What is non-invasive prenatal testing?

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.

The proportions of fragments derived from each chromosome (and, optionally, from individual segments of a chromosome) are determined by the test. In a mother with a chromosomally normal fetus, the proportion of fragments from each chromosome or chromosome segment will be within a narrow normal range. But if the fetus has an abnormal number of chromosomes, the fetal contribution for that chromosome or chromosome segment 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. We have used different methods that had been shown to provide high quality and consistent performance. At present, we are using the VeriSeq NIPT Solution v2 assay.

As part of the testing process, we assess the amount of fetal DNA in the mother’s blood sample before proceeding with chromosome analysis. This step 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 ensuring that there is sufficient feto-placental DNA in the maternal bloodstream, we cannot be certain that the result reflects the chromosomal status of the fetus.

Our commitment to quality means that we will only provide a result when there is clear evidence for, or against, the presence of a specific disorder. The reason why we occasionally cannot report a result for a specific disorder usually reflects the complex biology of pregnancy rather than limitations of the test method. This link explains some of these biological reasons.

The primary purpose of NIPT is to screen for Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13). These are the most common autosomal trisomies. They can cause moderate to profound intellectual disability and are associated with major congenital malformations. The screen for these trisomies is included in every NIPT that we provide.

A screen for the presence of a Y chromosome i.e. for fetal sex, is available as an option (no charge). This screen is not suitable for medical purposes, such as testing in the context of an X-linked recessive disorder.

A screen for abnormalities in the number of sex chromosomes, such as Turner syndrome (45,X), Klinefelter syndrome (47,XXY), XYY and XXX, is available as an option (no charge). Sex chromosome abnormalities are usually clinically milder than the trisomies. Detection of a sex chromosome abnormality will also reveal the fetal sex.

In rare situations, we are able to report the common trisomies but not report fetal sex or sex chromosome abnormalities. In this situation, we do not recommend that the NIPT be repeated as this is unlikely to provide a reliable result. As these are free options, we do not offer a refund should a result for fetal sex or sex chromosomes not be available. In other cases (also rare), we are unable to report regarding the risk of the common trisomies; in such situations, we do offer a refund. These rare outcomes usually reflect the complex biology of pregnancy rather than a technical failure of the test.

We also offer the option of a genome-wide NIPT screen for abnormalities in the number of chromosome segments i.e. duplications and deletions of chromosome material, that are greater than 7 million base pairs in size; this does not cover the X and Y chromosomes. The genome-wide NIPT screen also covers rare trisomies and monosomies of chromosomes other than 21, 18, 13, X and Y; these abnormalities are often limited to the placenta and may be associated with adverse pregnancy outcomes. The test performance, interpretation and management of genome-wide NIPT differs from that of the other tests and options described above; for further information, please refer to the NIPT Options technical bulletin. The option for genome-wide NIPT incurs an additional fee.

Please refer to the Resources page for further details about these chromosome disorders. 

NIPT is highly accurate, detecting more than 99% of fetuses with any of the common trisomies. This is a much better detection rate than observed with conventional first trimester screening and has resulted in a marked reduction in the number of invasive tests (CVS and amniocentesis) being provided nationwide. 

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.

Although NIPT is a very good screening test, 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. Most commonly this is due to the fetus and placenta having different numbers of chromosomes. These differences can also be due to the mother having an underlying chromosomal abnormality or due to technical limitations of the test; both such occurrences are rare.

NIPT does not detect every genetic abnormality in the fetus, or every developmental problem that might occur during pregnancy.

NIPT will not detect the following conditions:

• Less common or ‘atypical’ chromosome disorders. These make up approximately 20% of all chromosomal disorders identified at birth, and occur more commonly in pregnancies with fetal malformations and/or with very high risk scores on combined first trimester screening. Genome-wide NIPT may detect a small proportion of such chromosome disorders. These abnormalities can often be detected by invasive genetic testing, i.e. CVS or amniocentesis with microarray analysis.
• 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 this is a concern for your patient.
• Non-chromosomal disorders of the fetus, such as a neural tube defect or other malformation. Genome-wide NIPT can detect some chromosome abnormalities that are restricted to the placenta and compromise placental function. However, other chromosome abnormalities of the placenta, and non-chromosome disorders of placenta, will not be identified.

During 2016-2021, we offered the option of NIPT with a screen for the 22q11.2 microdeletion; this option was withdrawn from December 2021. We continue to offer cytogenetic FISH analysis for this microdeletion; for prenatal testing, this requires a sample of CVS or amniocytes. 

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

• the requesting clinician understands the purpose, performance and limitations of the test,
• the woman being tested is aware of 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.

These considerations are especially relevant for patients having the option of genome-wide NIPT as the test performance, interpretation and management of this test may not be familiar to the requesting clinician. For further information, please refer to the NIPT Options technical bulletin.