The Efficacy of Low-dose Aspirin in Pregnancy Among Women in Malaria-endemic Countries

Background: Low dose aspirin (LDA) is an effective strategy to reduce preterm birth. However, LDA might have differential effects globally, based on the etiology of preterm birth. In some regions, malaria in pregnancy could be an important modifier of LDA on birth outcomes and anemia. Methods: This is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birth. We enrolled a convenience sample of women in the ASPIRIN trial from the Democratic Republic of Congo (DRC), Kenya and Zambia. We used quantitative polymerase chain reaction to detect malaria. We calculated crude prevalence proportion ratios (PRs) for LDA by malaria for outcomes, and regression modelling to evaluate effect measure modification. We evaluated hemoglobin in late pregnancy based on malaria infection in early pregnancy. Findings: 1,446 women were analyzed, with a malaria prevalence of 63% in the DRC site, 38% in the Kenya site, and 6% in the Zambia site. Preterm birth occurred in 83 (LDA) and 90 (placebo) women, (PR 0.92, 95% CI 0.70, 1.22), without interaction between LDA and malaria (p=0.75). Perinatal mortality occurred in 41 (LDA) and 43 (placebo) pregnancies, (PR 0.95, 95% CI 0.63, 1.44), with an interaction between malaria and LDA (p=0.014). Hemoglobin was similar by malaria and LDA status. Interpretation: Malaria in early pregnancy did not modify the effects of LDA on preterm birth, but modified the effect of LDA on perinatal mortality. This effect measure modification deserves continued study as LDA is used in malaria endemic regions. Clinical Trial Registration Details: This is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birthThe ASPIRIN trial was registered in clinicaltrials.gov (NCT02409680). Funding Information: NICHD (UG1HD076465, UG1HD078437, UG1HD076461). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This study was approved by the relevant ethics committees at the institutions conducting the study at each site prior to the initiation of study activities. The study was also approved by the ethics committees at the partner U.S.-based institutions (University of North Carolina at Chapel Hill, Columbia University, University of Alabama at Birmingham and Indiana University) and by RTI International, the data coordinating center. All women provided informed consent prior to their participation in the sub-study.