Non-Invasive Prenatal Screening (NIPS)

As a prenatal genetic counsellor the most common question I am asked is, “What is the blood test to learn the baby’s sex?”. This test is called Non-Invasive Prenatal Screening (NIPS) and results include the sex of the baby and screening for specific genetic conditions.

How does the Non-Invasive Prenatal Screening (NIPS) work? 

Naturally there are cells that shed off the placenta and to move into the pregnant person’s bloodstream. Some of those cells pop open and release their DNA. By taking a blood sample from the pregnant person this free floating placenta DNA can be analysed. Due to this process another term for the test is cell free DNA testing.

What conditions are screened for in the test?

The screening provides information on whether the pregnancy is at high or low risk for specific genetic conditions. As highlighted above it can also reveal the sex of the baby. Males are expected to have an X and a Y chromosome, whereas females are expected to have two X chromosomes. The term “expected” is used here as there can be differences in the sex chromosomes, including having an extra sex chromosome in Klinefelter’s syndrome or a missing sex chromosome in Turner’s syndrome. These conditions can have a range of physical and developmental issues impacting traits such as fertility and height. 

The screening also includes other genetic conditions caused by extra chromosomes. Most people have two copies of each chromosome, however some people who have a genetic condition have an extra chromosome referred to as a Trisomy. Down syndrome is the most common trisomy condition which is caused by having an extra chromosome 21, therefore it is also referred to as Trisomy 21. The other two common extra chromosome conditions are Trisomy 13 and Trisomy 18. Some NIPS focus on these specific chromosomes, while others evaluate all the chromosomes. There are also NIPS that screen for microdeletion disorders; situations where pieces of a chromosome are missing. 

How accurate is the screening? 

NIPS is very accurate compared to other screenings. It has a high sensitivity (true positive rate) and specificity (true negative rate) of over 99% for most conditions. If you receive normal results (also known as low risk) the chance the test missed the conditions is typically around 1 in 10,000. This means there is still a 0.01% chance the pregnancy has a condition that was screened. 

If you received high risk results, it will be for a specific condition. As mentioned above Down syndrome is one of the most common conditions to be identified as high risk. The risk in these cases can be as high as 99% and is personalised based on a patient’s specific test. Therefore one person may receive a risk of 92% while another person receives a risk of 99%. 

What is the difference between NIPS and a CVS or amniocentesis? 

NIPS is a screening, therefore results show whether there is a low risk or high risk for specific genetic conditions. Another type of testing is invasive testing through either a chorionic villus sampling (CVS) or amniocentesis procedure. During the pregnancy the baby is surrounded by amniotic fluid which they are consistently drinking and peeing, so cells from their digestive tract are also released into the fluid. In these procedures a small piece of the placenta or a couple of tubes of amnio fluid, containing cells from the baby, are collected and sent to laboratories to analyse. These are considered diagnostic tests which provide a yes or no answer as to whether a pregnancy has a specific condition. Unlike NIPS, there is a risk of miscarriage after the invasive procedures, at a risk of between 1 in 400 and 1 in 800. This should always be taken into consideration when deciding whether to proceed with invasive testing.

When can I have a NIPS blood draw? How much blood is drawn?
Is there a risk to the pregnancy?

The blood draw for the non-invasive prenatal screening (NIPS) can be done as early as 9-10 weeks of pregnancy, depending on the laboratory your healthcare provider has selected. There is no end limit for the testing, so the test can also be performed in the second and third trimester. Most laboratories require one or two 10ml tubes of blood. There is no risk to the pregnancy, as this is a blood draw from the pregnant person’s arm and does not affect the fetus, and the risks for the pregnant person are those of a normal blood draw.

What are the two ways that laboratories analyse DNA from NIPS?

There are two main methods, massively parallel sequencing (MPS) and single nucleotide polymorphism (SNP). Most laboratories use the MPS method where all of the cell free DNA is analysed, including the DNA of the pregnant person. Then the ratio of DNA is evaluated for the chromosomes. For example, if there is an extra chromosome 21 identified, there is a higher risk for Down syndrome for the pregnancy. It is very unlikely the extra chromosome is from the pregnant person, by process of elimination it is probably from the pregnancy. 

In the SNP method, the pregnant person’s genetics and the pregnancy’s genetics are identified independently. People have differences in the spelling of their genetic code that makes them unique. These differences in spelling between people are known as “single nucleotide polymorphisms” or SNPs and is how the pregnant person’s genetics and the pregnancy’s genetics are sorted. The pregnancy’s genetics can then be focused on to screen for genetic disorders. Learn more about SNPs in our previous blog post. 

How quickly will I receive results? 

An average turnaround time for tests is five to ten calendar days. This will differ depending on the laboratory.

Can I do the test through an at home kit?

There are a few at home kits that claim to report the sex of the baby. However, the accuracy of the tests are not as high as medical grade testing you can receive through your healthcare provider. These at-home tests may not analyse all the chromosomes that are associated with genetic disorders, such as in the medical grade testing.

What is the cost of the test?

In the US, if you are over 35 years old at delivery, the test is most likely covered. In 2020, the American College of Obstetricians and Gynecologists (ACOG) published new guidelines, stating all pregnant people should be offered NIPS regardless of maternal age. This has led more insurance companies to increase their coverage for the screening. If the test is not covered, it will probably be a few hundred USD towards your deductible. Most laboratories also have cash options for a couple hundred USD which does not involve insurance companies. Ask your provider which laboratory company will be running your test and reach out to them directly for a personal quote. 

In the UK, NIPS for common genetic disorders (Down syndrome, Trisomy 13, and Trisomy 18) are included in the NHS service for high-risk pregnancies. For low-risk pregnancies, NIPS is available for a cost through private companies. In the UK these tests are typically ordered through midwives instead of genetic counsellors. (Thanks to Sarah C Robart for providing the UK genetic counselling perspective).

This article was originally published on Sano Genetics’ “Explained By A Genetic Counselor” blog series written by our genetic counselor, Kira Dineen.