Pre-EclampsiaPEARLSNCT05500989
PlacEntal Acute Atherosis RefLecting Subclinical Atherosclerosis
An observational study of Pre-Eclampsia and HELLP Syndrome, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Pregnancy is considered a cardiovascular (CV) stress test, and complicated pregnancies are associated with an increased risk for cardiovascular disease (CVD) later in life. Moreover, it is known that often the pregnancy induced CV adaptation does not resolve completely after a short postpartum (PP) period and it is… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pre-Eclampsia, HELLP Syndrome, Intrauterine Growth Restriction
- How many people
- 226 participants
- Where
- 1 siteNetherlands
- Study dates
- Nov 2016to Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study population consists of pregnant women who either develop pre-eclampsia or have a normotensive pregnancy. For the shorter follow up period, participants are recruited from the (labour) ward and from the outpatient clinic in MUMC+. Participants are also recruited externally from other hospitals if they contact us with an interest in this study. For the longer follow up period, case participants took part in an earlier study and agreed to be contacted for future studies. These participants were recruited through a letter with information about the study. Control participants were recruited when they contacted us with interest in this study.
Who may be able to join
- Women aged ≥ 18 years
- Controls: Women with an uncomplicated pregnancy at the moment of inclusion (i.e no foetal or maternal placental complications, such as pregnancy induced hypertension, preeclampsia or HELLP-syndrome, or small for gestational birth infancies)
- Cases: Women diagnosed with a preeclamptic pregnancy at the moment of inclusion
Who cannot join
- Women who do not want to be informed about the results of the tests, or women who do not want their general practitioner and specialist(s) to be informed about the test results
- Allergy or intolerance to glyceryl trinitrate, betablockers or iodinated contrast media.
- Controls: Pre-existing chronic hypertension treated with antihypertensive medication or autoimmune disorder.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Maastricht University Medical Center (MUMC+)
Maastricht, 6202 AZ
Gwyneth Jansen, MBBS, 043 - 38774145 ext. 0031, gwyneth.jansen@mumc.nl
Marc Spaanderman, MD, PhD, 043 - 38774774 ext. 0031, marc.spaanderman@mumc.nl
About this study
Pregnancy is considered a cardiovascular (CV) stress test, and complicated pregnancies are associated with an increased risk for cardiovascular disease (CVD) later in life. Moreover, it is known that often the pregnancy induced CV adaptation does not resolve completely after a short postpartum (PP) period and it is not clear whether these induced changes will resolve over a longer period of time (i.e. in the upcoming months/years after delivery).
Understanding the cardiac adaptation during pregnancy and the reversal process in the postpartum period, as well as the factors that influence this these processes, may provide us not only insight in this mechanism, but may help us in identifying factors that may be target points for modification.
Read the detailed description
The main goal of this study is to determine whether the presence of placental acute atherosis after pre-eclamptic pregnancies compared to normotensive pregnancies is related to the future development of subclinical atherosclerosis in the coronary arteries.
This information can be used to improve our prediction of which women have an increased risk of future cardiovascular disease and which women do not. This will allow us to better inform our postpartum population of the potential future risks of cardiovascular disease and could allow the timely implementation of primary prevention strategies. The investigators would also like to determine which blood biomarkers can also predict cardiovascular disease at an earlier stage as well as determining which of these biomarkers are present in hypertensive pregnancies.
This study is a longitudinal cohort study including women with pre-eclamptic pregnancies and normotensive pregnancies. Cases consist of women with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (early and late PE, with or without intra uterine growth restriction (IUGR)), whereas controls are women with an uncomplicated pregnancy.
The placenta is collected after the delivery and undergoes histopathological analyses. There are two follow up periods whereby one group of women is followed up 6 to 36 months postpartum and another group is followed up 10 to 20 years postpartum. At the follow up (6 to 36 months or 10 to 20 years), women attend for a series of measurements including CT angiography, transthoracic echocardiography, Flow medicated dilatation (FMD) and carotid intima media thickness (IMT) measurement. The visit will last approximately 5 hours in the Maastricht University Medical Centre (MUMC+). The only invasive procedure is a venepuncture where 75 ml blood will be extracted. The only unfavourable side effect can be a small hematoma (rare). Clinically, participants will be advised based on their risk profile following standard "cardiovascular (CV) risk management". Glycocalyx measurements and a FibroScan may be performed. Experience shows that this investigation is not experienced as uncomfortable. Also, 3 liters of exhaled air may be collected for volatile organic compound (VOCs) analysis. All measurements will be performed or supervised by an experienced researcher. These investigations are already approved previously in other Medical Ethics Committee (METC) applications (CMO-nr: 2008/226; 2009/004; 10-2-066). The other measurements (questionnaires, blood pressure (BP), weight measurement, urine collection, glycocalyx measurement, FibroScan and exhaled air collection) do not cause any discomfort for the patient aside from the time that it takes. On the other hand, potential health improvement and early detection of CV risk profiles and initiation of already existing effective prevention strategies that improve lifestyle are important benefits.
