s aim to give parents more information about potential future risk and about their unborn baby. Discussion about which tests are relevant and suited to you is an integral part of both pre-pregnancy and antenatal care. Screening tests are optional and it is best to be informed about the nature of the test and possible results before they are performed. Where a screening test is found to be abnormal patients are normally offered a follow up diagnostic test to confirm the finding.
Common genetic screening tests associated with pregnancy fall into two major categories.
- Reproductive carrier screening: This is parental screening for recessive genetic conditions. These are normally carried out pre-pregnancy but can also be performed in the early pregnancy (e.g. Prepair)
- Fetal genetic screening tests: These are aimed at assessing the risk of you baby being effected by certain common genetic conditions and are conducted during your pregnancy (e.g NIPT)
Other types of genetic testing include:
- Pre-implantation genetic testing and screening of embryos during IVF prior to embryo transfer
- Testing of parental karyotype for chromosomal abnormalities or specific genetic mutations that may effect fertility and miscarriage risk
- Diagnostic fetal testing. This is invasive testing of the fetus during pregnancy via Chorionic Villus Sampling or Amniocentesis.
Reproductive carrier screening for parents
Pre-pregnancy genetic screening is aimed at identifying couples who may be silent carriers of certain conditions that could affect the health of their future children. Genes are like a blueprint that directs the way our bodies grow and also function. We all carry changes (mutations) in our genes, some changes can cause genetic conditions while others are insignificant. Sometimes children can be effected by a condition when they inherit a similar gene change from each parent and end up with two abnormal copies.
Reproductive carrier screening is offered to all couples considering trying for a pregnancy and also in the early stages of pregnancy (preferably prior to 12 weeks). This form of testing can be carried out once and in most cases the results can be used for all future pregnancies. Testing is suitable for everyone including those with no apparent family history. The majority of couples will find they have a low chance of having children with an inherited genetic condition. Around 1 in 50 of couples will find out they have an increased chance. For these couples there is usually a 1 in 4 chance of having children effected with that condition.
The reason we offer screening is that in many instances there are reproductive treatment options available to couples who find they have an increased risk.
Important considerations with reproductive carrier screening
Is this screening right for me?
Choosing to have genetic carrier screening is a personal choice. It may help to discuss these with your partner and health professional before you go ahead. It can also be helpful to speak to a Genetic Counsellor to help make this decision.
Important questions to consider include:
- Would you use this information for reproductive planning or decision-making? Some people with an increased chance of having children with an inherited genetic condition choose to:
- Use IVF with genetic testing of embryos to avoid having children with the condition (common)
- Test during pregnancy (prenatal diagnostic testing via chorionic villus sampling amniocentesis) with the option to continue or end an affected pregnancy
- Do nothing differently, with the option to test the baby after birth
- Use a donor (sperm, egg or embryo) to avoid having children with the condition
- Adopt a child
Carrier Screening Testing options:
- prepair 3TM testing and couple testing for prepair 500+TM and prepair 1000+TM are performed by VCGS based in Melbourne. Individual prepair 500+ TMtesting is performed by an overseas partner lab in USA. https://www.vcgs.org.au/prepair-carrier-screening/
- eugene™ offer a similar range of tests: https://eugenelabs.com
Since 2023 prepair 3TMand eugeneTM core carrier screening options which assess the risk of Cystic Fibrosis, Spinal Muscular Atrophy and Fragile X are 100% covered by medicare attracting no out of pocket cost.
