A study for investigating effects on the brain, heart, clotting system during and after pregnancy and the pregnant woman's and partner's health in the postpartum period in pregnancies complicated by preeclampsia
| ISRCTN | ISRCTN13060768 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13060768 |
- Submission date
- 14/06/2020
- Registration date
- 27/07/2020
- Last edited
- 11/09/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Current plain English summary as of 04/01/2021:
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 60,000 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 health-related quality of life, general self-efficacy, anxiety and depression levels, childbirth experiences and breastfeeding, 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?
March 2018 to December 2032
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@obgyn.gu.se
2. Anna Karin Wikström (Uppsala University Hospital)
Anna-Karin.wikstrom@uu.se
_____
Previous 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 60,000 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
Contact information
Scientific
Diagnosvägen 14
Gothenburg
41650
Sweden
 ORCID ID |
0000-0001-5202-9428 |
|---|---|
| Phone | +46 707920780 |
| lina.bergman@obgyn.gu.se |
Scientific
Department of Women’s and children’s health
Akademiska sjukhuset
Uppsala
75195
Sweden
| Phone | +46 768498607 |
|---|---|
| Anna-Karin.wikstrom@uu.se |
Study information
| Study design | Prospective cohort study with control group |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | https://www.preeclampsiaresearch.com |
| 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 |
| Study acronym | GO PROVE and UPMOST |
| Study objectives | Women with preeclampsia demonstrate subclinical impaired organ function including endothelial dysfunction, cardiac dysfunction, and cerebral dysfunction. |
| Ethics approval(s) | 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 |
| Health condition(s) or problem(s) studied | 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 |
| Primary outcome measure | Current primary outcome measures as of 11/09/2024: 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 the 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 7. Cardiovascular indicators in women with preeclampsia and normotensive pregnancies at time of inclusion, at three and 12 months after birth 8. Complications related to preeclampsia at the time of enrolment, before delivery and before discharge from the hospital. Previous primary outcome measures: 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 | Current secondary outcome measures as of 04/01/2021: 1. Patient reported outcomes are measured by General Self-Efficacy scale, (GES) Hospital Anxiety and Depression Scale, (HADS), Edinburgh Postnatal Depression Scale, (EPDS) EuroQol—5 Dimensions (EQ-5D), EuroQol- Visual Analogue Scale (EQ-VAS), Post Traumatic Stress Disorder Checklist for DSM-5 (PCL-5) at diagnosis of preeclampsia and compared with healthy controls. The GES, HADS, EPDS, EQ-5D, EQ-VAS, Childbirth experience questionnaire,2 (CEC2), PCL-5 and the Breastfeeding self-efficacy scale short form (BSE) are re-evaluated 8-12 weeks after birth. The GES, HADS, EPDS, EQ-5D, EQ-VAS, CEQ2, PCL-5 and BES are again re-evaluated 1 year after birth. 2. Qualitative interviews will be performed six months after birth. The aims of the qualitative research in the project are to describe the women's and their partner’s lifeworld experiences of severe preeclampsia during pregnancy, childbirth and postnatal care. The target number of participants for the qualitative study are 15 to 20 women and partners. Open-ended questions will be used to collect the data. The women will be asked to describe their experiences of severe preeclampsia during pregnancy, childbirth and postnatal care. The interviews will last about 60 minutes and will be audio-recorded. All interviews will be transcribed verbatim. The data will be analyzed using thematic or phenomenological analysis. _____ Previous 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 study start date | 01/03/2018 |
| Completion date | 31/12/2032 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 200 women with preeclampsia and 100 women with normotensive pregnancies |
| Key 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 |
| Key exclusion criteria | Current participant exclusion criteria as of 10/01/2022: 1. Unable to give written informed consent 2. Magnetic resonance imaging (MRI) contraindications, including claustrophobia, for MR group only 3. Diabetes Mellitus before or during pregnancy, pre-existing cardiovascular, renal, or cerebral disease, or pre-existing hypertension for special investigations including MRI, echocardiography, cerebral doppler measurements, and cognitive function assessment Previous 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 |
| Date of first enrolment | 01/05/2019 |
| Date of final enrolment | 31/12/2025 |
Locations
Countries of recruitment
- Sweden
Study participating centres
Diagnosvägen 15
Gothenburg
41650
Sweden
Akademiska sjukhuset
Uppsala
75185
Sweden
Sponsor information
Hospital/treatment centre
Department of obstetrics and gynecology
Diagnosvägen 14
Gothenburg
41650
Sweden
| Phone | +46 313421000 |
|---|---|
| pernilla.dahm-kahler@vgregion.se | |
| Website | https://www.sahlgrenska.se/en/ |
"ROR" |
https://ror.org/04vgqjj36 |
Hospital/treatment centre
Department for women's and children's health
Akademiska sjukhuset
Uppsala
75185
Sweden
| Phone | 004618-611 00 00 |
|---|---|
| anna-karin.wikstrom@kbh.uu.se | |
| Website | https://www.akademiska.se/en/ |
|
"ROR" |
https://ror.org/01apvbh93 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Märta Lundqvists Foundation
- Location
- Sweden
Private sector organisation / Associations and societies (private and public)
- Alternative name(s)
- Göteborg Medical Society, Gothenburg Medical Society, Medical Society of Göteborg
- Location
- Sweden
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Jane and Dan Olssons Foundation
- Location
- Sweden
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Brain Foundation
- Location
- Sweden
Government organisation / Local government
- Alternative name(s)
- Region Västra Götaland, Västra Götaland Regional Council, Västra Götaland region, Västra Götalandsregiona, VGR
- Location
- Sweden
Results and Publications
| Intention to publish date | 01/08/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| 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 1 year will be finished in June 2022 and after that additional publications will be prepared. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 24/11/2021 | 26/11/2021 | Yes | No | |
| Results article | 18/04/2023 | 17/08/2023 | Yes | No |
Editorial Notes
11/09/2024: The following changes were made:
1. The study contacts were updated.
2. The primary outcome measures were changed.
3. The sponsor contact was updated.
17/08/2023: Publication reference added.
17/03/2023: The intention to publish date was changed from 01/03/2023 to 01/08/2023.
13/12/2022:The following changes were made to the trial record:
1. The recruitment end date was changed from 01/12/2023 to 31/12/2025.
2. The overall trial end date was changed from 01/06/2024 to 31/12/2032.
3. The intention to publish date was changed from 06/06/2022 to 01/03/2023.
24/06/2022: The contact confirmed the record is up to date.
10/01/2022: The participant exclusion criteria have been updated.
26/11/2021: Publication reference added.
14/09/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/06/2022 to 01/12/2023.
2. The overall end date was changed from 01/01/2023 to 01/06/2024.
3. The intention to publish date was changed from 31/12/2022 to 06/06/2022.
4. The plain English summary was updated to reflect these changes.
04/01/2021: The following changes were made to the trial record:
1. The secondary outcome measures were changed.
2. The link to the participant information sheet was added.
3. The plain English summary was updated to reflect these changes.
17/06/2020: Trial’s existence confirmed by the Ethics Review Authority, Uppsala
