One of the complex choices to make in early pregnancy is that of prenatal testing. In recent
years, several new tests have become available primarily aimed at testing for Down syndrome. These tests are offered in addition to the usual blood and urine tests in early pregnancy, and are also additional to the detailed ultrasound examination at around 20 weeks. These tests are looking for various genetic conditions in your baby.
These tests are optional but need to be considered carefully. You should not feel pressured to undertake any of these tests if you do not wish to do so. It is important to recognise that the choice of testing, and what you do with the results, is yours. I will give you advice on the different types of tests and options available but the ultimate decisions must rest with you.
There are two main groups of screening tests available to you:
- Genetic tests performed before or very early in pregnancy
- Prenatal tests performed at various stages throughout pregnancy
1. Genetic tests performed before or very early in pregnancy
Genetic carrier screening is now offered to all couples before or very early in pregnancy to see if they are carriers of particular genetic conditions that can affect their future children. Whilst some ethnic groups are more likely to carry some genetic changes, carrier screening is now offered regardless of ancestry. This testing usually only needs to be done once in a couple’s reproductive years as results will be applicable to all future pregnancies. Most babies born with these genetic conditions have no known family history of the condition. That is, the parents did not know that they were carriers of the same condition.
Genetic carrier screening can be done for the 3 commonest conditions in Caucasians (CF, SMA, fragile X) – this is now bulk billed through medicare as of November 2023. It can also be part of an expanded panel of almost 400 conditions (BEACON – DHM). If you are not a carrier of these conditions, you are at very low risk of having a child with any of these conditions. It is important to know that the current carrier tests detect the majority of carriers, but they cannot detect every single gene change that can cause these conditions.
A positive test in one person is common. The partner should be tested to see if they also carry the same defective gene. If both carry the defective gene, there is a 1:4 chance baby can be affected by the condition, and further testing may be required. Even if the couple are non-concordant, it is important to note that in the event of new relationships, a baby can be affected if the new partner is a concordant carrier. And family members of the positive case should consider testing, including the unborn child when they are ready to conceive.
Cystic fibrosis
Cystic fibrosis (CF) is an inherited condition that affects approximately 1 in 2,500 babies. One in 25 Caucasians are carriers of CF. If both parents are carriers, each of their children has a 25% chance of inheriting the disorder. CF causes thick mucus in the lungs and gut, resulting in recurrent lung infections that cause progressive damage and difficulty with digestion of food. Infants and children with CF require daily chest physiotherapy, frequent courses of antibiotics, and the need to take medicine to aid digestion. Until recently many children with CF died in early childhood but now the average life expectancy is about 40 years of age. There is no cure for cystic fibrosis but better treatments are under research and development.
The gene that causes CF is called CFTR. The test from VCGS will detect about 90% of people who are carriers of a cystic fibrosis gene change / mutation. 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 (FXS) is the most common cause of inherited intellectual disability affecting around 1 in 4,000 babies. Approximately 1 in 100-150 people are carriers of FXS. People with FXS can have developmental delay, learning difficulties, anxiety, autism and epilepsy. The features of FXS vary from mild to severe with males/persons with XY chromosomes more likely to be severely affected than females/persons with XX chromosomes. There is no cure for FXS although some educational, behavioural and medical interventions can improve outcomes. Some females/persons with XX chromosomes who are carriers of FXS may have early menopause.
FXS is caused by an increase in the length of a particular gene known as the FMR1 gene,
located on the X chromosome. The VCGS test will detect about 97% of people who are carriers of FXS. Only female/XX carriers of FXS are at increased chance of having a child with FXS (males can be carriers, but they cannot produce a child with FXS). Therefore, your partner does not need to be tested. If you are a carrier of FXS, your baby can inherit the FXS gene change. Your baby may then either be a carrier of FXS or may actually have FXS. FXS is a very complex genetic disorder and genetic counselling is highly recommended if you are found to be a carrier.
Spinal muscular atrophy
Spinal muscular atrophy (SMA) affects approximately 1 in 6,000 babies. One in 40 individuals
are carriers for SMA. SMA is a condition that affects nerves in the spinal cord and causes
muscles to get weaker. There are four types of SMA. SMA Type I is the most severe. Babies with SMA Type I have weak muscles from birth and usually do not live past two years of age. SMA Types II and III progress more slowly than Type I. Most children with SMA Types II or III are unable to stand or walk without help. Children with Types II and III SMA can live into early
adulthood, depending on the severity of the condition. People with SMA Type IV do not develop symptoms until adulthood. There is no cure for SMA, however there are treatments and interventions available aimed at managing symptoms and improving quality of life.
