Diagnostic Value of MicroRNA 210 In Preeclampsia

NCT ID: NCT03193554

Last Updated: 2020-05-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-01-01

Study Completion Date

2020-08-30

Brief Summary

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Pre-eclampsia is a disorder of pregnancy characterized by hypertension (defined as systolic blood pressure 140mmHg or diastolic blood pressure ⩾90 mmHg) and proteinuria (300 mg or greater in a 24 h urine specimen and/or protein to creatinine ratio of \> 0.30) . The disorder usually occurs after 20 weeks of pregnancy and worsens over time. Risk factors for pre-eclampsia include: obesity, prior hypertension, older age, and diabetes mellitus, primigravida and pregnant women with multiple gestation .

Healthy women pregnancy can be associated with resistance to the action of insulin on glucose uptake and utilization. Insulin Resistance (IR) is defined as decreased ability of target tissues such as liver, adipose tissue and muscle to respond to normal circulating concentrations of insulin. Insulin Resistance can be a result of a number of factors such as defective molecular structure of insulin, defective receptor functioning or defective signal transduction pathway .

Preeclampsia is associated with increased expression of Tumor necrosis Factor α and other inflammatory marker which causes Insulin Resistance. Increased Insulin Resistance leads to dyslipidemia that can worsen the placental ischemia leading to vicious cycle of ischemia-inflammation-Insulin Resistance-dyslipidemia-ischemia . Insulin resistance has also been hypothesized to contribute to the pathophysiology of preeclampsia. Compared to women who have normotensive pregnancies, women who develop preeclampsia are more insulin resistant prior to pregnancy .

The recognition that specific miRNAs are induced by hypoxia and are commonly dysregulated in preeclampsia raises the possibility that such miRNAs mediate the adverse effects of placental hypoxia in preeclampsia. MiRNAs present in maternal blood may have the potential to be used as biomarkers, as they are relatively stable and tissue specific . It was found that mir-210 is induced in patients with pre-eclampsia, whether mir-210 contributes to the pathogenesis of pre-eclampsia, a complex disorder widely believed to be associated with placental hypoxia .

Detailed Description

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Pre-eclampsia is a disorder of pregnancy characterized by hypertension (defined as systolic blood pressure ⩾140 mmHg or diastolic blood pressure ⩾90 mmHg) and proteinuria (300 mg or greater in a 24 h urine specimen and/or protein to creatinine ratio of \> 0.30) . The disorder usually occurs after 20 weeks of pregnancy and worsens over time . Preeclampsia is routinely screened during prenatal care .

In severe disease there may be red blood cell breakdown, a low blood platelet count, impaired liver function, kidney dysfunction, swelling, shortness of breath due to fluid in the lungs, or visual disturbances. Pre-eclampsia increases the risk of poor outcomes for both the mother and the baby . If left untreated, it may result in seizures at which point it is known as eclampsia or HELLP syndrome (hemolysis ,elevated liver enzymes , low platelets ) .

The clinical features of preeclampsia are caused by systemic maternal endothelial dysfunction resulting from a combination of preexisting maternal risk factors and abnormal placental development. Risk factors for pre-eclampsia include: obesity, prior hypertension, older age, and diabetes mellitus . It is also more frequent in a woman's first pregnancy and if she is carrying twins. The underlying mechanism involves abnormal formation of blood vessels in the placenta amongst other factors .

These maternal characteristics may contribute to oxidative stress, inflammation and vascular dysfunction, all of which have been implicated in the etiology of preeclampsia .

Healthy women pregnancy can be associated with resistance to the action of insulin on glucose uptake and utilization . Insulin Resistance is defined as decreased ability of target tissues such as liver, adipose tissue and muscle to respond to normal circulating concentrations of insulin. Insulin Resistance can be a result of a number of factors such as defective molecular structure of insulin, defective receptor functioning or defective signal transduction pathway .

Many maternal hormones and factors play role in causation of Insulin Resistance during pregnancy such as increased levels of serum cortisol, Tumor necrosis factor α , can interrupt the insulin signaling pathway and can lead to Insulin Resistance during normal pregnancy .

Women with increased Insulin Resistance are more prone to develop preeclampsia and gestational diabetes. Preeclampsia is associated with increased expression of Tumor necrosis factor α and other inflammatory marker which causes Insulin Resistance. Increased Insulin Resistance leads to dyslipidemia that can worsen the placental ischemia leading to vicious cycle of ischemia-inflammation-Insulin Resistance-dyslipidemia-ischemia .

Insulin resistance has also been hypothesized to contribute to the pathophysiology of preeclampsia. Compared to women who have normotensive pregnancies, women who develop preeclampsia are more insulin resistant prior to pregnancy .