- Medical subject headings
- Pre-Eclampsia, HELLP Syndrome, Fetal Growth Retardation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Short track controls | Controls are women (18 years or older) with an uncomplicated pregnancy (i.e no foetal or maternal placental complications, such as pregnancy induced hypertension, preeclampsia or HELLP-syndrome, or small for gestational birth infancies). Follow up roughly 18 months postpartum. | |
| Short track early PE with IUGR | These cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. | |
| Short track early PE without IUGR | Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. | |
| Short track late PE with IUGR | Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. | |
| Short track late PE without IUGR | Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. | |
| Long term follow up track cases | Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relationship between placental acute atherosis and subclinical coronary atherosclerosis at 1 year postpartum
Acute atherosis will be defined as the presence of subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as either present or absent.
Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.
The incidence of acute atherosis will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 1 year postpartum.
Measured: 1 year
Relationship between placental acute atherosis and subclinical coronary atherosclerosis at 15 years postpartum
Acute atherosis will be defined as the presence of subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as either present or absent.
Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.
The incidence of acute atherosis will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 15 years postpartum.
Measured: 15 years
Relationship between decidual vasculopathy and subclinical coronary atherosclerosis at 1 year postpartum
Decidual vasculopathy will be defined as the presence of subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. It will be measured as either present or absent.
Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.
The incidence of decidual vasculopathy will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 1 year postpartum.
Measured: 1 year
Relationship between placental decidual vasculopathy and subclinical coronary atherosclerosis at 15 years postpartum
Decidual vasculopathy will be defined as the presence of subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. It will be measured as either present or absent.
Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.
The incidence of decidual vasculopathy will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 15 years postpartum.
Measured: 15 years
Secondary outcomes (12)
Relationship between placental acute atherosis and clinical coronary atherosclerosis at 1 year postpartum
Acute atherosis will be defined as subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as present or absent.
Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Calcification score of their coronary arteries is based on the calcification seen on the CT scan. This is a continuous scoring system.
The Agatston method uses the weighted sum of lesions with a density above 130 hounsfield units (HU), multiplying the area of calcium by a factor related to maximum plaque attenuation.
The agatston score ranges from 0 and has no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk of coronary events, >400 = high risk of coronary events.
The incidence of acute atherosis will be compared with the average agatston score for the pre-eclamptic and normotensive groups at 1 year postpartum.
Measured: 1 year
Relationship between placental acute atherosis and clinical coronary atherosclerosis at 15 years postpartum
Acute atherosis will be defined as subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as present or absent.
Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Calcification score of their coronary arteries is based on the calcification seen on the CT scan. This is a continuous scoring system.
The Agatston method uses the weighted sum of lesions with a density above 130 HU, multiplying the area of calcium by a factor related to maximum plaque attenuation.
The agatston score ranges from 0 and has no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk of coronary events, >400 = high risk of coronary events.
The incidence of acute atherosis will be compared with the average agatston score for the pre-eclamptic and normotensive groups at 15 years postpartum.
Measured: 15 years
Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 1 year postpartum
Decidual vasculopathy defined as subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. (Present or absent) Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Calcification score of their coronary arteries is based on the calcification seen on the CT scan. This is a continuous scoring system.
The Agatston method uses the weighted sum of lesions with a density above 130 HU, multiplying the area of calcium by a factor related to maximum plaque attenuation.
Range 0 to no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk, >400 = high risk.
The incidence of decidual vasculopathy compared with average agatston score for the pre-eclamptic and normotensive groups at 1 year postpartum.
Measured: 1 year
Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 15 years postpartum
Decidual vasculopathy defined as subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. (Present or absent) Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Calcification score of their coronary arteries based on the calcification seen on the CT scan. This is a continuous scoring system.
