Non-Invasive Prenatal Testing (NIPT), also termed Non-Invasive Prenatal Screening (NIPS), is successfully making its way across Europe and elsewhere to become a part of state-funded prenatal screening.
So how does NIPT actually work?
NIPT is a simple blood test like any other blood test. During pregnancy cell-free fetal DNA (cffDNA) are in the mother's blood. CffDNA originates from the trophoblasts making up the placenta. By counting the baby's DNA fragments, we can project how many copies of chromosome 21 there are.
Nowadays, NIPT is used predominantly as secondary screening test to calculate the risk of Trisomy 21 (Down syndrome). It can also calculate the risk of Trisomy 13 (Patau Syndrome) and Trisomy 18 (Edwards Syndrome) as well as detect sex of the foetus.
Does NIPT put the foetus at risk?
As a non-invasive screening test, the blood test holds no risk to the pregnancy.
For some NIPT manufacturers this is actually the test’s main selling point.
Invasive diagnostic tests such as amniocentesis or chorionic villus sampling (CVS) are accurate but carry a 1-2% risk of miscarriage (according to the manufacturer of NIFTY test).
We are all more or less anxious when it comes to invasive diagnostics such as amniocentesis or CVS. However, for example the manufacturer of NIFTY test has made it a point within their marketing campaign to feed the flames of this anxiety by accentuating the risk of miscarriage associated with invasive diagnostics.
According to the most recent studies however, the risk is actually much lower and stands at only 0.11%. Furthermore, it is primarily associated with “the same components of combined screening that lead to an increased risk for fetal aneuploidies and therefore uptake of CVS, such as an increased fetal nuchal translucency and decreased maternal serum pregnancy associated plasma protein-A (PAPP-A), are also associated with an increased risk for miscarriage and stillbirth. Caroline Ogilvie and Ranjit Akolekar, Pregnancy Loss Following Amniocentesis or CVS Sampling—Time for a Reassessment of Risk; Dr. P. Wegrzyn, Opinion to RCOG, Non-invasive prenatal testing for chromosomal abnormality using maternal plasma DNA, Scientific Paper No. 15, March 2014”
How sensitive is NIPT?
The fact that cffDNA originates from the placenta may affect the test’s accuracy.
Who should use NIPT?
Common experience tells us that if the ultrasound shows abnormalities in the baby (including, in our cases, nuchal thickness of >3 mm) you should undergo invasive diagnostics such as amniocentesis. NIPT is not non-invasive or miscarriage risk-free, thus safer alternative to the completely-reliable invasive diagnostic amniocentesis. Questions then arise for whom is NIPT actually designed, if not for high-risk pregnancies?
Currently NIPT can be considered in the following situations:
NIPT is not recommended:
An invasive test is recommended by some reliable manufacturers:
What are the limitations of NIPT?
The following disorders may not always be detected by NIPT:
NIPT is not a diagnostic test. Its results are based merely on statistical risk calculations. Therefore, NIPT will not offer you yes or not answer. Instead, NIPT, as any other prenatal screenings, will provide you with a risk score.
NIPT shows a low risk
This means that no indications have been found for the presence of an extra copy of chromosome 21.
A low-risk NIPT result cannot exclude Trisomy 21 100%. A market standard for the available NIPT tests is that out of 100 foetuses with Trisomy 21, NIPT detects a minimum of 99 and misses a maximum of one.
Our own NIPT low-risk scores for Trisomy 21 ranged from 1:1696661 to 1:4738. They were considered conclusive, and no genetic follow-up was recommended. Even so, six months after conducting NIPT we gave birth to children with Down syndrome.
NIPT shows a high risk
This is a strong indication, but does not necessarily mean the foetus has Trisomy 21. When NIPT shows an abnormal number of chromosome 21, the result needs to be confirmed by an invasive test: chorionic villus sampling or an amniocentesis.
This additional diagnostic test provides direct information about the foetus' genetic material, which is the only way to say with certainty whether the foetus has Trisomy 21.
NIPT is unclear or failed
This occurs in three to five percent of tests. NIPT fails, which means the test cannot determine your personal risk of a foetus with Trisomy 21. This is mainly due to insufficient foetal DNA in your blood. This is for instance possible if the blood test is taken too early (depending on a given test before 10-12 weeks), but also if you are obese. Some therapies, e.g. heparin therapy, can influence the quality of the test.
In summary, if you have your prenatal screening conducted with a view to confirming certain abnormalities beyond any doubt, especially when some Trisomy indicators such as high nuchal thickness are identified during ultrasound, NIPT is not for you. Even if you use the test, you should not rely solely on its results. Remember, these are only statistics, and you should know for sure. Don’t take the chance.