Description

The "Antenatal Myo-inositol supplementation in pre-existing diabetes to promote normal neonatal outcomes (AMulet)" pilot study aims to inform the design of a future double-blind randomised controlled trial which can assess the benefits of myo-inositol supplementation in pregnant women with T2DM. Despite provision of the international standard of care, pregnancies complicated by diabetes remain at high risk of adverse perinatal and neonatal outcomes. Offspring exposed to maternal diabetes in-utero also face increased risks of obesity and cardiometabolic diseases later in life. Myo-inositol supplementation has been trialled in pregnancy for the prevention and treatment of gestational diabetes, as well as in non-pregnant adults with T2DM, where improvements in glycaemic regulation and reduced insulin resistance have been observed with supplementation. However, myo-inositol supplementation has not yet been studied in pregnancies with T2DM. The primary aim of the AMulet trial would be to assess whether myo-inositol supplementation in pregnancies with T2DM can support normal fetal size and neonatal wellbeing. The present AMulet pilot study will assess the feasibility and acceptability of conducting such a trial and, additionally, seek to investigate the biological mechanisms through which myo-inositol may influence maternal and offspring health outcomes.

This pilot will recruit 182 pregnant women with T2DM between 12-16 weeks' gestation into a double-blind placebo-controlled randomized study. All participants will be randomly assigned to either an intervention group (receiving supplementation of myo-inositol with folic acid) or a control group (receiving supplementation with folic acid only). Supplementation will be in the form of similar looking capsules to be taken twice daily from recruitment until delivery.

Data and samples will be collected longitudinally across three study visits during pregnancy that will be arranged to coincide with routine antenatal clinic visits where possible, and a fourth visit soon after delivery. Additionally, there will be two re-supply visits and a post-delivery videoconference call. Other study data comprising antenatal, peripartum, fetal and neonatal outcomes will be extracted from medical records during pregnancy and post-delivery to assess the primary and secondary outcomes.

The binary composite primary outcome of normal fetal/neonatal size and wellbeing will be assessed by analyses on an intention-to-treat basis. Secondary outcomes, comprising maternity and other infant outcomes, will be assessed and quantified in terms of relative risk or mean differences between study groups. Adverse events, participant feedback as well as mechanistic understanding will be obtained.

This structured approach will inform the design of a future RCT by gathering data on feasibility and acceptability, identifying potential issues in protocols and data collection tools, and facilitating sample size calculations for the main trial which will aim to support the optimization of maternal and offspring health outcomes in pregnancies complicated by pre-existing T2DM.