Low-Dose Aspirin Use in Pregnancy and the Risk of Preterm Birth: A Swedish Register-Based Cohort Study

ABSTRACT Evidence has shown that low-dose aspirin can reduce the risk of preeclampsia in women with risk factors; more recent evidence has shown that aspirin may also be useful for the prevention of spontaneous preterm birth, even among women without risk factors for preeclampsia. However, there are fewer studies examining the effectiveness of low-dose aspirin in this population, and the studies that have been done have generally been statistically underpowered. This study was meant to address this limitation in a large population of women who had previously experienced preterm birth, assessing whether low-dose aspirin treatment was associated with a lower risk for preterm birth. This study was a register-based cohort study performed using several different Swedish registries. The sample included all women with a first and second singleton birth between 2006 and 2019 and with a preterm birth in the first pregnancy. The primary outcome assessed was preterm birth during the second pregnancy, and secondary outcomes included assessment of preterm birth by severity (moderate preterm was between 32 and 36 weeks' gestation, and severe preterm was less than 32 weeks' gestation) and onset (spontaneous or medically indicated). The variable of interest was low-dose aspirin exposure or at least 1 dispensed prescription of 75 to 160 mg aspirin. The analysis included 22,127 women with a preterm birth in their first pregnancy followed by a second recorded pregnancy. Of this sample, 3057 (14%) were prescribed low-dose aspirin during their second pregnancy. Recurrent preterm birth occurred in 3703 individuals, of whom 547 (15%) had used low-dose aspirin. After adjusting for confounding variables, the incidence of preterm birth was lower in those using low-dose aspirin, with a marginal relative risk (mRR) of 0.87 (95% confidence interval [CI], 0.77–0.99). However, there was no difference in risk for moderate or severe preterm birth (moderate group: mRR, 0.90 [95% CI, 0.78–1.03]; severe group: mRR, 0.75 [95% CI, 0.54–1.04]). In adjusted analyses, there were no statistically significant differences for either medically indicated or spontaneous preterm birth between individuals who used low-dose aspirin and those who did not. The study was limited by its retrospective nature. In addition, the authors acknowledge that a dispensed prescription for aspirin does not necessarily equate to consistent intake of low-dose aspirin throughout a pregnancy. In addition, the population for this study was limited to those who had already experienced a preterm birth, which could affect the generalizability of the results. Although limited differences were found, a small protective effect could not be ruled out, and randomized controlled trials to understand more fully the effect low-dose aspirin might have on preterm birth would be helpful. Further research should also focus on whether the benefits of aspirin use during pregnancy outweigh the potential risks, as well as what the lowest effective dose might be.