Low-Dose Aspirin for the Prevention of Preterm Delivery in Nulliparous Women with a Singleton Pregnancy: A Randomised Multi-country Placebo Controlled Trial

Abstract

Background: Preterm birth remains a common cause of neonatal mortality with a disproportionate burden occurring in low and middle-income countries. Meta-analyses of low-dose aspirin to prevent preeclampsia suggest that the incidence of preterm birth may also be decreased, particularly if initiated before 16 weeks. Methods: We completed a randomised multi-country (Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, Zambia) double masked trial of aspirin (81 mg) daily compared to placebo initiated between 6 weeks and 0 days and 13 weeks and 6 days of pregnancy in nulliparous women between14 and 40 years of age with an ultrasound confirming gestational age and singleton viable pregnancy. Randomisation (1:1) was stratified by site. The primary outcome of preterm birth, defined as delivery prior to 37 weeks gestational age, was analyzed in randomised women with pregnancy outcomes at or after 20 weeks. This study is registered with ClinicalTrials.gov, number NCT02409680, and the Clinical Trial Registry, India, number CTRI/2016/05/006970. Findings: From March 2016 through June 2018, 11,976 women were assigned to aspirin (5,990 women) or placebo (5,986 women). Amongst randomised women, an evaluable birth outcome beyond 20 weeks occurred in 5787 women who received Aspirin and 5771 women who received placebo Preterm birth occurred in 11.6% of women randomised to aspirin and 13.1% randomised to placebo (Relative Risk [RR], 0.89; 95% CI, 0.81 to 0.98; Risk Difference, −0·02; 95% CI, −0·03, −0·01). Women randomised to aspirin were less likely to experience perinatal mortality (45.7/1000 vs 53.6/1000; RR, 0.86; 95%CI, 0.73 to 1.00). Other adverse maternal/neonatal events were similar between the two groups. Interpretation: In nulliparous women with singleton pregnancies, low dose aspirin initiated between 6 weeks and 0 days and 13 weeks and 6 days results in lower rates of preterm delivery before 37 weeks and perinatal mortality.