Detecting Trisomy 21: The Role of Non-Invasive Prenatal Screening

At the initial consultation, the healthcare professional collects a great deal of information. After a first assessment to establish your due date—to be confirmed later by ultrasound—the healthcare professional will ask about your current state of health, any medications you are taking, allergies you might have, and prior surgeries or experience with anesthesia. The healthcare professional will also review your family history and that of the child’s father. You will be asked about your physical activity, smoking status and working conditions, especially if you work in a high-risk environment. Your weight and blood pressure will also be recorded.

These health informations, combined with a physical exam, will be supplemented by blood and urine tests that will be used to check for common disorders such as anemia, diabetes, and immunity to certain infectious diseases. Your blood type and Rh factor will be determined, and you will be screened for a number of sexually transmitted and blood-borne infections (STBBIs), such as syphilis, human immunodeficiency virus (HIV), and hepatitis B.

The healthcare professional will provide you with information on fetal chromosomal screening, in particular trisomy 21, also called Down’s syndrome.

Trisomy 21 is by far the most common fetal chromosomal abnormality. Although it rarely occurs in young women (1 out of 1,528 births), its incidence increases rapidly with maternal age, with an incidence of 1 in 909 births among mothers aged 30 and 1 in 28 births in those aged 45 years.[3]

An accurate diagnosis of trisomy 21 depends on what is known as a karyotype test. This test analyzes a person’s chromosomes (humans are supposed to have 23 pairs of chromosomes). The sample collection methods for karyotyping, such as chorionic biopsy and amniocentesis, are considered invasive procedures that carry a significant risk of adverse effects, including miscarriage. Consequently, it is very important that only women exposed to a high risk of fetal abnormality undergo such procedures. Fortunately, other “non-invasive” methods can be used to assess the risk of trisomy.

Two exam types are available, usually accompanied by a nuchal translucency measurement when the ultrasound is done.

This test is offered free of charge by the MSSS to women who do not present any particular risk factor. It entails an analysis of a small number of biochemical components from two blood samples. The first sample is taken between the 10th and 13th week of pregnancy; the second, between the 14th and 19th week. The protein and hormone levels analyzed, which tend to be associated with maternal age and, often, nuchal translucency data, are used to assess the risk of the fetus carrying trisomy 21 or trisomy 18.

A low probability, namely less than 1/300, indicates a very low risk of delivering a baby with trisomy 21 (or 18), and no additional testing is required. In cases of high probability, i.e., greater than 1/300, another blood test, the non-invasive prenatal test (NIPT), will be recommended to the pregnant woman in order to more accurately assess the risk factor. The biochemical test cannot be used for multiple pregnancies.[3]

NIPT is based on the analysis of DNA fragments from fetal chromosomes normally found in maternal blood. These DNA fragments, representing each of the 23 chromosome pairs, can be analyzed to detect several anomalies, including the presence of extra chromosomes (trisomies). NIPT can be performed as early as the 10th week of pregnancy, without the need for biochemical testing in all instances.

Although more complex and costly than biochemical testing, NIPT has a much higher performance rate: it detects over 99% of fetuses carrying trisomy 21 versus 85% with the biochemical test. The number of false-positive results leading to unnecessary invasive sampling is also much lower with NIPT (0.3%) than with biochemical testing (3.6%).[4]

The different NIPT versions have very similar characteristics in terms of false-positive or false-negative results. However, they differ with respect to failure rate when the quantity of fetal DNA in the mother’s blood is very low or because of technical difficulties with tests that are not fully automated. Some tests have a failure rate of over 3%, or even 4%. The rate is around 0.1% with a fully automated analysis tool, like the Verifi test from Biron, which can be adapted to very low percentages of fetal DNA.[5]

The consequences of a high failure rate are anything but trivial. In many cases, mothers-to-be will require further sampling, resulting in additional delays that can be very distressing. Some of these women will have to undergo invasive techniques that, as already stated, have associated risks.[6]

The advantages of the Biron NIPT include:

• access to testing early in the pregnancy (as of the 10th week) without the need for a prior biochemical test
• availability throughout most of the pregnancy (between the 10th and the 40th week)
• fast results, namely in less than 5 days
• possibility of knowing the child’s sex as of the 10th week
• very high detection rates for trisomy 21, 18 and 13
• detection of abnormalities in the sex chromosomes (X, XXX, XXY, XYY)
• very low false-positive and failure rates, reducing the need for invasive techniques such as amniocentesis and chorionic biopsy
• privacy and confidentiality guaranteed by Biron thanks to attentive staff and low-volume waiting rooms
• reimbursable by most private insurers

With the nausea, physical changes, and very legitimate concerns about everything that is going on and what is to come, the first trimester of the pregnancy is generally the most anxiety-provoking.

The Internet is full of advice from health professionals about how best to approach the first trimester and the rest of the pregnancy. The Naître et grandir site provides a wealth of information, including a list of five ways to reduce stress:

• Learn to let go and think about your own well-being first by giving up non-essential activities.
• Take time to relax. Read, go for a walk or indulge in self-care like a nice warm bath.
• Remain active and pay attention to your diet and the quality of your sleep.
• Sign up for prenatal courses.
• Do not hesitate to share your concerns and needs with loved ones (spouse, family, friends, health professional).[7]

Biron can help ease the stress associated with some aspects of your first trimester. Ultrasounds, blood and urine tests, as well as prenatal genetic screening for trisomy 21 are just some of the services we offer.

We provide laboratory tests designed to help your doctor support you throughout your pregnancy.

Non-invasive prenatal test: Done in the first trimester of pregnancy, the Verifi test uses a blood sample to assess the risk of carrying a fetus with one of the most common congenital abnormalities: trisomy 21 (Down’s syndrome), trisomy 18 and trisomy 13.

Blood sampling and tests during the pregnancy: Different common tests are recommended in each trimester. These pregnancy follow-up exams can be performed at most of our sampling centres.