Early reliable markers for preeclampsia development is the involvement of microRNA in the pathogenesis and its possible role as an early biomarker for disease development. MicroRNAs (miRNAs) are a series of small (18-24 nt) endogenous noncoding single-stranded RNAs, which can regulate gene expression post transcriptionally by a nonperfect pairing of 6-8 nucleotides with target mRNAs . It is currently estimated that up to 30% of human genes may contain miRNAs' binding sites, which suggested a potential role of microRNAs as central regulators in the control of gene expression .

MicroRNAs have been implicated in a variety of human diseases, such as cardiovascular disease, primary muscular disorders, and cancer. In addition, miRNAs have been reported involved in regulating pregnancy process .

The human placenta exhibits a specific microRNA expression pattern that dynamically changes during pregnancy and is reflected in the maternal plasma .

The recognition that specific microRNAs are induced by hypoxia and are commonly dysregulated in preeclampsia raises the intriguing possibility that such microRNAs mediate the adverse effects of placental hypoxia in preeclampsia. The connection between microRNAs, adipose tissue, and insulin resistance may have a role in gestational diabetes mellitus pathophysiology. microRNAs present in maternal blood may have the potential to be used as biomarkers, as they are relatively stable and tissue specific .

MicroRNA 210 is identified as a unique hypoxia induced miRNA that is universally induced in various cell types. Using microRNA microarray it was found that microRNA 210 is overexpressed in placental tissue derived from patients with pre-eclampsia .

It was found whether microRNA 210 contributes to the pathogenesis of pre-eclampsia, a complex disorder widely believed to be associated with placental hypoxia. The results show that microRNA 210 is induced in patients with pre-eclampsia and in hypoxia treated trophoblast cells .

It has been found that microRNA 210 levels are dramatically increased in the placental tissue derived from patients with preeclampsia. In this issue, MicroRNA 210 levels in plasma from preeclampsia patients were significantly higher than those in gestational healthy controls. Furthermore, the expression levels of microRNA 210 seemed to correlate well with disease severity, suggesting a potential role of circulating microRNA 210 as novel biomarker for the diagnosis of preeclampsia.

Conditions

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Pre-Eclampsia

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Eligibility Criteria

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Inclusion Criteria

* Group 1: Pregnant women with insulin resistance .
* Group 2: Healthy pregnant women as control group .

Exclusion Criteria

\- 1- Female patients with any other type of malignant or benign tumours should be excluded from our study.

2- Past history of chemotherapy or surgical treatment of cancer. 3-Women who diagnosed as preeclamptic or diabetic
Minimum Eligible Age

20 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Yousra M Farghaly

principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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ASSIUT University

Asyut, , Egypt

Site Status RECRUITING

Assiut Unversity

Asyut, , Egypt

Site Status RECRUITING

Countries

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Egypt

Central Contacts

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Lubna Tag El-din, MD

Role: CONTACT

01001085510

Hanan Mohamed, MD

Role: CONTACT

01223971654

Facility Contacts

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Lobna

Role: primary

Lobna

Role: primary

References

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Al-Jameil N, Aziz Khan F, Fareed Khan M, Tabassum H. A brief overview of preeclampsia. J Clin Med Res. 2014 Feb;6(1):1-7. doi: 10.4021/jocmr1682w. Epub 2013 Dec 13.

Reference Type BACKGROUND
PMID: 24400024 (View on PubMed)

Bueno MJ, Perez de Castro I, Malumbres M. Control of cell proliferation pathways by microRNAs. Cell Cycle. 2008 Oct;7(20):3143-8. doi: 10.4161/cc.7.20.6833. Epub 2008 Oct 20.

Reference Type BACKGROUND
PMID: 18843198 (View on PubMed)

Eiland E, Nzerue C, Faulkner M. Preeclampsia 2012. J Pregnancy. 2012;2012:586578. doi: 10.1155/2012/586578. Epub 2012 Jul 11.

Reference Type BACKGROUND
PMID: 22848831 (View on PubMed)

Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-1131. doi: 10.1097/01.AOG.0000437382.03963.88. No abstract available.

Reference Type BACKGROUND
PMID: 24150027 (View on PubMed)

Morales Prieto DM, Markert UR. MicroRNAs in pregnancy. J Reprod Immunol. 2011 Mar;88(2):106-11. doi: 10.1016/j.jri.2011.01.004. Epub 2011 Feb 25.

Reference Type BACKGROUND
PMID: 21353310 (View on PubMed)

Roberts JM, Lain KY. Recent Insights into the pathogenesis of pre-eclampsia. Placenta. 2002 May;23(5):359-72. doi: 10.1053/plac.2002.0819.

Reference Type BACKGROUND
PMID: 12061851 (View on PubMed)

Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010 Aug 21;376(9741):631-44. doi: 10.1016/S0140-6736(10)60279-6. Epub 2010 Jul 2.

Reference Type BACKGROUND
PMID: 20598363 (View on PubMed)

Other Identifiers

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D V O MicroRNA210 I PET

Identifier Type: -

Identifier Source: org_study_id

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