Another good reason to recommend low-dose aspirin

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Evidence shows that daily low-dose aspirin during pregnancy can safely lower the risk of preeclampsia and other adverse outcomes.




Prescribe low-dose aspirin (eg, 81 mg/d) to pregnant women who are at high risk for preeclampsia because it reduces the risk of this complication, as well as preterm birth and intrauterine growth restriction.1

Strength of recommendation

A: Based on a systematic review and meta-analysis of 23 studies, including 21 randomized controlled trials.

Henderson J, Whitlock E, O’Connor E, et al. 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;160:695-703.

Illustrative case

A 22-year-old G2P1 pregnant woman at 18 weeks gestation who has a history of preeclampsia comes to your office for a routine prenatal visit. On exam, her blood pressure continues to be in the 110s/60s, as it has been for several visits. Her history puts her at risk of developing preeclampsia again, and you wonder if anything can be done to prevent this from happening.

The incidence of preeclampsia, which occurs in 2% to 8% of pregnancies worldwide and 3.4% of pregnancies in the United States, appears to be steadily increasing.2,3 Preeclampsia is defined as new-onset hypertension at >20 weeks gestation, plus proteinuria, thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, and/or cerebral or visual symptoms.4 The condition is associated with several adverse maternal and fetal outcomes, including eclampsia, abruption, intrauterine growth restriction (IUGR), preterm birth, stillbirth, and maternal death.2,4 Risk factors for preeclampsia include previous preeclampsia, maternal age ≥40 years, chronic medical conditions, and multi-fetal pregnancy.5

The only effective treatment for preeclampsia is delivery.4 Given the lack of other treatments, strategies for preventing preeclampsia would be highly valuable.

In 1996, the US Preventive Services Task Force (USPSTF) addressed this issue and concluded that there was insufficient evidence to recommend for or against using aspirin to prevent preeclampsia.6 More recently, Henderson et al1 conducted a systematic review and meta-analysis to support the USPSTF in a revision of its earlier recommendation.

STUDY SUMMARY: Aspirin use lowers risk of preeclampsia and preterm birth

Henderson et al1 evaluated the impact of low-dose aspirin on maternal and fetal outcomes among pregnant women at risk for preeclampsia. The review of 23 studies included 21 randomized placebo-controlled trials that evaluated 24,666 patients. Slightly more than half of the studies that evaluated maternal and fetal health benefits were graded as good-quality, and 67% of those that evaluated maternal, perinatal, and developmental harms were rated good-quality.

Most women were white and ages 20 to 33 years. Aspirin doses ranged from 60 mg/d to 150 mg/d; most studies used 60 mg/d or 100 mg/d. Aspirin was initiated between 12 to 36 weeks gestation, with 9 trials initiating aspirin before 16 weeks. In most trials, aspirin was continued until delivery.

Among women at high preeclampsia risk (10 studies), the pooled relative risk (RR) for perinatal death was 0.81 (95% confidence interval [CI], 0.65-1.01) for low-dose aspirin compared to placebo. However, this finding was not statistically significant (P=.78).

Researchers found no evidence of increased maternal postpartum hemorrhage with aspirin use.

Among women who received low-dose aspirin, researchers noted a 14% risk reduction for preterm birth (RR=0.86; 95% CI, 0.76-0.98); a 20% risk reduction for IUGR (RR=0.80; 95% CI, 0.65-0.99), and a 24% risk reduction for preeclampsia (RR=0.76; 95% CI, 0.62-0.95). The absolute risk reduction for preeclampsia was estimated to be 2% to 5%.

While the results for preterm birth, IUGR, and preeclampsia were statistically significant, the authors noted that these results could have been biased by small study effects (the tendency of smaller studies to report positive findings, which in turn can skew the results of a meta-analysis based primarily on such studies). The timing and dosage of aspirin had no significant effect on outcomes.

There was no evidence of increased maternal postpartum hemorrhage with aspirin use (RR=1.02; 95% CI, 0.96-1.09). Aspirin use did not seem to increase perinatal mortality among all risk levels (RR=0.92; 95% CI, 0.76-1.11; P=.65). No differences were noted in the toddlers’ development at 18 months.

WHAT'S NEW: Low-dose aspirin use is now recommended

The 1996 USPSTF recommendation concluded that there was insufficient evidence to recommend aspirin use for preventing preeclampsia. This systematic review and meta-analysis, along with findings from a 2007 Cochrane review7 and a meta-analysis from the PARIS Collaborative Group,8 provide good-quality evidence that aspirin reduces negative maternal and fetal outcomes associated with preeclampsia. In 2014, the USPSTF cited this evidence when it decided to recommend using low-dose aspirin (81 mg/d) to prevent preeclampsia in women who are at high risk for preeclampsia (Grade B).9 (For more on the USPSTF, see “Catching up on the latest USPSTF recommendations”.)


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