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#349 An ASA a day when a baby’s on the way?

Is acetylsalicylic acid (ASA) effective in preventing complications in pregnant women at risk of preeclampsia?

In women at risk for preeclampsia at ~12-28 weeks gestation, low-dose ASA (50-150mg) reduces risk of preeclampsia by an absolute ~2%, perinatal death by ~0.5%, and preterm birth by ~2% compared to placebo. The risk of postpartum hemorrhage is increased by up to ~1%.

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  • 7 systematic reviews (17-77 randomized controlled trials [RCTs]; 26,952-46,568 patients) from the last 5 years comparing ASA to placebo in pregnant women at varying preeclampsia risk.1-7 ASA usually initiated ~12-28 weeks, continued until delivery. Results statistically significant unless indicated.
    • Maternal Outcomes:
      • Preeclampsia: 5 systematic reviews (16-60 RCTs):1-5
        • 5-9.6% versus 5.8-11.8% (placebo), number needed to treat (NNT)=31-72.
      • Placental abruption: 3 systematic reviews (9-29 RCTs):1,3,4
        • 0.9-1.3% versus 0.7-1.2% (placebo) (not statistically different).
      • Postpartum hemorrhage (>500-1000mL blood loss): 4 systematic reviews (9-19 RCTs):1,3,4,6
        • 7-15.2% versus 3.3-14.3% (placebo), number needed to harm (NNH)=97-239 (1/4 systematic reviews not statistically different).4
    • Fetal outcomes:
      • Perinatal death: 3 systematic reviews (11-52 RCTs):1,3,4
        • 1-3.1% versus 2.7-3.5% (placebo), NNT=179-239.
      • Preterm delivery/birth: 2 systematic reviews with comprehensive data (18-47 RCTs):1,3
        • 0.9-16.6% versus 17.5-18.5% (placebo), NNT=54-64.
      • Fetal intracranial bleed: 1 systematic review (6 RCTs):4
        • Not statistically different.
    • Limitations: Inconsistent definitions of patients at risk for preeclampsia; infrequent reporting of serious maternal outcomes (examples: eclampsia, death); some large RCTs not included in all systematic reviews.

  • No clear difference in outcomes between 50-150 mg daily.1,3-5,7
  • Earlier initiation (<16-20 weeks) may enhance preeclampsia benefit based on subgroup analyses. No consistent trends for other outcomes.1-4,7
  • Sensitivity of clinical risk factors for predicting pre-eclampsia is <40%.8
  • Guidelines vary:
    • Common recommendations among guidelines for ASA use include, but not limited to:
      • Any high-risk factors (examples: prior preeclampsia, chronic hypertension, renal or autoimmune disease, diabetes) or,
      • At least 2 moderate-risk factors (examples: nulliparity, age >35-40, previous adverse pregnancy outcome).
    • Canadian: ASA 81-162mg daily preferably before 16 weeks until 36 weeks gestation.8
    • American: ASA 81mg daily initiated between 12-28 weeks gestation (optimally before 16 weeks) until delivery.9

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  • Brianne Desrochers PharmD candidate
  • Sasha Katwaroo PharmD candidate
  • Karen Toews MD CCFP
  • Jamie Falk PharmD

1. Duley L, Meher S, Hunter KE, et al. Cochrane Database Syst Rev. 2019: CD004659.

2. Wang Y, Guo X, Obore N, et al. Front Cardiovasc Med. 2022; 9:936560.

3. Choi YJ, Shin S. Am J Prev Med. 2021; 61(1):e31-e45.

4. Henderson JT, Vesco KK, Senger CA, et al. JAMA. 2021; 326(12):1192-1206.

5. van Doorn R, Mukhtarova N, Flyke IP, et al. PLoS One. 2021; 16(3):e0247782.

6. Jiang Y, Chen Z, Chen Y, et al. Am J Obstet Gynecol MFM 2023; 5:100878.

7. Turner JM, Robertson NT, Hartel G, et al. Ultrasound Obstet Gynecol. 2020; 55(2):157-169.

8. Magee LA, Smith GN, Bloch C, et al. J Obstet Gynaecol Can. 2022; 44(5):547–571.e1.

9. ACOG Committee. Obstet Gynecol. 2018; 132(1):254-256.

Authors do not have any conflicts of interest to declare.