Background
Phase 3, multicenter, double-blind, placebo-controlled RCT (ASPRE trial). 1,776 singleton pregnancies at high risk for preeclampsia identified by first-trimester combined screening algorithm (11–13 weeks): uterine artery Doppler PI, mean arterial pressure, serum PlGF, and PAPP-A. Risk cutoff: ≥1 in 100 for preterm preeclampsia. Conducted at 13 centers in UK, Spain, Italy, Belgium, Greece, and Israel. This was the first adequately powered trial using biomarker-based screening to select high-risk patients.
Interventions and follow up
Arm A: Aspirin 150 mg orally once daily at bedtime from 11–14 weeks until 36 weeks of gestatio
Arm B: Placebo tablet once daily at bedtime (identical appearance)
Primary endpoint: Preterm preeclampsia (delivery with preeclampsia at <37 weeks)
mFollow up: Delivery
Arm B: Placebo tablet once daily at bedtime (identical appearance)
Primary endpoint: Preterm preeclampsia (delivery with preeclampsia at <37 weeks)
mFollow up: Delivery
Results
Preterm preeclampsia: 1.6% vs 4.3%, OR 0.38 (95% CI 0.20–0.74), P=.004 — 62% relative risk reduction
Term preeclampsia (>37 weeks): 4.3% vs 4.8%, OR 0.95 — NS
Preterm birth <37 weeks: 10.0% vs 11.8% — NS
SGA <10th percentile: 12.1% vs 13.7% — NS
Perinatal mortality: 0.5% vs 0.8% — NS
Term preeclampsia (>37 weeks): 4.3% vs 4.8%, OR 0.95 — NS
Preterm birth <37 weeks: 10.0% vs 11.8% — NS
SGA <10th percentile: 12.1% vs 13.7% — NS
Perinatal mortality: 0.5% vs 0.8% — NS
Adverse events
Main adverse events: No significant difference in neonatal, fetal, or maternal hemorrhagic complications. PPH similar. Congenital anomalies similar. Aspirin 150 mg well-tolerated at bedtime.
Conclusions
Low-dose aspirin 150 mg/day started at 11–14 weeks significantly reduced the incidence of preterm preeclampsia by 62% in high-risk women identified by first-trimester biomarker screening, establishing a new standard for preeclampsia prevention based on risk stratification.
Key Limitations
Key Limitations: Screening algorithm was complex and requires specialized first-trimester assessment not universally available. Benefit restricted to preterm preeclampsia — no reduction in term preeclampsia (the more common form). Earlier CLASP trial used lower doses (75 mg) and showed no benefit, possibly because it was underpowered and used unselected patients. Adherence monitoring was based on self-report and pill counts — imperfect. Multicenter European trial may not generalize to all populations.
Clinical Context
ASPRE validated first-trimester combined screening for preeclampsia prediction and established aspirin 150 mg at bedtime as effective prophylaxis in high-risk women. ISUOG, FIGO, NICE, and ACOG (2021 low-dose aspirin task force) now recommend aspirin 81–150 mg for women at high risk for preeclampsia, started before 16 weeks. The trial shifted practice from universal low-dose aspirin to biomarker-guided prophylaxis. ACOG recommends 81 mg (available US formulation) while European guidelines favor 150 mg.
References
References: Rolnik DL et al, NEJM 2017 (ASPRE primary)