For Doctors

What is Non-Invasive Prenatal Testing?

Non-invasive prenatal testing (NIPT) describes a DNA-based blood test that measures the probability of trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome) or 22q11.2 deletion (DiGeorge syndrome), if selected, with greater accuracy than traditional first trimester screening.

NIPT requires a single blood draw which poses no threat to the fetus, and can be done as early as 10 weeks’ gestation.

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How Does NIPT Work?

NIPT helps healthcare professionals give expectant parents accurate information about the most common fetal aneuploidies (abnormalities of chromosome number) and chromosome deletions. By delivering clear information about these chromosomal disorders earlier in pregnancy, NIPT may minimise anxiety and reduce the need for follow-up invasive procedures due to false positive results.

NIPT involves testing millions of short fragments of DNA in maternal plasma. Some of these fragments will have come from the placenta, and most will be from the mother.

For the detection of aneuploidies, the number of fragments derived from each chromosome is determined by the Harmony Prenatal Test. In a mother with a chromosomally normal fetus (euploid), the proportion of fragments from each chromosome will be within a narrow normal range. But if the fetus has an abnormal number of chromosomes, the fetal contribution for that chromosome will be abnormal and will distort the overall proportion.

A number of different methods have been developed for NIPT, and others are under development. Sonic Genetics regularly reviews the various implementations of NIPT and assesses their performance, scope and cost. Sonic Genetics uses the Harmony Prenatal Test for NIPT.

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Greater confidence

As part of the testing process, the Harmony NIPT includes and reports a precise and accurate measurement of the amount of fetal DNA in the blood sample before proceeding with chromosome analysis. This step is very important as it ensures that there is enough of the fetal DNA available in the sample to provide a reliable result and that it is not the mother’s DNA alone being analysed. Without the detection and measurement of the fetal fraction as part of the NIPT, you cannot be certain that the result is reflecting the chromosomal status of the fetus.

Our commitment to quality means that we will only provide a result when there is very clear evidence for, or against, the presence of a specific disorder. The reason why we occasionally cannot report a specific test usually reflects the complex biology of pregnancy and is not due to a failing in the laboratory. This publication explains some of these biological reasons.

What does NIPT screen for?

NIPT screens for Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13). These are the most common autosomal trisomies. They cause moderate to profound intellectual disability and are associated with major congenital malformations. DiGeorge syndrome (22q11.2 deletion) is also available as an optional screen, if selected. This syndrome can cause heart defects, poor immune system function, a cleft palate and low levels of calcium in the blood. Its features vary widely, even among those with the same deletion.

Sex chromosome abnormalities, such as Turner syndrome (45,X) and Klinefelter syndrome (47,XXY), can also be detected, but with reduced accuracy. Sex chromosome abnormalities are often clinically milder than other chromosomal abnormalities. Testing for sex chromosome abnormalities will also reveal the fetal sex.

If fetal sex cannot be reported, the manufacturer of the testing kit does not recommend that the Harmony Prenatal Test be repeated (referenced here). The experience of testing hundreds of thousands of women has shown that repeat testing is unlikely to provide a reliable result for fetal sex.

The main purpose of non-invasive prenatal tests such as Harmony is to screen for major chromosomal changes (i.e. trisomy 21, 18 or 13, or 22q11.2 deletion) which affect the health of the tested baby. It is not designed or intended to primarily be a tool to determine the fetal sex. We are pleased to offer fetal sex as an additional test at no charge, and are careful to report sex only if the result is clear. As this is a free supplementary test, we do not offer a refund should a result not be available.

It is important to note that chromosomal abnormalities vary widely in the severity of the problems they cause. Some methods can detect trisomies of other chromosomes; however, these trisomies almost always result in spontaneous miscarriage. Harmony is the only NIPT performed in Australia that has been extended to detect rare, small deletions of chromosome 22 (specifically, 22q11.2 deletion).

How accurate is NIPT?

NIPT is highly accurate, detecting:

  • More than 99% of fetuses with trisomy 21
  • More than 95% of fetuses with trisomy 18, trisomy 13 or abnormalities of sex chromosomes
  • More than 75% of fetuses with a 22q11.2 deletion

These are much better detection rates than are observed with conventional first trimester screening for those trisomies (85% for trisomy 21, 50% for trisomy 18 and 50% for trisomy 13). NIPT is also much better at identifying fetuses with normal chromosomes than conventional first trimester screening; more than 99.9% of normal fetuses are categorised correctly by NIPT, versus 95% by conventional first trimester screening.

NIPT is a very good screening test, but it is not a diagnostic test. There will occasionally be a difference between the result of the test and the actual chromosomal status of the fetus. This can be due to the fetus and placenta having different numbers of chromosomes. Such differences can also be due to the mother having an underlying chromosomal abnormality. It is rare for such differences to be due to technical failure of the test.

What is NOT included in NIPT?

NIPT does not detect every genetic abnormality in the fetus, nor every developmental problem that might occur during pregnancy.

NIPT will not detect the following conditions:

  1. Less common or ‘atypical’ chromosomal abnormalities. These make up approximately 20% of all chromosomal abnormalities, and occur more commonly in pregnancies with fetal malformations and/or with very high risk scores on combined first trimester screening. These abnormalities can often be detected by invasive genetic testing, i.e. CVS or amniocentesis.
  2. A specific mutation that might be known to run in the family, e.g. cystic fibrosis or Huntington disease. Please contact us on 1800 010 447 if you are concerned about this possibility.
  3. Non-chromosomal disorders, such as neural tube defects, placental abnormalities and intra-uterine growth retardation.

This list of exclusions is not complete.

NIPT does not screen for all chromosomal abnormalities. It does not screen for other genetic disorders or birth defects.

Before using NIPT

NIPT is a powerful investigative screen that carries major clinical implications for the mother and fetus. Before proceeding with the test, it is vital that:

  • Clinicians understand the purpose, performance and limitations of the test
  • Patients are informed about these aspects of the investigation, and
  • Appropriate consent is provided before the test is initiated.

Sonic Genetics requires that patients provide written consent for this test to assure the clinician and patient that these issues are understood.