Condition category
Pregnancy and Childbirth
Date applied
14/06/2020
Date assigned
27/07/2020
Last edited
27/07/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background And study aims
Preeclampsia is one of the most serious complications of pregnancy affecting between 3% and 8 % of pregnancies worldwide. Preeclampsia leads to over 60000 maternal deaths annually and for every preeclampsia related death, there are probably 50 to 100 other women who experience significant morbidity.

Preeclampsia is a multi-system disorder involving the blood vessels, kidneys, liver, brain, lungs, and heart of the mother, and the fetus and placenta. In severe cases, preeclampsia might cause heart failure, kidney failure, blood clotting disorders, seizures (eclampsia), stroke, and restriction of the fetus's ability to grow.

The causes of preeclampsia are not completely known but it is suggested that it is based on problems with the function of the placenta. Factors associated with pre-existing problems with the function of the blood vessels, such as diabetes, cardiac disease, and obesity, can also predisposing mothers to preeclampsia. The only cure is delivery.

Currently, there is a lack of evidence on how to assess organ failure due to severe preeclampsia. There are only a few tests available to evaluate the function of the liver, kidney, and blood clotting. Currently, there are no systems for predicting or assessing the function of the brain, heart, and blood vessels.

A better understanding of the causes and underlying changes that take place leading to organ failure would allow the development of more accurate prediction and assessment tools which would allow for faster, more accurate, and/or preventative treatment in these cases. This would lead to better outcomes for the mother and the child.

The overall aim of this study is to set up the Preeclampsia project and biobank at Sahlgrenska University Hospital, Gothenburg, Sweden and Uppsala University Hospital, Uppsala, Sweden, to facilitate laboratory-based research on preeclampsia and to contribute to a safer and more patient-centered management of women with preeclampsia. Specifically, this study aims to follow a group of women with preeclampsia, and women without. Blood samples, brain and heart scans, cognitive function tests, and measurements of blood flow, blood pressure and blood clotting will be collected. These will be compared to the outcomes of these pregnant women to see which of these measurements serve as an accurate marker for worse outcomes, to allow for better future treatment.

There is also a lack of data regarding women’s and their partners experiences of preeclampsia during pregnancy and postpartum in a Swedish setting. Interviews with women with preeclampsia from other settings have described preeclampsia as a fearful, powerless, painful and/or life-threatening event and inadequate clinical management and care, although many women felt lucky to survive. By increasing the knowledge about how women and their partners experience preeclampsia and the consequences regarding self-efficacy, breastfeeding and anxiety, improvements could be made to personalized management and when following up after a pregnancy complicated by preeclampsia.

Who can participate?
Women over 18 years of age, either diagnosed with preeclampsia or with healthy pregnancies (to serve as a comparison).

What does the study involve?
The study will collect characteristics and lifestyle data, blood samples, brain and heart scans, cognitive function tests, and measurements of blood flow, blood pressure and blood clotting, as well as information on the women and their partner's perspective of preeclampsia, rating of their health and wellbeing, and childbirth experiences, through interviews. This information will be collected during the pregnancy and 8-12 weeks and one year after the delivery has taken place.

What are the possible benefits and risks of participating?
This study is an observational study and so the risks associated with participating are low. Beyond the additional measurements taken, participants will be receiving standard care. After a blood sample is drawn the participant might have a small bruise. When the participants are examined in the MRI camera or undergoing heart ultrasound, there might be unexpected findings. If this happens they will be referred to a specialist for further management. The results from the study will be processed on a group level and individual results of the investigations will not be revealed for the individual research participant.

Where is the study run from?
Sahlgrenska University Hospital, Gothenburg and Uppsala University Hospital, Uppsala (Sweden).

When is the study starting and how long is it expected to run for?
From March 2018 to January 2023. Recruitment started in May 2019 at Sahlgrenska and in December 2019 at Uppsala.

Who is funding the study?
The Swedish Brain Fund, Gothenburg Medical Society, Jane and Dan Olsson's foundation, Märta Lundqvist foundation, and Regional Research Funds, Västra Götaland (Sweden).

Who is the main contact?
1. Lina Bergman (Sahlgrenska University Hospital)
lina.bergman.2@gu.se
2. Anna Karin Wikström (Uppsala University Hospital)
anna-karin.wikstrom@kbh.uu.se

Trial website

https://www.preeclampsiaresearch.com

Contact information

Type

Scientific

Primary contact

Dr Lina Bergman

ORCID ID

http://orcid.org/0000-0001-5202-9428

Contact details

Diagnosvägen 15
Gothenburg
41650
Sweden
+46 707920780
lina.bergman.2@gu.se

Type

Scientific

Additional contact

Prof Anna-Karin Wikström

ORCID ID

Contact details

Department of Women’s and children’s health
Akademiska sjukhuset
Uppsala
75195
Sweden
+46 768498607
Anna-karin.wiksrom@kbh.uu.se

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

Nil known

Study information

Scientific title

Investigating organ complications in preeclampsia during and after pregnancy and the pregnant woman's and partner's health in the postpartum period: An observational cohort study involving the GO PROVE - Gothenburg Preeclampsia Obstetric Adverse Events and UPMOST - Uppsala Pregnancy Complication Study

Acronym

GO PROVE and UPMOST

Study hypothesis

Women with preeclampsia demonstrate subclinical impaired organ function including endothelial dysfunction, cardiac dysfunction, and cerebral dysfunction.

