Hypertensive Disorder of Pregnancy, Preeclampsia
Conditions
Keywords
Preeclampsia, Hypertensive Disorders of Pregnancy, Hypertension, Obstetric Medicine, Cardio-Obstetrics, Cardiovascular outcomes, Pregnancy complications, Arterial Stiffness, Endothelial Glycocalyx, Endothelial dysfunction, Uric Acid, Oxidative stress, Xanthine oxidase, Lipids
Brief summary
The present study is a single-centre prospective study that will enrol pregnant women during their first trimester of pregnancy (11+0 - 13+6 weeks of gestation). During pregnancy, women will undergo standard clinical evaluation and management. During the two study visits (enrollment and 24+0 - 27+6 weeks of gestation) the investigators will perform arterial tonometry (Pulsepen) and in vivo darkfield microscopy (Glycocheck) to evaluate endothelial and vascular function. A urine sample and a blood sample for specific study analyses on metabolic profile, endothelial and angiogenic markers will be collected. Pregnancy outcomes will be collected at delivery and five years after delivery all the participants will be interview to collect long-term cardiovascular outcomes. Serum endothelial and angiogenic markers will be evaluated only in participants who will develop hypertensive disorders of pregnancy and in an equal number of controls matched for age and body mass index at the time of conception.
Detailed description
Primary aim: To determine the role of the combination of arterial tonometry and endothelial glycocalyx measurement in predicting the risk of developing hypertensive disorders in pregnancy. Secondary aims: * To determine the association between circulating markers of angiogenesis and endothelial dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1) and the development of hypertensive disorders of pregnancy. * To define the trends of serum uric acid, lipids and xanthine oxidase activity in normotensive and hypertensive pregnancies. * To determine the ability of the combination of arterial tonometry and endothelial glycocalyx measurement, performed in the two study visits during pregnancy, in predicting the risk of long-term maternal cardiovascular disease.
Interventions
DEVICEArterial applanation tonometry
Arterial applanation tonometry will be performed at the carotid and femoral level by the PulsePen device (Software WPulsePen version 2.3.1, DiaTecne, Milan, Italy), while the subject is lying in the horizontal position and after 5 minutes of rest.
DEVICEIn vivo endothelial glycocalyx measurement
The in vivo microscopy (GlycoCheck system) is performed in the sublingual capillaries during the morning, with the participant sitting on a chair. The sublingual capillaries are visualized using an SDF video microscope (Capiscope handheld, KK Research technology Ltd).
DIAGNOSTIC_TESTSerum markers of angiogenesis and endothelial dysfunction
ELISA assays to measure serum circulating markers of angiogenesis and endothelial dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1).
DIAGNOSTIC_TESTBlood chemistry test
Immunochemistry analysis of serum levels of uric acid, total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, Lipoprotein (a)
DIAGNOSTIC_TESTSerum xanthine oxidase activity
Serum xanthine oxidase (XO) activity will be assessed in blood samples measuring the ability of XO to produce uric acid
Sponsors
IRCCS Azienda Ospedaliero-Universitaria di Bologna
University of Bologna
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
The study is a single group study (Principal Arm) with a sub-group of participants undergoing additional experimental analyses. The additional analyses will be performed in participants who will develop hypertensive disorders of pregnancy and matched (age and body mass index before conception) controls with healthy pregnancies.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Age greater than or equal to 18 years * Single pregnancy * No previous pregnancies lasting more than 12 weeks * Participant willing and able to give informed consent for participation in the study
Exclusion criteria
* Intermediate-high risk of genetic abnormalities and/or need to perform invasive tests (amniocentesis, villocentesis) * History of solid organ or hematopoietic stem cell transplantation * Chronic renal failure (eGFR≤45ml/min/1.73m2) * Chronic treatment with antihypertensive drugs and/or xanthine oxidase (XO) inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Perfused Boundary Region (PBR) | Baseline visit (11/13+6 weeks of pregnancy) | Micron |
| Carotid-femoral pulse wave velocity (cf-PWV) | Baseline visit (11/13+6 weeks of pregnancy) | m/s |
| Number of participants with hypertensive disorders of pregnancy | From date of enrolment until the date of first documented diagnosis of hypertensive disorder of pregnancy, according to the International Society for the Study of Hypertension in Pregnancy Criteria, assessed up to one week after delivery | Number of participants diagnosed during pregnancy with any hypertensive disorder of pregnancy |
| Number of participants with preeclampsia | From date of enrolment until the date of first documented diagnosis of preeclampsia, according to the International Society for the Study of Hypertension in Pregnancy Criteria, assessed up to one week after delivery | Number of participants diagnosed during pregnancy with preeclampsia according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Angiopoietin 1 (ANG-1) | Baseline visit (11/13+6 weeks of pregnancy) | ng/ml |
| Serum Angiopoietin 2 (ANG-2) | Baseline visit (11/13+6 weeks of pregnancy) | ng/ml |
| Serum Endothelin-1 (ET-1) | Baseline visit (11/13+6 weeks of pregnancy) | Serum concentration assessed by ELISA (pg/ml) |
| Serum Intercellular adhesion molecule-1 (ICAM-1) | Baseline visit (11/13+6 weeks of pregnancy) | ng/ml |
| Serum Vascular Cell Adhesion Molecule-1 (VCAM-1) | Baseline visit (11/13+6 weeks of pregnancy) | ng/ml |
| Number of participants with long-term cardiovascular outcomes | Interview 5 years after delivery | Number of participants diagnosed with stroke, myocardial infarction, heart failure or hospitalized for cardiovascular disease in the 5 years after delivery |
Countries
Italy
Contacts
CONTACTArrigo Francesco Giuseppe Cicero, MD, PhD
CONTACTCristina Scollo, BD
PRINCIPAL_INVESTIGATORArrigo Francesco Giuseppe Cicero, MD, PhD
IRCCS University Hospital of Bologna, Italy. University of Bologna, Italy.
Outcome results
None listed