Multiparametric Assessment of Maternal Vascular Function in the Prediction of Hypertensive Disorders of Pregnancy (EDIPE)

Multiparametric Assessment of Maternal Vascular Function in the Prediction of Hypertensive Disorders of Pregnancy

Multiparametric Assessment of Maternal Vascular Function as a New Diagnostic and Prognostic Tool for Hypertensive Disorders of Pregnancy and Preeclampsia - EDIPE Study

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.

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.

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

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.

The entire cohort of participants will undergo all experimental procedures. Participants who will develop hypertensive disorders of pregnancy and matched participants with healthy pregnancies will also undergo serum endothelial and angiogenic markers assessment.

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.

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).

ELISA assays to measure serum circulating markers of angiogenesis and endothelial dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1).

Immunochemistry analysis of serum levels of uric acid, total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, Lipoprotein (a)

Serum xanthine oxidase (XO) activity will be assessed in blood samples measuring the ability of XO to produce uric acid

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 preeclampsia according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria.

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 with stroke, myocardial infarction, heart failure or hospitalized for cardiovascular disease in the 5 years after delivery

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

All de-identified IPD that underlie results in a publication for all primary and secondary outcome measures will be shared.

Access to IPD can be requested by qualified researchers engaging in independent scientific research, and provided after review and approval of a research proposal and execution of a Data Sharing Agreement (DSA).