Low-dose aspirin is associated with reduced spontaneous preterm birth in nulliparous women

Preterm birth is one of the leading causes of perinatal morbidity and mortality. Clinical data suggest that low-dose aspirin may decrease the rate of overall preterm birth, but investigators have speculated that this is likely due to a decrease in medically indicated preterm birth through its effect on the incidence of preeclampsia and other placental disease. We hypothesized that low-dose aspirin may also have an impact on the mechanism of spontaneous preterm labor.

Our objective was to determine whether low-dose aspirin reduces the rate of spontaneous preterm birth in nulliparous women without medical comorbidities.

This is a secondary analysis of a randomized, placebo-controlled trial of low-dose aspirin for the prevention of preeclampsia in healthy, low-risk, nulliparous women. Low-risk women were defined by the absence of hypertension, renal disease, diabetes, other endocrine disorders, seizures, heart disease, or collagen vascular disease. Our study was limited to singleton, nonanomalous gestations. Women were eligible if they had prior pregnancy terminations but not prior spontaneous pregnancy loss <20 weeks. Current pregnancies that resulted in a loss or termination <20 weeks or antepartum stillbirth or had missing follow-up data were excluded. The treatment intervention was 60 mg of aspirin, initiated at 13-25 weeks' gestation or matching placebo. The primary outcome was spontaneous preterm birth <34 weeks' gestation. Secondary outcomes included spontaneous preterm birth <37 weeks and overall preterm birth <37 and <34 weeks. Baseline demographics and primary and secondary outcomes were compared between treatment groups. A logistic regression model was used to adjust for confounders related to spontaneous preterm birth.

Of 2543 included women, 1262 (49.6%) received low-dose aspirin and 1281 (50.4%) placebo. Baseline characteristics were similar between groups, except for marital status. The rate of spontaneous preterm birth <34 weeks was 1.03% (n = 13) and 2.34% (n = 30) in the low-dose aspirin and placebo group, respectively (odds ratio, 0.43, 95% confidence interval, 0.26-0.84). Additionally, the rate of spontaneous preterm birth <37 weeks was 6.58% (n = 83) in the low-dose aspirin group and 7.03% (n = 90) in the placebo group (odds ratio, 0.97, 95% confidence interval, 0.71-1.33), and the rate of overall preterm birth <37 weeks was 7.84% (n = 99) in the low-dose aspirin group and 8.2% (n = 105) in the placebo group (odds ratio, 0.97, 95% confidence interval, 0.72-1.31). After adjustment for variables that were clinically relevant or statistically significant, including body mass index, race, tobacco use, marital status, and education level, there was a significant reduction in spontaneous preterm birth <34 weeks in the low-dose aspirin group (adjusted odds ratio, 0.46, 95% confidence interval, 0.23-0.89). The rates of overall preterm birth <34 and <37 weeks and spontaneous preterm birth <37 weeks were similar in women who received low-dose aspirin compared with placebo.

Low-dose aspirin is associated with a substantial decrease in spontaneous preterm birth <34 weeks in healthy nulliparous women without comorbidities. These findings suggest a new therapeutic option for preterm birth prevention that requires further study.