Precision Medicine for Prediction & Prevention of Early Pre-eclampsia

Sunnybrook Health Sciences Centre

Status: Unknown

Conditions: Pre-Eclampsia

Treatments: Diagnostic Test: Enhanced PE Screening

Study type: Interventional

Funder types: Other

Identifiers

NCT04412681

PEprotocol

Details and patient eligibility

About

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).

Full 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.

Enrollment: 1,000 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Women with a singleton pregnancy > 18 years old
2. Not on low dose aspirin
3. Carrying a live fetus with crown rump length (CRL) between 41 and 84mm
4. Able to provide informed consent
5. Having a nuchal translucency ultrasound

Exclusion criteria

1. Women with a singleton pregnancy < 18 years old
2. Women currently taking low dose aspirin
3. Women declining a nuchal translucency ultrasound
4. Women unable to provide informed consent
5. Women with a multiple pregnancy
6. Women with a demised fetus or a CRL <41mm and >84mm

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

1,000 participants in 1 patient group

PE Enhanced Screening

Experimental group

Description:

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

Treatment:

Diagnostic Test: Enhanced PE Screening