Effect of Post Covid-19 Hypoxia on Placenta of Normal Pregnant Women: A Possible Role of Hypoxia Inducible Factor-1α.

Study Overview
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Brief Summary
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To study the risk of hypoxia in placenta of normal pregnant women infected with covid-19 during third trimester of pregnancy.

Detailed Description
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Hypoxaemia is an ominous sign of COVID-19, and it is usually an indicator of disease severity. An oxygen saturation above 90% is associated with better outcomes. Hypoxia indicates an imbalance of oxygen delivery to tissues and leads to compromised function. The hypoxia-inducible factors (HIF) are considered master regulators of oxygen homeostasis and are oxygen level sensitive. HIF1a is a heterodimeric transcription factor that bind to hypoxia response elements, which participates through the regulation of the expression of several genes in numerous cellular events such as O2 sensing, glucose metabolism, lipid metabolism, angiogenesis and other aspects of endothelial biology. PIGF is a proangiogenic protein and member of the vascular endothelial growth factor (VEGF) family. It is one of the key molecules in angiogenesis and vasculogenesis especially during embryogenesis and placental trophoblast is the main source of PIGF throughout the gestational period of pregnancy. It shares structural as well as amino acid sequence similarity with VEGF, but PIGF has binding afﬁnity only for VEGF receptor1(VEGFR-1). The inter-and intramolecular cross-talk between the VEGFR-1 and VEGFR-2 is regulated by PIGF. It binds toVEGFR-1 and displaces VEGF from this receptor, which results in activation and intermolecular trans phosphorylation of VEGFR-2 thereby amplify the VEGF-induced angiogenesis. Hypoxic environment is essential for the proliferation and differentiation of cytotrophoblast for maintenance of materno-fetal circulation at early periods of pregnancy. But its prevalence in later stages of pregnancy causes several complications that may lead to maternal and fetal morbidity and mortality. Several researchers have proved that the overexpression of HIF-1α is associated with the increased maternal serum concentration of soluble Fms-like tyrosine kinase 1 (sFlt1) during hypoxic conditions. High circulating levels of sFlt1 exerts an antiangiogenic state that is associated with low levels of proangiogenic factors, such as PIGF, and inhibition of PIGF with its receptor VEGFR-1. Currently, there is no information regarding the expression of HIF-1a in normal pregnant women with COVID-19 infection and its potential involvement in the placentation of this condition. Therefore, in the present work we will detect the expression of hypoxia induced factor 1a (HIF1a) and possible molecular link between the expression of HIF-1α and PIGF based on previous studies which show significant negative association between HIF-1α and PIGF expression in patients suffering from preeclampsia.

Official Title
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Effect of Post Covid-19 Hypoxia on Placenta of Normal Pregnant Women: A Possible Role of Hypoxia Inducible Factor-1α.

Conditions
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Hif-1α Covid-19

Intervention / Treatment
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* Diagnostic Test: HiF-1 alpha measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: * Pregnant women who come for termination of pregnancy by CS or vaginal delivery Gestational age is between 28-40 weeks. The women will be divided into two groups: Covid-19 infection during 3rd trimester group (n = 25) Control normal pregnancy group (n = 25). Exclusion Criteria: 1) Diabetes mellitus 2) Chronic hypertension 3) Preeclampsia 4) Acute or chronic infectious diseases or other chronic illness 5) Twins pregnancy 6) Anti phospholipid antibody syndrome

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Post covid infected group<br>normal pregnant women infected by covid during 3rd trimester | Diagnostic Test: HiF-1 alpha measurement<br>* HIF1- α is a heterodimeric transcription factor that bind to hypoxia response elements, which participates through the regulation of the expression of several genes in numerous cellular events such as O2 sensing, glucose metabolism, lipid metabolism, angiogenesis and other aspects of endothelial biology<br>|
| Control group<br>normal pregnant women | Diagnostic Test: HiF-1 alpha measurement<br>* HIF1- α is a heterodimeric transcription factor that bind to hypoxia response elements, which participates through the regulation of the expression of several genes in numerous cellular events such as O2 sensing, glucose metabolism, lipid metabolism, angiogenesis and other aspects of endothelial biology<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean difference between HIF-1 between study groups | real time PCR and Immunohistochemistery of Hif-1α | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hif-1α covid-19