A meta-analysis «Roberge S, Nicolaides K, Demers S et al. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis. Am J Obstet Gynecol 2017;216(2):1»2 included 45 trials with a total of 20 909 pregnant randomized to 50–150 mg of aspirin daily. When aspirin was initiated at ≤16 weeks, there was a significant reduction and a dose-response effect for the prevention of pre-eclampsia (RR 0.57, 95% CI 0.43 to 0.75; P < .001), severe pre-eclampsia (RR 0.47, 95% CI 0.26 to 0.83; P = .009), and fetal growth restriction (RR 0.56, 95% CI 0.44 to 0.70; P < .001) with higher dosages of aspirin being associated with greater reduction of the 3 outcomes. Similar results were observed after the exclusion of studies at high risk of biases. When aspirin was initiated at >16 weeks, there was a smaller reduction of pre-eclampsia. Aspirin initiated at >16 weeks was not associated with a risk reduction or a dose-response effect for severe pre-eclampsia (RR 0.85, 95% CI 0.64 to 1.14; P = .28) and fetal growth restriction (RR 0.95, 95% CI 0.86-1.05; P = .34).
An open-label randomized trial «Amro FH, Blackwell SC, Pedroza C, et al. Aspirin 162 mg vs 81 mg for preeclampsia prophylaxis in high-risk obese individuals: a comparative effectiveness open-label randomized trial (ASPREO). Am J Obs»4 comparing 162 mg aspirin with 81 mg included 220 obese pregnant women with risk factors for pre-eclampsia. Pre-eclampsia occurred in 35% in the 162 mg aspirin group and 40% in the 81 mg aspirin group (posterior RR 0.88; 95% credible interval, 0.64 to 1.22). Rates of indicated preterm birth because of preeclampsia (21% vs 21%), small for gestational age (6.5% vs 2.9%), abruption (2.8% vs 3.0%), and postpartum hemorrhage (10.0% vs 8.8%) were similar between groups.
A Cochrane review «Antiplatelet agents for preventing pre‐eclampsia and its complications»1 «Duley L, Meher S, Hunter KE et al. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2019;2019(10):. »1 included 77 studies with a total of 40 249 women. Antiplatelet agent (mostly low-dose aspirin - 50 to150 mg) was compared with placebo/no antiplatelet agent. Antiplatelet agents reduced the risk of proteinuric pre-eclampsia by 18%, number needed to treat for one women to benefit (NNTB) 61 (95% CI 45 to 92). There was a small (9%) reduction in preterm birth <37 weeks, NNTB 61 (95% CI 42 to 114) and a 14% reduction infetal deaths, neonatal deaths or death before hospital discharge, NNTB 197 (95% CI 115 to 681). Antiplatelet agents probably slightly increase postpartum haemorrhage > 500 mL.
| Outcome | Relative effect (95% CI) | Assumed risk - Placebo/no antiplatelet | Corresponding risk - Antiplatelet agents | No of Participants (studies) Quality of the evidence |
|---|---|---|---|---|
| Proteinuric pre-eclampsia | RR 0.82 (0.77 to 0.88) | 92 per 1000 | 16 fewer per 1000 (22 fewer to 11 fewer) | 36 716 (60) High |
| Any reported infant death (fetal, neonatal, or before hospital discharge) | RR 0.85 (0.76 to 0.95) | 33 per 1000 | 5 fewer per 1000 (9 fewer to 1 fewer) | 35 391 (52) High |
| Preterm birth (before 37 weeks' gestation) | RR 0.91 (0.87 to 0.95) | 175 per 1000 | 16 fewer per 1000 (23 fewer to 9 fewer) | 35 212 (47) High |
| Small-for-gestational age | RR 0.84 (0.76 to 0.92) | 47 per 1000 | 7 fewer per 1000 (11 fewer to 3 fewer) | 35 761 (50) High |
| Pregnancy with serious adverse outcome (composite including maternal death, baby death, pre-eclampsia, small-for-gestational age, preterm birth) | RR 0.90 (0.85 to 0.96) | 197 per 1000 | 20 fewer per 1000 (30 fewer to 8 fewer) | 17 382 (13) High |
| Postpartum haemorrhage > 500 mL | RR 1.06 (1.00 to 1.12) | 143 per 1000 | 9 more per 1000 (0 fewer to 19 more) | 23 769 (19) Moderate |
A nationwide cohort study «Kupka E, Hesselman S, Gunnarsdóttir J, et al. Prophylactic Aspirin Dose and Preeclampsia. JAMA Netw Open 2025;8(2):e2457828.»5 included 13 828 women using either 150–160 mg or 75 mg of aspirin. Among women using 150 to 160 mg of aspirin, 443 (9.5%) developed preeclampsia compared with 812 (8.9%) of those using 75 mg of aspirin (adjusted RR 1.07; 95% CI 0.93 to 1.24). Additionally, the risk of postpartum hemorrhage between the groups was similar (adjusted RR 1.08; 95% CI 0.90 to 1.30).
An RCT «Hoffman MK, Goudar SS, Kodkany BS et al. Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controll»3 in low and middle income countries included 11 976 women randomly assigned to low-dose aspirin (81 mg) or placebo initiated before week 14. Preterm birth before 37 weeks occurred in 668 (11.6%) of the women who took aspirin and 754 (13.1%) of those who took placebo (RR 0.89, 95% CI 0.81 to 0.98, p=0·012). In aspirin group, there were reductions in perinatal mortality (0.86 [CI 0.73 to 1.00, p=0·048], fetal loss (infant death after 16 weeks' gestation and before 7 days post partum; 0.86 [0.74 to 1.00], p=0·039), early preterm delivery (<34 weeks; 0.75 [0.61 to 0.93], p=0.039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0.38 [0.17 to 0.85], p=0.015). Other adverse maternal and neonatal events were similar between the two groups.
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