Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the U.S. Preventive Services Task Force

Ann Intern Med. 2014 May 20;160(10):695-703. doi: 10.7326/M13-2844.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Advisory Committees
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Female
  • Fetal Growth Retardation / etiology
  • Fetal Growth Retardation / prevention & control
  • Humans
  • Pre-Eclampsia / drug therapy*
  • Pre-Eclampsia / mortality
  • Pregnancy
  • Premature Birth / etiology
  • Premature Birth / prevention & control
  • Randomized Controlled Trials as Topic


  • Aspirin