Preconception use of low dose aspirin therapy may improve reproductive outcomes in women with 1 or 2 prior pregnancy losses, according to a post hoc per protocol analysis of the EAGeR trial (ClinicalTrials.gov: NCT00467363) recently published in the Annals of Internal Medicine.

Women who have experienced a prior pregnancy loss are at risk for a recurrent pregnancy loss, defined as at least 2 failed clinical pregnancies, and other reproductive complications. Low dose aspirin (usually 81mg/day) is commonly used in prenatal health for the prevention or delay in the onset of preeclampsia in high-risk patients. Postconception low dose aspirin has been extensively studied and prescribed to prevent pregnancy loss in patients with recurrent pregnancy losses, despite lack of clinical efficacy.1,2 There are few studies on the preconception use of low dose aspirin therapy for the prevention of pregnancy loss.

The EAGeR (Effects of Aspirin in Gestation and Reproduction) study, published in The Lancet in 2014, was a multicenter, block-randomized, double-blinded, placebo-controlled trial. The study included 1078 women (aged 18-40 years) with 1 or more prior documented pregnancy losses. Participants were randomly assigned to receive low dose aspirin (81mg/day) or placebo. Although the trial’s intention-to-treat resulted in a 10% increase in live birth rates with the use of preconception low dose aspirin therapy, the results were nonsignificant. 2 The trial did not show benefit in preventing recurrent pregnancy losses.2

According to the original EAGeR trial, 15% of participants permanently discontinued the study drug and 6% of participants temporarily discontinued the study drug as compared to 13% and 8% in the placebo group, respectively.2 Side effects, such as bleeding, nausea and vomiting, as well as hCG-detected pregnancy, were strongly associated with nonadherence. The current reanalysis suggests that for every 100 women with 1 or 2 documented pregnancy losses who were adherent to low dose aspirin use at least 4 times per week over the follow up time of 36 weeks’ gestation, there would be 8 more hCG-detected pregnancies, 6 fewer pregnancy losses, and 15 more live births as compared to placebo.3 


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Although Naimi and colleagues observed benefits in using preconception low dose aspirin to improve pregnancy outcomes in women with previous pregnancy losses, the post hoc analysis was an observational study performed under ideal conditions. Therefore, the study does not reflect the real-world setting and may be prone to bias due to the selection of patients, exclusion of missing data, and higher adherence rates. Higher adherence rates to the study drug were reported in participants who were white, more likely to be married, have higher income (>$40,000), and less likely to smoke.3 Women who do not have similar baseline characteristics may have different reproductive results due to the lack of adherence.    

The authors of the study concluded that preconception low dose aspirin use may improve pregnancy outcomes in women with a history with pregnancy loss and emphasized efforts to improve adherence rates of aspirin therapy. Although data presented in the post hoc analysis were promising and low dose aspirin use may be more cost-effective than other conception alternatives, further studies are necessary to determine clinical efficacy and if the benefits outweigh the risks in using low dose aspirin therapy solely for the improvement of pregnancy outcomes in the absence of pregnancy complications, such as preeclampsia. Currently, the American College of Obstetricians and Gynecologists does not recommend the use of low dose aspirin prophylaxis for the prevention of early pregnancy loss.1     

References

  1. Low-dose aspirin use during pregnancy. ACOG Committee Opinion. No. 743. American College of Obstetricians and Gynecologists. Obstet Gynecol 2018. 132:e44-52.
  2. Schisterman E, Silver R. and Lesher L, et al. Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial. The Lancet. Published Apr 2, 2014. doi: 10.1016/S0140-6736(14)60157-4.
  3. Naimi AI, Perkins NJ, Sjaarda LA, et al. The effect of preconception-initiated low-dose aspirin on human chorionic gonadotropin-detected pregnancy, pregnancy loss, and live birth. Ann Intern Med. Jan 26, 2021. doi: 10.7326/M20-046.