The Agatston method uses the weighted sum of lesions with a density above 130 HU, multiplying the area of calcium by a factor related to maximum plaque attenuation.
Range 0 to no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk, >400 = high risk.
The incidence of decidual vasculopathy compared with average agatston score for the pre-eclamptic and normotensive groups at 15 years postpartum.
Measured: 15 years
Incidence of placental acute atherosis at 1 year postpartum
Acute atherosis will be defined as the presence of subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as either present or absent.
The incidence of acute atherosis will be compared for the pre-eclamptic and normotensive groups at 1 year postpartum.
Measured: 1 year
Incidence of placental acute atherosis at 15 years postpartum
Acute atherosis will be defined as the presence of subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as either present or absent.
The incidence of acute atherosis will be compared for the pre-eclamptic and normotensive groups at 15 years postpartum.
Measured: 15 years
Incidence of placental decidual vasculopathy at 1 year postpartum
Decidual vasculopathy will be defined as the presence of subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. It will be measured as either present or absent.
The incidence of decidual vasculopathy will be compared for the pre-eclamptic and normotensive groups at 1 year postpartum.
Measured: 1 year
Incidence of placental decidual vasculopathy at 15 years postpartum
Decidual vasculopathy will be defined as the presence of subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. It will be measured as either present or absent.
The incidence of decidual vasculopathy will be compared for the pre-eclamptic and normotensive groups at 15 years postpartum.
Measured: 15 years
Incidence of subclinical coronary atherosclerosis at 1 year postpartum
Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.
The incidence of each of the subcategories of subclinical coronary atherosclerosis will be compared for the pre-eclamptic and normotensive groups at 1 year postpartum.
Measured: 1 year
Incidence of subclinical coronary atherosclerosis at 15 years postpartum
Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.
The incidence of each of the subcategories of subclinical coronary atherosclerosis will be compared for the pre-eclamptic and normotensive groups at 15 years postpartum.
Measured: 15 years
Incidence of clinical coronary atherosclerosis at 1 year postpartum
Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Each patient will receive a calcification score of their coronary arteries based on the calcification seen on the CT scan. This is a continuous scoring system.
The Agatston method uses the weighted sum of lesions with a density above 130 HU, multiplying the area of calcium by a factor related to maximum plaque attenuation: 130-199 HU, factor 1; 200-299 HU, factor 2; 300-399 HU, factor 3; and ≥ 400 HU, factor 4.
The agatston score ranges from 0 and has no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk of coronary events, >400 = high risk of coronary events.
The average agatston score will be compared for the pre-eclamptic and normotensive groups at 1 year postpartum.
Measured: 1 year
Incidence of clinical coronary atherosclerosis at 15 years postpartum
Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Each patient will receive a calcification score of their coronary arteries based on the calcification seen on the CT scan. This is a continuous scoring system.
The Agatston method uses the weighted sum of lesions with a density above 130 HU, multiplying the area of calcium by a factor related to maximum plaque attenuation: 130-199 HU, factor 1; 200-299 HU, factor 2; 300-399 HU, factor 3; and ≥ 400 HU, factor 4.
The agatston score ranges from 0 and has no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk of coronary events, >400 = high risk of coronary events.
The average agatston score will be compared for the pre-eclamptic and normotensive groups at 15 years postpartum.
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2022
- Study startNov 2016
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pre-EclampsiaStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 226 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marc Spaanderman, MD, PhD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05500989
- Sponsor's protocol ID
- Modified NL52556.068.15
- Other IDs
- METC 152019
- Acronym
- PEARLS
- Status last verified
- Dec 2024
- First submitted
- 5 May 2022
- Last updated
- 5 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jansen G, Alers RJ, Janssen EB, Jorissen LM, Morina-Shijaku E, Severens-Rijvers C, van 't Hof A, van Drongelen J, Scholten RR, Al-Nasiry S, Stevens D, Ganzevoort W, Gordijn S, Cornette J, Mihl C, Kietelaer B, Ghossein-Doha C, Spaanderman ME. PlacEntal Acute atherosis RefLecting Subclinical systemic atherosclerosis in women up to 20 years after pre-eclampsia (PEARLS): research protocol for a cohort study. BMJ Open. 2025 May 24;15(5):e100542. doi: 10.1136/bmjopen-2025-100542.
