Cardiac and Immune Cell Function in Preeclampsia

NCT04508582 | Completed

• 1 other identifier: IRAS 281197
• Study Type: observational
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

Preeclampsia is a multi-system vascular disease which affects 2-5% of pregnancies. It is also a risk factor for the development of cardiovascular disease later in life and a number of functional and structural cardiac changes have been found in this population of patients. In mouse models disruption of a group of immune cells, neutrophils, has led to alteration of the placenta and offspring consistent with those seen in preeclampsia. These mice also have an abnormal cardiac function and structure (Nadkarni et al 2016). The investigators hypothesis that this may also occur in humans. This study aims to intimately link the maternal immunological and vascular components of cardiac dysfunction in women preeclampsia. The investigators hypothesise that in preeclampsia activated neutrophils may affect maternal immune system thus leading to myocardial injury and altered cardiac function. The study intends to identify the mechanisms by which the maternal immune system (focusing on neutrophil and T-cell subsets) affects cardiac function in women with preeclampsia. Specific aims to be addressed are: Aim 1: To correlate specific neutrophil phenotype(s) and function to cardiac function in women with preeclampsia during pregnancy Aim 2: To test whether specific activated neutrophil phenotype persists postpartum and whether this neutrophil phenotype correlates with cardiac function in women with preeclampsia postpartum The study population will comprise of 3 groups:

1. 1.Normotensive pregnant (\~33 patients)
2. 2.Pregnancy-induced hypertension (PIH; New-onset hypertension after 20 weeks without proteinuria; \~33 patients)
3. 3.Preeclampsia (\~34 patients)

Conditions

Preeclampsia; Hypertension; Pregnancy Induced Hypertension; Pregnancy Related; Cardiovascular Diseases; Cardiovascular Risk Factor; Heart Diseases

Keywords

Immunology, neutrophil, t-cell, placenta

Outcome Measures

Primary Outcomes (1)

• Immune function and cardiac function in preeclampsia

  To correlate maternal immune cell phenotype(s) and function to cardiac function in women with preeclampsia

  3 years

Secondary Outcomes (1)

• Postpartum immune function and cardiac function in preeclampsia

  3 years

Study Arms (3)

Women with Pre-eclampsia

De novo hypertension after 20 weeks gestation with evidence of end organ dysfunction.

Diagnostic Test: Cardiovascular magnetic resonance; Diagnostic Test: Echocardiography; Diagnostic Test: Blood test

Women with Pregnancy-induced hypertension

De novo hypertension after 20 weeks gestation without evidence of end organ dysfunction.

Diagnostic Test: Cardiovascular magnetic resonance; Diagnostic Test: Echocardiography; Diagnostic Test: Blood test

Healthy pregnant controls

Low risk women at booking as per NICE guidelines without any medical condition throughout pregnancy

Diagnostic Test: Cardiovascular magnetic resonance; Diagnostic Test: Echocardiography; Diagnostic Test: Blood test

Interventions

Cardiovascular magnetic resonance DIAGNOSTIC_TEST

Imaging of the heart with CMR, without use of contrast agents.

Also known as: CMR

Healthy pregnant controls; Women with Pre-eclampsia; Women with Pregnancy-induced hypertension

Echocardiography DIAGNOSTIC_TEST

Imaging of the heart with ultrasound.

Also known as: echo

Healthy pregnant controls; Women with Pre-eclampsia; Women with Pregnancy-induced hypertension

Blood test DIAGNOSTIC_TEST

Time- matched blood samples will be taken from patients to assess immune cell phenotype and function, paying particular attention to neutrophil and T-cell phenotype. Plasma samples will be collected for the analyses of cardiac specific factors (BNP, troponin) as well as measurement of steroid hormones (progesterone and oestradiol), and soluble inflammatory and anti-inflammatory mediators

Healthy pregnant controls; Women with Pre-eclampsia; Women with Pregnancy-induced hypertension

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients attending The Royal London Hospital for antenatal care

You may qualify if:

• Age \> 18 years
• Singleton pregnancy
• Live fetus at 11-13 weeks of gestation
• Informed, written consent

You may not qualify if:

• Unwilling or unable to give consent
• Pre-eclamptic women with pre-existing conditions

Sponsors & Collaborators

• Queen Mary University of London: lead
• British Heart Foundation: collaborator
• Barts & The London NHS Trust: collaborator

Study Sites (1)

Barts Health NHS Trust, The Royal London Hospital

London, E1 1BB, United Kingdom

Location

Related Publications (5)

• Nadkarni S, Smith J, Sferruzzi-Perri AN, Ledwozyw A, Kishore M, Haas R, Mauro C, Williams DJ, Farsky SH, Marelli-Berg FM, Perretti M. Neutrophils induce proangiogenic T cells with a regulatory phenotype in pregnancy. Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):E8415-E8424. doi: 10.1073/pnas.1611944114. Epub 2016 Dec 12.

  PMID: 27956610 BACKGROUND

• Herrey AS, Francis JM, Hughes M, Ntusi NAB. Cardiovascular magnetic resonance can be undertaken in pregnancy and guide clinical decision-making in this patient population. Eur Heart J Cardiovasc Imaging. 2019 Mar 1;20(3):291-297. doi: 10.1093/ehjci/jey162.

  PMID: 30462196 BACKGROUND

• Wenger NK. Recognizing pregnancy-associated cardiovascular risk factors. Am J Cardiol. 2014 Jan 15;113(2):406-9. doi: 10.1016/j.amjcard.2013.08.054. Epub 2013 Oct 6.

  PMID: 24188889 BACKGROUND

• Bellenger NG, Davies LC, Francis JM, Coats AJ, Pennell DJ. Reduction in sample size for studies of remodeling in heart failure by the use of cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2000;2(4):271-8. doi: 10.3109/10976640009148691.

  PMID: 11545126 BACKGROUND

• Grothues F, Smith GC, Moon JC, Bellenger NG, Collins P, Klein HU, Pennell DJ. Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol. 2002 Jul 1;90(1):29-34. doi: 10.1016/s0002-9149(02)02381-0.

  PMID: 12088775 BACKGROUND

MeSH Terms

Conditions

Pre-Eclampsia; Hypertension; Hypertension, Pregnancy-Induced; Cardiovascular Diseases; Heart Diseases

Interventions

Echocardiography; Caves; Hematologic Tests

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Geological Phenomena; Physical Phenomena; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Environment and Public Health; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Suchita Nadkarni

  Queen Mary University London

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2020
• First Posted: August 11, 2020
• Study Start: January 7, 2020
• Primary Completion: March 6, 2024
• Study Completion: March 6, 2024
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)