First-trimester Prediction of Preeclampsia (PREDICTION)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02189148 |
Recruitment Status :
Completed
First Posted : July 14, 2014
Last Update Posted : July 23, 2019
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease |
---|
Preeclampsia Severe Preeclampsia Fetal Growth Restriction Preterm Birth |
Background: Preeclampsia (PE) is a placenta-mediated pregnancy complication related to adverse maternal and neonatal outcomes, including intra-uterine growth restriction (IUGR) and perinatal death. A growing body of evidence suggests that the preterm and severe forms of PE are associated with deep placentation disorders that occur early in gestation. Over the last decade, maternal characteristic and first-trimester biomarkers, including some that are already used for aneuploidy screening (PAPP-A) have been strongly related to the preterm and early forms of PE, suggesting that early prediction is possible. Preventive measures are actually recommended (low-dose aspirin; calcium) or under investigation (folic acid; low-molecular weight heparin; anti-oxidant) in high-risk women. However, only women with chronic disease or prior adverse pregnancy outcomes are eligible for these measures while most cases of PE occur in nulliparous women. Moreover, there are actually no clear guidelines for clinicians in Canada whose pregnant patients have one or several risk factors for preeclampsia (obesity, chronic hypertension, low PAPP-A, etc.). On the other hand, it has been suggested that prediction of PE, and particularly the most severe cases, is possible with high sensitivity and specificity by using a combination of anamnestic, biophysical, biochemical and ultrasonographic biomarkers using the web-based Fetal-Medicine Foundation (FMF) screening test. This suggests that a strategy of prediction and prevention of PE and other placenta-mediated complications is becoming possible for nulliparous women as well. However, certain major concerns must be addressed: 1) The FMF screening test has not been validated prospectively; 2) a controversy exists about the need and feasibility of Doppler ultrasound in the general population.
Objectives:
- To validate the 11-13 week FMF screening test for early-onset PE and a composite of placenta-mediated outcomes (preterm PE, IUGR <3rd percentile, stillbirth); and
- To compare the screening test with and without uterine artery (UtA) Doppler;
- To explore the efficiency of new potential biomarkers (ADAM-12; Placental protein (PP) -13; placental and subplacental volume; placental vascularization) for prediction of PE in our population.
Methods: A multicenter prospective observational study of nulliparous women recruited between 11 3/7 - 13 6/7 weeks (maternal characteristics; BMI; Mean arterial pressure (MAP); PAPP-A; placental growth factor (PIGF); UtA Doppler…) and followed until delivery. Delivery and neonatal data will be collected through chart reviews. Detection rates for early-onset PE (primary outcome) and other adverse pregnancy outcomes will be measured using the 11-13 weeks FMF screening test with and without UtA Doppler results. A case-cohort study will be performed using stored serum samples and three-dimensional ultrasound volume acquired at the 11-13 weeks visit.
Feasibility and power calculation: We estimate a minimum incidence of early-onset PE of 0.7%. A minimum of 7,600 women will be necessary to demonstrate that the FMF screening test is at least 80% sensitive and 90% specific where it is expected that it will be 95% sensitive and 92% specific. We will have the power to detect an absolute difference of 15% in the detection rate between the different screening strategies (± Doppler). Recruitment will take 3.0 years. The overall study will take 5.0 years.
Expectations: First, our research will potentially provide a validated, highly sensitive and specific, and cheap tool to help clinicians' decision in the care of nulliparous women with risk factors for PE. In case of negative results, the clinician will have good evidence to reassure the patients facing abnormal maternal serum screening values. The validation of a first-trimester screening strategy will strengthen clinical research on PE providing new information on the natural evolution of the disease. Finally, this study will contribute to develop the optimal design for randomized trials aiming at the prevention of early-onset PE and other placenta-mediated complications of pregnancy.
