Predicting Late-onset Preeclampsia at 10-14 Weeks of Pregnancy

NCT ID: NCT04075708

Last Updated: 2020-10-19

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

COMPLETED

Total Enrollment

1427 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-08-13

Study Completion Date

2020-09-01

Brief Summary

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The aim of this study is to make it easier to predict late-onset preeclampsia at 11-14 weeks of pregnancy. This will be done by measuring certain proteins in the mother's blood together with obtaining the mother's medical history, ultrasound of the mother's blood supply to the uterus, and her blood pressure.

All expectant mothers who meet the inclusion criteria will be invited to participate in the study, and those that agree will have the above mentioned factors measured at their first trimester scan appointment. The data will be registered in an online database, and the blood samples will be saved in a biobank at the hospital.

When the women have then given birth around six months later, the data will be analyzed, and whether or not the individual woman ended up developing preeclampsia will be found out from her medical records. It will then be possible to see if blood samples, medical history, blood supply to the uterus, and/or blood pressure are connected to development of preeclampsia.

Detailed Description

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The aim of this study is to improve the current first-trimester screening regimes for early detection of late-onset preeclampsia (PE) using maternal serum biomarkers in combination with maternal history, uterine artery flow, and mean arterial blood pressure.

Hypothesis: Matrix metalloproteinase 7 (MMP-7) in combination with maternal history, uterine artery flow and mean arterial blood pressure can improve the detection rate of late onset PE.

The Fetal Medicine Foundation (FMF) algorithm is developed with the objective of identifying women at high risk of PE in the first trimester of pregnancy, allowing for effective prophylactic use of low-dose acetylsalicylic acid (ASA) started before 16 weeks of pregnancy. The algorithm utilizes Bayes' theorem by combining maternal characteristics and medical history with uterine artery pulsatility index (PI), mean arterial pressure (MAP), maternal serum pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF) and has been validated in several populations. It has been shown to identify up to 90% of early-onset PE (EO-PE) cases, however, the detection rate of late-onset PE (LO-PE) remains low and the biomarkers PAPP-A and PlGF do not appear to significantly improve performance of screening for these cases compared to screening by maternal characteristics and medical history alone.

An abundance of biomarkers have been suggested and researched for the prediction of LO-PE and of these, matrix metalloproteinase 7 (MMP-7) has shown to be a potentially useful predictor with a sensitivity of 69% at a false positive rate (FPR) 20% at 8-16 weeks of pregnancy. Additionally, MAP appears to be a relatively good predictor for LO-PE at the same gestational age (GA). Ultimately, the search for more accurate biomarkers and prediction models for PE and especially for LO-PE remains relevant and necessary, both with regards to improving antenatal care and taking the necessary precautions for PE mothers, researching potential treatments, and gaining a better understanding of PE pathophysiology altogether.

This study will be a nested case-control study carried out as a sub-study of the larger multicenter study "Preeclampsia Screening in Denmark" (PRESIDE) comprising six major hospitals in Denmark, including Odense University Hospital (OUH). Throughout the time period September 2019 to March 2020, 1400 participants are expected to enroll in PRESIDE through OUH with the goal of validating the FMF screening algorithm in a Danish population. These women will be giving birth from March to June 2020. In our sub-study, the case group will consist of women diagnosed with PE after 34 weeks of gestation. With an expected late-onset PE incidence of 2,5%, the sample size of the case group will be n=35. The control group will include 165 participants who were not diagnosed with PE in their pregnancies.

All information regarding maternal characteristics and medical history are collected as part of standard procedure during first trimester screening for chromosomal abnormalities and is stored in theOUH fetal medicine database Astraia. Uterine artery flow values will be entered in Astraia along with these data. Mean arterial pressure (MAP) measurements will be automatically transferred to a REDCap database where all study data, including consent forms and outcome data, will be stored. For all participants, information regarding pregnancy and neonatal outcome will be collected from registers and individual patient files. The collected blood samples will be stored and analyzed after the child is born and hence, the PE risk will only be calculated after delivery. Venous blood will be sampled, and aliquots will be stored as part of a research biobank and a biobank for future research at the Department of Clinical Biochemistry and Pharmacology (KBF), OUH. The samples for measurement of MMP-7 will be taken from the biobank for future research and will be performed in the Biomarker Laboratory at the KBF research unit by an automated immunoassay analyzer system (Tritius) using a Human Total MMP-7 Quantikine ELISA Kit.

The cohort consists of pregnant women assigned to the Department of Obstetrics at Odense University Hospital for their first trimester nuchal translucency between September 2019 and March 2020; who are included/excluded according to the criteria; and who agree to enroll in the study. The potential participants will receive information about the study by e-boks (online communication platform) when they book their appointment for the first trimester scan and will be approached by project staff upon arrival to the department on the day of the scan. Those who agree to receive more information will be orally informed by project staff about the project and its implications. Each participant will provide written consent followed by blood sampling, MAP measurements, and ultrasound procedures.

Conditions

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Preeclampsia

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Case-group

The case group will consist of women diagnosed with PE after 34 weeks of gestation.

No interventions assigned to this group

Control-group

The control group will include 165 participants who were not diagnosed with PE in their pregnancies.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* A planned first trimester nuchal translucency scan
* Informed consent
* Gestational age 11-14 weeks at the first trimester scan

Exclusion Criteria

* Age \< 18 years
* ≥ 2 fetuses
* Participants must read and understand Danish or English
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Southern Denmark

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lene Sperling, M.D., PhD

Role: STUDY_CHAIR

Odense University Hospital

Locations

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Odense University Hospital

Odense, , Denmark

Site Status

Countries

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Denmark

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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2019-031 PIKBF PRESIDE

Identifier Type: -

Identifier Source: org_study_id

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