Ethics approval

1. Approved 10/12/2018, Regional ethics committee Gothenburg (Box 2110, 75002 Uppsala, Sweden; +46 104750800; registrator@etikprovning.se), ref: 955-18
2. Approved 27/02/2019, Etikprövningsmyndigheten (Box 2110, 75002 Uppsala, Sweden; +46 104750800; registrator@etikprovning.se), ref: 2019-00309

Study design

Prospective cohort study with control group

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Organ impairment in preeclampsia

Intervention

Women are included at the time of diagnosis of preeclampsia or at the corresponding gestational age for women with normotensive pregnancies. At inclusion, blood samples are drawn and women are asked to answer questions about background characteristics and current signs and symptoms of preeclampsia. Additional information is retrieved from the medical charts. Subgroups of women are then asked to participate in organ specific evaluations including ultrasound of the heart, measurement of peripheral vascular resistance, cognitive function scoring, cerebral blood flow measurement through doppler technique and magnetic resonance imaging of the brain. At delivery, additional biological samples are drawn and for some deliveries, placental biopsies are collected. All biological samples are stored in a biobank provided by the respective hospital. Women are followed up after delivery with questionnaires about their health and the experience of childbirth together with their partner. At one year postpartum, organ specific evaluations are repeated together with an additional blood sample and some background characteristics and symptom scores are repeated.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Organ dysfunction is measured using the following at inclusion in the study and after delivery:
1. Cognitive function is measured by magnetic resonance imaging (resting state) and a series of validated objective tests such as WAIS, SRB1, and Deary test, and, in addition, a subjective test called cognitive failure questionnaire
2. Cerebral blood flow regulation is measured by doppler technique and magnetic resonance imaging
3. Cerebral biomarkers are measured in cerebrospinal fluid and plasma by ELISA and SIMOA technique
4. Cardiac biomarkers are measured in plasma by automated laboratory based instruments used in clinical care.
5. Coagulation is measured by thrombelastogram - ROTEM and Multiplate
6. Cardiac function is measured by transthoracic echocardiography

Secondary outcome measures

Patient reported outcomes are measured by General Self-Efficacy scale, Hospital Anxiety and Depression Scale, Edinburgh Postnatal Depression Scale, E-Q-5D visual analogue scale, Post Traumatic Stress Disorder Checklist for DSM-5, Childbirth experience questionnaire, and the Breastfeeding self-efficacy scale short form after delivery

Overall trial start date

01/03/2018

Overall trial end date

01/01/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Preeclampsia cohort:
1. Primiparous and parous pregnant women
2. Aged ≥18 years
3. Diagnosis of preeclampsia after gestational week 20

Control cohort:
1. Primiparous and parous women
2. Aged ≥18 years
3. Healthy pregnancies matched for gestational age

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

200 women with preeclampsia and 100 women with normotensive pregnancies

Participant exclusion criteria

1. Unable to give written informed consent
2. Pre-existing hypertension
3. Diabetes Mellitus before or during pregnancy
4. Pre-existing cardiovascular, renal, or cerebral disease
5. Magnetic resonance imaging (MRI) contraindications, including claustrophobia, for MR group only

Recruitment start date

01/05/2019

Recruitment end date

01/06/2022

Locations

Countries of recruitment

Sweden

Trial participating centre

Sahlgrenska Academy
Department of obstetrics and gynecology Diagnosvägen 15
Gothenburg
41650
Sweden

Trial participating centre

Uppsala University
Department of women's and children's health Akademiska sjukhuset
Uppsala
75185
Sweden

Sponsor information

Organisation

Sahlgrenska University Hospital

Sponsor details

Department of obstetrics and gynecology
Diagnosvägen 15
Gothenburg
41650
Sweden
+46 313421000
nils.crona@vgregion.se

Sponsor type

Hospital/treatment centre

Website

https://www.sahlgrenska.se/en/

Organisation

Uppsala University Hospital

Sponsor details

Department for women's and children's health
Akademiska sjukhuset
Uppsala
75185
Sweden
004618-611 00 00
anna-karin.wikstrom@kbh.uu.se

Sponsor type

Hospital/treatment centre

Website

https://www.akademiska.se/en/

Funders

Funder type

Charity

Funder name

Märta Lundqvists Stiftelse

Alternative name(s)

Märta Lundqvists Foundation

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both publically funded and privately funded)

Location

Sweden

Funder name

Göteborgs Läkaresällskap

Alternative name(s)

Göteborg Medical Society, Gothenburg Medical Society, Medical Society of Göteborg

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

Sweden

Funder name

Jane och Dan Olssons Stiftelse

Alternative name(s)

Jane and Dan Olssons Foundation

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both publically funded and privately funded)

Location

Sweden

Funder name

Hjärnfonden

Alternative name(s)

Brain Foundation

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both publically funded and privately funded)

Location

Sweden

Funder name

Västra Götalandsregionen

Alternative name(s)

Region Västra Götaland

Funding Body Type

government organisation

Funding Body Subtype

Local government

Location

Sweden

Results and Publications

Publication and dissemination plan

In 2020, a protocol will be published. The first phase of inclusions is estimated to be finished in June 2021. After this, the data will be analyzed and the first publications will be planned. The follow up at one year will be finished in June 2022 and after that additional publications will be prepared.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

31/12/2022

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

17/06/2020: Trial’s existence confirmed by the Ethics Review Authority, Uppsala . .