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
John Hill, DO
Department of Family Medicine, University of Colorado, Denver
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.
Evidence summary
Systematic reviews show aspirin lowers rates of preeclampsia
Four SRs published between 2001 and 20071-4 and a Cochrane Review updated in 20065 have demonstrated that low-dose aspirin helps to prevent preeclampsia, reduction in preterm delivery rates, and decreased perinatal mortality.
The 2001 SR by Duley1 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 Coomarasamy2 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.
TABLE
Low-dose aspirin reduces risk of preeclampsia, but how does it affect other maternal and fetal outcomes?
| STUDY (YEAR) | DEVELOPMENT OF PREECLAMPSIA | PRETERM DELIVERY | NEONATAL DEATH | SGA OR LOW BIRTH WEIGHT | RISK OF ABRUPTION & BLEEDING |
|---|---|---|---|---|---|
| Duley (2001)1 | Moderate-risk patients: 15% reduction High-risk patients: 15% reduction NNT=100 | 8% reduction NNT=72 | 14% reduction NNT= 250 | 8% reduction* | Not reported |
| Coomarasamy (2003)2 | 14% reduction | 14% reduction | 21% reduction | 215-g weight gain in aspirin group | No significant clinical difference in risk RR=0.98) |
| Ruano (2005)3 | Low-risk patients: no significant reduction High-risk patients: 13% reduction | Not reported | |||
| Askie (2007)4 | 10% reduction | 10% reduction | 9% reduction | 10% reduction | No significant clinical difference in risk (RR=0.90–1.15) |
| Cochrane (2007)5 | 19% reduction NNT=69 (overall), 118 (moderate risk), 18 (high-risk) | 7% reduction NNT=83 | 16% reduction NNT=227 | 8% reduction* | No significant clinical difference in risk (RR=1.06) |
| * Borderline for statistical significance (RR=0.92). | |||||
| SGA, small for gestational age; NNT, number needed to treat; RR, relative risk. | |||||
Ruano’s 2005 SR3 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 Askie4 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.