Aspirin delays preterm birth in pregnancies at high risk for preterm pre-eclampsia: evidence from randomized clinical trial in Asia

Abstract

OBJECTIVES: To investigate the impact of aspirin administration on the incidence of preterm birth, according to the type of delivery and gestational age at preterm birth, and to examine the hypothesis that aspirin delays preterm delivery. METHODS: This was a secondary analysis of a multicenter stepped-wedge cluster randomized trial of a first-trimester screen-and-prevent strategy for preterm pre-eclampsia (PE), which included 18 maternity/diagnostic units in 10 regions across Asia between 1 August 2019 and 28 February 2022. Women deemed to be at high risk for preterm PE according to a Bayes' theorem-based triple test, i.e. those with an adjusted risk for preterm PE of ≥ 1 in 100, received low-dose aspirin from < 16 weeks until 36 weeks' gestation. Outcome measures were the incidence of early preterm birth (24 + 0 to 31 + 6 weeks' gestation) and late preterm birth (32 + 0 to 36 + 6 weeks). The treatment effect of aspirin on the rate of preterm birth, stratified by gestational age at birth, type of delivery and presence of pregnancy complications, was estimated by computing the relative risks (RR) between the aspirin and non-aspirin groups with their 95% CIs. A shift model was designed to evaluate the effect of aspirin on preterm birth, based on the hypothesis that aspirin delays a preterm birth to a more advanced gestational age. RESULTS: In the randomized trial, 42 897/48 647 women accepted screening for preterm PE. Following exclusions, 10 294 and 27 965 women were included in the non-intervention and intervention phases, respectively. Of the 4688 women at high risk for preterm PE, 2909 (62.05%) received aspirin in the trial. Aspirin was associated with a 42% reduction in the risk of early preterm birth (adjusted relative risk (aRR), 0.577 (95% CI, 0.380-0.852)), and there was a significant upward trend in the rate of late preterm birth accordingly (test for trend, P < 0.01). Similar findings were observed for iatrogenic preterm birth and pregnancies with a small-for-gestational-age neonate. Additionally, aspirin was associated with a 60% reduction in the risk of iatrogenic early preterm birth in pregnancies with PE (aRR, 0.398 (95% CI, 0.192-0.788)). However, aspirin did not have a significant effect on iatrogenic late preterm birth in pregnancies with PE. Aspirin significantly delayed early preterm birth, with the effect decreasing by 0.26 (95% credibility interval, -0.40 to -0.05) weeks for each week of advancing gestation. At 24 weeks, aspirin delayed delivery by 3.63 weeks, while at 37 weeks, the delay was only 0.25 weeks. CONCLUSIONS: This secondary explanatory analysis found that early administration of aspirin could effectively reduce the risk of early preterm birth in women at high risk for preterm PE. While the reasons for preterm birth are often multifactorial, this study provides greater insight into the relationship between aspirin and different types of preterm birth at different gestational ages. Our findings support the hypothesis that aspirin helps to prevent preterm birth by delaying the timing of delivery, with a greater impact observed for deliveries that would have occurred at an earlier gestational age had aspirin not been administered. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.