Non-inavasive prenatal testing (NIPT)
What is NIPT?
Non-invasive prenatal test (NIPT) is a blood test taken from the mother from as early as 9+1-10+0 weeks’ gestation, to give an indication of whether the baby is at high or low chance of having trisomy 21 (Down syndrome). It can also be used to screen for trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome).
NIPT is a screening test. Published data for the Illumina NIPT shows a detection rate of of 99.9%of cases of trisomy 21, 18 and 13.
NIPT is not a diagnostic test. For a definitive answer, an invasive test such as chorionic villous sampling (CVS) or amniocentesis is recommended.
Which NIPT do you recommend?
We recommend Illumina testing for screening for trisomies 21, 18 and 13. We no longer offer Harmony testing as we have been made aware of it's higher "no result" rate when compared with Illumina.
We can also offer the SAFE test and Panorama test (including the extended microdeletion panel). Please enquire for more information.
How does NIPT work?
During pregnancy, the placenta (afterbirth) releases tiny fragments of DNA into the mother’s bloodstream. By looking at the placental DNA in the mother’s blood, NIPT is able to predict whether or not the baby is more likely to have a chromosomal condition such as Down’s syndrome, Edward’s Syndrome or Patau’s Syndrome.
Who can have NIPT?
NIPT can be performed in women aged 18 years or over and with a singleton or twin pregnancy at any stage of pregnancy from 9+1 weeks (Panorama) or 10+0 weeks (Illumina and SAFE), but the gestation must be confirmed by an ultrasound scan. Please be aware that the "no result" rate may be higher, the earlier in gestation the test is performed.
Most NIPT cannot currently be used for multiple pregnancies other than twins, in the case of a “vanishing twin” or if you have active cancer, an underlying chromosomal or genetic condition, or if you have undergone a blood transfusion, transplant surgery, immunotherapy or stem cell therapy in the last 3 months. Please discuss this with us if this is the case and we can advise on the most appropriate course of action.
What might the results of Illumina testing show?
Low probability of trisomy 21, 18 and 13
In the majority of cases, Harmony will show that there is a low probability that the baby has these conditions. This is usually reported as a chance of less than 1 in 10,000. A low probability result does not completely exclude the possibility that the baby has trisomy 21, 18, or 13.
High probability of trisomy 21, 18 or 13
In a small number of cases, the Harmony test shows that there is a high probability that the baby has trisomy 21 or 18 or 13. This is usually reported as a chance of more than 99 in 100. This does not mean that the baby definitely has one of these conditions. I will discuss the next step with you should this occur. An invasive test will be necessary (CVS or amniocentesis) if you want to be certain if the baby has one of these conditions.
Inconclusive
In about 2% of cases the test does not give a result (more common in multiple pregnancies). This is usually due to technical problems with the analysis of the sample related to insufficient levels of fetal DNA in the blood sample and does not necessarily mean that there is a problem with the baby. I will discuss the options with you, should this occur, but the test can be repeated (at no extra cost) with a successful result in 50-60% of cases.
How accurate is Illumina?
The "accuracy" of a screening test is usually defined by:
1. The detection rate (the proportion of affected pregnancies which are correctly identified by the test as being “high probability”).
2. The positive predictive value (the likelihood that an individual with a “high probability” test result truly has the condition)
3. The false positive rate (the proportion of unaffected pregnancies which are incorrectly identified as “high probability”).
The detection rate for trisomy 21 is more than 99 in 100 and the false positive rate is less than 1 in 1000. This means NIPT can correctly identify 99 out of every 100 pregnancies that have trisomy 21 and that for every 1000 negative tests, one baby will actually have trisomy 21. The positive predictive value is dependent on your background risk, but overall is about 80% which means that if you have a “high probability” result, the chance that your pregnancy is affected with trisomy 21 is 4 out 5 (80%).
