Metformin Impact on Maternal and Infant Cardiometabolic Health

Increasing numbers of older, obese women with poor cardiometabolic health (dyslipidaemia, hyperglycaemia, hypertension) are embarking on pregnancy.

One in six of these high-risk pregnancies are complicated by an indicated preterm birth due to fetal growth restriction (FGR) or fetal overgrowth and/or maternal complications including gestational diabetes and pre-eclampsia.

The cumulative cost of neonatal care, childhood and adult disease in individuals born preterm has been estimated at 1-3 billion pa in the UK.

Older age, obesity, dyslipidaemia and hypertension are major risk factors for placental disease leading to FGR and pre-eclampsia.

Conversely, hyperglycaemia is associated with fetal overgrowth and is therefore treated with hypoglycaemic agents such as metformin during pregnancy.

In women with hyperglycaemia and concurrent risk factors for placental disease, the impact of metformin on placental function, fetal growth, and postnatal outcomes is not known.

To address this evidence gap, I will perform an RCT which will incorporate a novel method of tracking fetal growth and investigate the impact of metformin on maternal and infant metabolic health at 12 months.

The impact of metformin on gene expression and placental function will be assessed in placentas from women exposed (or not) to metformin.

In the wider group of women with poor cardiometabolic health, I will map maternal disease biomarkers and fetal growth to molecular placental disease subtypes who have developed a range of pregnancy complications.

The goals of this work are to improve pregnancy outcomes in women with poor cardiometabolic health by, (1) producing evidence to personalise the prescription of metformin (2) refining current diagnostic criteria to better reflect placental disease molecular subtypes, (3) understanding the associations between cardiometabolic health and placental disease such that drugs to treat hyperglycaemia, hypertension, dyslipidaemia can be tested in the right women.