NON-INVASIVE TESTING
This is an innovative non-invasive prenatal screening test — simple, risk-free and highly accurate — which analyses free fetal cell DNA (cell-free DNA, cfDNA) in the pregnant mother's blood. Its purpose is to give a strong indication of whether the fetus is at high or low risk of a chromosomal abnormality.
NIPT is based on the discovery by Professor Dennis Lo and his colleagues that the total DNA in maternal plasma contains large amounts of fetal DNA (3.4%–6.2%). Its average concentration increases twelvefold during pregnancy, and it disappears two hours after birth. The method relies on a new technology known as massively parallel genomic sequencing, which within a few days can quantify millions of fragments of free DNA and give results with great sensitivity.
What NIPT detects:
- The commonest chromosomal abnormalities: Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), Patau syndrome (trisomy 13)
- Aneuploidies of the sex chromosomes: Turner syndrome (XO)
- Klinefelter syndrome (XXY), triple X (XXX), Jacobs syndrome (XYY)
- The sex of the fetus
- Where there are specific indications from the fetus, it is possible to test for certain microdeletion syndromes (DiGeorge, Angelman, Prader-Willi, Cri-du-chat and 1p36 deletion syndromes) at additional cost. In these cases, however, the number of cases tested so far is not large enough for the reliability of the results to be assessed with certainty.
Until now the only way to know for certain whether a fetus has a chromosomal abnormality has been through invasive tests such as chorionic villus sampling (11th–15th week of pregnancy) or amniocentesis (from the 16th week to the end of pregnancy).
These tests involve taking trophoblast tissue from the placenta, or amniotic fluid from the amniotic sac, with a needle, and carry a risk of miscarriage of about 1%. NIPT requires no procedure, as it is done with a simple blood test. It is therefore 100% safe for both the mother and the fetus.
The reliability of the test:
Clinical studies have shown that the method is extremely accurate in detecting the commonest fetal trisomies. It detects 99–99.5% of fetuses with trisomy 21, 98–99.6% of those with trisomy 18 and 80–100% of those with trisomy 13. It is still less accurate than amniocentesis or chorionic villus sampling, and for that reason it is not a diagnostic test. At the same time, it tends to be more accurate than first-trimester nuchal translucency.
Who can have NIPT:
- Any woman carrying a live fetus whose length on ultrasound corresponds to at least 10 weeks of pregnancy or more.
- Any pregnant woman who wishes to have non-invasive prenatal screening.
- Pregnant women whose biochemical and ultrasound findings in the first or second trimester show a high risk of chromosomal aneuploidy.
- For high-risk pregnancies in which invasive prenatal testing is contraindicated — for example placental abruption, an increased risk of miscarriage, HBV or HIV infection and so on.
- It can be requested for singleton pregnancies arising either from natural conception or after IVF treatment, whether with the mother's own eggs or with donor eggs, and even for a surrogate pregnancy.
The test is not always possible. In about 5% of cases no result is obtained. This is for technical reasons and has to do with the fact that the fraction of cfDNA circulating in the mother's blood may not be enough to isolate — the test is more likely to fail in obese women, for example.
For now the high detection rates quoted above are limited to trisomies 21, 18 and 13; other, rarer chromosomal abnormalities cannot be detected.
When the result is given:
Results are usually ready within 2 weeks, and both the treating doctor and the mother are notified immediately, by e-mail or by letter.
Interpreting the result: if NIPT shows an increased risk that the fetus has trisomy 21, 18 or 13, this does not mean that the fetus definitely has one of these syndromes, although it is extremely likely. In that case further testing with one of the invasive methods (amniocentesis or chorionic villus sampling) is indicated. Equally, a normal NIPT result does not guarantee a normal fetus.
When the test can be done and what is required:
NIPT can be performed from the 10th week of pregnancy. Any woman who wishes to have the test, and decides to do so after signing a consent form, has a simple blood sample of 10 ml of venous blood taken in our laboratory. The sample is then placed in a special tube and sent, together with all the mother's personal details, abroad (to the USA or Europe) where the test is carried out. No other laboratory tests are performed on this blood sample.
What are the limitations of NIPT?
The method is not diagnostic, which means that it cannot replace invasive testing for chromosomal abnormalities (chorionic villus sampling or amniocentesis). It detects more than 99% of fetuses affected by Down syndrome, while for trisomies 18 and 13 the detection rates are slightly lower.
If the test shows a low risk (below 1:10,000) of trisomy 21, 18 or 13, then the chance that the fetus is affected by one of these syndromes is very remote. Even so, there is an extremely small chance that some fetuses with trisomies are not detected, since not all chromosomal abnormalities can be diagnosed — because of mosaicism (the simultaneous presence of normal and abnormal cells) in the placenta, in the mother or in the fetus, or for other reasons.
In conclusion, free fetal DNA does not replace the accuracy of prenatal diagnosis by CVS or amniocentesis. Finally, all results must be interpreted by a clinician, taking into account the ultrasound findings as well as the clinical and family history.
Are other tests needed? As already mentioned, NIPT does not give information about other, rarer chromosomal abnormalities. It does not detect mosaicism or translocations and gives no information about structural abnormalities. It is therefore recommended that all the usual ultrasound examinations are carried out as normal — at 11–13 weeks and at 20–22 weeks to check the fetal anatomy, and at 30–32 weeks to check fetal growth.
Repeat samples
There needs to be enough fetal DNA in the maternal blood for NIPT to give a result. A higher maternal weight and an early gestational age may contribute to low levels of fetal DNA. If the amount of fetal DNA in the sample is not enough (in fewer than 5% of cases) a further blood sample will be needed from the mother. This is tested at no extra charge.
Which commercial tests are there, and where are they done?
- NIPT is carried out in the laboratories of particular companies in the USA and in Europe.
- Nifty Europe (BGI)
- Harmony -USA (Ariosa Diagnostics)
- Materni T21 Plus-USA (Sequenom)
- Verify-USA (Verinata)
- Panorama- USA (Natera)
The Embryocosmos centre performs all of the above tests apart from Nifty. Our medical staff are always available to talk with you and answer any question about this very important prenatal screening test.