Oxidative stress and endothelial function in normal pregnancy versus pre-eclampsia, a combined longitudinal and case control study

Abstract

Background: Pre-eclampsia (PE) is related to an impaired endothelial function. Endothelial dysfunction accounts for altered vascular reactivity, activation of the coagulation cascade and loss of vascular integrity. Impaired endothelial function originates from production of inflammatory and cytotoxic factors by the ischemic placenta and results in systemic oxidative stress (OS) and an altered bioavailability of nitric oxide (•NO). The free radical •NO, is an endogenous endothelium-derived relaxing factor influencing endothelial function. In placental circulation, endothelial release of •NO dilates the fetal placental vascular bed, ensuring feto-maternal exchange. The Endopreg study was designed to evaluate in vivo endothelial function and to quantify in vitro OS in normal and pre-eclamptic pregnancies.

Methods/design: The study is divided into two arms, a prospective longitudinal study and a matched case control study. In the longitudinal study, pregnant patients ≥18 years old with a singleton pregnancy will be followed throughout pregnancy and until 6 months post-partum. In the case control study, cases with PE will be compared to matched normotensive pregnant women. Maternal blood concentration of superoxide (O2•) and placental concentration of •NO will be determined using EPR (electron paramagnetic resonance). Endothelial function and arterial stiffness will be evaluated using respectively Peripheral Arterial Tonometry (PAT), Flow-Mediated Dilatation (FMD) and applanation tonometry. Placental expression of eNOS (endothelial NOS) will be determined using immune-histochemical staining. Target recruitment will be 110 patients for the longitudinal study and 90 patients in the case-control study.

Discussion: The results of Endopreg will provide longitudinal information on in vivo endothelial function and in vitro OS during normal pregnancy and PE. Adoption of these vascular tests in clinical practice potentially predicts patients at risk to develop cardiovascular events later in life after PE pregnancies. •NO, O2•- and eNOS measurements provide further inside in the pathophysiology of PE.

Trial registration: This trial has been registered on clinicaltrials.gov. ClinicalTrials.gov Identifier: NCT02603913 . Registered October 2015.

Keywords: Electron paramagnetic resonance; Endothelial (dys) function; Maternal outcome; Nitric oxide; Oxidative stress; Pre-eclampsia.

Conflict of interest statement

Ethics approval and consent to participate

The Research and Ethics committee of the Antwerp University Hospital approved the study protocol (Belgian number: B300201524783), and written informed consent was obtained from all subjects.

Consent for publication

Not applicable.

Competing interests

Professor Yves Jacquemyn serves on the Editorial Board of BMC Pregnancy and Childbirth as Associate Editor. All other authors have no competing interests to declare.

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Figures

Fig. 1

Study design and key assessments. Study design and data collection overview. PI = pulsatility index; PP = postpartum; * Assessments at moment of diagnosis; ** Laboratory parameters tested include NLR, MPV (mean platelet volume), platelet count, Fe, transferrin and ferritin

Fig. 2

Representative reactive hyperaemia peripheral arterial tonometry recordings of subjects with normal and abnormal reactive hyperaemic response. Normal response is characterized by a distinct increase in the signal amplitude after cuff release compared with baseline