NIPT – Non Invasive Prenatal Testing

Whilst invasive, diagnostic procedures like amniocentesis, chorionic villus sampling and percutaneous umbilical cord sampling are still being used to detect chromosome abnormalities and birth defects, specialists in the field of prenatal diagnosis have a consensus that these tests will, in the not too distant future, be phased out and replaced entirely with NIPT (noninvasive prenatal testing), a type of test which relies on analysis of cell-free fetal DNA in the maternal blood samples. However, the full clinical utility of non-invasive prenatal testing/cffDNA testing has yet to be established and currently NIPT testing is considered a screening test and not a diagnostic test.

Other names commonly used

The American College of Medical Genetics & Genomics (ACMG) labeled the testing “Non-Invasive Prenatal Screening” or “NIPS.”

The test is sometimes also referred to as NIPD which stands for a non-invasive prenatal diagnostic test- this term could however be misleading as using cell free fetal DNA to establish chromosomal abnormalities is not a in most cases a diagnostic test but a screening test (which means it would fall under the same umbrella as other prenatal tests such as ultrasounds and serum testing). However, in some cases, maternal blood sampling can be used as a diagnostic test (for example in the case of  achondroplasia) to confirm certain conditions.

What is an NIPT test?

NIPT is a new type of genetic test that screens for birth defects and inherited diseases. A non-invasive prenatal test is a type of prenatal screening test that uses maternal blood. Specifically, it is based on the analysis of cell-free fetal DNA in the maternal blood stream (the entire volume of blood circulating through a person).

The cell free fetal DNA can be found in the maternal blood stream from the very early stages of pregnancy. The fetal cells (sometimes whole or sometimes just in fragments) find their way into the blood stream through the placenta which although acts as barrier in keeping the fetal blood stream and maternal blood stream separate, it does not completely hinder cellular exchange of fetal and maternal cells. This exchange of cellular material makes NIPT possible.

NIPT testing means expectant mothers can test for Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), or Patau syndrome (trisomy 13) as well as other conditions that are a result of missing, incomplete or duplicate chromosomes. Other conditions which can be detected include Monosomy X (Turner syndrome) and Triploidy/vanishing twin detection. The test offers up to 99.9% accurate results but it is very important to note that this high accuracy rate is largely imperceptible in low-risk populations, for example, amongst mothers who are under the age of 30. A woman with no history of aneuploidies and who is under the age of 30 already has a 99.9% chance of NOT having a baby with any chromosomal abnormalities or birth defects.

One important note to take down is that non-invasive prenatal testing is not a diagnostic test. In other words, it will not confirm with certainty that the unborn baby carries the chromosomal mutation/ abnormality. Non-invasive prenatal diagnosis is actually classified as a screening test and would fall into the same category of prenatal testing such as maternal serum testing and ultrasounds. The NIPT test can be seen in conjunction with other tests such as maternal serum testing. If the NIPT test provides a negative result, there is a very low risk of any birth defects and generally no further testing is recommended. Diagnostic tests come into the equation in cases where the NIPT gives a positive result. A positive result raises a red flag and will require deeper investigation. Diagnostic tests include chorionic villus sampling and amniocentesis and can be used to rule out any abnormalities.

What does the American Congress of Obstetricians and Gynecologists say about NIPT testing?

The American Congress of Obstetricians and Gynecologists and other professional organizations recommend cfDNA testing only for high-risk pregnancies, and specify that abnormal results should be confirmed by invasive testing before any action is taken.

By high risk pregnancies we mean pregnancies in which the pregnant mother is at a relatively advanced age. The chances of a Down syndrome child as well as of other chromosomal abnormalities are believed to increase in women who conceive above age 35. At age 40, the chances of having a Down syndrome child increase dramatically.

To look at some figures provided by the National Down Syndrome Society:

  • A 25-year-old woman has a 1 in 1,200 chance of having a baby with Down syndrome;
  • by 35, the risk has increased to 1 in 350;
  • by age 40, to 1 in 100;
  • by 49, it’s 1 in 10

Conclusions to NIPT

Noninvasive prenatal testing is a very useful and powerful screening test. It is not however, diagnostic and only indicative. ALL positive NIPT results should result in further diagnostic testing. The test is only advised and useful to women who are at increased risk of having a child with a birth defect or chromosomal abnormality.