AbstractObjectiveTo assess the impact of low‐dose aspirin (LDA) starting in early pregnancy on delaying preterm hypertensive disorders of pregnancy.DesignNon‐prespecified secondary analysis of a randomised masked trial of LDA.SettingThe study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR) clusters, a prospective, population‐based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Pakistan, India (two sites‐Belagavi and Nagpur) and Guatemala.PopulationNulliparous singleton pregnancies between 6⁺⁰ weeks and 13⁺⁶ weeks in six low‐middle income countries (Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, Zambia) enrolled in the ASPIRIN Trial.MethodsWe compared the incidence of HDP at delivery at three gestational age periods (<28, <34 and <37 weeks) between women who were randomised to aspirin or placebo. Women were included if they were randomised and had an outcome at or beyond 20 weeks (Modified Intent to Treat).Main Outcome MeasuresOur primary outcome was pregnancies with HDP associated with preterm delivery (HDP@delivery) before <28, <34 and <37 weeks. Secondary outcomes included small for gestational age (SGA) <10th percentile, <5th percentile, and perinatal mortality.ResultsAmong the 11 976 pregnancies, LDA did not significantly lower HDP@delivery <28 weeks (relative risk [RR] 0.18, 95% confidence interval [CI] 0.02–1.52); however, it did lower HDP@delivery <34 weeks (RR 0.37, 95% CI 0.17–0.81) and HDP@delivery <37 weeks (RR 0.66, 95% CI 0.49–0.90). The overall rate of HDP did not differ between the two groups (RR 1.08, 95% CI 0.94–1.25). Among those pregnancies who had HDP, SGA <10th percentile was reduced (RR 0.81, 95% CI 0.67–0.99), though SGA <5th percentile was not (RR 0.84, 95% CI 0.64–1.09). Similarly, perinatal mortality among pregnancies with HDP occurred less frequently (RR 0.55, 95% CI 0.33–0.92) in those receiving LDA. Pregnancies randomised to LDA delivered later with HDP compared with those receiving placebo (median gestational age 38.5 weeks vs. 37.9 weeks; p = 0.022).ConclusionsIn this secondary analysis of a study of low‐risk nulliparous singleton pregnancies, early administration of LDA resulted in lower rates of preterm HDP and delivery before 34 and 37 weeks but not in the overall rate of HDP. These results suggest that LDA works in part by delaying HDP.