Does Adherence Modify Low-Dose Aspirin Effects in Pregnancy? Post Hoc Analysis From a Multi-Centre Trial

Objective: To evaluate if the effect of low-dose aspirin (LDA) commenced between 6 and 13 weeks of gestational age (GA) on preterm delivery (PTD) is modified by total exposure. Design: Post hoc analysis of a randomized controlled trial. Setting: Hospitals in low-resource settings in Africa, Asia and Latin America. Population: Outcomes were obtained for 11 908/11943 women at 6 0/7 to 13 6/7 weeks' GA randomized. Methods: Women received prepackaged two-week medication allotments. Adherence was assessed by pill counts every 2 weeks. Estimated relative risk and 95% confidence interval data for each outcome at each GA of treatment initiation weeks were obtained by fitting a Poisson model to each outcome, adjusting for site, treatment arm and GA at treatment initiation. Main Outcomes Measures: The primary outcome was PTD. Secondary outcomes included PTD < 34 weeks and perinatal mortality including analysis by region. Results: The median gestational age at treatment initiation was 10.1 weeks (IQR 8.6, 12.0). 85.5% of the mothers had over 90% adherence to treatment. For each 1 week increase of GA at treatment initiation, the treatment risk ratio did not change for PTD [RR 0.97 (95% CI, 0.93, 1.02)], PTD < 34 weeks [< 0.98 (0.89, 1.07)] or perinatal mortality [1.04 (0.96, 1.12)], with no evidence of effect modification. For each 5% increase in adherence, the treatment risk ratio did not change for PTD [1.01 (0.99, 1.04)], PTD < 34 weeks [< 0.99 (0.95, 1.03)] or perinatal mortality [1.02 (0.98, 1.06)], indicating no meaningful interaction with adherence. There was no effect modification by region. Conclusions: This analysis shows that the results of PTD, PTD < 34 weeks and perinatal mortality were not dependent on the timing of the initiation or adherence to treatment. Trial Registration: ClinicalTrials.gov identifier: NCT02409680.