Matthew K. Hoffman, Christiana Care
Shivaprasad S. Goudar, Jawaharlal Nehru Medical College, KLE University
Bhalachandra S. Kodkany, Jawaharlal Nehru Medical College, KLE University
Mrityunjay Metgud, Jawaharlal Nehru Medical College, KLE University
Manjunath Somannavar, Jawaharlal Nehru Medical College, KLE University
Jean Okitawutshu, Kinshasa School of Public Health
Adrien Lokangaka, Kinshasa School of Public Health
Antoinette Tshefu, Kinshasa School of Public Health
Carl L. Bose, University of North Carolina at Chapel Hill
Abigail Mwapule, University Teaching Hospital
Musaku Mwenechanya, University Teaching Hospital
Elwyn Chomba, University Teaching Hospital
Waldemar A. Carlo, University of Alabama at Birmingham
Javier Chicuy, Instituto de Nutrición de Centro América y Panamá
Lester Figueroa, Instituto de Nutrición de Centro América y Panamá
Ana Garces, Instituto de Nutrición de Centro América y Panamá
Nancy F. Krebs, University of Colorado Denver
Saleem Jessani, Aga Khan University
Farnaz Zehra, Aga Khan University
Sarah Saleem, Aga Khan University
Robert L. Goldenberg, Columbia University
Kunal Kurhe, Lata Medical Research Foundation
Prabir Das, Lata Medical Research Foundation
Archana Patel, Lata Medical Research Foundation
Patricia L. Hibberd, Boston University School of Public Health
Emmah Achieng, Moi University School of Medicine
Paul Nyongesa, Moi University School of Medicine
Fabian Esamai, Moi University School of Medicine
Edward A. Liechty, Indiana University
Norman Goco, RTI International
Jennifer Hemingway-Foday, RTI International
Janet Moore, RTI International
Tracy L. Nolen, RTI International
Elizabeth M. McClure, RTI International
Marion Koso-Thomas, National Institutes of Health
Menachem Miodovnik, National Institutes of Health
R. Silver, University of Utah
Richard J. Derman, Thomas Jefferson UniversityFollow
ASPIRIN Study Group

Document Type


Publication Date



This article is the author’s final published version in The Lancet, Volume 395, Issue 10220, January 2020, Pages 285-293.

The published version is available at Copyright © Hoffman et al.


BACKGROUND: Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation.

METHODS: ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks' gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970.

FINDINGS: From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks' gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (<34 >weeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups.

INTERPRETATION: In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality.

FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.