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. 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. 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. 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. Funded by the Eunice Kennedy Shriver
National Institute of Child Health and Human Development.