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.
NIPT helps healthcare professionals give expectant parents accurate information about the most common fetal aneuploidies 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 proportion of fragments derived from each chromosome is determined by the test. In a mother with a chromosomally normal fetus, 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. We use a variety of methods that have been shown to provide high quality and consistent performance.
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 the measurement of the fetal fraction as part of the test, 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 genetics, pregnancy, and test limitations. This link explains some of these biological reasons.
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.
Sex chromosome disorders, such as Turner syndrome (45,X) and Klinefelter syndrome (47,XXY) can also be detected. Sex chromosome disorders are often clinically milder than other chromosome disorders. Testing for sex chromosome disorders will also reveal the fetal sex.
If fetal sex cannot be reported, we do not recommend that the NIPT be repeated. 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 NIPT is to screen for major chromosome disorders (i.e. trisomy 21, 18 or 13, and 22q11.2 deletion) which affect the health of the tested baby. It is not primarily intended to be a test of fetal sex. We do offer assessment of fetal sex as an option for no charge, and are careful to report fetal sex only if the result is clear. (As this is a free supplementary test, we do not offer a refund should a result for fetal sex not be available).
Please refer to the Resources page for further details about these chromosome disorders.
Some providers offer NIPT that detect other chromosome disorders such as rare microdeletions and mosaic trisomies.
• Rare microdeletions and duplications can cause serious problems in the developing baby and child. However, there is limited information regarding the accuracy of NIPT in detecting such disorders. NIPT misses some microdeletions (false negative results) and, because of the rarity of individual microdeletions, the majority of abnormal reports are incorrect (false positive results) with subsequent invasive testing showing the fetus to be normal. Sonic Genetics provides testing for the 22q11.2 microdeletion only as it is the most common microdeletion and there is extensive information regarding the performance of this test. At present, we do not recommend using NIPT to screen for other disorders.
• Rare autosomal trisomies involving chromosomes other than 21, 18 and 13 are usually limited to the placenta i.e. mosaic trisomy. At this stage, the identification of a pregnancy with a mosaic trisomy provides little useful information to assist in the further management of the pregnancy. In many instances, the fetus is unaffected and the only outcome from evaluation of the fetus is maternal anxiety. In other instances, there is ultrasound evidence of an abnormality (which requires evaluation in its own right) or unavoidable fetal demise. At present, we do not recommend using NIPT to screen for mosaic trisomies.
NIPT is highly accurate, detecting more than 99% of fetuses with trisomy 21. This is a significantly improved detection rate than observed with conventional first trimester screening for trisomy 21 (85%) therefore reducing the number of invasive confirmatory tests undertaken.
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. 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 failure of the test but 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. 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, 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 malformations.
NIPT is a powerful test that carries major clinical implications for the mother and fetus. Before proceeding with the test, it is vital that
• The requesting clinician understand the purpose, performance and limitations of the test
• The woman being tested is 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.