Preconception Low-Dose Aspirin Lowers Risk of Repeat Pregnancy Loss

By Lisa Rapaport

January 26, 2021

(Reuters Health) - Women with a history of pregnancy losses who initiate low-dose aspirin prior to subsequent pregnancies have a greater chance of live birth than counterparts who don't take aspirin, a new clinical trial suggests.

The trial included 1,227 women aged 18 to 40 years with a history of one or two pregnancy losses who were trying to conceive. They were randomized 1:1 to take either 81mg a day of aspirin or a placebo through six menstrual cycles, and, through week 36 of pregnancy if they conceived. All participants also took 400 mcg daily of folic acid.

"There is some evidence suggesting that the type of pregnancy loss we studied - women with one or two pregnancy losses - is the result of underlying inflammation," said lead study author Ashley Naimi, an associate professor of epidemiology at the Rollins School of Public Health at Emory University in Atlanta.

"Aspirin does have anti-inflammatory properties, and thus we sought to study whether it would lead to meaningful changes in the risk of pregnancy loss in this group of women," Naimi said by email.

Women in the study who took aspirin over the entire follow-up period were more likely to have an hCG-detected pregnancy (relative risk 1.12) and live birth (RR 1.33) and less likely to have a pregnancy loss (RR 0.69) than women on placebo over the entire follow-up period.

Per protocol analysis found that for every 100 women, taking low-dose aspirin at least five days a week would lead to 8 more pregnancies, 6 fewer pregnancy losses, and 15 more live births. The benefits of aspirin on pregnancy outcomes were reduced in women who took it less than four days per week.

Overall, 74% of women were adherent to treatment regimens for at least two days a week throughout the follow-up period, and 62% of participants took their aspirin or placebo pill at least six days a week, the study team reports in the Annals of Internal Medicine.

Adherence was not associated with side effects, including bleeding (RR 1.10) and nausea or vomiting (RR 0.99), the authors note. But several factors were associated with a subsequent reduction in adherence including bleeding in the previous week (RR 0.80), nausea or vomiting (RR 0.84), and hCG-detected pregnancy (RR 0.60).

One limitation of the study is that the participants were generally more educated and affluent than the general population. In addition, there were too few cases of rare adverse events like preterm birth and preeclampsia to evaluate the per protocol effect of aspirin, the researchers point out.

Though pregnancy loss is a complex set of events and mostly driven by genetic issues, data support the concept that a key to developing a healthy pregnancy is the development of a healthy placenta, said Dr. Matthew Hoffman, chair of Obstetrics & Gynecology and director of the Center for Women & Children's Health Research at ChristianaCare in Wilmington, Delaware.

"For the placenta to form it must invest itself in the lining of the uterus and divert the mother's blood supply to allow appropriate oxygenation and nutrition of the baby," Dr. Hoffman, who wasn't involved in the study, said by email.

"To do this there has to be complex remodeling that can be inhibited by either maternal inflammation or inappropriate clotting," Dr. Hoffman added. "Aspirin is well described to reduce both inflammation and inappropriate clotting."

SOURCE: Annals of Internal Medicine, online January 25, 2021.