Cost-effectiveness of low-dose aspirin for the prevention of preterm birth: a prospective study of the Global Network for Women's and Children's Health Research.

BACKGROUND: Premature birth is associated with an increased risk of mortality and morbidity, and strategies to prevent preterm birth are few in number and resource intensive. In 2020, the ASPIRIN trial showed the efficacy of low-dose aspirin (LDA) in nulliparous, singleton pregnancies for the prevention of preterm birth. We sought to investigate the cost-effectiveness of this therapy in low-income and middle-income countries. METHODS: In this post-hoc, prospective, cost-effectiveness study, we constructed a probabilistic decision tree model to compare the benefits and costs of LDA treatment compared with standard care using primary data and published results from the ASPIRIN trial. In this analysis from a health-care sector perspective, we considered the costs and effects of LDA treatment, pregnancy outcomes, and neonatal health-care use. We did sensitivity analyses to understand the effect of the price of the LDA regimen, and the effectiveness of LDA in reducing both preterm birth and perinatal death. FINDINGS: In model simulations, LDA was associated with 141 averted preterm births, 74 averted perinatal deaths, and 31 averted hospitalisations per 10 000 pregnancies. The reduction in hospitalisation resulted in a cost of US$248 per averted preterm birth, $471 per averted perinatal death, and $15·95 per disability-adjusted life year. INTERPRETATION: LDA treatment in nulliparous, singleton pregnancies is a low-cost, effective treatment to reduce preterm birth and perinatal death. The low cost per disability-adjusted life year averted strengthens the evidence in support of prioritising the implementation of LDA in publicly funded health care in low-income and middle-income countries. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial.

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 ClinicalTrials.gov, 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.