So you've had a previous pregnancy with trisomy 18, and you're pregnant again and considering testing options. Or maybe your baby has clinical features of trisomy 18 on ultrasound and you're wondering if you can avoid an amniocentesis by scheduling a non-invasive test. Or you've had a non-invasive test that came back as ‘positive’ for trisomy 18 and you want to know how accurate it is.
Either way, here is the low-down on non-invasive testing.
What is Non-Invasive Prenatal Testing?
Non-Invasive Prenatal Testing (NIPT) involves taking a blood sample from you, at any time from 9 to 10 weeks of pregnancy (as dated by ultrasound). The sample is sent off to a lab which analyses the cell-free fetal DNA in your blood. Fragments of your own DNA (cell-free maternal DNA) and fragments of your baby's DNA (cell-free fetal DNA) circulate in your blood from around the 4th to 5th weeks of pregnancy, but do not reach detectable levels until around 9-10 weeks.
What does NIPT screen for?
NIPT can be used to screen for an increasing number of conditions. The standard non-invasive tests offered privately in the UK (and occasionally on the NHS as part of a research trial) screen for the three most common chromosomal disorders:
- Trisomy 21 (Down's syndrome)
- Trisomy 18 (Edwards' syndrome)
- Trisomy 13 (Patau's syndrome)
Each test may also screen for other rare genetic conditions, but their detection rates for these conditions are often lower. Most non-invasive testing can tell you your baby's sex.
NIPT has also been used to screen for single-gene disorders such as achondroplasia and Apert syndrome, for cystic fibrosis, and for sex-linked genetic disorders. These tests are currently only offered to families at high risk.
If I get a positive result on a non-invasive test, does that mean my baby definitely has trisomy 18?
No. All non-invasive tests for aneuploidies are considered to be screening tests, not diagnostic tests.
- A screening test shows whether your baby is at high or low risk of having the condition.
- A diagnostic test tells you whether your baby has or hasn't got the condition.
It is currently recommended that ‘positive’, or ‘high-risk’, non-invasive test results for trisomy 21, 18 or 13 are followed up with a diagnostic test, like amniocentesis or Chorionic Villus Sampling (CVS), to confirm the result.
If it is just a screening test, why am I paying £600 for it? Why not just have the normal NHS screening?
NIPT tests are more accurate screening tests than any screening tests currently available on the NHS.
Most NIPT tests, for example, are 99.9% accurate at detecting fetuses with Down's syndrome. So for every 1000 women who are told they are at high risk of having a baby with Down's syndrome after having one of these tests, 999 will indeed have a baby with Down's syndrome. One women's follow-up diagnostic test will turn out to be negative.
With combined screening (the standard NHS offering), around 90% of fetuses with Down's syndrome will be detected, and the false positive rate will be less than 3%. This means that 10% of fetuses with Down's syndrome will not be identified at the combined screening, and 3 in 100 women's follow-up diagnostic tests will turn out to be negative.
One further reason to consider NIPT over combined screening is that the latter is only possible between 10 and 14 weeks of pregnancy. If for some reason you have missed this window, you will be offered the quadruple test instead, between 14 and 20 weeks of pregnancy. However, not only is the quadruple test less accurate than the combined test; it also, in many cases, only tests for trisomy 21 (though trisomy 18, as well as spina bifida, may be tested for at some hospitals or in some circumstances). NIPT has no cut-off date.
Can a positive NIPT result be wrong?
NIPT is highly accurate, but it is possible to get a false positive. This usually occurs for one of the following reasons:
- There was a twin present, whose DNA remains circulating alongside the surviving baby's. It is not always possible to identify the presence of a twin who miscarried very early on using ultrasound.
- The fetal DNA comes from the placenta. It is possible for the placenta to contain abnormal DNA even though the baby does not (this is known as ‘confined placental mosaicism’).
- Maternal DNA is mistaken for the baby's and a maternal problem is incorrectly identified as a fetal problem.
Can a negative NIPT result be wrong?
Yes. Detection rates, especially those for trisomy 18 and trisomy 13, vary widely between tests. If the test is done early on in pregnancy, it may be that the levels of fetal DNA are not yet high enough. If the mother has a raised BMI, this may make the test less accurate due to higher levels of cell-free maternal DNA. And, as with any lab procedure, there can be errors in testing at times.
My first baby had trisomy 18. Will the test detect my first baby's DNA in my blood, and does that make it more likely that I'll get a positive result?
Cell-free fetal DNA clears from maternal blood within 72 hours of birth, so this is very unlikely to be a problem. You can have non-invasive prenatal testing even if you had a previous baby with a trisomy.
I'm having twins. Can I have NIPT?
Yes. NIPT for twins and multiples is possible. If your twins are identical, then it is straightforward, and may indeed be easier than with a singleton as there will be higher amounts of cell-free fetal DNA circulating. If your twins are non-identical, then it is possible to identify whether one twin has the condition (although not which one), and even to identify how much DNA there is from each twin in your blood. This is all still being looked at, and some tests are better than others for multiple pregnancies, so it is worth asking about the accuracy for twins when deciding which test to opt for.
So I've decided to go ahead with NIPT, but Panorama, NIFTY, MaterniT21, Harmony... what's it all about?
These are different brands of NIPT, and they test in different labs, cost different amounts and are more or less easily available. It is worth considering what you are testing for. Below are the main tests available in the UK.
- Genesis Serenity
(NHS North East Thames Regional Genetics Laboratory,
Great Ormond Street)
(NHS West Midlands Regional Genetics Laboratory,
Birmingham Women's Hospital)
It is worth asking...
- What are the detection rates for trisomy 21, trisomy 18 and trisomy 13?
- What is the false positive rate for each of these? (That is, how many women who get a positive result will not actually have a baby with the condition?)
- What else are you screening for, and what are the detection and false positive rates for that?
- How do I access the test? (For the NHS laboratories, you may need an NHS referral.)
- How much does the test cost?
- How long will it take to receive the results?
- How will the results be reported? (Some are reported as risk factors – eg. ‘1 in 10000’ – and some as ‘positive’ or ‘negative’.)
- How early in pregnancy can I have the test?