Molecular Screening Method for Preeclampsia (PREMOM)

Study Overview
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Brief Summary
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Preeclampsia (PE) is a major obstetric complication with short- and long-term consequences for the mother and the fetus. Early screening tools to reduce its mortality and morbidity, as well as to prevent the life-threatening consequences are needed. Thus, the detection of women at risk of suffering PE is key to apply preventive and treatment strategies. Recently, the maternal contribution to PE based on defective decidualization has been evidenced and new technical approaches developed to detect circulating biomolecules in blood such as RNA fragments. The main objective of this study is to evaluate the diagnostic precision of the molecular profile from the maternal blood analysed for the early screening of early onset preeclampsia (EOPE).

Detailed Description
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The hypothesis is that there is a unique molecular profile in peripheral blood specific to women who develop EOPE that allow an early assess woman´s risk of developing this pregnancy complication. The purposed study is a biomedical, prospective, multicentre, case-control aimed to determine the predictive value and diagnostic precision of the maternal blood molecular profile for the early screening of EOPE. Late-onset preeclampsia (LOPE) and other pregnancy complications (such as preterm birth, intrauterine growth restriction, gestational diabetes, placenta previa, placental abruption, placenta accreta, premature rupture of preterm membranes, antepartum fetal death, uterine rupture and previous vasa, among others) could be analysed as a secondary outcome. Subjects will be 9585 pregnant women recruited between 9 and 14 gestational weeks. Participants will provide peripheral blood sample at three different times during pregnancy to be characterised at molecular level in the iPremom laboratories (Igenomix Preeclampsia SLU) after their obstetric outcome was known. Once the 50% of the total enrolment is achieved, an interim analysis will be conducted by an independent external committee. Data will be registered in an electronic Case Report Form (eCRF) specifically designed for this study. Monitoring activities and data verification will be performed during the whole study to ensure data quality, integrity and transparency. The total estimated duration of the study is 30 months, of which the first 18 months will correspond to the recruitment period of the participants.

Official Title
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Prospective Clinical Study for the Early Detection of Preeclampsia Based on the Molecular Screening at the First Trimester of Pregnancy

Conditions
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Preeclampsia

Intervention / Treatment
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* Procedure: Peripheral blood collection in cases group
* Procedure: Peripheral blood collection in control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients whose written informed consent approved by the Ethics Committee (EC) has been obtained, after having been duly informed of the nature of the study and voluntarily accepted to participate after being fully aware of the potential risks, benefits and any discomfort involved. Women over the age of 18 at the time of signing the informed consent form. Pregnant women with single gestation between weeks 9 and 14 of gestation. Exclusion Criteria: Known malignancy History of organ transplant or bone marrow transplant. Maternal transfusion in the last 8 weeks prior to taking the sample. Early gestational loss Existence of serious or uncontrolled bacterial, fungal or viral infections that, in the opinion of the investigator may interfere with the patient's participation in the study or the evaluation of the results of the study. Other circumstances or difficulties that, in the investigator's opinion, may suppose a risk to the subject or reduce the chances of obtaining satisfactory data to achieve the objectives of the study.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Cases group<br>Women recruited between 9 and 14 gestational weeks diagnosed with preeclampsia or other complication at the end of pregnancy | Procedure: Peripheral blood collection in cases group<br>* Maternal peripheral blood will be collected 3 times during pregnancy (1st, 2nd and 3rd trimester) and clinical data compiled in cases group<br>|
| Control group<br>Women recruited between 9 and 14 gestational weeks without diagnosis of preeclampsia or other complication at the end of the pregnancy | Procedure: Peripheral blood collection in control group<br>* Maternal peripheral blood will be collected 3 times during pregnancy (1st, 2nd and 3rd trimester) and clinical data compiled in control group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic precision of EOPE at molecular level | Sensitivity, specificity, positive and negative predictive value using the clinical outcome of pregnancy as a gold standard parameter | 33 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic precision of LOPE and other pregnancy complications at molecular level | Sensitivity, specificity, positive and negative predictive value using the clinical outcome of pregnancy as a gold standard parameter | 33 weeks | 
| Characterization of molecular profile in maternal blood | Molecular profile (DNA/RNA/proteins/metabolites) associated to gestational age, epidemiological and clinical variables | 33 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preeclampsia, Early onset Preeclampsia (EOPE), Late onset Peeclampsia (LOPE), First trimester, Early screening, Circulating RNA (C-RNA), Molecular profile, Blood