Oxidative Stress and Endothelial Function in Pregnancy Complications

NCT02603913 | Unknown

• 1 other identifier: UZA-Endopreg-2015-1
• Study Type: observational
• Target: 330
• Locations: 1 country
• Sites: 1

Brief Summary

Pregnancy complications like pre-eclampsia (PE), pregnancy induced hypertension (PIH), intra-uterine growth restriction (IUGR) and preterm labor (PTL), (i.e. the major part of complications in pregnancy) are related to an impaired endothelial function. Endothelial dysfunction accounts for altered vascular reactivity, activation of the coagulation cascade and loss of vascular integrity. Nitric oxide (NO), a free radical molecule derived from L-Arginine by NOS (Nitric Oxide Synthase), is an endogenous endothelium-derived relaxing factor influencing endothelial function. In the placental circulation, endothelial release of NO dilates the fetal placental vascular bed and thus ensures feto-maternal exchange. The impaired endothelial function in pregnancy complications originates from production of inflammatory and cytotoxic factors by the ischemic placenta and results in oxidative stress and an altered bioavailability of NO. Measurement of endothelial function using peripheral artery tonometry and determination of ROS (reactive oxygen species) and RNS (reactive nitrogen species) using Electron Paramagnetic Resonance (EPR) gives an idea of the oxidative stress that took place and the degree of endothelial dysfunction that occurred during pregnancy.

Conditions

Pregnancy Complications; Endothelial Dysfunction

Keywords

Pre-eclampsia; Pregnancy induced hypertension; Preterm birth; Intra-uterine growth restriction; Oxidative stress

Outcome Measures

Primary Outcomes (1)

• Oxidative stress. Measurement of nitric oxide and eNOS in placental tissue and superoxide in maternal serum using EPR and western blotting.

  Single center prospective longitudinal study: To evaluate the oxidative stress profile in normal pregnancies. Multicenter matched case-control study: To compare the oxidative stress profile in normal versus complicated pregnancies.

  Pregnancy - 6 months postpartum

Secondary Outcomes (6)

• Endothelial function (using Endopat®)

  Pregnancy - 6 months postpartum

• Arterial stiffness (Pulse wave velocity, pulse wave analysis using Sphygmocor ®).

  Pregnancy - 6 months postpartum

• Pregnancy outcome

  Pregnancy - 6 months postpartum

• Pulsatility index uterine artery (using doppler ultrasound).

  Pregnancy - 6 months postpartum

• Mean platelet volume (MPV (fL))

  Pregnancy - 6 months postpartum

Study Arms (5)

Normal pregnancy

Normal uncomplicated pregnancy

Pre-eclampsia

Hypertension (\>140 mmHg systolic or \>90 mmHg diastolic) developing after 20 weeks gestation and the coexistence of one or more of the following new onset conditions: 1. Proteinuria (\>300 mg/day) 2. Other maternal organ dysfunction * renal insufficiency (creatinine \>90 μmol/L) * liver involvement (elevated transaminases - and/or severe right upper quadrant or epigastric pain) * neurological complications (eclampsia, altered mental status, blindness, stroke, hyperreflexia when accompanied by clonus, severe headaches when accompanied by hyperreflexia, persistent visual scotomata) * hematological complications (thrombocytopenia, disseminated intravascular coagulation, hemolysis) 3. Uteroplacental dysfunction

Pregnancy induced hypertension

New onset of hypertension (\>140 mmHg systolic or \>90 mmHg diastolic) after 20 weeks gestation, without proteinuria, in a previously normotensive woman.

Preterm birth

Babies born alive before 37 weeks of pregnancy are completed.

Intra-uterine growth restriction

Moderate IUGR is an estimated fetal weight and / or abdominal circumference \< 10th percentile for its gestational age Severe IUGR is an EFW (estimated fetal weight) and/ or AC (abdominal circumference) \< 5th percentile for its gestational age

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Patients will be included at one of the participating tertiary obstetrical centers (UZA, ZOL, Erasmus MC, MUMC). They will be included at the beginning of pregnancy in the longitudinal studies. In the case-control study, they will be included at the moment of diagnosis and compared to normotensive controls, matched for maternal and gestational age, parity, smoking behavior, BMI and ethnic group.

