Reproductive Health · 2017
ASPRE Trial: Aspirin for Prevention of Preterm Pre-eclampsia
Aspirin for Evidence-Based Preeclampsia Prevention Trial
Pre-eclampsia complicates roughly 3 to 5 percent of pregnancies globally and remains a leading cause of maternal and perinatal mortality. Low-dose aspirin had been studied in pre-eclampsia prevention for decades, with earlier trials and meta-analyses showing modest reductions in risk among women considered high-risk based on clinical factors. The problem was that risk stratification using clinical characteristics alone, such as nulliparity, obesity, or chronic hypertension, identified a wide and heterogeneous population in which any drug effect was diluted. The Fetal Medicine Foundation in London, under Kypros Nicolaides, had been developing a more precise first-trimester screening algorithm that combined uterine artery Doppler pulsatility index, mean arterial pressure, placental growth factor, and pregnancy-associated plasma protein-A.
ASPRE recruited 1,776 women identified as high-risk by that validated algorithm at 13 maternity units in the United Kingdom, Spain, Italy, Belgium, Greece, Israel, and Canada. Screening occurred between 11 and 13 weeks of gestation. Women meeting the risk threshold were randomized to 150 mg aspirin at night or placebo, with treatment continuing until 36 weeks. The higher aspirin dose, 150 mg rather than the 81 mg more commonly used in the United States, was chosen based on pharmacokinetic data suggesting better platelet inhibition in pregnancy with the larger dose taken at bedtime.
The primary outcome, preterm pre-eclampsia defined as delivery before 37 weeks, occurred in 1.6% of the aspirin group and 4.3% of the placebo group, an odds ratio of 0.38. Term pre-eclampsia rates did not differ significantly between groups. That asymmetry was clinically meaningful because preterm pre-eclampsia, particularly early-onset disease before 34 weeks, carries substantially higher rates of maternal organ dysfunction, fetal growth restriction, and neonatal morbidity than term disease. The ability of aspirin to reduce the severe form while leaving the milder form largely unaffected reinforced a view that the two subtypes may have distinct pathophysiology, with placental insufficiency playing a larger role in the preterm variant.
David Peebles and colleagues at UK sites contributed to trial oversight, and the results were published in the New England Journal of Medicine in August 2017. The response from obstetric medicine was broadly favorable, though implementation required accepting first-trimester biochemical and Doppler screening as routine practice, which was not standard in all health systems. A subsequent ASPRE subgroup analysis examining perinatal outcomes, published in 2019, confirmed reductions in preterm birth and neonatal intensive care admission in the aspirin group.
Several major guidelines, including those from ISUOG and the FIGO, incorporated the trial's screening-plus-aspirin approach. The US Preventive Services Task Force recommendation for low-dose aspirin in high-risk pregnancies, updated in 2021, cited ASPRE alongside earlier meta-analyses. The practical question that remained in many settings was whether the combined first-trimester screening algorithm could be deployed affordably and equitably in lower-resource environments where pre-eclampsia burden is highest.
Key People
- Kypros Nicolaides — Principal investigator; designed the first-trimester screening algorithm
- David Peebles — Co-investigator; contributed to trial oversight at UK sites
- Argyro Syngelaki — Fetal Medicine Foundation biostatistician; contributed to algorithm validation
- Liona Poon — Co-investigator; led analysis of placental biomarker screening performance
N Engl J Med. 2017;377(7):613-622
Related landmarks
- 2017 · WOMAN Trial: Tranexamic Acid for Postpartum Hemorrhage (Reproductive Health)
- 2004 · Women's Health Initiative: Estrogen-Alone Hormone Therapy (Reproductive Health)
- 2002 · Magpie Trial: Magnesium Sulfate for Pre-eclampsia (Reproductive Health)
- 2002 · Women's Health Initiative: Estrogen plus Progestin Hormone Therapy (Reproductive Health)