Victorian Clinical Genetics Services Murdoch Children's Research Institute The Royal Children's Hospital Flemington Road, Parkville VIC 3052 P (03) 8341 6201 W vcgs.org.au

NIPT fact sheet

Test failure result - what does this mean?

This fact sheet is for women and their partners who receive an analysis Most often, the cells with rare trisomy algorithm failure from the percept non-invasive prenatal test (NIPT) offered by are present only in the placenta and the Victorian Clinical Genetics Services (VCGS). This information is not applicable baby has normal chromosomes. This to test results reported by other NIPT service providers. is called confined placental mosaicism (CPM). Sometimes the baby will have As part of the service offered by VCGS, women and couples have the the mosaicism. If this occurs there is an opportunity to discuss their result with a VCGS genetic counsellor at no increased chance the baby may have additional cost. Genetic counsellors are experts in assisting people to physical and intellectual problems. understand genetic results and make informed decisions about further testing options. Possible explanations for What does this result mean? this result: NIPT is a way for women to get an accurate estimate of the chance that their There is a high chance that the rare baby has one of the most common chromosome conditions: trisomy 21 (Down trisomy is present in the placenta. syndrome), trisomy 18 and trisomy 13. An analysis algorithm test failure occurs However, this does not mean the trisomy when the NIPT detects an unusual score for a chromosome that does not is also present in the baby. This is called involve one of the common trisomies (e.g. trisomy for chromosome 16). a false positive result. The calculated score for each chromosome is very important for ensuring A false positive result means that the overall accuracy of the NIPT. To avoid an inaccurate test result being although NIPT indicates the presence of generated, the NIPT test is automatically cancelled. This occurs in about 1 in a rare trisomy, the baby does not have 650 pregnancies tested using percept NIPT (1). this condition. The only way to provide a definitive diagnosis is to have an An analysis algorithm test amniocentesis with chromosome testing. Possible causes of false positive failure does not mean the results for rare trisomy from NIPT baby definitely has a rare include: Confined placental mosaicism (CPM) chromosome condition. This is caused by a population of cells in the placenta with three copies of the If this test cancellation occurs, the laboratory undertakes additional analysis chromosome instead of the usual two. to determine the cause. In most instances this will show that a ‘rare trisomy’ These cells are confined to the placenta is present. Occasionally other causes may be found or suspected. The finding and are not present in the baby. of a rare trisomy does not mean the baby has the condition. Only a diagnostic Co-twin demise procedure such as amniocentesis can confirm if the baby has a rare trisomy. When one twin was lost earlier in pregnancy due to the rare trisomy. What is a rare trisomy? Maternal mosaicism Rare trisomy occurs when the baby or the placenta has three copies of a Very rarely, the mother may carry the rare chromosome instead of the usual two. Rare trisomies involve chromosomes trisomy mosaicism in her blood. If this is other than 13, 18 or 21. Most pregnancies with rare trisomies miscarry before suspected, further testing of the mother 10-12 weeks of gestation. A pregnancy that progresses beyond this period may may be recommended. have mosaicism, which means there is a mixture of normal cells and cells with the rare trisomy.

CT-W-178 V1 01/01/18 pg 1 of 2 What are the next steps? All women who receive an analysis algorithm test failure caused by a rare trisomy Only an invasive should discuss this with their doctor. If an ultrasound scan shows a healthy pregnancy, women should be offered the option of further testing; however women diagnostic procedure do not need to have further testing. It is their choice. Referral for genetic counselling with chromosome may be helpful in supporting women and their partners with making decisions about further testing options. testing can confirm Further testing options: if the baby has • A follow up ultrasound is recommended if this was not already done in the a rare trisomy or period immediately prior to blood collection. This may show that the other chromosome pregnancy has failed. This is more common early in pregnancy (e.g. if NIPT was done at 10 weeks). condition. • If abnormalities are seen on the ultrasound, it is more likely that the baby may have the rare trisomy. A CVS can be performed at 12-13 weeks to provide additional information. An amniocentesis might also be required. The need for Who can I speak to an amniocentesis may depend on the ultrasound findings and the CVS results. about this result? • If no abnormalities are seen on the ultrasound, it is more likely that the baby It is recommended that women does not have the rare trisomy. However, there is still an increased chance with an analysis algorithm test that baby may have mosaicism for the rare trisomy. It is suggested that the failure discuss this result with their woman consider having an amniocentesis at around 15-16 weeks gestation. doctor. Their doctor can refer them Amniocentesis will give the most definitive result in these circumstances. to speak with a VCGS genetic Depending on the rare trisomy that was found on NIPT, other genetic testing counsellor at no additional cost. may be recommended. Alternatively, women and their partners can contact a VCGS What are diagnostic procedures? genetic counsellor directly on CVS and amniocentesis are diagnostic procedures available during pregnancy that 03 9936 6402. can identify for certain if the baby has a chromosomal condition. However, because Genetic counsellors are experts in rare trisomy is sometimes present in the placenta but not the baby, an amniocentesis communicating genetic information is usually the preferred procedure in these circumstances. and assisting people to understand CVS involves passing a fine needle into the developing placenta (chorion) under complex genetic results. They can ultrasound guidance and drawing a few small fragments of tissue into a syringe. CVS support women in making informed carries a small risk of miscarriage (1 in 500 or 0.2%)*, generally within two weeks decisions that are right for them of the procedure. CVS analyses placental tissue. If the cause of the rare trisomy is and their family. confined placental mosaicism, there is a chance the woman will need to also have an amniocentesis. It is for this reason that VCGS suggests waiting for an amniocentesis if the ultrasound is normal. Contact details VCGS Prenatal Testing Team Amniocentesis involves the removal of a small sample of fluid from the sac around Murdoch Children’s the developing baby. Under ultrasound guidance, a fine needle is inserted through Research Institute the mother’s abdomen to obtain the fluid. The fluid contains cells that are shed The Royal Children’s Hospital, naturally from the fetus. Amniocentesis carries a very small risk of miscarriage (1 in Flemington Road Parkville 3052 1000 or 0.1%)*, generally within two weeks of the procedure. P (03) 9936 6402 What are diagnostic tests? F (03) 8341 6366 After the CVS or amniocentesis procedure, chromosome analysis is performed. This E [email protected] can include FISH, karyotype, and microarray. These laboratory tests are considered W vcgs.org.au/perceptNIPT diagnostic tests. FISH: stands for ‘Fluorescence In Situ Hybridisation’. This test looks at whether The information on this fact sheet the cells contain the correct number of chromosomes for the common conditions is based on a comprehensive (chromosomes 13, 18, 21, X, Y). This is a rapid, preliminary test with results available assessment of outcomes from in 1-2 working days. 30,000 women who have had percept NIPT#. Karyotype: looks at the size, shape and number of chromosomes to determine whether there are any extra, missing or abnormal chromosomes present. Results are usually available in 10-14 days. Microarray (or molecular karyotype): a detailed test that provides more information than the karyotype. This very sensitive test looks for extra or missing segments of DNA in the chromosomes. Results are usually available in 10 -14 days. perce ® cell-free DNA prenatal test *Akolelar R et al. Ultrasound Obstet Gynecol, 2015, Jan;45(1): 16-26. pt # VCGS data on file. CT-W-178 V1 01/01/18 pg 2 of 2