Results take around 2-4 weeks to be processed following collection and you will be contacted with the results.
| Prepair 3 3 genes | Prepair 500+ over 600 genes | Prepair 1000+ over 1200 genes | |
|---|---|---|---|
| Conditions | Screens for common inherited conditions: cystic fibrosis (CF), spinal muscular atrophy (SMA) and fragile X syndrome (FXS) | Screens for over 500 genetic conditions | The most comprehensive option that looks for over 750 conditions including CF, SMA and FXS |
| Screen | Biological female usually screened first. Partner only screened if female is a carrier for CF or SMA | Both biological parents are screened together (couple based test), individual option available | Both biological parents are screened together (couple based test) |
| Time | Takes 2 weeks | Takes 5-6 weeks | Takes 5-6 weeks |
| Cost | Bulk billed (if Medicare eligible) $389 (non-Medicare eligible) | $975 per couple (Medicare eligible) $1364 oer couple (non-Medicare eligible) | $1500 per couple (Medicare eligible) $1889 per couple (non-Medicare eligible) |
Cystic fibrosis
Cystic Fibrosis is an inherited condition that primarily affects the lungs and digestive system. 1 in 25 people are unaffected carriers and it affects 1 in 2500. Individuals with CF develop an abnormal amount of thick mucus within the lungs and gut. In the lungs, this mucus traps bacteria resulting in recurrent infections. Within the gut, the mucus impairs digestion of food. Infants, children and adults with CF require daily chest physiotherapy to clear the mucus from the lungs and enzyme replacement medication to aid in food digestion. CF is a serious condition and there is no cure. Individuals with CF have a shortened life span with lung failure being the major cause of death. A couple is only at risk of having a child with CF if both parents are carriers of the condition. If the tests show that you are a carrier for CF, your partner will be offered testing to clarify the risks for your child / children.
Fragile x syndrome
Fragile X syndrome is the most common cause of inherited intellectual disability. 1 in 250 people are carriers with 1 in 4000 affected. People with FXS can have developmental delay, learning difficulties, anxiety, autism, epilepsy as well as some physical characteristics. The features of FXS vary from mild to severe and males are more likely to be severely affected than females. There is no cure for FXS although some educational, behavioural and medical interventions can improve outcomes. Some females who are carriers are at risk of developing fertility problems and going through the menopause early. Only female carriers of FXS are at increased chance of having a child with FXS. Therefore, your partner does not need to be tested.
Spinal muscular atrophy
Spinal muscular atrophy is a condition that affects nerves in the spinal cord and causes muscles to get weaker. 1 in 40 people are carriers with 1 in 6000-10000 affected. There are four types of SMA, with SMA type 1 being the most common and the most severe. prepair™ only looks for genetic causes of SMA type 1 which will identify around 95% of SMA carriers. Babies with SMA type 1 have weak muscles from birth and usually do not live past two years of age. There is no cure for SMA, however there are treatments and interventions available aimed at managing symptoms and improving quality of life. If the tests show that you are a carrier for SMA, your partner will be offered testing to clarify the risks for your child / children.
Testing during pregnancy
(prenatal screening)
Every baby has a small chance of having a chromosomal or genetic condition. Prenatal screening is primarily aimed at identifying babies with the more common specific chromosomal or genetic conditions such as Down Syndrome (Trisomy 21), Edward Syndrome (Trisomy 18), Patau Syndrome (Trisomy 13) and Turners Syndrome (Monosomy X). Early structural abnormalities may also be identified on ultrasound. Screening poses no risk to your baby.
Prenatal screening is entirely voluntary and is offered so as to give patients more information about their unborn baby. Where a result is abnormal the next step is to decide whether to proceed with definitive invasive diagnostic testing such as chorionic villus sampling (CVS) or amniocentesis. These tests pose a small risk to the baby. Where a serious abnormality is confirmed patients have the option of terminating the pregnancy. Alternately patients can continue with the pregnancy with the additional information aiding preparation, planning and care. You will be supported and assisted with your decision either way.
Down Syndrome has been the focus of screening during pregnancy for many years as it is one of the most common chromosomal cause of intellectual disability in children and adults. This condition is caused by the baby having three copies of chromosome 21, instead of the usual two copies. It is usually a random as opposed inherited condition. Its frequency in the population is about 1 in 800 and it has effects on both health and learning. The chromosomal conditions Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13) are also screened for. These conditions are associated with disability, pregnancy loss or death in the newborn. With the advent of non-invasive pre-natal testing (NIPT) the chromosomal condition Turner’s syndrome (Monosomy X) is also screened for. This is a condition that affects girls and can result in short stature, under-developed ovaries and other potential health problems.
