Aspirin for Optimising Pregnancy Outcome in Pregestational Diabetes The IRELAnD Study (Investigating the Role of Early Low-dose Aspirin in pre-existing Diabetes)

Background: The role of aspirin in reducing the risk of preeclampsia and improving perinatal outcome for pregnancies complicated by a diagnosis of pregestational diabetes mellitus has been investigated in few studies, which have revealed conflicting results. The arteriopathic characteristic of type I and type II diabetes, coupled with the pro-thrombotic nature of pregnancy, confer on aspirin a potential to ameliorate placental insufficiency-mediated morbidity frequently observed in these high risk pregnancies.

Objectives: To investigate the proportion of eligible women with pregestational diabetes who participated in the pilot phase of a randomised trial of low-dose aspirin therapy in pregnancy, compliance with the study protocol, as judged subjectively ( using self-reporting and pill count) and objectively ( using platelet aggregation testing) and analysis of all adverse events occurring after randomisation.

Study Design: A phase IV, multi-centre, randomised, open label trial investigating the use of aspirin for optimising pregnancy outcome in pregestational diabetes.

Materials and Methods: Participants were randomised to aspirin 75mg or no aspirin (controls). Aspirin (Nu-Seals®PA 943/6/1) was administered once daily by oral ingestion from the first trimester (initiated between 8+0 and 11+6 weeks) to 36 weeks’ gestational age for women with pregestational diabetes mellitus (type I or II). The patient population included women with a singleton pregnancy < 12 weeks of gestation, with type I or type II diabetes of at least six months duration prior to conception.

Results: A total of 47 patients with pregestational diabetes were screened and 31 were deemed eligible ( 66%). Twenty-four patients agreed to participate in the study and were recruited, 13 in the aspirin group and 11 in the non-aspirin group. The proportion that presented prior to the gestational age cut-off of 12 weeks was 45/47 (96%). The participation rate among eligible women was 77% (24/31). The most common criterion for ineligibility was miscarriage (17%) and only 2/47 (4%) of women screened were already taking aspirin. Compliance was measured subjectively using diary card and pill count and that was supported by subjective test for platelet aggregation using light transmission aggregometry. Therefore 11 out of 13 patients were deemed compliant as per compliance criteria (85%).

Conclusions: Platelet function testing was deemed to be informative for reflecting patient compliance with aspirin therapy, and for demonstrating non-response to aspirin among women judged to be compliant through other compliance-assessment methods. This pilot study is a precursor for a definitive large randomised controlled trial aiming to assess if low-dose aspirin initiated in the first trimester reduces obstetric complications related to placental dysfunction in the setting of pre-existing diabetes.