Preeclampsia Aspirin Prevention

Preeclampsia affects 3-5% of pregnancies worldwide and remains a leading cause of maternal and perinatal morbidity and mortality. Early mechanistic research identified an imbalance between thromboxane (vasoconstrictor) and prostacyclin (vasodilator) in preeclamptic placentas, providing the rationale for low-dose aspirin as a preventive intervention. The CLASP trial (Collaborative Low-dose Aspirin Study in Pregnancy, 1994) was the first large RCT, randomizing over 9,000 women to aspirin 60mg or placebo. CLASP showed only a non-significant 12% reduction in preeclampsia, but subgroup analyses suggested greater benefit when aspirin was initiated before 20 weeks gestation. This timing signal would prove crucial in subsequent research.

An individual patient data meta-analysis by Askie and colleagues (2007) pooled data from 31 RCTs (over 32,000 women) and confirmed that aspirin modestly reduced preeclampsia by 10% overall, but by 25% when initiated before 16 weeks. The critical proof came from Bujold's systematic review (2010) which showed a 53% reduction in preeclampsia when aspirin was started at or before 16 weeks at doses of 100mg or higher, compared to minimal benefit with later initiation. These dose-response and timing-response findings crystallized the understanding that aspirin must be started early in pregnancy (ideally first trimester) to prevent the defective placentation that leads to preeclampsia, rather than treating established disease.

The ASPRE trial (Aspirin for Evidence-Based Preeclampsia Prevention, 2017) was the landmark multicenter RCT that integrated screening and treatment into a unified strategy. Using the Fetal Medicine Foundation first-trimester combined screening algorithm (incorporating maternal factors, uterine artery Doppler, mean arterial pressure, and PIGF), 1,776 high-risk women identified by screening were randomized to aspirin 150mg nightly versus placebo starting at 11-14 weeks. ASPRE demonstrated a 62% reduction in preterm preeclampsia (before 37 weeks), the most clinically dangerous form. This trial established the paradigm of first-trimester risk-stratified screening combined with early aspirin prophylaxis. Subsequent analyses confirmed that bedtime dosing optimized the antiplatelet effect and that adherence to aspirin >90% was necessary for the full preventive benefit.

ACOG (2018) recommends low-dose aspirin (81mg daily) starting at 12-28 weeks (optimally before 16 weeks) for women at high risk of preeclampsia based on clinical risk factors. NICE recommends aspirin 150mg daily from 12 weeks for women with one or more high-risk factors. The International Society for the Study of Hypertension in Pregnancy (ISSHP) and the Fetal Medicine Foundation advocate the combined first-trimester screening algorithm used in ASPRE to identify high-risk women for targeted aspirin prophylaxis. The USPSTF recommends low-dose aspirin (81mg/day) for preeclampsia prevention in women at high risk, initiated after 12 weeks of gestation. There is ongoing debate about dose (81mg vs 150mg) and screening approach (risk-factor-based vs algorithm-based).

Aspirin prophylaxis for preeclampsia prevention is now a cornerstone of antenatal care worldwide. The key debates center on the optimal screening strategy (simple risk factor-based per ACOG/NICE vs combined algorithm per FMF/ASPRE), aspirin dose (81mg standard in North America vs 150mg in Europe/Australia based on ASPRE), and optimal timing of initiation. First-trimester combined screening using biomarkers is being progressively adopted, particularly in Europe and Australia, but cost and access barriers limit implementation in low-resource settings. Research continues into additional preventive strategies (calcium, L-arginine, pravastatin) and into refining risk prediction models using machine learning and additional biomarkers. The ultimate goal is a personalized prevention strategy that identifies every woman at risk early enough for effective intervention.