Low-dose aspirin, smoking status, and the risk of spontaneous preterm birth.

OBJECTIVE: We evaluated the relationship between aspirin supplementation and perinatal outcomes for potential effect modification by smoking status.

STUDY DESIGN: A secondary analysis of two multicenter trials for which prophylactic aspirin supplementation was given to either low- or high-risk women for prevention of preeclampsia (PE). We examined the effect of aspirin by smoking status using the Breslow-Day test. Primary outcomes for this analysis were PE and preterm birth (PTB) < 37 weeks. We also examined PTB subtypes, small for gestational age (SGA), and neonatal intensive care unit (NICU) admission.

RESULTS: The effect of prenatal aspirin on the risk of PE did not differ by smoking status (relative risk [RR] 95% confidence interval [CI] for smokers; RR 95% CI for nonsmokers) in low-risk (Breslow-Day p = 0.32) or high-risk (RR 95% CI for smokers; RR 95% CI for nonsmokers) (Breslow-Day p = 0.58) women. Among women at low risk for PE, the effect of aspirin supplementation on PTB was not different for nonsmokers (RR 1.00 [95% CI 0.8-1.3]) or smokers (RR 0.80 [95% CI 0.4-1.7]), (Breslow-Day p = 0.54). Aspirin was protective for PTB in nonsmokers (RR 0.80 [95% CI 0.7-0.9]), but not in smokers (RR 1.1 [95% CI 0.9-1.4]) in the high-risk group (Breslow-Day p = 0.03). Aspirin was also associated with increased spontaneous and early PTB and NICU admission in smokers and not nonsmokers in the high-risk group only.

CONCLUSION: Aspirin supplementation was associated with worse outcomes related to preterm birth in smokers in a high-risk but not low-risk cohort.