Pre-eclampsia research

Pre-eclampsia is a multi-system syndrome of pregnancy which is classically defined as the new onset of hypertension and proteinuria in the second half of pregnancy, and which resolves after childbirth. Pre-eclampsia affects 3-5% of first-time mothers and causes critical illness in about 1:250 pregnancies. Childbirth remains the only cure, but the decision to deliver needs to balance opposing risks to mother and infant. Immediate childbirth is good for maternal health, but the infant may suffer complications of prematurity. Conversely, delayed childbirth may be beneficial for fetal maturity but exposes the mother to the escalating risks of an unpredictable multi-system syndrome.

Risk factors for pre-eclampsia are the same as for cardiovascular disease (CVD) outside of pregnancy. Specifically, chronic hypertension, hyperlipidaemia, family history of CVD and older age. For this reason, women who have had pre-eclampsia are identified as at risk of cardiovascular disease in later life. However, the strongest risk factor for pre-eclampsia is a first pregnancy. Women who didn’t have pre-eclampsia in their first pregnancy are at very low risk of developing pre-eclampsia in a future pregnancy.

Around 12 weeks of pregnancy, the risk of pre-eclampsia can be refined by measures of blood flow to the uterus and of a placental factor (PAPP-A). Inadequate adaptation of maternal spiral arteries to deliver more blood to the growing placenta in early pregnancy, leads to relative placental ischaemia, reduced fetal growth and in vulnerable women, to pre-eclampsia.

Just as daily Aspirin 150mg reduces the risk of recurrent cardiovascular events outside of pregnancy, so too Aspirin 150mg taken each evening from the first trimester until 36 weeks’ gestation, reduces the risk of pre-term pre-eclampsia.

1. Through a large multi-centre clinical trial, we wish to discover whether statins, that protect against CVD outside of pregnancy, might also reduce the risk of pre-eclampsia during pregnancy.

The processes by which the placenta, (which is like the fetus, genetically half-maternal and half-paternal), invades the maternal uterine placental bed involves a delicate interaction of immunological and angiogenic factors. Placental derived growth factors involved in placental angiogenesis have altered expression in pre-eclampsia and fetal growth restriction, which are also involved in cardiovascular disease.

2. Dr Agata Ledwozyw PhD investigated the relationship between maternal immunosuppressive factors and placental angiogenic factors in women at risk of pre-eclampsia. 

An intriguing observation from outside of pregnancy is the phenomenon of remote ischaemic pre-conditioning (RIPC). When a cuff is placed around a limb to occlude blood flow for just a few minutes, it can have a beneficial effect on vascular blood flow elsewhere in the body.

3. Dr Tamara Kubba completed her PhD in 2022 having shown that women with pre-eclampsia have an improvement in their endothelial function 24 hours after 3 x 5-minute episodes of ischaemic precondition.

Tamara’s research now forms a great opportunity to investigate whether repeated RIPC might reduce the risk of pre-eclampsia in women at high-risk.