Preconception to pOst-partum Study of Cardiometabolic Health in Primigravid PregnancY

Pre-eclampsia (PE), gestational hypertension (GH) and fetal growth restriction (FGR) share a common aetiology in that they arise from complex interactions between defective placentation, trophoblast dysfunction and the maternal cardiovascular and other systems. These placental syndromes affect approximately one in five nulliparous women and are a leading cause of maternal and child morbidity. Although usually considered self-limiting, and cured by delivery, placental syndromes are associated with an increased risk of maternal hypertension, diabetes and cardiovascular disease (CVD) in later life. Indeed, as summarised by NICE, PE is associated with a 4-fold increased risk of hypertension, and 2-fold excess risk of ischaemic heart disease and stroke. Similarly, Danish National Registry data show that women with GH have a 6-fold risk of subsequent hypertension, a 3-fold risk of diabetes and a 2-fold risk of CVD; similar to that reported for PE.

Whilst these risks have most impact in later life, they are evident almost immediately - women who develop hypertension in pregnancy have a 12 to 25-fold risk of developing permanent hypertension in the year after giving birth, compared to women with a normotensive pregnancy. Approximately one third of women in their 40s who had a hypertensive pregnancy, develop hypertension over the subsequent decade, compared with only 11% who had a normotensive pregnancy. Precursors of CVD (i.e. pre-clinical phenotypes) are also apparent in the early post-partum period in women who experience a placental syndrome. Increased aortic stiffness, elevated carotid intima-media thickness (cIMT) and left ventricular dysfunction have all been reported in women with previous PE/GH and FGR.

Whether placental syndromes simply "unmask" women with pre-existing (pre-conception) poor cardiometabolic health, or cause later maternal diabetes and CVD, remains unknown. If the former is correct, then improving cardiometabolic health in young women prior to conception could be key to reducing the incidence of placental syndromes. Conversely, if placental syndromes lead to CVD and diabetes independently of established cardiometabolic risk factors (e.g. by causing end organ damage), a focus on CVD/diabetes prevention in this high-risk group of women is likely to reduce the burden of these diseases. To date, studies with pre-conception measures of cardiometabolic risk factors are few, modest in patient number and detail, and have yielded conflicting results.

The study will test definitively, the hypothesis that placental syndromes adversely affect cardiometabolic health post-partum, independently of women's pre-conception cardiometabolic health. To do this, an observational, prospective study of healthy, nulliparous women, recruited pre-pregnancy will be undertaken.

Recruitment of the study population will utilise local advertisements and networks, social media and charitable organisations involved in pregnancy research. The study focus is nulliparous women to maximize the occurrence of placental syndromes (risk is highest in first pregnancies), and to remove any confounding effect of previous pregnancies.