Precision Medicine for Prediction & Prevention of Early Pre-eclampsia

Study Overview
=================
Brief Summary
-----------------
This study aims to evaluate the feasibility of implementing a clinical model for precision screening of early pre-eclampsia into the current prenatal screening service at Sunnybrook Health Sciences Center (SHSC).

Detailed Description
-----------------
Pre-eclampsia (PE) represents a pregnancy-specific systemic disorder that affects 3-8% of all pregnancies. In developed countries PE is considered a major public health problem responsible for severe maternal complications such as coagulopathy, renal and liver failure, stroke, and maternal death (>76,000 maternal death annually). The traditional approach to screening for preeclampsia endorsed by national guidelines is based on a combination of maternal characteristics along with medical, obstetric and family history. However, although these methods are simple and easy to perform, maternal factors can only identify less than 35% of all preeclampsia and approximately 40% of preterm-preeclampsia at a false- positive rate of 10%. More recently, multivariate analysis has been used to develop predictive models for preeclampsia that can be applied as early as 11-13+6 weeks gestation. One such algorithm, developed by the Fetal Medicine Foundation UK(MFM UK), incorporates maternal risk factors, uterine artery doppler, mean arterial pressure, and serum markers of placental function and placental growth factor. The FMFUK algorithm has been shown to predict approximately 75-90% of those women destined to develop preeclampsia prior to 37 and 34 weeks respectively, at a false positive rate of 10%. This algorithm has been validated prospectively in several studies, including the prediction of other placental mediated complications of pregnancy, such as fetal growth restriction and perinatal death. The new clinical model will include the following additions to the existing first trimester screening for aneuploidy: Additional Clinical History Blood pressure measurements Ultrasound for uterine artery Doppler measurements Expanded prenatal screening requisition Quality assurance training of ultrasound technicians for the uterine artery doppler measurements Fetal Medicine Foundation validated risk calculation algorithm Communicate results of the risk calculation algorithm from NYGH to SHSC and participant health care providers. While the ultimate goal will be to scale up and adapt this new clinical model, this protocol focuses on the feasibility of implementing the new clinical model at a single centre, Sunnybrook Health Sciences Centre.

Official Title
-----------------
Using Precision Medicine for the Prediction and Prevention of Early Pre-eclampsia: A Feasibility Study at Sunnybrook Health Sciences Centre.

Conditions
-----------------
Pre-Eclampsia

Intervention / Treatment
-----------------
* Diagnostic Test: Enhanced PE Screening


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women with a singleton pregnancy > 18 years old Not on low dose aspirin Carrying a live fetus with crown rump length (CRL) between 41 and 84mm Able to provide informed consent Having a nuchal translucency ultrasound Exclusion Criteria: Women with a singleton pregnancy < 18 years old Women currently taking low dose aspirin Women declining a nuchal translucency ultrasound Women unable to provide informed consent Women with a multiple pregnancy Women with a demised fetus or a CRL <41mm and >84mm

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PE Enhanced Screening<br>The PE screening program entails the following for all participants: provision of additional demographic and risk factors provision of mean arterial pressure standard nuchal translucency scan as part of their first trimester screening (FTS) with the addition of the measurement of the uterine artery Doppler by a certified sonographer standard blood sample (as part of the FTS) results of the PE screening (in the format of a screening report) will be provided to the study team and participant's healthcare provider | Diagnostic Test: Enhanced PE Screening<br>* To better identify women at risk for pre-eclampsia during pregnancy.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Screening Tool | Implementation of the screening: To assess the feasibility, the investigators will judge success if the full screening process without deviation is completed for at least 90% of consented participants. | 11.3-13.6 weeks gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of Screening | Reproducibility of the FMFUK studies. Planning a recruitment of 1000 participants and anticipating a 10% positive rate, the invetigators expect to follow 100 screen positive and 900 screen negative pregnancies. | 11.3-13.6 weeks gestation | 
| Acceptability of Screening Tool to Participants | Proportion of acceptance/offer to implementation study. The investigators expect to obtain consent from 80% of pregnant women eligible for the study. | 11.3-13.6 weeks gestation | 
| Compliance with low dose ASA for screen positive participants. | The investigators will assess the rate of initiation and maintenance of low dose ASA ( SHSC standard of care) as measured by phone follow-up at 16,22,26,32 and 36 weeks gestation, (2) follow-up at placental scan visit and (3) follow-up at delivery. Success will defined as 80% compliance. | 16-36 weeks gestation |