Low-dose aspirin and preterm birth: a randomized controlled trial.

OBJECTIVE

To evaluate the association between low-dose aspirin initiated before conception and the risk of preterm birth.

METHODS

This was a secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial. Women with a history of pregnancy loss (original stratum: one loss less than 20 weeks of gestation during the previous year; expanded stratum: one or two losses with no restrictions on timing or gestational age of the losses) were randomized to either daily low-dose aspirin (81 mg, n=615) and folic acid or folic acid alone (placebo; n=613). Preterm birth was compared between groups using intent-to-treat analysis.

RESULTS

Preterm birth rates were 4.1% (22/535 low-dose aspirin) and 5.7% (31/543 placebo) (relative risk [RR] 0.72, 95% confidence interval [CI] 0.42-1.23); spontaneous preterm birth rates were 1.1% (6/535 low-dose aspirin) and 2.2% (12/543 placebo) (RR 0.51, 95% CI 0.19-1.34); medically indicated preterm birth rates were 2.6% (14/535 low-dose aspirin) and 2.9% (16/543 placebo) (RR 0.89, 95% CI 0.44-1.80). After restriction to confirmed pregnancies using inverse probability weighting, preterm birth rates were 5.7% and 9.0% (RR 0.63, 95% CI 0.37-1.09) and spontaneous preterm birth rates were 1.4% and 3.2% (RR 0.44, 95% CI 0.17-1.18). In confirmed pregnancies in the original stratum, preterm birth occurred in 3.8% and 9.7% of the low-dose aspirin and placebo groups, respectively (RR 0.39, 95% CI 0.16-0.94).

CONCLUSION

Preconception low-dose aspirin was not significantly associated with the overall rate of preterm birth. Although the study was underpowered for this secondary analysis, numeric trends in favor of benefit, particularly in the women with a recent, single early pregnancy loss, warrant further investigation.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov, www.clinicaltrials.gov, NCT00467363.