Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

Preeclampsia is a systemic hypertensive disorder in pregnancy that increases risks for serious maternal and neonatal health complications including eclamptic seizures, stroke, small for gestational age, intrauterine growth restriction (IUGR), preterm birth, placental abruption, and death. The incidence of preeclampsia in the United States was approximately 46.6 per 1000 deliveries in 2014, with a significant increase in preeclampsia with severe features in the decade preceding. In 2014, the US Preventive Services Task Force (USPSTF) recommended the use of low-dose (81 mg/d) aspirin after 12 weeks of gestation for asymptomatic pregnant women at high risk for preeclampsia. This analysis was conducted to update that recommendation based on new research since the previous USPSTF review. This analysis was framed with 3 key questions in mind to evaluate the efficacy of aspirin in reducing sequelae of preeclampsia: effectiveness of aspirin in reducing adverse maternal, perinatal, child, or combined health outcomes in pregnant persons at increased risk of preeclampsia; effectiveness of aspirin in preventing preeclampsia; and potential harms of aspirin use to prevent preeclampsia during pregnancy. Literature search was conducted from January 2013 to January 2021. To evaluate the benefits of aspirin, the analysis included randomized clinical trials and individual participant data meta-analyses among those at increased risk for preeclampsia, and to evaluate the harms of aspirin, eligible articles were expanded to include observational studies in lower-risk populations. A total of 23 studies met inclusion for this systematic review, with 18 evaluating pregnant individuals at increased risk of preeclampsia and 5 evaluating those at average risk. The timing of aspirin treatment varied significantly among included trials, ranging from initiation at 9 to 38 weeks and cessation from 34 weeks or when preeclampsia developed through delivery. Dosage ranged from 50 to 100 mg/d, with the majority using either 60 mg/d (6 trials) or 100 mg/d (9 trials). Pooled analysis revealed that when compared with placebo, aspirin use was significantly associated with a reduced risk of preeclampsia (relative risk [RR], 0.85; 95% confidence interval [CI], 0.75-0.95), perinatal mortality (RR, 0.79; 95% CI, 0.66-0.96), preterm birth (RR, 0.80; 95% CI, 0.67-0.95), and IUGR (RR, 0.82; 95% CI, 0.68-0.99). Aspirin initiation before 20 weeks' gestation was significantly associated with increased effectiveness for preventing preterm birth and small for gestational age/IUGR, and aspirin dosages greater than 75 mg/d were associated with increased effectiveness for prevention of preterm birth. No significant difference was observed in either postpartum hemorrhage (RR, 1.03; 95% CI, 0.94-1.12), placental abruption (RR, 1.15; 95% CI, 0.76-1.72), nor any other less commonly reported perinatal harms. The results of this systematic review found that low-dose aspirin is effective for preventing preeclampsia and related perinatal morbidity and mortality for individuals at increased risk for preeclampsia. Limitations to the evidence presented here include heterogeneity in dosage and timing and that most participants in the included trials were White despite well-known disparities in morbidity from preeclampsia experienced by Black women in the United States.