Low-Dose Aspirin for Prevention of Morbidity and Mortality From Preeclampsia: A Systematic Evidence Review for the U.S. Preventive Services Task Force

Abstract

BACKGROUND: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. PURPOSE: To systematically review benefits and harms of low-dose aspirin for preventing morbidity and mortality from preeclampsia. DATA SOURCES: MEDLINE, Database of Abstracts of Reviews of Effects, PubMed, and Cochrane Central Register of Controlled Trials (January 2006 to June 2013); previous systematic reviews, clinical trial registries, and surveillance searches for large studies (June 2013 to February 2014). STUDY SELECTION: Randomized, controlled trials (RCTs) to assess benefits among women at high preeclampsia risk and RCTs or large cohort studies of harms among women at any risk level. English-language studies of fair or good quality were included. DATA EXTRACTION: Dual quality assessment and abstraction of studies. DATA SYNTHESIS: Two large, multisite RCTs and 13 smaller RCTs of high-risk women (8 good-quality) were included, in addition to 6 RCTs and 2 observational studies of average-risk women to assess harms (7 good-quality). Depending on baseline risk, aspirin use was associated with absolute risk reductions of 2% to 5% for preeclampsia (relative risk [RR], 0.76 [95% CI, 0.62 to 0.95]), 1% to 5% for intrauterine growth restriction (RR, 0.80 [CI, 0.65 to 0.99]), and 2% to 4% for preterm birth (RR, 0.86 [CI, 0.76 to 0.98]). No significant perinatal or maternal harms were identified, but rare harms could not be ruled out. Evidence on long-term outcomes was sparse, but 18-month follow-up from the largest trial found no developmental harms. LIMITATIONS: Benefits may have been overestimated due to small-study effects. Predictive intervals were not statistically significant. Future studies could shift findings toward the null. CONCLUSION: Daily low-dose aspirin beginning as early as the second trimester prevented clinically important health outcomes. No harms were identified, but long-term evidence was limited.