Screening test options:
Ultrasound and nuchal translucency scan
This is an ultrasound scan conducted between 11 and 14 weeks of your pregnancy. It provides an excellent early assessment of the baby’s anatomy in addition to measuring the nuchal translucency. Nuchal translucency is the thickness of a fluid filled space in the soft tissue at the back of a baby’s neck. An increased nuchal translucency is often normal but can also signify an increased risk of genetic abnormalities such as Down syndrome and certain structural abnormalities. If an increased nuchal translucency is identified further testing is then offered. This would take the form of amniocentesis or chorionic villus sampling (CVS) depending on gestation. It is recommended that all patients have this ultrasound in addition to any other screening tests performed. Nuchal translucency scans are still commonly performed alongside Non-invasive prenatal screening (NIPS).
Non-invasive prenatal testing (NIPT or NIPS)
NIPT is a maternal blood test that is collected from 10 weeks onward during your pregnancy. A small amount of a baby’s genetic material makes its way into the maternal circulation during pregnancy (cell free DNA). This test assesses that genetic material to detect Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), Trisomy 13 (Patau syndrome) and Turner syndrome (Monosomy X). It also identifies the gender of your baby. The test is highly sensitive with a >98% detection rate for Down Syndrome, Edwards Syndrome, and Patau syndrome and a >95% detection rate for Turner syndrome. There are two main providers of the test in Melbourne – Percept™ and Harmony™ with a cost of $449 and $430 respectively. Unfortunately, this test is not currently covered by Medicare or private health insurance. Results take up to 5 business days to return. In the event of an abnormal result further diagnostic testing in the form of amniocentesis or CVS is offered to definitively assess if the baby is affected.
There is a chance that samples sent for NIPT will not return a result. In 2-3% of samples, the laboratory is unable to give you a result from the first blood collection. If this happens, you will be asked to provide another blood sample for analysis. A result is successful in 2 out of 3 cases where a second sample is collected.
First trimester combined screening (FTCS)
FTCS is the older first trimester screening option that sometimes still in use. It combines the results of the nuchal translucency ultrasound scan with a blood test performed between 11 and 14 weeks. The result is further adjusted by the patient’s age. FTCS aims to detect Down syndrome, Edwards syndrome and Patau syndrome. Unfortunately, it is less likely to detect all of these and has a higher false positive rate than NIPT. An approximate out of pocket cost for the blood test after Medicare is $70, which is added to the cost of the ultrasound. Results of this testing are reported as low risk or increased risk. In most cases where a result suggests increased risk (>1:300) the baby will be normal. Nonetheless further testing is offered and this may be via NIPT (further screening) or a diagnostic test such as amniocentesis or CVS.
Quadruple test
(maternal serum screening test)
The quadruple test is an older second trimester screening test that is preformed between 15 and 20 weeks assessing the risk of baby having Down Syndrome, Edward Syndrome or a Neural Tube defect. It consists of a single blood test. The out of pocket cost after Medicare rebate is $70 and results take about one week to return. This test is significantly less likely to detect Down Syndrome than both NIPT and FTCS and for this reason is not recommended.
| Test for Down Syndrome | Weeks (+days) Pregnant | Detection rate | False positive rate | Positive predictive value |
|---|---|---|---|---|
| Nuchal Translucency Ultrasound | 11+1-13+6 | 70% | 5 | |
| NIPT | >10 | 99% | 1% | 45% |
| FTCS | 11+1-13+6 | 85% | 5% | 7-10% |
| Quadruple Test | 15-20 | 75% | 5% | 2-3% |
Positive predictive value (PPV): if the screening test result is abnormal the PPV is the probability that the baby actually has that abnormality.
