Elsevier

The Lancet

Volume 384, Issue 9937, 5–11 July 2014, Pages 29-36
The Lancet

Articles
Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial

https://doi.org/10.1016/S0140-6736(14)60157-4Get rights and content

Summary

Background

Preconception-initiated low-dose aspirin might positively affect pregnancy outcomes, but this possibility has not been adequately assessed. Our aim was to investigate whether low-dose aspirin improved livebirth rates in women with one to two previous pregnancy losses.

Methods

In this multicentre, block-randomised, double-blind, placebo-controlled trial, women aged 18–40 years who were attempting to become pregnant were recruited from four medical centres in the USA. Participants were stratified by eligibility criteria—the original stratum was restricted to women with one loss at less than 20 weeks' gestation during the previous year, whereas the expanded stratum included women with one to two previous losses, with no restrictions on gestational age or time of loss. Women were block-randomised by centre and eligibility stratum in a 1:1 ratio. Preconception-initiated daily low-dose aspirin (81 mg per day) plus folic acid was compared with placebo plus folic acid for up to six menstrual cycles; for women who conceived, study treatment continued until 36 weeks' gestation. Participants, trial staff, and investigators were masked to the assigned treatment. The primary outcome was livebirth rate, which was analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00467363.

Findings

Overall, 1228 women were recruited and randomly assigned between June 15, 2007, and July 15, 2011, 1078 of whom completed the trial and were included in the analysis (535 in the low-dose aspirin group and 543 in the placebo group). 309 (58%) women in the low-dose aspirin group had livebirths, compared with 286 (53%) in the placebo group (p=0·0984; absolute difference in livebirth rate 5·09% [95% CI −0·84 to 11·02]). Pregnancy loss occurred in 68 (13%) women in the low-dose aspirin group, compared with 65 (12%) women in the placebo group (p=0·7812). In the original stratum, 151 (62%) of 242 women in the low-dose aspirin group had livebirths, compared with 133 (53%) of 250 in the placebo group (p=0·0446; absolute difference in livebirth rate 9·20% [0·51 to 17·89]). In the expanded stratum, 158 (54%) of 293 women in the low-dose aspirin group and 153 (52%) of 293 in the placebo group had livebirths (p=0·7406; absolute difference in livebirth rate 1·71% [−6·37 to 9·79]). Major adverse events were similar between treatment groups. Low-dose aspirin was associated with increased vaginal bleeding, but this adverse event was not associated with pregnancy loss.

Interpretation

Preconception-initiated low-dose aspirin was not significantly associated with livebirth or pregnancy loss in women with one to two previous losses. However, higher livebirth rates were seen in women with a single documented loss at less than 20 weeks' gestation during the previous year. Low-dose aspirin is not recommended for the prevention of pregnancy loss.

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (US National Institutes of Health).

Introduction

Pregnancy loss is a common adverse event, estimated to occur in up to 30% of conceptions.1 Women who have had a pregnancy loss are at increased risk of having a subsequent loss and other adverse pregnancy events.2 The pathophysiological mechanisms that lead to adverse pregnancy outcomes are not fully understood, although decreased blood flow and increased inflammation can have important roles.3 Since aspirin can improve blood flow and reduce inflammation in reproductive organs,4 it might be useful for the improvement of pregnancy outcomes.

Post-conception use of low-dose aspirin has been studied extensively with respect to recurrent pregnancy loss (usually defined as at least two losses) and is often prescribed to prevent pregnancy loss, despite its unproven efficacy.5, 6, 7, 8, 9, 10, 11, 12, 13, 14 Preconception use of low-dose aspirin improves endometrial growth and vascularisation in women undergoing in-vitro fertilisation (IVF).15 Thus, preconception-initiated low-dose aspirin might positively affect downstream pregnancy outcomes during a crucial treatment window. However, this possibility has not been extensively assessed.

The aim of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was to assess whether daily preconception-initiated treatment with low-dose aspirin improves the livebirth rate compared with placebo in women with one to two previous pregnancy losses.

Section snippets

Study design and participants

EAGeR was a multicentre, block-randomised, double-blind, placebo-controlled clinical trial in four university medical centres in the USA. Inclusion and exclusion criteria have been detailed elsewhere.16 Briefly, initial inclusion criteria (applied for recruitment of the original stratum) included women aged 18–40 years who were actively trying to conceive and who had a history of only one previous pregnancy loss at less than 20 weeks' gestation during the previous year; up to one previous

Results

1228 women were recruited and randomly assigned in blocks (by centre and eligibility stratum) between June 15, 2007, and July 15, 2011. 1078 participants completed the study and were included in the analysis (figure 1). Treatment groups were similar with respect to the assessed demographic and baseline characteristics (table 1).

Among all trial participants, the treatment groups did not differ significantly with respect to the primary outcome of livebirth rate, although a significant difference

Discussion

Overall, preconception-initiated treatment with low-dose aspirin was not significantly associated with livebirth rates, pregnancy loss, or other pregnancy complications. To our knowledge, this is the first study to show that preconception-initiated low-dose aspirin does not decrease the risk of pregnancy loss in women without a history of recurrent pregnancy loss (ie, only one to two previous losses). Thus, our data do not support the general use of low-dose aspirin to decrease the risk of

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