You may qualify if:

• Prospective longitudinal study:
• Pregnant women ≥ 18 years old with a singleton pregnancy
• Case-control study:
• Pregnant women ≥ 18 years old with a singleton pregnancy and \> 20 weeks of pregnancy.
• Cases: Pre-eclampsia, PIH, IUGR, Preterm birth (cfr groups)

You may not qualify if:

• gestational diabetes
• multiple pregnancies
• fetal abnormalities
• hypercholesterolemia
• renal disease
• auto-immune disorders
• connective tissue disease
• intake of low-dose aspirin or vitamin C supplements (\>500mg/day)

Sponsors & Collaborators

• Universiteit Antwerpen: lead
• University Hospital, Antwerp: collaborator
• Ziekenhuis Oost-Limburg: collaborator
• Maastricht University Medical Center: collaborator
• Erasmus Medical Center: collaborator

Study Sites (1)

University Hospital Antwerp

Edegem, Antwerp, 2650, Belgium

RECRUITING

Related Publications (6)

• Chen X, Scholl TO. Maternal biomarkers of endothelial dysfunction and preterm delivery. PLoS One. 2014 Jan 22;9(1):e85716. doi: 10.1371/journal.pone.0085716. eCollection 2014.

  PMID: 24465662 BACKGROUND

• Yinon D, Lowenstein L, Suraya S, Beloosesky R, Zmora O, Malhotra A, Pillar G. Pre-eclampsia is associated with sleep-disordered breathing and endothelial dysfunction. Eur Respir J. 2006 Feb;27(2):328-33. doi: 10.1183/09031936.06.00010905.

  PMID: 16452588 BACKGROUND

• Bhavina K, Radhika J, Pandian SS. VEGF and eNOS expression in umbilical cord from pregnancy complicated by hypertensive disorder with different severity. Biomed Res Int. 2014;2014:982159. doi: 10.1155/2014/982159. Epub 2014 May 14.

  PMID: 24959596 BACKGROUND

• Sikkema JM, van Rijn BB, Franx A, Bruinse HW, de Roos R, Stroes ES, van Faassen EE. Placental superoxide is increased in pre-eclampsia. Placenta. 2001 Apr;22(4):304-8. doi: 10.1053/plac.2001.0629.

  PMID: 11286565 BACKGROUND

• Tranquilli AL, Dekker G, Magee L, Roberts J, Sibai BM, Steyn W, Zeeman GG, Brown MA. The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP. Pregnancy Hypertens. 2014 Apr;4(2):97-104. doi: 10.1016/j.preghy.2014.02.001. Epub 2014 Feb 15. No abstract available.

  PMID: 26104417 BACKGROUND

• Mannaerts D, Faes E, Gielis J, Van Craenenbroeck E, Cos P, Spaanderman M, Gyselaers W, Cornette J, Jacquemyn Y. Oxidative stress and endothelial function in normal pregnancy versus pre-eclampsia, a combined longitudinal and case control study. BMC Pregnancy Childbirth. 2018 Feb 27;18(1):60. doi: 10.1186/s12884-018-1685-5.

  PMID: 29482567 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood and placenta samples

MeSH Terms

Conditions

Pregnancy Complications; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Premature Birth

Condition Hierarchy (Ancestors)

Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Obstetric Labor, Premature; Obstetric Labor Complications

Study Officials

• Dominique AM Mannaerts, MD

  Universiteit Antwerpen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yves Jacquemyn, MD PhD

CONTACT

003238213905; yves.jacquemyn@uza.be

Dominique AM Mannaerts, MD

CONTACT

003238215334; mannaerts.dominique@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 18, 2015
• First Posted: November 13, 2015
• Study Start: November 1, 2015
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: October 31, 2016

Record last verified: 2016-10

Locations

BE (1)