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

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).