NIPT for Down syndrome

A guide for patients and healthcare professionals

What is NIPT for Down syndrome?

It is now possible to use NIPT to detect Down syndrome and three of the other common aneuploidies: Edwards syndromePatau syndrome and Turner syndrome.

Further research and evaluation is necessary before these tests are introduced into the NHS, although they are already available in the private sector.

This guide will cover the key facts that patients and health professionals need to know about NIPT for Down syndrome.

‘It is now possible to use NIPT to test for Down syndrome, and other common aneuploidies’

How does NIPT detect Down syndrome?

People normally have 23 pairs of chromosomes in each cell (see the karyotype, below left). Each chromosome is made of a coil of DNA which contains our genes. These give instructions to our body to tell it how to workDown syndrome occurs when a person has an extra copy of chromosome 21 (see the karyotype, below right). Having this extra genetic information is what causes the physical and mental characteristics of people who have Down syndrome. For more information about Down syndrome, click here.

Female-karyotype-labelled               Down-syndrome-karyotype-labelled

NIPT for Down syndrome works by analysing the DNA fragments present in the maternal plasma during pregnancy. This is known as cell-free DNA. Most of this cell-free DNA comes from the mother (cell-free maternal DNA), but around 10%-20% of it comes from the unborn baby (cell-free fetal DNA).

Each chromosome has sequences of DNA that are specific to that particular chromosome. Therefore, by analysing and counting all the DNA sequences that link or map to each individual chromosome, the total amount of chromosome 21 in the mother’s blood can be compared with the amount of the other chromosomes. If the baby has Down syndrome, there will be slightly more sequences that map to chromosome 21 than expected, indicating that there is more chromosome 21 present than normal. This allows very accurate prediction of pregnancies where the fetus is likely to have Down syndrome.

Cell-free fetal DNA (cffDNA) comes from the placenta. It is first detectable from about 4-5 weeks’ gestation and reaches the required level needed to test for Down syndrome by 10 weeks’ gestation in most pregnancies. The cffDNA is cleared from the maternal circulation within the first hour after birth, and therefore we know that it is specific to the woman’s current pregnancy. However, it is important to remember that NIPT for Down syndrome analyses both the baby’s and the mother’s cell-free DNA.

How is NIPT different from the combined/quadruple test?

Although both tests involve a sample of maternal blood, NIPT analyses the cell-free DNA in the mother’s blood, whereas the combined and quadruple test analyses the mother’s hormone levels. With more than 98% accuracy, NIPT is more accurate than the first trimester combined test or second trimester quadruple test for estimating the chance or the risk that the baby has Down syndrome.

‘NIPT is more accurate than the combined or quadruple test for estimating the risk of Down syndrome’

What results can we get from NIPT for Down syndrome?

There are three possible results from NIPT for Down syndrome:

  • Positive: Predicted to be affected by Down syndrome. An invasive test should be offered to confirm the result.
  • Negative: Highly unlikely to be affected by Down syndrome.
  • Inconclusive: Inconclusive results happen in up to 4% of cases. This is usually because the proportion of fetal DNA present in the sample is not high enough to give an accurate result. NIPT may be repeated with the hope that the cffDNA levels will have increased due to the increased gestation.

NIPT detects around 98% of all babies with Down, Edwards and Patau syndromes.

Why are the results not 100% accurate?

Both positive and negative results may be inaccurate due to the following reasons:

False positives

These occur in around 0.3% of cases (or 1 in 300). Possible causes of false positive results include:

  • When used early in pregnancy, cell-free DNA from a ‘vanishing twin’ may be present, as the placenta continues to shed fetal DNA after embryonic demise. A scan is needed to look for multiple pregnancies or an empty sac prior to the test.
  • The cell-free fetal DNA comes from the placenta, and we know that sometimes there are ‘cell lines’ that grow in the placenta but not the baby. This is called ‘confined placental mosaicism’ causing a false positive result, which reflects an abnormal cell line that is only present in the placenta but not present in the baby.
  • Very occasionally, because we are testing all the cell-free DNA in the mother’s blood (this includes the mother’s and the baby’s DNA), we may detect a problem that is present in the mother but not the baby.

False negatives

NIPT detects more than 98 out of 100 of all babies with Down, Edwards and Patau syndromes. Possible causes of false negative results include:

  • The proportion of fetal DNA present in the blood is too low. This may be due to early gestation or to the mother’s BMI being high. A scan is needed to confirm gestation prior to the test.
  • The cell-free fetal DNA comes from the placenta, and we know that sometimes there are ‘cell lines’ that grow in the placenta but not the baby. This can cause a false negative result if an abnormal cell line is only present in the baby but not in the placenta.
  • Technical issues.

‘NIPT detects more than 98 out of 100 babies with Down syndrome’

Who is eligible for the test?

NIPT for Down syndrome is not yet available in the NHS. However, research is being done to evaluate the technology and assess how it may be introduced.

It is possible that in the future NIPT could replace current screening tests or diagnostic tests. However, it is currently being evaluated as an additional step in the existing screening pathway. As described before, there are false positive results and it is likely that invasive testing will be required to confirm a positive NIPT result for the foreseeable future.

Click here for further information about the NHS evaluation study of NIPT for aneuploidy.

‘NIPT is currently being evaluated as an additional step in the existing screening pathway’

Where is the test available?

NIPT for Down syndrome is not currently available through the NHS. However, many private clinics are offering the test to all women.

Blood samples are sent for testing in the US and results are usually returned within two weeks. The price of the test is between £400 and £900.

For more information visit the ARC website.

Key counselling issues

There are several issues women should be encouraged to consider before deciding whether to have NIPT. They are discussed in the video below.

Testing for other aneuploidies

NIPT will also provide results for three rarer chromosomal conditions:

Edwards syndrome (trisomy 18)

  • An extra copy of chromosome 18 is present.
  • NIPT detects elevated levels of chromosome 18 DNA sequences, which would suggest the baby has Edwards syndrome.
  • Detection of Edwards syndrome is as accurate as for Down syndrome (>98%).

Patau syndrome (trisomy 13)

  • An extra copy of chromosome 13 is present.
  • NIPT detects elevated levels of chromosome 13 DNA sequences, which would suggest the baby has Patau syndrome.
  • Detection of Patau syndrome is as accurate as for Down syndrome.

Turner syndrome

  • Only one copy of the X chromosome is present in a female baby.
  • NIPT detects a reduced level of X chromosome sequences and no Y chromosome sequences, indicating that the baby is likely to have Turner syndrome.
  • Detection of Turner syndrome is not as accurate as for the other aneuploidies.

For information on other ways in which NIPT is being used, see our other guides for patients and healthcare professionals.

‘NIPT can also detect Edwards, Patau and Turner syndromes’