Aspirin, Birthweight, and Large-For-Gestational-Age Neonates: A Secondary Analysis of the ASPRE Trial

Abstract

Objective: To investigate the effects of aspirin on the distribution of birthweight and its impact on the rates of large-for-gestational-age (LGA) neonates.

Design: Secondary analysis of the Combined Multimarker Screening and Randomised Patient Treatment with Aspirin for Evidence-based Preeclampsia Prevention (ASPRE) trial.

Setting: Thirteen hospitals in England, Spain, Belgium, Greece, Italy and Israel.

Population: Participants of the ASPRE trial at increased risk of preterm pre-eclampsia (PE) who had a live birth.

Methods: We compared the birthweight distributions and the rates of LGA neonates between the trial groups. Analyses were stratified according to the presence of pre-existing diabetes mellitus and the development of PE, and logistic regression was used to investigate independent predictors of LGA neonates with birthweight above the 90th percentile.

Main outcome measures: Birthweight distribution and rates of LGA neonates.

Results: Among 1571 singleton, live neonates (777 from the aspirin group and 794 from the placebo group), aspirin was associated with a shift in birthweight from < 2500 to 2500-4000 g, and birthweight percentile from < 25th to 25th-75th percentiles, with no significant increase in LGA neonates (5.5% vs. 6.2%, p = 0.667). Logistic regression demonstrated a significant interaction between treatment and pre-existing diabetes (p-value 0.034), and a positive association between maternal weight and LGA neonates (adjusted odds ratio 1.040, 95% confidence interval 1.030-1.051, p < 0.001).

Conclusions: Aspirin use is associated with increased birthweight without increasing the rate of LGA neonates. Among women with pre-existing diabetes, aspirin may be associated with a higher rate of LGA neonates, warranting further investigation.

Keywords: ASPRE trial; LGA; aspirin; birthweight; first trimester; large‐for‐gestational‐age; macrosomia; prevention; pre‐eclampsia; pre‐existing diabetes.