BACKGROUND AND PURPOSE:

• Low-dose aspirin for early preeclampsia prevention appears to decrease preterm birth rates
• Hoffman et al. (The Lancet, 2020) assessed whether daily low-dose aspirin early in pregnancy reduces the incidence of preterm delivery

METHODS:

• Randomized, multi-country, double-masked, placebo-controlled trial (RCT)
• Participants
  • Nulliparous women | Singleton pregnancy
  • Between 18 to 40 years (minors aged ≥14 years if permitted by individual ethics boards in the Democratic Republic of the Congo, Kenya, and Zambia)
  • Excluded if had medical conditions (e.g., diabetes or hypertension) or fetal anomalies identified
  • Ultrasound confirmed dates
• Setting
  • Six countries (Low- and middle-income countries): India, Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia
• Interventions
  • Low-dose aspirin (81 mg) daily
  • Placebo
• Study design
  • Randomization 1:1, stratified by site
  • Aspirin or placebo started between 6w0d and 13w6d | Continued until 36w7days or delivery
  • Research staff, health providers, and patients were blinded to pill contents
• Primary outcome
  • Incidence of preterm birth (<37 weeks)
• Secondary outcomes
  • There were multiple predefined secondary outcomes including those related to maternal and neonatal morbidity and mortality
• Data analysis
  • Incidence of preterm birth analyzed at or after 20 weeks (intention to treat)
  • Stratified by site
  • Relative risk (RR) estimates and associated confidence intervals were calculated
• Serious adverse events: Assessed in all women who received ≥1 dose of drug or placebo

RESULTS:

• A total of 11,976 women were enrolled
  • Low-dose aspirin: 5990 women
  • Placebo: 5986 women
  • 5780 women in the aspirin group and 5764 in the placebo group were included in the primary outcome analysis
• Preterm birth was less frequent in the aspirin group (p=0.012)
  • Aspirin group: 11.6%
  • Placebo group: 13.1%
  • RR 0.89 (95% CI, 0.81 to 0.98)
• For women in the aspirin group, the following perinatal complications were also reduced
  • Perinatal mortality
    • RR 0.86 (95% CI, 0.73 to 1.00; p=0.048)
  • Fetal loss (infant death >16 weeks’ gestation and <7 days postpartum)
    • RR 0.86 (95% CI, 0.74 to 1.00; p=0.039)
  • Early preterm delivery (<34 weeks)
    • RR 0.75 (95% CI, 0.61 to 0.93; p=0.039)
  • The incidence of women who delivered <34 weeks with hypertensive disorders of pregnancy
    • RR 0.38 (95% CI, 0.17 to 0.85; p=0.015)
• Other adverse maternal and neonatal events did not show significant differences between the 2 groups

CONCLUSION:

• For nulliparous women with singleton pregnancies in low- and middle-income countries, low-dose aspirin started early in pregnancy had a positive impact on pregnancy outcomes by reducing preterm labor and perinatal mortality
• Authors recognize an important limitation of their study – they do not differentiate between iatrogenic and spontaneous preterm birth
  • Purposeful, as included centers may not have the capacity to determine cause
  • Most common reason for induced preterm birth would be hypertension and FGR
  • The authors state that

…ultimately, the decreases in preterm birth and perinatal mortality with low-dose aspirin therapy are the most meaningful outcomes to women and their children, regardless of the causative mechanism

Learn More – Primary Sources:

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

Related ObG Topics:

ASPRE Trial: A Combined Risk Algorithm and Use of Aspirin to Prevent Preterm Preeclampsia

Does Low Dose Aspirin Reduce the Risk of Spontaneous Preterm Birth?

Can Aspirin Decrease Risk of Placental Abruption and Antepartum Hemorrhage?