A new genomic test has just been added to the public prenatal screening program. Due to its high accuracy, this simple test will help reduce by 90% the number of amniocenteses performed on pregnant women most at risk for carrying a fetus with trisomy. 

Following in the footsteps of Ontario and British Columbia, the Government of Québec announced in April 2018 that it will add a genomic test to its prenatal screening program for trisomy 21 – or Down syndrome – for pregnant women most at risk. The test has existed for a few years now, but was not yet covered by the public health system.

This decision was based in large part on findings of the pan-Canadian PEGASUS study, spearheaded by François Rousseau, medical researcher at the Centre hospitalier universitaire de Québec-Université Laval Research Centre and at the Faculty of Medicine at Université Laval, and Sylvie Langlois, medical researcher at the Department of Medical Genetics at the University of British Columbia. Policymakers expect the test to reduce by 90% the number of amniocenteses.

Analyzing chromosomes in the mother’s blood

The two researchers conducted a study among 4,000 women and confirmed that they could detect 99% cases of Down syndrome by using a genomic test to analyze the blood of the mother, which mixes with the blood of the fetus during pregnancy. The standard test analyzes hormones and proteins and only identifies 85% of cases.

The genomic test involves sequencing 7 million fragments of DNA containing maternal blood to analyze fragments on chromosomes 13, 18 and 21. These chromosomes are the ones involved in trisomy. Children with trisomy have three, rather than two copies of one of these chromosomes. By counting the number of fragments from each chromosome, some of which come from the placenta, it is possible to detect the extra chromosomes. These indicate the presence of trisomy. In such a case, the mother is then advised to undergo an amniocentesis to confirm the diagnosis.

Focusing on women at risk

“Québec has chosen to offer this genomic test only to women who, based on the standard test, show an elevated risk of having a baby with trisomy,” explains Dr. François Rousseau. Currently, 2,600 women test positive for this elevated risk every year after undergoing the two standards blood tests taken in the 1st and 2nd trimesters. By April 2019, before sending these moms-to-be directly to an amniocentesis, they will be offered the publicly funded genomic test to confirm whether their baby is, in fact, at a high risk for trisomy.

“The genomic test is not intended to replace amniocentesis, which is still the only way to diagnose with 100% certainty cases of trisomy 13, 18 or 21 using a sample of amniotic fluid. The idea is to limit its use to high-risk cases,” notes Dr. Rousseau. He estimates that we could go from 2,600 amniocenteses a year to only 260. Currently, some 2,340 women needlessly face the stress of an amniocentesis. Of this number, 8 lose their baby due to complications associated with this invasive technique.

Testing all pregnant women?

Given the advantages of genomic screening, many experts believe it could become the method of choice for the detection of trisomy. François Rousseau and his team are convinced. As part of the PEGASUS 2 project, they will be documenting probative data on the advantages and disadvantages of replacing conventional blood tests with genomic screening for all pregnant women.

With conventional testing, only one in 20 positive results ends up being accurate. So could the genomic test help to reduce the stress that often comes with the traditional method? “We are conducting a randomized clinical trial among 10,000 pregnant women to determine if genomic testing will lead to a faster, more accurate diagnosis and whether it will reduce the level of stress of moms-to-be,” explains Dr. Rousseau.

The researcher and his colleagues also want to assess the costs and benefits of screening for other chromosome anomalies in fetuses using the genomic test.  “Many detectable anomalies have no real impact, so it may not be a detail worth sharing with parents-to-be,” he notes.

Finally, in order to train doctors and support couples who choose to undergo the genomic test, Dr. Rousseau and his team will study how to implement, on a large scale, the shared decision-making tools developed during PEGASUS 1.  In the end, what’s important for the researcher and his team is to be able to inform women of their screening options for trisomy so that each of them can make her own decision based on her personal values.