Diagnostic testing
Invasive tests such as amniocentesis or chorionic villus sampling, are used to definitively diagnose genetic or chromosomal conditions in unborn babies. These tests are normally performed where a increased risk screening result has been returned. CHORIONIC VILLUS SAMPLING (CVS) CVS involves passing a needle under ultrasound guidance into the placenta between 11 and 13 weeks gestation. A small amount of placental tissue is collected for testing. A full chromosomal analysis is performed which takes 8-14 working days to complete. A more rapid FISH test is also conducted identifying a specific set of conditions including trisomies 21, 18 and 13, with results available after 24-48 hours. The sensitivity of CVS for detection of Down syndrome is almost 100%. Very occasionally a technical problem growing the placental cells in the laboratory can occur. If so, an amniocentesis may be required later in pregnancy. The risk of miscarriage from the procedure itself is 0.2-1% (the risk of spontaneous miscarriage at this gestation is approximately 2%).
Amniocentesis
Amniocentesis is performed from 15 weeks gestation. It involves taking a small sample of amniotic fluid from around the developing baby using a needle under ultrasound guidance. A full chromosomal analysis is performed and takes 8-14 working days to complete. A more rapid FISH test can be performed on the sample identifying a specific set of conditions, including the trisomies 21, 18 and 13, with results available after 24-48 hours. The sensitivity of amniocentesis for detection of Down syndrome is almost 100%. Occasionally there can be a technical failure to grow the cells in the laboratory but this is very uncommon. The risk of miscarriage from the procedure itself is approximately 0.1-0.5%.
Pre-implantation genetic testing of embryos – IVF
Patients undergoing IVF treatment will be given the option for testing embryos prior to transferring them to the uterus.
Preimplantation genetic testing for aneuploidy (PGT-A)
PGT-A, previously known as preimplantation genetic screening (PGS), screens embryos for how many chromosomes they have. The term ‘aneuploid’ describes an abnormal or unbalanced quantity of chromosomes. The term ‘euploid’ describes a normal or balanced quantity of chromosomes. PGT-A involves taking a small sample of cells from an embryo to determine the quantity of chromosomes contained in that sample. The embryo is then frozen while results are pending.
Preimplantation genetic testing for structural rearrangements (PGT-SR)
PGT-SR is a test that can be performed to determine if an embryo has inherited a balanced or unbalanced form of a chromosome structural rearrangement. This screens embryos for their chromosome quantity. Chromosome structural rearrangements are changes from the normal size or arrangement of chromosomes, which are structures that contain all our genetic material. Individuals with structural chromosome rearrangements are at an increased risk of producing embryos or conceptions with extra or missing genetic material, also referred to as unbalanced embryos. Embryos or conceptions with unbalanced chromosomes typically do not lead to successful pregnancy. The aim of PGT-SR is to determine which embryos have balanced chromosomes and selecting for transfer these ‘balanced’ embryos with the highest chance of success.
Preimplantation genetic testing for monogenic/single gene condition (PGT-M),
PGT-M previously known as preimplantation genetic diagnosis (PGD) is an embryo genetic test for individuals who know they are at an increased risk of passing on a known genetic condition. PGT-M can be performed on embryos to greatly reduce the risk of having an affected child. PGT-M involves custom designing a test for each couple and their specific genetic change to identify and select unaffected embryos for transfer. PGT-M is available for individuals who are at increased risk of passing on a specific single- gene condition. You may consider PGT-M if: You and your partner are known carriers of the same recessive genetic condition (for example cystic fibrosis, spinal muscular atrophy, beta thalassaemia) You are a carrier of an X-linked genetic condition (for example Fragile X syndrome, Duchenne Muscular Dystrophy). You or your partner have or are at risk of having a single-gene condition (for example Huntington’s disease, Marfan syndrome) You or your partner have a gene mutation associated with a hereditary cancer syndrome (for example BRCA1, BRCA2, TP53). You or your partner have had a child or pregnancy affected with a single gene condition.
