Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05856318 |
| Other study ID # |
POPPY |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 24, 2023 |
| Est. completion date |
December 2052 |
Study information
| Verified date |
April 2024 |
| Source |
Cambridge University Hospitals NHS Foundation Trust |
| Contact |
Heike Templin |
| Phone |
0044 1223 250874 |
| Email |
cuh.poppycctu[@]nhs.net |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Women who experience placental complications (syndromes) during pregnancy, such as
pre-eclampsia (high blood pressure and kidney problems), gestational hypertension (high blood
pressure during pregnancy) and fetal growth restriction (baby being small) have twice the
risk of developing heart disease and diabetes later in life, compared to women who have a
healthy pregnancy.
This study aims to assess risk factors for heart disease and diabetes in women who are
actively trying to conceive, before and during their pregnancy, and 9-12 months after
delivery of their baby, to see whether placental syndromes make a difference to their heart
health. This will allow us to understand, if, and how, placental syndromes increase the risk
of heart disease and diabetes, and, therefore, how best to reduce this risk and potentially
prevent placental syndromes in the future. The investigators will also recruit women who are
NOT planning pregnancy, as a control group.
Description:
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.
The study does not involve randomisation of participants; participant study arm will be
determined by individuals and their intention to conceive during the determined study period,
or not, in line with the inclusion/exclusion criteria.
A sufficient number of women will be recruited to the Pregnancy arm of the study to yield
1500 viable pregnancies (~3000 women, based on our feasibility data). Of these, the
investigators anticipate that 135 women will experience a placental syndrome, taking into
account attrition. A Non-Pregnancy study arm, women voluntarily planning not to conceive
during their involvement in the study; n~500 will also be recruited, to act as a control arm.
Individual participant study duration will last between approximately 12 and 33 months
dependent on study arm and timings around pregnancy and follow-up. For those in the
Non-Pregnancy arm study duration will last approximately 18 months, ending after the second
follow up visit. Study duration for those in the Pregnancy arm will vary, between 12 months
and 33 months, dependent on time from recruitment to pregnancy occurrence and/or occurrence
of placental syndrome; those (Pregnancy arm) participants who do not become pregnant will
experience a shorter study duration (12 months) and only a proportion of those experiencing a
healthy pregnancy will attend a final follow-up visit 18 months after delivery.
The output of this study will primarily aim to determine to what extent the association
between placental syndromes and maternal cardio-metabolic health post-pregnancy is explained
by pre-pregnancy subclinical cardiometabolic health. As secondary aims the study also aims to
determine which aspects of pre-pregnancy cardiometabolic health impact on women's
cardiovascular adaptation to pregnancy; whether haemodynamic maladaptation is an early
pregnancy biomarker for the later clinical manifestations of placental dysfunction; and
whether an uncomplicated pregnancy results in improved maternal cardiometabolic health
post-partum. Finally, the investigators will determine whether pre-pregnancy cardiovascular
risk factors affect the rate of early fetal loss (miscarriage), which will answer an
important clinical question, as recurrent miscarriage is associated with increased
cardiovascular risk.
