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Genetics

Non-invasive prenatal test (NIPT)

Many couples would like to follow the development of their child as early as possible. As part of prenatal care, it is possible to have a screening test for trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome). Trisomies are chromosomal disorders (the corresponding chromosome is present three times instead of twice). In most cases, they are not hereditary and can arise spontaneously in any pregnancy, however more frequently at an older maternal age (from about 35 years). These anomalies can be detected early in pregnancy.

What is the non-invasive prenatal test?

NIPT is a screening procedure that provides evidence for the presence of the most common chromosomal disorders (trisomy 21, 18 and 13) in an unborn child. NIPT uses cell-free fetal DNA derived from exfoliated cells of the placenta that circulates in maternal blood. The Illumina CE-certified VeriSeq NIPT Solution v2 assay is used, utilizing whole-genome next-generation sequencing (NGS) technique for high accuracy and reliability.

What can be determined with the NIPT?

Next to the common trisomies mentioned above, if desired, full or partial anomalies of all chromosomes can be investigated. In addition, determination of the child's sex or an examination for anomalies of the sex chromosomes (Turner, triple X, Klinefelter, XYY syndrome) can also be performed upon request.

When can NIPT be performed?

NIPT may be done at any time after the 10th completed week of pregnancy (for Belgium patients governmental reimbursement is foreseen from the 12th completed week of pregnancy onwards).
NIPT has not been validated at gestational ages less than 10 completed weeks. There may be insufficient fetal DNA present in the maternal plasma to provide a reliable result, and samples under 10 weeks will not be accepted for testing.

How safe is the NIPT?

The sensitivity (detection rates) of NIPT is very high, typically 99%, especially for the common trisomies. This in combination with a very low false positive rate (0,1%). Possible causes of false-positive results include placental mosaics, "vanishing twin", chromosomal abnormalities, and maternal malignancies. An abnormal result in the NIPT should always be verified by invasive diagnostics.

Contact

Dr. Pharm. Clin. Biol. Kehoe Kaat: kaat.kehoe@aml-lab.be

Prof. Dr. Vanden Broeck Davy: davy.vandenbroeck@aml-lab.be

 

Yes. It is required to use a special request form to ensure that the essential information to interpret the analytical result is obtained correctly.
The NIPT request will not be processed unless the request form is received and signed by both the referring clinician and the patient.
Please contact genetics@aml-lab.be for any further enquire.

The turnaround time for our NIPT is approximately 2–4 business days from receipt of specimen into the laboratory.
On rare occasions, further analysis of the sample may be required before a result can be issued; in some of these instances, a repeat blood collection and analysis (at no additional charge) may be recommended.

NIPT provides a specific test for the following common chromosome disorders:
  • Trisomies of chromosomes 21, 18 and 13 (standard test)
  • Trisomies of all chromosomes, including  partial (>7Mb) deletions/duplications of  chromosomes (extended test)
  • Abnormal numbers of X and Y chromosomes (singleton pregnancies only)
The chromosome disorders that would not be detected by NIPT are often associated with abnormal ultrasound features in the fetus. For this reason, NIPT is not recommended as the primary test if there are structural abnormalities noted on ultrasound; invasive genetic testing is the more appropriate investigation.

In approximately 1:1,000 pregnancies, the cells of the outer placenta (the cytotrophoblast) have an abnormal number of chromosomes compared to the developing fetus. This can potentially cause a false positive i.e. NIPT identifies a chromosome abnormality in the placental DNA circulating in the mother’s plasma but the baby turns out to be fine. For this reason, a NIPT result that indicates a high probability of a chromosome disorder must be confirmed by invasive genetic testing before making any major decision about the pregnancy.

Conversely, in 0,1% fetuses with a major chromosome disorder, the placental chromosomes may be normal. NIPT may report that there is no evidence of a chromosome disorder while the developing fetus actually has a chromosome disorder i.e. a false negative result. For this reason, a “low risk” NIPT result that is at variance with firm evidence of a fetal problem e.g. malformation evident on ultrasound, must be reviewed and invasive genetic testing considered.

The chromosome disorders detected by NIPT are usually new genetic errors that do not run in families, and have occurred as new events in the developing fetus. NIPT does not provide information about the inheritance of single-gene disorders, such as cystic fibrosis, fragile X syndrome and other familial disorders.
If either partner has a personal or family history of a specific genetic disorder, this should be evaluated in its own right as NIPT is unlikely to be a suitable screening test for that disorder.

No. NIPT examines DNA fragments from the fetus and placenta that are circulating in the mother’s blood. These DNA fragments last only an hour or so and are replaced continuously from the placenta throughout the pregnancy. Once the baby has been born, the remaining fragments of the baby’s DNA disappear from the mother’s circulation within a couple of hours. As a result, there are no remaining DNA fragments from the baby that might interfere with NIPT in a subsequent pregnancy.

Yes. NIPT can be used in IVF pregnancies using egg or sperm from the couple or donor IVF pregnancies where a surrogate is used.
Please provide details on the request form as this information is important for the test algorithm.

NIPT is not recommended if the fetus is known to have major congenital malformations. It is recommend that a dating/viability scan be performed just prior to sample collection for NIPT.
Malformations could be caused by a variety of chromosome disorders or be non-chromosomal in origin. NIPT provides an assessment for selected chromosome disorders, and in this setting the underlying disorder may be missed by NIPT. The more appropriate genetic investigation may be invasive testing by CVS or amniocentesis with fetal chromosome studies by microarray.
Useful information can also be gained from the 11-13 week ultrasound (e.g. major structural malformations), even if it is not used to screen for chromosomal abnormalities. The 18-20 week detailed structural scan is still indicated, even when NIPT gives a low risk result.

No. If the event of fetal demise, fetal DNA can continue to be detected in the maternal circulation for weeks or even months while the placenta remains in situ. NIPT cannot determine whether the fetal DNA has come from a viable or non-viable fetus.
In the event of a demised twin (or “vanishing twin”), the fetal DNA from that twin may compromise the accuracy of NIPT of the surviving twin. Our NIPT has not been validated in the presence of a demised twin, and NIPT is not able to be performed if there is known to be a demised twin at the time of sample collection.

The NIPT assay assumes that the mother has normal chromosomes and normal amounts of DNA in her blood. The accuracy of NIPT could be compromised by any maternal condition which fails to meet these assumptions e.g. triple X syndrome, mosaic chromosome disorder, cancer, recent blood transfusion, and bone marrow or organ transplantation. NIPT is not able to be performed in such settings.