Dr. François Rousseau and Dr. Sylvie Langlois

Project Title

PEGASUS: PErsonalized Genomics for prenatal Aneuploidy Screening USing maternal blood


Each year in Canada, 450,000 women become pregnant. 70% of them choose to participate in population-based prenatal screening. The current approach, integrated screening, calculates a personal risk of having a fetus with Trisomy 21 (T21) from the combination of results of maternal serum biomarkers in the first and second trimesters with nuchal translucency (a fetal ultrasound marker). Among these women, the detection rate of T21 is 85%, with 4% having a positive screening result. This translates in approximately 10,000 pregnant women undergoing invasive prenatal diagnostic testing (amniocentesis) to confirm 315 cases of T21, at the cost of 70 procedure-related losses of unaffected fetuses. Several genomics-based non-invasive prenatal testing (NIPT) methods have been developed to detect fetal T21, and two other trisomies (T18 and T13), through genomic analysis of circulating cell-free fetal DNA in maternal blood.


The goal of the PEGASUS project was to provide the necessary evidence-base to make informed decisions around the implementation of genomics-based NIPT for aneuploidies (T21, T18, T13) by assessing the comparative performances of 2 NIPT techniques, the balance of benefits, harms and use of resources while taking into account the personal values of couples, and developing and validating appropriate educational and shared decision-making support tools. A total of 3,819 pregnant women were recruited for this study. Blood samples were obtained and NIPT assays were compared. Cost effectiveness simulations for the province of Québec were performed. A pan-Canadian survey of women, their partners and healthcare providers was conducted to explore the attitudes, values and concerns of these stakeholders. A legal analysis of providers’ liability for offering NIPT was conducted and an analysis of intellectual property issues related to NIPT technologies was performed through a workshop engaging leading experts in the field. Information and shared decision making tools were developed for prenatal screening for trisomies 13, 18 and 21 as well as for second-tier NIPT as a screening test prior to invasive testing. In addition, we have web based training programs for health professionals (e.g. midwifes, family physicians, obstetrician gynecologists).


The NIPT analysis of the full cohort has just been completed (April 2017), statistical analyses are ongoing and final results are expected during summer of 2017. Preliminary results for 3700 pregnancies tested blindly with two different NIPT methods in three different laboratories and compared to a reference standard test suggest a detection rate close to 99% and a false positive rate below 0.5% for T13, T18 and T21. NIPT performed in public clinical laboratories appears to have the same diagnostic performances as commercially available NIPT.  The data of the cost effectiveness simulation showed that implementation of NIPT as a second tier test, followed by amniocentesis if NIPT is abnormal, would be cost neutral in Québec and would reduce the number of invasive procedures by over 90%, and with them the number of fetal losses. Innovative informational resources, including video testimonials from parents raising children with T21, are under development. Decision-aid tools to promote and support shared decision making were developed and validated as well as their accompanying training programs, and research on their uptake will allow optimal use of these tools in Canada as NIPT is being rolled out.

Of note, the PEGASUS project involves 30 investigators and collaborators in 12 universities in Canada and abroad, as well as key Canadian stakeholders. PEGASUS project co-leaders also include Dr. Daniel Reinharz (U Laval) for the health economic analyses, Dr. Vardit Ravitsky (U of Mtl) and Dr. Tim Caulfield (U of Alberta) for the ethical, legal and social studies, Dr. France Légaré (U laval) and Dr. Brenda Wilson (U of Ottawa) for implementation tools. PEGASUS recruitment centers were lead by Dr. Sylvie Langlois (Vancouver), Dr. Jo-Ann Johnson (Calgary), Dr. Mark Walker (Ottawa), Dr. François Audibert (Montréal) and Dr. Jean Gekas (Québec City). The PEGASUS investigators directing the clinical laboratory validation and implementation of NIPT assays are Dr. Aly Karsan (Vancouver), Dr. Guy Rouleau (Montréal) and Dr. François Rousseau (Québec City).

Contact information

Dr. François Rousseau
Hôpital Saint-François-d'Assise
10, rue de l'Espinay
Québec (Québec) G1L 3L5
Tel: 418-525-4470
Email: francois.rousseau@mac.com

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