Low-dose aspirin to prevent preeclampsia and growth restriction in nulliparous women identified by uterine artery Doppler as at high risk of preeclampsia: A double blinded randomized placebo-controlled trial

PLoS One. 2022 Oct 19;17(10):e0275129. doi: 10.1371/journal.pone.0275129. eCollection 2022.

Abstract

Introduction: This trial evaluates whether daily low-dose aspirin initiated before 16 weeks of gestation can reduce preeclampsia and fetal growth restriction in nulliparous women identified by first-trimester uterine artery Dopplers as at high risk of preeclampsia.

Methods: This randomized, blinded, placebo-controlled, parallel-group trial took place in 17 French obstetric departments providing antenatal care. Pregnant nulliparous women aged ≥ 18 years with a singleton pregnancy at a gestational age < 16 weeks of gestation with a lowest pulsatility index ≥ 1.7 or a bilateral protodiastolic notching for both uterine arteries on an ultrasound performed between 11+0 and 13+6 weeks by a certified sonographer were randomized at a 1:1 ratio to 160 mg of low-dose aspirin or to placebo to be taken daily from inclusion to their 34th week of gestation. The main outcome was preeclampsia or a birthweight ≤ 5th percentile. Other outcomes included preeclampsia, severe preeclampsia, preterm preeclampsia, preterm delivery before 34 weeks, mode of delivery, type of anesthesia, birthweight ≤ 5th percentile and perinatal death.

Results: The trial was interrupted due to recruiting difficulties. Between June 2012 and June 2016, 1104 women were randomized, two withdrew consent, and two had terminations of pregnancies. Preeclampsia or a birthweight ≤ 5th percentile occurred in 88 (16.0%) women in the low-dose aspirin group and in 79 (14.4%) in the placebo group (proportion difference 1.6 [-2.6; 5.9] p = 0.45). The two groups did not differ significantly for the secondary outcomes.

Conclusion: Low-dose aspirin was not associated with a lower rate of either preeclampsia or birthweight ≤ 5th percentile in women identified by their first-trimester uterine artery Doppler as at high risk of preeclampsia.

Trial registration: (NCT0172946).

Trial registration: ClinicalTrials.gov NCT01729468.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin / therapeutic use
  • Birth Weight
  • Female
  • Humans
  • Infant, Newborn
  • Male
  • Pre-Eclampsia* / drug therapy
  • Pre-Eclampsia* / prevention & control
  • Pregnancy
  • Pregnancy Trimester, First
  • Uterine Artery* / diagnostic imaging

Substances

  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT01729468

Grants and funding

The trial was funded by a government grant “Programme Hospitalier de Recherche Clinique National” PHRCN-2008. The government did not have a role in designing the study, interpreting the results or writing the manuscript.