Study of the Efficacy of New Non-invasive Prenatal Tests for Screening for Fetal Trisomies Using Maternal Blood

Summary

Each year, 450,000 Canadian women become pregnant and, as a result of their participation in prenatal screening for Down syndrome, approximately 10,000 of them will have an amniocentesis (i.e. sampling of liquid surrounding the fetus) and of those, 315 will be found to carry a baby with Down syndrome and 70 normal pregnancies will be lost from complications of the procedure. It has been discovered recently that, during pregnancy, there is fetal DNA in maternal blood in sufficient quantities to be analysed and methods have been proposed to detect the presence or not of a fetus with Down syndrome using maternal blood. The introduction of genomic blood testing as proposed in the context of this project could lead to increased detection of Down syndrome, less invasive screening with 9700 amniocentesis avoided each year in Canada, improving the peace of mind of pregnant women, and preventing the accidental loss of 70 normal fetuses, at a lower overall cost than current practice. However, these methods still need to be validated before being appropriately introduced in routine care.

The study hypothesis is that new genomics-based non-invasive methods using fetal-DNA in maternal blood during pregnancy can be more effective than current prenatal screening methods for fetal aneuploidy.

This project will carry out an independent study that will validate the performance and utility of different new genomic technologies for screening in pregnant women using maternal blood. The team of researchers will compare the real-life performance of different non-invasive assays and strategies to screen for fetal aneuploidy, and identify an evidence-based cost-effective approach for implementation of this new technology in the Canadian health care system. The deliverables of this project will enable decision makers, pregnant women and their partner to make informed choices pertaining to prenatal genetic screening and diagnosis, such as screening for Down syndrome, and reduce the risk to pregnancies associated with amniocentesis.

Conditions

• Trisomy 21
• Trisomy 18
• Trisomy 13

Interventions

OTHER

Integrated prenatal screening for Down's syndrome

Analysis of several serum biochemical markers, and fetal nuchal translucency by ultrasound, with computation of an individual risk of fetal aneuploidy.

OTHER

Serum QUAD Assay for aneuploidy screening

Series of biochemical markers with results integrated into a computational estimate of risk of fetal aneuploidy

OTHER

Semiconductor MPSS NIPT assay using ccfDNA in maternal blood

Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using a targeted NIPT assay.

OTHER

Optical-based MPSS NIPT assay using ccfDNA in maternal blood

Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using an un-targeted NIPT assay.

OTHER

Harmony™ Test (Ariosa Diagnostics)

Test that is commercially available (Ariosa Diagnostics). (will be used for benchmarking purposes in a subset of each arm)

Sponsors & Collaborators

• Laval University

  collaborator OTHER

• Genome Canada

  collaborator OTHER

• Genome Quebec

  collaborator OTHER

• Genome British Columbia

  collaborator INDUSTRY

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• CHU de Quebec-Universite Laval

  lead OTHER

Principal Investigators

• Francois Rousseau, MD MSc FRCPC · Universite Laval and CHU de Quebec

• Sylvie Langlois, MD FRCPC · University of British Columbia

Study Design

Allocation

NON_RANDOMIZED

Purpose

SCREENING

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

19 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-11-30

Primary Completion

2017-06-30

Completion

2017-06-30

Countries

• Canada

Study Locations