Clinical Question

Does initiating low-dose aspirin use in early pregnancy reduce the incidence of preterm birth among nulliparous patients with singleton gestation?

Bottom Line

The routine use of low-dose aspirin, 81 mg daily, starting as early as six weeks' gestational age provided a statistically significant absolute risk reduction (nearly 2 percentage points) in the incidence of preterm birth among nulliparous patients with singleton gestation in resource-poor countries. No significant treatment harms were observed, but the study was not powered to assess rare events. It is not clear whether the results can be generalized to patients in advanced economies. (Level of Evidence = 1b)

Synopsis

The study was carried out at seven community sites in six resource-poor countries (India, Pakistan, Zambia, Democratic Republic of Congo, Guatemala, and Kenya). The authors enrolled 11,976 nulliparous patients at least 14 years of age with singleton pregnancies and randomized them to receive 81 mg of aspirin or placebo starting between 6 0/7 and 13 6/7 weeks' gestational age and continued until 37 0/7 weeks' or delivery. Patients were excluded for allergy to aspirin, previous aspirin use for at least seven days during the pregnancy, more than two first-trimester pregnancy losses, or medical conditions that might be considered a contraindication to study participation (e.g., diabetes mellitus or hypertension). Further screening required a blood pressure of less than 140/90 mm Hg, a hemoglobin level of at least 7 g per dL (70 g per L), and a viable fetus without anomaly. For the primary outcome of preterm birth, the authors planned a modified intention-to-treat analysis to include only patients who delivered at 20 0/7 weeks' gestation or later (n = 11,558). At least 90% adherence to treatment based on pill counts was high: approximately 85%. Preterm birth before 37 0/7 weeks' occurred in 11.6% (668 out of 5,780) of patients in the aspirin group vs. 13.1% (754 out of 5,754) in the placebo group (relative risk = 0.89; 95% CI, 0.81 to 0.98; P = .012; number needed to treat = 66; 95% CI, 37 to 308). The authors estimated the absolute risk difference at 2%. More than 20 secondary outcomes were considered and treated as exploratory. Among those outcomes that were statistically significant and better in the aspirin group were early preterm delivery (less than 34 weeks) and fetal loss after 16 weeks' gestation and up to seven days postpartum. There were no differences in the overall incidence of hypertensive disorders, maternal bleeding problems, and fetal growth abnormalities. There were no statistically significant harms of aspirin treatment, although the study was not powered to assess rare catastrophic outcomes.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (primary care)

Reference: Hoffman MK, Goudar SS, Kodkany BS, et al.; ASPIRIN Study Group. Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial [published correction appears in Lancet. 2020;395(10228):e53]. Lancet. 2020;395(10220):285–293.