PubMed 40413047
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PlacEntal Acute Atherosis RefLecting Subclinical Atherosclerosis
- ClinicalTrials.gov ID
- NCT05500989
- Acronym / sponsor ID
- PEARLS / Modified NL52556.068.15
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 226 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- Nov 2016 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 15 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pregnancy is considered a cardiovascular (CV) stress test, and complicated pregnancies are associated with an increased risk for cardiovascular disease (CVD) later in life. Moreover, it is known that often the pregnancy induced CV adaptation does not resolve completely after a short postpartum (PP) period and it is not clear whether these induced changes will resolve over a longer period of time (i.e. in the upcoming months/years after delivery).
Understanding the cardiac adaptation during pregnancy and the reversal process in the postpartum period, as well as the factors that influence this these processes, may provide us not only insight in this mechanism, but may help us in identifying factors that may be target points for modification.
Detailed description
The main goal of this study is to determine whether the presence of placental acute atherosis after pre-eclamptic pregnancies compared to normotensive pregnancies is related to the future development of subclinical atherosclerosis in the coronary arteries.
This information can be used to improve our prediction of which women have an increased risk of future cardiovascular disease and which women do not. This will allow us to better inform our postpartum population of the potential future risks of cardiovascular disease and could allow the timely implementation of primary prevention strategies. The investigators would also like to determine which blood biomarkers can also predict cardiovascular disease at an earlier stage as well as determining which of these biomarkers are present in hypertensive pregnancies.
This study is a longitudinal cohort study including women with pre-eclamptic pregnancies and normotensive pregnancies. Cases consist of women with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (early and late PE, with or without intra uterine growth restriction (IUGR)), whereas controls are women with an uncomplicated pregnancy.
The placenta is collected after the delivery and undergoes histopathological analyses. There are two follow up periods whereby one group of women is followed up 6 to 36 months postpartum and another group is followed up 10 to 20 years postpartum. At the follow up (6 to 36 months or 10 to 20 years), women attend for a series of measurements including CT angiography, transthoracic echocardiography, Flow medicated dilatation (FMD) and carotid intima media thickness (IMT) measurement. The visit will last approximately 5 hours in the Maastricht University Medical Centre (MUMC+). The only invasive procedure is a venepuncture where 75 ml blood will be extracted. The only unfavourable side effect can be a small hematoma (rare). Clinically, participants will be advised based on their risk profile following standard "cardiovascular (CV) risk management". Glycocalyx measurements and a FibroScan may be performed. Experience shows that this investigation is not experienced as uncomfortable. Also, 3 liters of exhaled air may be collected for volatile organic compound (VOCs) analysis. All measurements will be performed or supervised by an experienced researcher. These investigations are already approved previously in other Medical Ethics Committee (METC) applications (CMO-nr: 2008/226; 2009/004; 10-2-066). The other measurements (questionnaires, blood pressure (BP), weight measurement, urine collection, glycocalyx measurement, FibroScan and exhaled air collection) do not cause any discomfort for the patient aside from the time that it takes. On the other hand, potential health improvement and early detection of CV risk profiles and initiation of already existing effective prevention strategies that improve lifestyle are important benefits.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Short track controls | – | –Controls are women (18 years or older) with an uncomplicated pregnancy (i.e no foetal or maternal placental complications, such as pregnancy induced hypertension, preeclampsia or HELLP-syndrome, or small for gestational birth infancies). Follow up roughly 18 months postpartum. |
| Short track early PE with IUGR | – | –These cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. |
| Short track early PE without IUGR | – | –Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. |
| Short track late PE with IUGR | – | –Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. |
| Short track late PE without IUGR | – | –Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. |
| Long term follow up track cases | – | –Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study population consists of pregnant women who either develop pre-eclampsia or have a normotensive pregnancy. For the shorter follow up period, participants are recruited from the (labour) ward and from the outpatient clinic in MUMC+. Participants are also recruited externally from other hospitals if they contact us with an interest in this study. For the longer follow up period, case participants took part in an earlier study and agreed to be contacted for future studies. These participants were recruited through a letter with information about the study. Control participants were recruited when they contacted us with interest in this study.
