Oxidative Stress and Endothelial Function in Pregnancy Complications: Development of a New Screening Algorithm
试验速览
- 阶段
- 不适用
- 入组人数
- 330
- 试验地点
- 1
- 主要终点
- Oxidative stress. Measurement of nitric oxide and eNOS in placental tissue and superoxide in maternal serum using EPR and western blotting.
研究概览
简要总结
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.
详细描述
INTRODUCTION. In normal pregnancy vascular remodelling of the maternal uterine spiral arteries occurs. Trophoblast cells invade the spiral arterioles within the first 12 weeks of pregnancy and replace the muscular wall of the vessels converting them into wide bore, low resistance, large capacity vessels, a process normally completed by 20 weeks gestation. The pathogenesis of generalized endothelial dysfunction in complicated pregnancies is subdivided into two phases. The first phase exists of a poor trophoblast invasion of the spiral arteries during the placentation process, causing failure to transform the placental bed arteries from high to low resistance vessels. This results in local ischemia, reperfusion damage and oxidative stress. The local damage activates the second phase where enhanced production of anti-angiogenic factors and oxidative stress products results in systemic inflammation, endothelial activation and decreased endothelial nitric oxide. In case the endothelial damage is most outspoken, thrombotic micro-angiopathy is induced with platelet-fibrin thrombi in micro-vessels. The angiopathy results in consumption of circulating platelets, causes hemolysis in affected micro-vessels and reduces portal blood flow in the liver, finally resulting in periportal necrosis, a condition seen in severe pre-eclampsia (PE).
HYPOTHESIS.
- Increased oxidative stress and endothelial dysfunction are present early in pregnancy when pregnancy complications will develop later on.
- Oxidative stress and endothelial dysfunction are not entirely independent from each other and can be measured.
- Oxidative stress can be reduced and endothelial function can be improved by interventions that will reduce the risk of developing pregnancy complications.
Thus: measurement and integration in an algorithm of oxidative stress and endothelial function in early pregnancy will allow us to determine which pregnancies will benefit from preventive interventions. This selection will optimize targeted interventions on high risk pregnancies without overtreatment of others.
METHODOLOGY
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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)
- •Exclusion criteria:
- •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)
排除标准
- 未提供
结局指标
主要结局
Oxidative stress. Measurement of nitric oxide and eNOS in placental tissue and superoxide in maternal serum using EPR and western blotting.
时间窗: Pregnancy - 6 months postpartum
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.
次要结局
- 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)
- Neutrophil-lymphocyte ratio (NLR)(Pregnancy - 6 months postpartum)
研究者
Prof Yves Jacquemyn
Professor
Universiteit Antwerpen