Non-invasive prenatal testing (NIPT): Frequently asked questions

NIPT may be done at any time after the 10th completed week of pregnancy. However, the usefulness of information obtained after 20 weeks may be limited by other factors, such as the interventions available at later gestations.

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.

Yes.

We require a special request form to ensure that we obtain the required information to interpret the analytical result correctly. We will not process a request for NIPT unless the special request form is received and signed by both the referring clinician and the patient.

Download NIPT request form

This is an editable version of the request form so you can add patients’ details electronically. Please save this to your desktop and open it in Adobe Acrobat Reader so it will have full functionality. The dates need to be entered in this format DD/MM/YYYY to work correctly, or you can use the drop-down calendar option. This can then be printed and signed, barcode label added and sent with the sample as usual.

The turnaround time for our NIPT is approximately 3–5 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.

HSL Genetics NIPT provides a specific test for the following common chromosome disorders:

• trisomies of chromosomes 21, 18 and 13 (standard test)
• abnormal numbers of X and Y chromosomes (singleton pregnancies only)

These chromosome disorders account for approximately 80% of all chromosome disorders identified at birth. This means that the remaining 20% of the chromosome disorders are not detected by HSL’s NIPT. These other disorders could potentially be identified by invasive genetic testing (amniocentesis or CVS), and this carries a small risk of a miscarriage.

The chromosome disorders that would not be detected by HSL’s 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 1:2,000 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 up to 1% of 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.

Combined first trimester screening (maternal serum screening with fetal ultrasound) and NIPT provide complementary information about the fetus. There is overlap in the range of conditions that they detect, and each screening method can identify abnormalities that will be missed by the other. For this reason, some clinicians recommend combined first trimester screening and, subject to the result, NIPT. Others recommend detailed ultrasound and NIPT for all patients.

Yes.

The accuracy of NIPT is dependent on knowing the accurate gestational age and the number of fetuses. In early pregnancy, this is best determined by ultrasound. An early ultrasound can also provide clinically significant information that may require assessment before committing to NIPT e.g. the detection of major malformations or fetal demise. We recommend that a dating/viability scan be performed just prior to sample collection for NIPT.

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.

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.

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.

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 decision about which date is more likely to be correct must be resolved by the doctor responsible for managing the pregnancy. NIPT does not provide any information regarding gestation.

It may be preferable to defer collecting a blood sample for NIPT until a gestation of 10 completed weeks as determined by the later date. In other words, it is usually preferable to err on the side of taking a sample for NIPT later rather than earlier in the pregnancy.

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.

There is an inverse relationship between maternal body weight and the concentration of fetal DNA (fetal fraction) in maternal plasma. With increasing body weight, there is an increasing probability that there will be insufficient fetal DNA to provide a reliable result. There is no maternal weight threshold at which we do not recommend NIPT. A woman who weighs 140 kg will, on average, have a fetal fraction that is approximately half that of a woman weighing 70 kg.

This relationship between maternal weight and fetal DNA does not compromise the accuracy of NIPT as we confirm that there is sufficient fetal DNA to produce a reliable result in every maternal blood sample tested. However, this relationship does increase the possibility that we cannot provide a result because there is insufficient fetal DNA.

There have been reports of some women having strikingly abnormal NIPT results that seem to be incorrect, i.e. the fetal chromosomes are normal when checked. Some of these women have subsequently been found to have cancer. The abnormal NIPT result reflected abnormal DNA from the cancer in the mother’s circulation rather than abnormal DNA from the fetus.

These are rare events (a handful of instances among millions of women tested). The reliability of NIPT in detecting cancer during pregnancy is not known. We do not recommend NIPT as a method of screening for cancer.

The NIPT assays used by HSL are designed to provide a very clear indication regarding the probability of the developing fetus having, or not having, a specific chromosome disorder. In more than 99% of women tested, we are able to provide a very clear indication either way.

However, in a small number of instances, we may be unable to provide an assessment for all conditions considered in the test, or for only some conditions.

There are various reasons why NIPT cannot provide a clear answer for one or more of the questions being asked by the requesting doctor:

• There may be insufficient fetal DNA present for an assessment about a specific disorder. Some conditions may be harder to resolve than others.
• There may be uncommon harmless variations in the DNA from either mother or fetus that interfere with the assessment for a given disorder.
• The placenta may have a mixture of normal and abnormal DNA that differs from that of the fetus, making it impossible to provide a confident answer regarding a specific disorder.