Post hoc findings show more live births, fewer pregnancy losses compared to placebo

Regular use of low-dose aspirin prior to conception and during pregnancy was associated with improved pregnancy outcomes among women with a history of miscarriage in a post hoc, per protocol analysis of data from the randomized EAGeR clinical trial.

Among women who had experienced one or two prior pregnancy losses, taking a low dose aspirin (LDA) five to seven days a week, compared to placebo, was associated with eight more human chorionic gonadotropin-directed pregnancies, 15 more live births, and six fewer pregnancy losses for every 100 women enrolled in the trial.

Published online January 25 in Annals of Internal Medicine, the post hoc analysis of the Effects of Aspirin on Gestation and Reproduction trial, which enrolled just over 1,200 women treated at four university medical centers in the United States, found that use of low dose aspirin at least four times per week before conception through gestation week 36 was associated with a 30% increase in live births.

Original results from the trial, published in 2014, demonstrated a 10% increase in live births among the LDA group relative to placebo but showed no significant impact on pregnancy loss.

“These earlier findings were subject to complications often affecting intention-to-treat analyses, most notably nonadherence to assigned treatment, which may be influenced by common pregnancy symptoms,” wrote post hoc analysis lead researcher Ashley Naimi, PhD, of Emory University in Atlanta, and colleagues.

The researchers wrote that the post hoc findings from EAGeR trial support “the need to focus on improving adherence to daily low dose aspirin to maximize the efficacy on pregnancy outcomes.”

“Our study is the first to our knowledge to shed light on the optimal timing of low dose aspirin therapy, suggesting maximum benefits by initiating treatment before and early in pregnancy,” Naimi and colleagues wrote. “Indeed, the first stages of pregnancy, before a woman’s usual first encounter with prenatal care, may be an early window for preventing pregnancy loss and improving the chances of live birth.”

Recently published results from the larger ASPIRIN randomized trial, involving 12,000 women in 6 countries, also found lower rates of preterm birth, perinatal mortality, and fetal loss, as well as fewer hypertensive events during pregnancy, among women treated with low dose aspirin compared to those in the placebo arm of the study.

“In light of this recent trial, as well as the present study, evidence is growing for the positive effects of daily low dose aspirin use on pregnancy outcomes,” the researchers wrote.

In the EAGeR post hoc analysis, adherence to LDA or placebo was assessed by measuring pill bottle weights at regular intervals during follow-up, and the study’s primary outcomes included human chorionic gonadotropin (hCG)-detected pregnancy, pregnancy losses, and live births.

Adherence was defined as use of LDA or placebo on at least five of seven consecutive days, and changes were evaluated visually with a locally weighed scatter plot smoother. Baseline characteristics were compared between women defined as adherent for 70% or more of their person-time versus those adherent for less than 70% of their person-time.

During the first week of follow-up, 96% of women were adherent to the study protocol. Among women who conceived, adherence dropped from an average of 74% before conception to 64% after conception. A total of 54% of the study participants adhered to the protocol for 70% or more of their person-time in the trial.

Among the main findings:

  • Per protocol effect estimates suggested that taking aspirin over the entire follow-up resulted in more hCG-detected pregnancies (RR, 1.12 [95% CI, 1.02-1.23]), fewer pregnancy losses (RR, 0.69 [95% CI, 0.50-0.95]), and more live births (RR, 1.33 [95% CI, 1.08-1.64]) compared with taking placebo throughout follow-up.
  • In additive terms, these estimates amount to 8 more hCG-detected pregnancies (95% CI, 4.64-10.96 pregnancies), 6 fewer pregnancy losses (95% CI, −12.00 to −0.20 losses), and 15 more live births (95% CI, 7.65-21.15 births) for every 100 women in the study.
  • The effects of aspirin on live birth and pregnancy loss were observed when aspirin was taken early enough after conception. This trend was particularly notable for pregnancy loss.

Sensitivity analyses suggested that missing adherence, bleeding, and nausea data were unlikely to explain the differences observed between the per protocol and intention-to-treat effects.

“Following the recent call for per protocol analyses of randomized trials, our results suggest that preconception LDA use by women with previous pregnancy loss may improve pregnancy outcomes,” the researchers wrote.

“Specifically, early adoption of LDA with maximal daily adherence promoted pregnancy and live birth and protected against pregnancy loss in women trying to become pregnant after a history of pregnancy loss. Efforts geared toward improving daily adherence to LDA may yield improvements in aspirin’s effectiveness on reproductive outcomes for women trying to conceive.”

  1. Regular use of low-dose aspirin prior to conception and during pregnancy was associated with improved pregnancy outcomes among women with a history of miscarriage in a post hoc per protocol analysis of data from the randomized EAGeR clinical trial.

  2. In post hoc analysis of the EAGeR trial, use of low dose aspirin at least four times per week before conception through gestation week 36 was associated with a 30% increase in live births.

Salynn Boyles, Contributing Writer, BreakingMED™

Funding for this research was provided by grants from the National Institutes of Health.

Lead researcher Ashley Naimi and other main researchers reported no relevant conflicts related to this study.

Cat ID: 41

Topic ID: 83,41,730,41,192,925