The detection rate for trisomies 18 and 13 is also reported as 99 in 100 and the false positive rate is less than 1 in 1000. Previous studies have suggested that the overall positive predictive value for trisomy 18 is 37%. The detection rate and false positive rate for trisomy 13 are similar to trisomy 18, but the certainty of this is less well established. The positive predictive value is about 49%.
NIPT in twin pregnancies
In twin pregnancies, the reported detection rate of trisomy 21 by NIPT testing is high, but lower than that in singleton pregnancy, whereas the false-positive rate appears to be equally low. The number of cases of trisomy 18, and more so trisomy 13, is too small for accurate assessment of the predictive performance and therefore in twins, screening for T18/13 is probably best undertaken using first trimester combined assessment (maternal age, nuchal translucency and maternal hormone levels).
Screening in non-identical twin pregnancy poses some pregnancy management difficulties if one baby is affected, whilst the other is not. We will discuss the implications of this before you decide to undergo screening. A high probability Harmony result reflects the probability that the pregnancy involves at least one affected fetus but it is not possible to know which, from this test alone. An ultrasound scan may be helpful but ultimately, only invasive testing will provide a definitive answer. Identical twins will either both be affected or both unaffected except in extremely rare cases.
Can NIPT detect any other conditions?
Illumina test does not routinely provide information on any other chromosomal abnormalities, other than sex chromosome aneuploidy (if requested). Although other forms of NIPT (e.g. Panorama) can be used to screen for a variety of other genetic conditions including sex chromosome aneuploidy, 22q11.2 and other microdeletions, routine testing for these conditions is not currently recommended as test performance has not been validated in sufficiently large studies. Please ask about these additional tests if you would like further information or are considering them.
NIPT does not provide information on physical abnormalities or fetal growth, nor does it provide information on any other of the rarer chromosomal abnormalities. It is therefore important that you still have an ultrasound scan between 12+0-13+6 weeks to measure the nuchal translucency and check for any fetal structural defects and at 20+0-22+0 weeks for a detailed examination of the anatomy and around 32+0-36+0 weeks to examine the growth of the baby. If there is an increased nuchal translucency or fetal structural defect detected at your first trimester scan, this could suggest an increased chance of one of the rarer chromosome imbalances. In such cases, you may wish to have a diagnostic test such as chorionic villous sampling or amniocentesis.
Can the NIPT reveal the sex of the baby?
NIPT predicts the fetal sex by quantification of the Y (“male”) chromosome. A "female" result indicates no detection of Y chromosome and a "male" result indicates detection of Y chromosome. It does not routinely test for sex chromosome aneuploidy. For twin pregnancies, a male result indicates only that there is either one or two male fetuses.
How can I get the test?
You will need to arrange a scan and consultation with Dr Meekai To prior to having the test.
You will be asked to read an information leaflet about NIPT, prior to your scan.
At the scan, you will be counselled about NIPT and alternative options and
and you will be asked to sign a consent form if you wish to proceed.
Following the scan, you will be seen by a nurse at the OneWelbeck Women’s Health Clinic for blood sampling (one tube of blood is taken for NIPT).
When will the results of Illumina test be available and how will I receive my results?
The results from the test are usually available within 7 days and we will send these by encrypted email if you have low probability results. In all other circumstances, we arrange a telephone call or consultation with you to discuss the results. In rare circumstances it may take longer to get a result and this is usually due to technical issues. We will let you know as soon as possible if we are informed there might be a delay or if a repeat sample is required. Panorama tests usually takes 14 days.
What is the cost of the Illumina test?
The cost of Illumina/SAFE and Panorama basic is £295, and you will be invoiced directly by the OneWelbeck Women’s Health Clinic, which, if settled immediately after the blood test, will avoid incurring any additional invoicing fees.
The costs of the scans and consultations are separate. Please contact us for further details of scans and fees.
For more information and support you can visit
https://www.nuffieldbioethics.org/wp-content/uploads/NIPT-ethical-issues-full-report.pdf