controlled trials that compared aspirin to placebo in nulliparous women were eligible. Methods This study was reported in accordance with the PRISMA 2020 checklist. The primary outcomes of this study were the rates of preterm birth at less than 37 weeks and less than 34 weeks of gestation. The secondary outcomes included postpartum hemorrhage, placental abruption, cesarean section, any hypertensive disorder of pregnancy and small for gestational age. Relative risks with their 95% confidence intervals were calculated for analysis. Heterogeneity was assessed by Cochran's Q test and Higgins's I-2. A random-effects model was used when I-2 was > 50% to generate the RR and 95% CI; otherwise, a fixed-effects model was used. The risk of publication bias was assessed by funnel plots. We performed sensitivity analysis by sequentially omitting each included study to confirm the robustness of the analysis. Results Seven studies with a total of 29,029 participants were included in this review. Six studies were assessed as having a low risk of bias or an unclear risk of bias, and one study was judged as having a high risk of bias. In nulliparous women, low-dose aspirin was associated with a significant reduction in the rate of preterm birth at less than 34 weeks of gestational age (RR 0.84,95% CI: 0.71-0.99; I-2 = 0%; P = 0.04), but we did not observe a significant difference in the rate of preterm birth at less than 37 weeks of gestation (RR 0.96,95% CI: 0.90-1.02; I-2 = 31%; P = 0.18). Low-dose aspirin was associated with a significant increase in the rates of postpartum hemorrhage (RR 1.32,95% CI: 1.14-1.54; I-2 = 0%; P = 0.0003), placental abruption (RR 2.18,95% CI: 1.10-4.32; I-2 = 16%; P = 0.02) and cesarean section (RR 1.053, 95% CI: 1.001-1.108; I-2 = 0%; P = 0.05) in nulliparous women. We also did not observe a significant effect of low-dose aspirin on the rates of any hypertensive disorder of pregnancy (RR 1.05, 95% CI: 0.96-1.14; I-2 = 9%; P = 0.28) or small for gestational age (RR 0.96, 95% CI: 0.91-1.02; I-2 = 0%; P = 0.16) in nulliparous women. Funnel plots indicated that no significant publication bias existed in this meta-analysis. Except for preterm birth at less than 34 weeks of gestation, placental abruption and cesarean section, the sensitivity analysis showed similar results, which confirmed the robustness of this meta-analysis. Conclusions Low-dose aspirin might reduce the risk of preterm birth at less than 34 weeks of gestation in nulliparous women. The use of low-dose aspirin in nulliparous women increased the risk of postpartum hemorrhage and might increase the risk of placental abruption and cesarean section.