The impact of risk factors on aspirin's efficacy for the prevention of preterm birth

Abstract

Background: The ASPIRIN Trial was a landmark study that demonstrated a reduction in preterm birth (PTB) and hypertensive disorders of pregnancy (HDP) in nulliparous women who received low-dose aspirin (LDA). All women in the study had at least one moderate-risk factor for preeclampsia, nulliparity. Unlike current United States Preventative Service Task Force (USPSTF) guidelines, which recommend LDA for two or more moderate-risk factors, women in this study were randomized to receive LDA regardless of the presence or absence of an additional risk factor. Objective: To compare how low-dose aspirin (LDA) differentially benefits nulliparous women with and without additional preeclampsia risk factors for the prevention of preterm birth (PTB) and hypertensive disorders of pregnancy (HDP). Study design: This is a non-pre-specified secondary analysis of the ASPIRIN trial that randomized nulliparous women with singleton pregnancies from six low-middle income countries to receive LDA or placebo. Our primary exposure was having an additional preeclampsia risk-factor beyond nulliparity. Our primary outcome was PTB before 37 weeks and our secondary outcomes included PTB before 34 weeks, PTB before 28 weeks, HDP, and perinatal mortality. Results: Among 11,558 nulliparous women who met the inclusion criteria, 66.8% had no additional risk factors. LDA similarly reduced the risk of PTB <37 weeks in women with and without additional risk factors (RR 0.75 vs. 0.85, p=0.35). Additionally for our secondary outcomes, LDA similarly reduced the risk of PTB <28 weeks, HDP, and perinatal mortality in women with and without additional risk factors. The reduction of PTB <34 weeks with LDA was significantly greater in women without additional risk factors compared to those with an additional risk factor (RR 0.69 vs. 1.04, p=0.04). Conclusion: LDA's ability to prevent PTB, HDP, and perinatal mortality is similar in nulliparous women with and without additional risk factors. Professional societies should consider recommending LDA to all nulliparous women.