The Impact of Risk Factors on Aspirin's Efficacy for the Prevention of Preterm Birth


      In 2014, the USPTF recommended that women with two moderate risk factors for preeclampsia be considered for low dose aspirin (LDA) therapy to prevent preeclampsia but stated that “the evidence was less certain for this approach”. In 2020, the ASPIRIN trial showed that LDA decreased the rate of preeclampsia as well as preterm birth (PTB) in nulliparous women. We sought to determine if women with an additional risk factor beyond being nulliparous differentially benefitted from LDA for preventing PTB and hypertensive disorders of pregnancy (HDP) compared to women who did not have a second risk factor.

      Study Design

      This is a non-prespecified secondary analysis of the ASPIRIN trial that included randomized nulliparous women with singleton pregnancies from low-middle income countries to LDA (81mg) or placebos. Subjects were divided by the presence of at least one risk factor in addition to nulliparity; age > 35, obesity, and being African, versus those without an additional risk factor. The primary outcome was PTB. The secondary aim was to evaluate the implications of administering LDA to nulliparous women versus the current USPTF guidelines (two or more moderate risk factors) on PTB and HDP.


      11,558 nulliparous women from 6 different countries met inclusion criteria. Overall, 33.2% of women had an additional risk factor (Table 1). LDA equally reduced the risk of PTB among women with and without risk factors in addition to nulliparity (RR 0.95 vs. 0.85, p=0.35). LDA also decreased the risk of HDP, perinatal mortality, and PTB < 28 weeks in an equal manner among groups (Table 2). Women without a second risk factor were less likely to have a PTB< 34 weeks compared to women with two risk factors (P=0.041). By administering LDA to all nulliparous women rather than according to current USPTF guidelines, 86 PTBs were prevented in this cohort (Table 2).


      The risk reduction of PTB is equally demonstrated amongst women with only one moderate risk factor compared to those who have two. Professional societies should consider extending low dose aspirin to all nulliparous women.
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