Clinical trial NCT05806372: Biomarkers of CVD Dysfunction in Hypertensive Disorders of Pregnancy
Official title: Biomarkers of Maternal Cardio-vascular Dysfunction in Pregnancies Complicated by Hypertensive Disorders of Pregnancy
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Cardiovascular Diseases
Pregnancy
Keywords: Cardiomyocytes
microRNA,
hypertensive disorders of pregnancy
Lead sponsor: IRCCS Burlo Garofolo
Sponsor class: OTHER
First posted: 2023-04-10
Enrollment: 128
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Singleton pregnant women between 24 and 40 gestational weeks with HDP (with and without fetal growth disorder) and normotensive (controls)

Brief summary: Profound and concomitant cardiovascular hemodynamic changes, necessary to support fetoplacental development and its increasing supply demands, occur during a physiological pregnancy characterized by an increase in cardiac output, heart rate and plasma volume, and fall in vascular resistance and blood pressure. The result of these changes is a volume overload that will lead to a compensatory transient left ventricular eccentric hypertrophy. This, together with the pro-inflammatory state typical of pregnancy, represents the pregnancy as a stress-test for the maternal cardiovascular system. Pregnancies complicated by hypertensive disorders of pregnancy (HDP), particularly those with early onset and/or complicated by intrauterine fetal growth restriction (FGR), are characterized by a cardiovascular maladaptation. Women who experienced HDP in pregnancy, especially pre-eclampsia (PE), more often develop later in life ischemic heart disease, hypertension and stroke, obesity, dyslipidemia, and end-stage renal disease.

Regardless its clinical impact, very little knowledge is available on the mechanisms by which PE could lead to cardiovascular disease (CVD), and, especially, to heart failure after pregnancy. Preliminary results suggest a cross-talk between pregnancy-induced biomarkers and cardio-vascular system. Particularly, cultures of neonatal rat cardiomyocytes and fibroblasts were used to investigate the role of the serum of women with HDP in regulating their proliferation. 5-ethynyl-2'-deoxyuridine (EdU) was administered to label DNA synthesis in proliferating cells. After 3 days of in vitro culture, EdU incorporation was analyzed upon immunofluorescence staining using specific antibodies by high content microscopy. A possible protective effect exerted by the selected sera against apoptosis was evaluated, as well, by Caspase activation. Moreover, the effect of cardiomyocytes and fibroblasts proliferation and apoptosis on maternal hemodynamic parameters was evaluated using median regression models. These data show that the serum of women with HDP triggers a net increase in the percentage of proliferating cardiomyocytes compared to controls. Moreover, there were relationship between cardiomyocytes and fibroblasts proliferation and maternal hemodynamics parameters thus, supporting the hypothesis that the serum of women with HDP may contain factors capable of stimulating cardiac cells in response to the cardiovascular stress-test


Eligibility criteria: Inclusion Criteria:

CASES:

1. Pregnant women affected by HDP
2. Women ≥18 years old
3. Women able to give an informed consent

CONTROLS

1. Uneventful pregnancy of women ≥18 years old
2. Women able to give an informed consent

Exclusion Criteria:

1. No informed consent
2. Women \<18 years old
3. Presence of other maternal pathologies as viral disease, diabetes
4. Fetal chromosomal/structural anomalies

Primary outcomes:
measure: Number of biomarkers predicting cardiomyocyte hypertrophy and fibroblast proliferation
timeFrame: During pregnancy, at the time of HDP diagnosis
measure: Number of biomarkers predicting cardiomyocyte hypertrophy and fibroblast proliferation
timeFrame: 24 months post-partum
Secondary outcomes:
Other outcomes:
Locations:
city: Trieste
country: Italy
facility: IRCCS Burlo Garofolo
Study officials:
affiliation: IRCCS materno infantile Burlo Garofolo
name: Tamara Stampalija, MD
role: STUDY_DIRECTOR
References: