Cardiometabolic Health in First Time Pregnancy

NCT ID: NCT05856318

Last Updated: 2024-04-09

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 3500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-05-24
• Study Completion Date: 2052-12-31

Brief 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.

Detailed 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.

Conditions

Cardiometabolic Health; Pregnancy Related; Diabetes; Placental; Syndrome, Dysfunction; Heart Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Pregnancy ~3000 participants

Actively planning to conceive within approximately 12 months of study registration. No previous pregnancies.

No interventions assigned to this group

Non-Pregnancy ~500 participants

Not planning to conceive within 18 months of study registration. No previous pregnancies.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

To be included in the trial the participant must:

• Nulliparous (no previous pregnancy beyond 20 weeks' gestation)
• Actively considering pregnancy within approximately 12 months
• Aged between 18 and 45 years
• Ability to consent and willing to participate

To be included in the trial the participant must:

• Nulliparous (no previous pregnancy beyond 20 weeks' gestation)
• Not planning to conceive during next 18 months
• Aged between 18 and 45 years
• Ability to consent and willing to participate

Exclusion Criteria

The presence of any of the following will preclude participant inclusion:

• Currently pregnant
• Established infertility
• Planning or actively using fertility treatments (e.g. IVF, ICSI, FET, IUI)
• Assigned male sex at birth
• Autoimmune disease (e.g. rheumatoid arthritis, lupus)
• Thrombophilia
• Type 1 diabetes
• Known advanced chronic kidney disease (stages 4-5)
• Malignant hypertension
• Clinically manifest CVD (e.g. previous myocardial infarction, stroke)
• Active cancer/being treated for cancer currently (other than skin cancer)
• Any other condition preventing full participation in the study

The presence of any of the following will preclude participant inclusion:

• Currently pregnant
• Planning or actively using fertility treatments (e.g. IVF, ICSI, FET, IUI)
• Assigned male sex at birth
• Autoimmune disease (e.g. rheumatoid arthritis, lupus)
• Thrombophilia
• Type 1 diabetes
• Known advanced chronic kidney disease (stages 4-5)
• Malignant hypertension
• Clinically manifest CVD (e.g. previous myocardial infarction, stroke)
• Active cancer/being treated for cancer currently (other than skin cancer)
• Any other condition preventing full participation in the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Cambridge

OTHER

Sponsor Role: collaborator

University of Bristol

OTHER

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: collaborator

King's College London

OTHER

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: collaborator

St George's, University of London

OTHER

Sponsor Role: collaborator

University of Glasgow

OTHER

Sponsor Role: collaborator

Wellcome Trust

OTHER

Sponsor Role: collaborator

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Dr Ian B Wilkinson

Head of Division, Division of Experimental Medicine & Immunotherapeutics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ian Wilkinson, MD

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospitals NHS Foundation Trust

Locations

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Site Status: RECRUITING

NHS Greater Glasgow and Clyde

Glasgow, , United Kingdom

Site Status: RECRUITING

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status: NOT_YET_RECRUITING

King's College Hospital NHS Foundation Trust

London, , United Kingdom

Site Status: NOT_YET_RECRUITING

St George's University Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status: NOT_YET_RECRUITING

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status: RECRUITING

Manchester University NHS Foundation Trust

Manchester, , United Kingdom

Site Status: NOT_YET_RECRUITING

Countries

United Kingdom

Central Contacts

Heike Templin

Role: CONTACT

cuh.poppycctu@nhs.net

0044 1223 250874

Facility Contacts

Site PI: Carmel McEniery

Role: primary

Site PI: Christian Delles

Role: primary

Site PI: David Williams

Role: primary

Site PI: Lucilla Poston

Role: primary

Site PI: Asma Khalil

Role: primary

Site PI: Christoph Lees

Role: primary

Laura Ormesher

Role: primary

Other Identifiers

POPPY

Identifier Type: -

Identifier Source: org_study_id