Study Type : | Observational |
Actual Enrollment : | 7554 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Official Title: | First-trimester Prediction of Preeclampsia and Other Placenta-mediated Pregnancy Complications |
Study Start Date : | November 2014 |
Actual Primary Completion Date : | December 2017 |
Actual Study Completion Date : | March 2018 |

Group/Cohort |
---|
Cohort
Each participant will :
|
- early onset preeclampsia [ Time Frame: diagnosed between 20 and 34 weeks of gestation ]Preeclampsia will be defined according to the Canadian Guidelines for Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy guidelines, as de novo hypertension with diastolic blood pressure >90 mmHg on two occasions at least four hours apart, after 20 weeks of pregnancy, associated with proteinuria ≥300 mg/24 h or at least '2 +' protein on urine dipstick or an adverse conditions
- Severe preeclampsia [ Time Frame: between 20 and 42 weeks of gestation ]Severe Preeclampsia will be defined by the presence of at least one of the following adverse condition: 1) systolic blood pressure ≥ 160 mmHg and diastolic blood pressure ≥ 110 mmHg after 4 h of bed rest, 2) proteinuria ≥ 5 g/24 h or at least '3 +' protein on urine dipstick, or 3) oliguria < 400 ml/24 h; 4) cerebral or visual disturbances; epigastric pain; pulmonary edema or cyanosis; thrombocytopenia <100,000mm
- Fetal growth restriction [ Time Frame: between 20 and 42 weeks of gestation ]Fetal growth restriction will be defined as a birth weight below the 10th centile (or below the 3rd centile for severe FGR) of Canadian reference growth charts.
Biospecimen Retention: Samples Without DNA

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
Nulliparous women who will deliver in one of the participating center:
CHUL Hospital, Quebec city, QC Hôpital Saint-François-d'Assise, Quebec city, QC CHU Ste-Justine, Montreal, QC Southern Alberta Maternal Fetal Medicine Centre, Calgary, Alberta Sinai Health System, Mount Sinai Hospital, Toronto, Ontario
Inclusion Criteria:
- gestational age between 11 3/7 and 13 6/7 weeks;
- nulliparous women (no previous delivery ≥ 20 weeks).
Exclusion Criteria:
- pregnant women <18 years old at recruitment;
- multiple pregnancies;
- fetal congenital malformation;
- positive for HIV or hepatitis C or hepatitis B;
- negative fetal heart at recruitment;
- women planning a delivery outside the participating hospitals;
- women not able to provide an informed consent to the study.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02189148
Canada, Alberta | |
South Alberta Maternal Fetal Medicine Centre, University of Calgary | |
Calgary, Alberta, Canada | |
Canada, Ontario | |
Sinai Health System, Mount Sinai Hospital | |
Toronto, Ontario, Canada, M5G 1X5 | |
Canada, Quebec | |
CHU Ste-Justine | |
Montreal, Quebec, Canada, H3T 1C5 | |
CHU de Québec | |
Quebec city, Quebec, Canada, G1V 4G2 |
Principal Investigator: | Emmanuel Bujold, MD, MSc | CHU de Québec | |
Principal Investigator: | François Audibert, MD, MSc | St. Justine's Hospital |
Responsible Party: | Emmanuel Bujold, Principal Investigator, CHU de Quebec-Universite Laval |
ClinicalTrials.gov Identifier: | NCT02189148 |
Other Study ID Numbers: |
CIHR-MOP-133672 B14-05-2024 ( Other Identifier: CER-CHU de Quebec ) |
First Posted: | July 14, 2014 Key Record Dates |
Last Update Posted: | July 23, 2019 |
Last Verified: | July 2018 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Prediction Preeclampsia Preterm birth Pregnancy Placenta Intra-uterine growth restriction |
fetal growth restriction Ultrasound Doppler Biomarkers PAPP-A Placental growth factor (PlGF) |
Premature Birth Pre-Eclampsia Fetal Growth Retardation Obstetric Labor, Premature Obstetric Labor Complications |
Pregnancy Complications Hypertension, Pregnancy-Induced Fetal Diseases Growth Disorders Pathologic Processes |