Early Prediction of Preeclampsia Using arteriaL Stiffness in High-risk prEgnancies (PULSE)

Early Prediction of Preeclampsia Using arteriaL Stiffness in High-risk prEgnancies; a Multinational Study (PULSE)

Despite advances in obstetric care, preeclampsia (PE) remains the leading cause of maternal death and disability in both developed and developing countries, contributing to over 70,000 maternal and 500,000 fetal deaths annually worldwide. PULSE was designed using a preventative medicine approach, focusing on improving early detection of PE as opposed to managing symptoms after onset. The study aims to uncover the earliest possible signs of PE using a combination of novel clinical tools and established diagnostic techniques to better identify, track, and manage high risk pregnant women. Specifically, PULSE will be examining the incorporation of a non-invasive test for the measurement of arterial stiffness, which has been shown to be predictive of hypertensive disorders. This test, in combination with a wide range of blood biomarkers, detailed ultrasound imaging, and a comprehensive battery of physical and mental health questionnaires, represents the largest, most comprehensive preventative PE study to date. The results of this work has the potential to revolutionize the way PE and other hypertensive disorders of pregnancy are managed and treated and can serve to inform the design of future preventative clinical research studies.

Study Overview

• Status: Recruiting
• Conditions: Pre-Eclampsia; Arterial Stiffness; High Risk Pregnancy
• Intervention / Treatment: Diagnostic test: Arterial Stiffness and Wave Reflection

Detailed Description

Existing predictive tools for preeclampsia (PE), including clinical characteristics, blood pressure, blood biomarkers, and uterine artery Doppler indices, have, at best, moderate predictive properties. While maternal symptoms often resolve with the delivery of the placenta, the burden of PE extends beyond pregnancy; afflicted women are at 3.1-fold increased odds of developing hypertension and 2.3-fold increased odds for cardiovascular disease later in life compared to women with uncomplicated pregnancies. Placental pathogenic changes associated with PE occur weeks to months before clinical manifestations develop, presenting a window of opportunity to identify early those women who will develop PE. The goal of the study investigators is to capitalize on this window and develop strategies for early prediction of PE.

As a composite measure of vascular health, measurement of arterial stiffness and wave reflection could represent a promising non-invasive tool for PE prediction. This multi-national 5-year observational prospective study aims to recruit 2400 participants across 8 sites in Canada, the US, and the UK. Participants will undergo 2 assessments, one in the first trimester (10 - 13 weeks gestation) and one in the second trimester (18 - 21 weeks gestation), which involve vascular measurements (arterial stiffness, blood pressure), blood sample collection, psychosocial and demographic questionnaires, and Uterine Artery Doppler imaging (only at second visit). Post-natal outcome measurements will be collected via medical charts for each participant 6-8 weeks post-partum. The primary objective of the study is to determine if, and to what extent, arterial stiffness and wave reflection parameters improve early prediction of PE beyond that achieved by currently available predictors in high-risk pregnancies.

• Study Type: Observational
• Enrollment (Anticipated): 2400

Contacts and Locations

• Study Contact: Name: Helena Papacostas, PhD; Phone Number: 42478 514 934-1934; Email: helena.papacostasquintanilla@mail.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Recruiting
      • Royal Victoria Hospital
      • Principal Investigator: Stella S Daskalopoulou, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Pregnant women at high risk of developing preeclampsia

Description

Inclusion Criteria:

• Singleton pregnancy
• Presence of at least 1 high-risk factor or 2 moderate-risk factors for pre-eclampsia

Exclusion Criteria:

• >14 weeks gestation
• Multiple pregnancy
• History of heart disease, stroke, or peripheral arterial disease
• Infectious diseases/conditions, such as Hepatitis B/C, HIV, and COVID19

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis of pre-eclampsia	According to the Society of Obstetricians and Gynaecologists (SOGC) guidelines, upon the presence of 2 criteria: 1) hypertension; chronic (pre-dating pregnancy or diagnosed <20 weeks' gestation) or de novo/gestational (diagnosed ≥20 weeks') hypertension along with 2) de novo end-organ dysfunction	up to 6 weeks post-partum (after delivery)

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: University of British Columbia; University of Iowa; University of North Carolina, Chapel Hill; Lawson Health Research Institute; Laval University; University of Glasgow; Université de Montréal
• Investigators: Principal Investigator: Stella S Daskalopoulou, MD, PhD, Research Institute of the McGill University Health Centre

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: March 1, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Actual): June 9, 2022
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Eclampsia; Pre-Eclampsia
• Other Study ID Numbers: MP-37-6854

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No