Does initiating low-dose aspirin (acetylsalicylic acid) beyond 20 weeks of gestation help prevent preeclampsia?

Low-Dose Aspirin for Preeclampsia Prevention: Initiation Beyond 20 Weeks

Low-dose aspirin initiated beyond 20 weeks of gestation is less effective for preventing preeclampsia compared to earlier initiation, and optimal benefit is achieved when started between 12-16 weeks of gestation. 1, 2, 3

Timing of Initiation

• The American College of Obstetricians and Gynecologists recommends initiating low-dose aspirin between 12 and 16 weeks of gestation for optimal effect in women at high risk for preeclampsia 2, 4
• Multiple meta-analyses suggest that low-dose aspirin for preeclampsia prevention is more effective when initiated prior to 16 weeks of gestation 1, 5
• Starting low-dose aspirin at 16 weeks or earlier was associated with a significant 53% reduction in preeclampsia risk (RR 0.47,95% CI 0.34-0.65), while initiation after 16 weeks showed only a non-significant 19% reduction (RR 0.81,95% CI 0.63-1.03) 5
• The USPSTF found that stratified comparisons did not show that timing of aspirin initiation (<16 weeks) had a significant effect on preeclampsia prevention, though most studies in their analysis initiated aspirin before 20 weeks 1

Effectiveness Based on Timing

• Low-dose aspirin started at 16 weeks or earlier demonstrated greater reductions in:
  • Severe preeclampsia (91% reduction, RR 0.09,95% CI 0.02-0.37) 5
  • Intrauterine growth restriction (56% reduction, RR 0.44,95% CI 0.30-0.65) 5
  • Preterm birth (78% reduction, RR 0.22,95% CI 0.10-0.49) 5
• The World Health Organization recommends that 75 mg of aspirin should be initiated before 20 weeks of gestation for women at high risk of preeclampsia 6

Dosage Considerations

• The most commonly studied dosages are 60-81 mg/day in the US, though some evidence suggests higher doses (100-150 mg) may be more effective 2, 3, 6
• The Royal College of Obstetricians and Gynecologists recommends 150 mg of aspirin daily, while the National Institute of Health and Care Excellence suggests risk stratification with 75 mg for moderate risk and 150 mg for high risk 6
• For women with diabetes, a higher dose of 100-150 mg/day is recommended 3

Duration of Therapy

• Once initiated, low-dose aspirin should be continued until delivery for maximum benefit 2, 4
• A study evaluating discontinuation at 28 weeks found no significant reduction in preeclampsia incidence compared to controls (22.0% vs. 16.8%; p = 0.20) 7

Pitfalls and Caveats

• Initiating aspirin beyond 20 weeks significantly reduces its effectiveness in preventing preeclampsia and related adverse outcomes 5
• Women with chronic hypertension may have less benefit from standard low-dose aspirin (81 mg), with some studies showing no significant reduction in superimposed preeclampsia in this population 1
• Women with higher BMI (>40 kg/m²) may require dose adjustment, as obesity can limit aspirin absorption and increase platelet regeneration, potentially reducing effectiveness 1, 3
• The mechanism for preeclampsia involves defective placentation in early pregnancy, which explains why earlier initiation of aspirin therapy is more effective 8