PlacEntal Acute Atherosis RefLecting Subclinical Atherosclerosis

NCT05500989 | Recruiting DMC

• 2 other identifiers: Modified NL52556.068.15METC 152019
• Study Type: observational
• Target: 226
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Pre-Eclampsia; HELLP Syndrome; Intrauterine Growth Restriction; Pregnancy

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  15 years

Secondary Outcomes (12)

• Relationship between placental acute atherosis and clinical coronary atherosclerosis at 1 year postpartum

  1 year

• Relationship between placental acute atherosis and clinical coronary atherosclerosis at 15 years postpartum

  15 years

• Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 1 year postpartum

  1 year

• Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 15 years postpartum

  15 years

• Incidence of placental acute atherosis at 1 year postpartum

  1 year

Study Arms (6)

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.

Eligibility Criteria

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

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.

You may qualify if:

• Women aged ≥ 18 years

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University Medical Center (MUMC+)

Maastricht, 6202 AZ, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 40413047 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples for biomarker analyses

MeSH Terms

Conditions

Pre-Eclampsia; HELLP Syndrome; Fetal Growth Retardation

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Fetal Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Growth Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Marc Spaanderman, MD, PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gwyneth Jansen, MBBS

CONTACT

043-38774145; gwyneth.jansen@mumc.nl

Marc Spaanderman, MD, PhD

CONTACT

043-38774774; marc.spaanderman@mumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2022
• First Posted: August 15, 2022
• Study Start: November 1, 2016
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 5, 2024

Record last verified: 2024-12

Locations

NL (1)