Does low-dose aspirin reduce preeclampsia and other maternal-fetal complications?

Journal of Family Practice, Jan, 2008 by Robert Gauer, Michel Atlas, John Hill

Evidence-based answer

Yes. The use of low-dose aspirin during pregnancy decreases the risk of preeclampsia for women considered at increased risk. The effect is smaller for women without risk factors (strength of recommendation [SOR]: A, based on randomized controlled trials [RCTs] and systematic reviews [SRs] of RCTs).

Rates of preterm delivery, perinatal death, and incidence of small-for-gestational age infants are decreased for women treated with low-dose aspirin (SOR: A, based on SRs and RCTs). A meta-analysis of RCTs has found no increased rates of harm from low-dose aspirin therapy, including placental abruption or other antepartum bleeding complications (SOR: A, based on SRs and RCTs).

Clinical commentary

I prescribe 81 mg/day of aspirin for women with previous severe preeclampsia

Confused about when to use aspirin in pregnancy? You're not alone. Over my 20 years of practice, I have reacted to disparate guidelines ranging from "never use aspirin in pregnancy" to "always use low-dose aspirin." This review helps simplify my clinical practice. With the benefit of evidence from multiple RCTs over the past 7 years, I now personally use 81 mg of aspirin each day in 2 groups of women: those who had severe preeclampsia in a prior pregnancy, and those who develop signs of preeclampsia or strong risk factors for it before the third trimester in their current pregnancy.

John Hill, DO

Department of Family Medicine, University of Colorado. Denver

* Evidence summary

Systematic reviews show aspirin lowers rates of preeclampsia

Four SRs published between 2001 and 2007 (l-4) and a Cochrane Review updated in 2006 (5) have demonstrated that low-dose aspirin helps to prevent preeclampsia, reduction in preterm delivery rates, and decreased perinatal mortality.

The 2001 SR by Duley (1) included 39 trials and 30,563 patients. Patients were classified either as high-risk (previous severe preeclampsia, diabetes, chronic hypertension, renal disease, or autoimmune disease) or moderate-risk (remainder of subjects). Four individual studies (with a combined weight of 27%) did not support aspirin therapy. The largest trial not supporting aspirin therapy included 6275 subjects and had a relative risk of 1.14 (95% CI, 0.94-1.38).

Most studies in this review compared aspirin alone with placebo (28,802 subjects). However, 4 studies either compared combination therapy with aspirin or other thromboprophylaxis therapy (dipyridamole, heparin, or ozagrel). Although there were differences in risk stratification, variable doses of aspirin, and varied gestational age at trial entry, all studies reported an overall 15% reduction of preeclampsia (RR=0.85; 95% CI, 0.78-0.92).

The 2003 SR by Coomarasamy (2) included 14 trials and 12,416 patients. The study exclusively evaluated high-risk pregnancies: women with history (or family history) of preeclampsia, chronic hypertension, gestational diabetes, or renal disease. The overall reduction in preeclampsia was 14% (relative risk [RR]=0.86; 95% confidence interval [CI], 0.76-0.96). Results were consistent across RCTs, and only 2 of the 14 studies (with a combined weight of 7.1%) did not support aspirin therapy.

Ruano's 2005 SR (3) included 22 trials with 33,598 subjects and specifically compared low-risk vs high-risk patients. The authors concluded that there was no significant reduction in preeclampsia with the use of low-dose aspirin in the low-risk arm (RR=0.95; 95% CI, 0.81-1.11), and a 13% reduction among high-risk subjects (RR=0.87; 95% CI, 0.79-0.96). (3)

A 2007 meta-analysis by Askie (4) included 31 trials with 32,217 women and their 32,819 infants. Main outcomes (regardless of initial maternal risks) were 1) onset of preeclampsia, 2) neonatal death, 3) preterm birth at <34 weeks gestation, 4) infant small for gestational age, and 5) pregnancy with serious adverse outcome. Results of these outcome measures consistently showed a relative risk reduction of 10% for subjects taking low-dose aspirin, except for neonatal deaths, which had a 9% reduction. This study also suggested that multiparous women and women with a history of hypertensive disorder of pregnancy may derive a larger benefit from low-dose aspirin.

A Cochrane Review (5) updated in 2007 demonstrated that low-dose aspirin provided a moderate (19%) reduction in the overall risk of developing preeclampsia. New stratified analysis of the data indicates that in moderate-risk women, antiplatelet therapy is associated with a 15% reduction, and that high-risk women have a 27% reduction in the risk of developing preeclampsia. The effect on small-for-gestational-age infants revealed no overall clinically significant differences.

Aspirin dosing: One study recommends >75 mg/day

Studies varied in the aspirin dosage they used and duration of treatment. In all RCTs, the dose of aspirin ranged from 50 mg/day to 150 mg/day. Earlier trials used lower doses of aspirin (50-75 mg/day), while recent trials used 100 mg or more per day.

Early RCTs revealed no correlation between the dose of aspirin and the prevention of preeclampsia. However, Villar et al (6) showed a greater effect among women treated with doses greater than 75 mg/day of aspirin (RR=0.49; 95% CI, 0.38-0.63). (6)