Investigating the Role of Early Low Dose Aspirin in Diabetes

Objective: Aspirin is widely advocated for obstetric risk modification, yet trials rarely include pre-gestational diabetes (PGDM). The aim of this study was to assess the effect of aspirin on adverse perinatal outcome (APO) in pregnancies complicated by PGDM.

Methods: We conducted a double-blinded, placebo-controlled RCT at 6 university-affiliated centres. Type 1 or 2 DM patients were randomly allocated to aspirin 150mg daily or placebo from 11-14 weeks’ gestation until 36 weeks. The primary outcome was a composite measure of APO (PET,FGR, PTB <34 weeks’ gestation or perinatal mortality). Secondary endpoints were composite maternal morbidity, composite neonatal morbidity and glycaemic control. A sample size of 328 was required for 35% reduction in the primary outcome with 85% power (2-sided type I error 0.05), however the trial was stopped for recruitment challenges within the study timeframe. Data were analysed using SAS 9.4®. Treatment groups were compared using t-tests, chi-square tests and Repeated Measures analysis for longitudinal data.

Results: 191 patients were eligible; 134 were enrolled (67 randomized to aspirin and 67 placebo). Baseline characteristics were similar between groups. Treatment compliance was very high (97% for aspirin, 94% for placebo). The composite measure of APO did not differ between groups (25% aspirin vs 21% placebo, p = 0.796). The aspirin group required significantly lower insulin dosing throughout pregnancy. On average, there was 86% increase in insulin requirements in the placebo group, compared to 57%increase for aspirin-treated patients over the same gestational period (p = 0.002, Fig 1). Lower serial HbA1c levels were observed with aspirin than placebo, although not statistically significant.

Conclusion: In this double-blinded, placebo-controlled RCT, aspirin did not reduce the risk of APO. Compared to placebo, aspirin-treated patients required significantly less insulin throughout pregnancy, indicating a beneficial effect of aspirin on DM control. Aspirin may exert a plausibly placenta-mediated effect on PGDM that is not limited to its antithrombotic properties.