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

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