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

Not Applicable

Completed

• Conditions: Trisomy 21; Trisomy 18; Trisomy 13
• Interventions: Other: Integrated prenatal screening for Down's syndrome; Other: Serum QUAD Assay for aneuploidy screening; Other: Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Other: Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Other: Harmony™ Test (Ariosa Diagnostics)

• Registration Number: NCT01925742
• Lead Sponsor: CHU de Quebec-Universite Laval

Brief 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.

Detailed Description

The present study is a real life comparative effectiveness study that will compare the performances and costs of several prenatal screening modalities for fetal aneuploidy (see interventions).

Study Timeline

• Study First Submitted: 2013-08-16
• Study First Submitted QC: 2013-08-16
• Study First Posted: 2013-08-20
• Study Start: 2013-11
• Status Verified: 2016-04
• Primary Completion: 2017-06
• Study Completion: 2017-06
• Last Update Submitted: 2018-02-21
• Last Update Posted: 2018-02-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 3819

Inclusion Criteria

Not provided

Exclusion Criteria

• women with multiple gestations
• women with twin demise (spontaneous or elective) at any gestational age
• women with active or history of malignancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low Risk of aneuploidy	Semiconductor MPSS NIPT assay using ccfDNA in maternal blood	Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics)
Low Risk of aneuploidy	Optical-based MPSS NIPT assay using ccfDNA in maternal blood	Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics)
High risk of aneuploidy	Integrated prenatal screening for Down's syndrome	Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics) (subset)
Low Risk of aneuploidy	Integrated prenatal screening for Down's syndrome	Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics)
Low Risk of aneuploidy	Serum QUAD Assay for aneuploidy screening	Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics)
High risk of aneuploidy	Serum QUAD Assay for aneuploidy screening	Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics) (subset)
Low Risk of aneuploidy	Harmony™ Test (Ariosa Diagnostics)	Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics)
High risk of aneuploidy	Semiconductor MPSS NIPT assay using ccfDNA in maternal blood	Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics) (subset)
High risk of aneuploidy	Optical-based MPSS NIPT assay using ccfDNA in maternal blood	Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics) (subset)
High risk of aneuploidy	Harmony™ Test (Ariosa Diagnostics)	Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics) (subset)

Primary Outcome Measures

Name	Time	Method
Number of cases with Fetal trisomy 21, 18 or 13	6 weeks after the delivery date	Only pregnant women will be recruited, fetal outcome will be assessed by fetal karyotype or at or after delivery.

Secondary Outcome Measures

Name	Time	Method
Number of women with assay failure	At end of pregnancy.

Trial Locations

Locations (5)

Foothills Medical Centre; 🇨🇦 Calgary, Alberta, Canada

Children's & Women's Health Centre; 🇨🇦 Vancouver, British Columbia, Canada

CHU de Québec; 🇨🇦 Quebec City, Quebec, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

CHU Ste-Justine; 🇨🇦 Montreal, Quebec, Canada