Non-Invasive Prenatal Testing

A Cypriot Geneticist explains

Since the discovery that DNA carries our genetic information in the form of a code, efforts began in the 70s in order to develop methods to read-out and decipher this code i.e. to sequence DNA. Since then, the DNA sequencing technology has been vastly improved and now it is regularly applied in prenatal testing, enabling the determination of the health and condition of an unborn foetus.

In order to gain more information on prenatal testing, we came in contact with Stelia Pissaridou, a geneticist working in a diagnostic laboratory in London, carrying out Non-Invasive Prenatal Testing (NIPT) at a daily basis. Stelia kindly agreed to tell us more about the science and technology behind NIPT as well as other useful information that can be found in the following interview.

• To begin with, can you tell us what we mean by the term Non-Invasive Prenatal testing (NIPT)?
• As its name implies, NIPT is a non-invasive test that screens for chromosomal abnormalities. It is completely safe as it only requires a 7ml blood sample from the mother and it can be done as early as 10 weeks onwards in the pregnancy.
• Can you describe the process of NIPT at your lab?
• Briefly, we first receive the blood samples and log them in our system appropriately. Then, we extract the plasma from the maternal blood and then from that we further extract the cell-free DNA (cfDNA). Next, we prepare Next Generation Sequencing libraries (collection of DNA fragments) using the isolated cfDNA which is finally sequenced on a Next Generation Sequencer in order to unravel the genetic information.

Plasma extraction from maternal blood

• Can you describe the science behind NIPT?
• NIPT basically uses cell-free maternal DNA which includes a small percentage of cell-free DNA originating form the placenta of the foetus.
• What does NIPT check for?
• It screens for Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome) as well as sex chromosome aneuploidies (Turner’s, Klinefelters, Triple X) and of course foetal sex determination (if parents wish to know — some prefer the surprise!).

Sequencing cell-free DNA from maternal blood

• What are the most common abnormalities that you see and how often do you see them?
• Most common is trisomy 21 (Down’s syndrome) and is more often in mothers of advanced maternal age. Frequency depends on your sample type, i.e. if the mother is of advanced maternal age (>35 years old), if there was a previous history of an affected pregnancy etc. So it depends what population you are testing.
• What happens next if you detect an abnormal number of chromosomes?
• We report the aneuploidy and we also offer genetic counselling to the expecting parents if they want to. The genetic counsellor can explain in detail the results and also explain and discuss with the couple all the options they have. The counsellor also explains what a genetic screening is and is then a responsibility of the expecting parents’ physician to advise them further. For positive results we would recommend that the couple follow up the results with an invasive test before making any decisions, as NIPT is a screening test and false positives can occur. If it’s a suspected result, we welcome a redraw free of charge.
• How accurate are the results?
• The test has a 98.89% sensitivity and 99.79% specificity, so very accurate.
• How long does it take to get the results?
• We, as a lab quote 3–5 working days, i.e. 7 calendar days from the day we receive the blood sample.
• Who normally takes these tests and whom do you advise to take these tests?
• We do not advise patients as we are only a testing laboratory but most physicians recommend it. There are some test indications like advanced maternal age, history of an affected pregnancy, a positive/high serum screen and of course an abnormal ultrasound. The test however can be done for every woman who wishes to take it for a peace of mind. There are also parents that cannot wait and only take the test to learn the gender of their baby. Also, many pregnant women use forums and discuss with each other, so if one has taken the test, she will recommend it to others.
• How does NIPT differ from other prenatal tests?
• What I believe is the most important thing, is the fact that it is the earliest way (and safest) to test whether a pregnancy is healthy or not. As I mentioned earlier, the test can be done from as early as 10 weeks in the pregnancy and with just a tube of blood. Before NIPT, the only option after a high-risk serum screen (poor performance metrics) was an amniocentesis or a chorionic villus sampling (CVS), both carrying a miscarriage risk. Now you have the option of a genetic screening without the risk of a miscarriage.

We would like to thank Stelia Pissaridou for providing us with the information required to write this article.

For further information regarding NIPT you may contact Stelia directly at stelia.pissaridou@genesisgenetics.org or visit the site: http://www.genesis-serenity.com/?gclid=CL7o8dncptMCFYoK0wodPAkBqA