Preconception Low-Dose Aspirin and Pregnancy Outcomes

Abstract

Women with a history of pregnancy loss are at increased risk of a subsequent loss and other adverse pregnancy outcomes. The pathophysiologic mechanisms responsible for pregnancy loss are unclear. It is believed that decreased blood flow and increased inflammation may play an important role in pregnancy loss and other adverse pregnancy events. Because aspirin can improve blood flow and reduce inflammation in reproductive organs, it has been hypothesized that giving aspirin to women attempting to conceive might improve pregnancy outcomes. Many health care providers prescribe low-dose preconception aspirin therapy for women who have had a pregnancy loss and who would like to get pregnant again. However, the efficacy of this treatment is unproven. The aim of the EAGeR (Effects of Aspirin in Gestation and Reproduction) trial was to determine whether preconception treatment with low-dose aspirin would reduce the risk of pregnancy loss in women with 1 or 2 previous pregnancy losses. The study was a multicenter, block-randomized, double-blind, placebo-controlled trial conducted in women aged 18 to 40 years with a history of pregnancy loss who were attempting to become pregnant. Participants were recruited from 4 university medical centers in the United States. The original stratum included women who had 1 loss at less than 20 weeks’ gestation during the previous year. Because of slow enrollment, the stratum was expanded to include women with 1 to 2 previous losses without any restrictions on gestational age or time of loss. Prior to conception, women were randomized to receive either low-dose aspirin (81 mg/d) plus folic acid or placebo plus folic acid for up to 6 menstrual cycles. Treatment was continued until 36 weeks’ gestation for women who became pregnant. Trial staff, investigators, and participants were masked to the assigned treatment. The primary study outcome was live birth rate. Data were analyzed according to intention to treat. Of the 1228 women randomly assigned between 2007 and 2011, 1078 (88%) completed the trial and were included in the analysis (535 in the aspirin group and 543 in the placebo group). A total of 309 women (58%) in the low-dose aspirin group became pregnant and later gave birth, compared with 286 (53%) in the placebo group (absolute difference, 5.09%; 95% confidence interval [CI], −0.84% to 11.02%; P = 0.10). Pregnancy loss occurred in 68 (13%) of the women in the aspirin group and in 65 (12%) of the women in the placebo group (P = 0.78). Among women in the original stratum, who had a single recent pregnancy loss, live births occurred in 62% (151/242) of women in the aspirin group, compared with 53% (133/250) of those in the placebo group; the absolute difference was 9.2%, with a 95% CI of 0.51% to 17.89%, P = 0. 045. In the expanded stratum, however, no significant difference between treatment groups occurred in live birth rates (54% [158/293] in the low-dose aspirin group vs 52% [153/293] in the placebo group; absolute difference, 1.71%; 95% CI, −6.37% to 9.79%; P = 0.74). Major adverse events in both treatment groups were similar. Low-dose aspirin was associated with increased vaginal bleeding, but this was not associated with pregnancy loss. The use of preconception-initiated low-dose aspirin to prevent recurrent pregnancy loss is not supported by these data. Further studies are needed to investigate the apparent increased birth rate among women who had a single well-documented loss at less than 20 weeks’ gestation during the previous year.