Key inclusion criteria (3 listed)
- Women aged ≥ 18 years
- Controls: Women with an uncomplicated pregnancy at the moment of inclusion (i.e no foetal or maternal placental complications, such as pregnancy induced hypertension, preeclampsia or HELLP-syndrome, or small for gestational birth infancies)
- Cases: Women diagnosed with a preeclamptic pregnancy at the moment of inclusion
Key exclusion criteria (3 listed)
- Women who do not want to be informed about the results of the tests, or women who do not want their general practitioner and specialist(s) to be informed about the test results
- Allergy or intolerance to glyceryl trinitrate, betablockers or iodinated contrast media.
- Controls: Pre-existing chronic hypertension treated with antihypertensive medication or autoimmune disorder.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Relationship between placental acute atherosis and subclinical coronary atherosclerosis at 1 year postpartum
Time frame: 1 year
Acute atherosis will be defined as the presence of subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as either present or absent. Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis. The incidence of acute atherosis will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 1 year postpartum.
Relationship between placental acute atherosis and subclinical coronary atherosclerosis at 15 years postpartum
Time frame: 15 years
Acute atherosis will be defined as the presence of subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as either present or absent. Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis. The incidence of acute atherosis will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 15 years postpartum.
Relationship between decidual vasculopathy and subclinical coronary atherosclerosis at 1 year postpartum
Time frame: 1 year
Decidual vasculopathy will be defined as the presence of subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. It will be measured as either present or absent. Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis. The incidence of decidual vasculopathy will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 1 year postpartum.
Relationship between placental decidual vasculopathy and subclinical coronary atherosclerosis at 15 years postpartum
Time frame: 15 years
Decidual vasculopathy will be defined as the presence of subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. It will be measured as either present or absent. Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis. The incidence of decidual vasculopathy will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 15 years postpartum.
12 secondary outcomes
Relationship between placental acute atherosis and clinical coronary atherosclerosis at 1 year postpartum
Time frame: 1 year
Relationship between placental acute atherosis and clinical coronary atherosclerosis at 15 years postpartum
Time frame: 15 years
Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 1 year postpartum
Time frame: 1 year
Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 15 years postpartum
Time frame: 15 years
Incidence of placental acute atherosis at 1 year postpartum
Time frame: 1 year
Incidence of placental acute atherosis at 15 years postpartum
Time frame: 15 years
Incidence of placental decidual vasculopathy at 1 year postpartum
Time frame: 1 year
Incidence of placental decidual vasculopathy at 15 years postpartum
Time frame: 15 years
Incidence of subclinical coronary atherosclerosis at 1 year postpartum
Time frame: 1 year
Incidence of subclinical coronary atherosclerosis at 15 years postpartum
Time frame: 15 years
Incidence of clinical coronary atherosclerosis at 1 year postpartum
Time frame: 1 year
Incidence of clinical coronary atherosclerosis at 15 years postpartum
Time frame: 15 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
- Derived from this study: PubMed 40413047Jansen G, Alers RJ, Janssen EB, Jorissen LM, Morina-Shijaku E, Severens-Rijvers C, van 't Hof A, van Drongelen J, Scholten RR, Al-Nasiry S, Stevens D, Ganzevoort W, Gordijn S, Cornette J, Mihl C, Kietelaer B, Ghossein-Doha C, Spaanderman ME. PlacEntal Acute atherosis RefLecting Subclinical systemic atherosclerosis in women up to 20 years after pre-eclampsia (PEARLS): research protocol for a cohort study. BMJ Open. 2025 May 24;15(5):e100542. doi: 10.1136/bmjopen-2025-100542.
Related trials for Pre-Eclampsia
Recruiting
Exercise to Improve Heart and Metabolic Health After Childbirth in Women at High Risk for Preeclampsia
Postpartum Exercise, Cardiometabolic Health
RecruitingObservational study
Molecular Study of the Maternal-fetal Interface in Preeclampsia.
Preeclampsia
Active, not recruitingObservational study
The CoPenHagen PREeClampsia and cardIOvascUlar diSease Study
Pre-Eclampsia, Atherosclerosis
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Not yet recruitingPhase 2
Furosemide vs Placebo in Severe Preeclampsia Postpartum
Severe Preeclampsia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marc Spaanderman, MD, PhD principal investigator
Maastricht University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pre-Eclampsia and HELLP Syndrome, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gwyneth Jansen, MBBS (043-38774145, gwyneth.jansen@mumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relationship between placental acute atherosis and subclinical coronary atherosclerosis at 1 year postpartum (time frame: 1 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05500989, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2024.