There are two genes which cause SMA, called the SMN1 and SMN2 genes. The test will detect about 97% of people who are carriers of SMA. A couple is only at risk of having a child with SMA if both parents are carriers of the condition. 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.
2. Options for prenatal screening
There is now a bewildering array of tests available during pregnancy and thinking about these types of tests can be quite confronting as they can detect some serious medical conditions in a baby. It is important to realise that by having any of these tests there is no assumption that you will terminate a pregnancy should it be affected. Please be assured that if there is a serious condition detected, I will support informed decision making and perform a termination of pregnancy, if requested.
No testing
Some people choose to do no additional prenatal testing at all. Perhaps the risk of these
conditions are considered to be low, or because termination of pregnancy would not be
considered under any circumstances. This is a completely appropriate decision that is entirely yours to make. I would still recommend routine pregnancy blood tests and a 20 week ultrasound, which we can discuss at your appointments.
Non-invasive prenatal testing (NIPT)
Several non-invasive prenatal genetic tests are available, which all test a maternal blood sample from 10 weeks of pregnancy. These tests analyse cell-free fetal DNA found in the mother’s blood to detect Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), Trisomy 13 (Patau syndrome) and Turner syndrome. The test is highly sensitive for downs syndrome – 99% (this means if there were 100 downs babies in 100,000 mums, the test would pick up 99 of the 100, but miss the 1:100,000). I recommend all my patients consider NIPT as it is the best non-invasive screening test for Down syndrome available (in terms of sensitivity). The cost is about $450, and there is no Medicare rebate or private health coverage. Results are available within 3-5 days from the time the sample is received by the laboratory. If you have a positive result, you will need a diagnostic test to determine if the baby is truly affected. A positive test does NOT mean the baby is affected. Only 50% of positive tests are true positives.
First trimester combined screening (FTCS)
The FTCS involves combining the results of the nuchal translucency scan with the results of a blood test performed between 11 and 14 weeks. The FTCS is directed at detecting Down
syndrome, Edwards syndrome and Patau syndrome. An approximate out of pocket cost for the blood test after Medicare is $70, but this does not include the cost of the ultrasound. Results of this testing are reported as low risk or increased risk. Increased risk results (>1:300) do not mean there is something wrong with the baby, just that additional testing can be performed to clarify the result. Most babies with an increased risk on the combined first trimester test are completely normal. Results will be available within one week from when the blood test was taken.
3. Diagnostic testing
Diagnostic tests are performed in patients who have high-risk prenatal screening tests, or are particularly high risk for genetic problems for other reasons. They are confirmatory for the presence of genetic abnormalities.
Chorionic villus sampling (CVS)
CVS involves passing a needle into the placenta between 11 and 13 weeks gestation. A small
amount of placental tissue is taken and a chromosome analysis is then performed by the
pathology laboratory. Full results take approximately 8-14 working days to become available.
FISH testing is a more rapid test on the sampled tissue that detects a smaller number of
conditions, including trisomies 21, 18 and 13, and the results of this are available within 24-48 hours at an additional cost. Further details of the actual procedure will be given to you if this is the option you choose. The sensitivity of CVS for detection of Down syndrome is virtually 100%. The only exception would be a technical problem growing the placental cells in the laboratory, and in these unlikely circumstances an amniocentesis may be required later in pregnancy. The risk of miscarriage from the procedure itself is 0.2-1% (you must remember that there is a risk of spontaneous miscarriage at this gestation of approximately 2%).
Amniocentesis
Amniocentesis involves taking a small sample of amniotic fluid from around the developing baby after 15 weeks gestation. Only a small amount of fluid is taken but this is enough for a full chromosome analysis to be performed. Full results take approximately 8-14 working days to become available. FISH testing is a more rapid test on the sampled tissue that detects a smaller number of conditions, including trisomies 21, 18 and 13, and the results of this are available within 24-48 hours at an additional cost. The sensitivity of amniocentesis for detection of Down Syndrome is virtually 100%. As with CVS, there may be a technical failure to grow the cells in the laboratory but this is extremely uncommon. The risk of miscarriage from the procedure itself is approximately 0.1-0.5%. The risk of spontaneous miscarriage at this gestation is 0.5%.
| Test | Weeks pregnant | Detection of Down Syndrome (sensitivity) | False positive rate | Positive predictive value |
| NT test Only | 11-14 | 70% | 5% | – |
| NIPT | >10 | 99.9% | <0.1% | 45-90% |
| Combined first trimester test (NT + bloods) | 11-14 | 90-95% | 5% | 7-10% |
| CVS | 11-13 | 100% | 0.1% | 100% |
| Amniocentesis | >15 | 100% | 0.1% | 100% |