Diagnostic (Invasive) Testing

Diagnostic tests give a definitive diagnosis of fetal chromosome abnormalities such as Down syndrome and many other uncommon genetic conditions. Diagnostic tests are always invasive-meaning that a sample of the pregnancy tissue is taken using ultrasound guided needle placement.

There are 2 commonly utilised tests:

• Chorionic Villus Sampling (CVS)
• Amniocentesis

Women can choose to have either test.

Rarely, fetal blood sampling (FBS) is performed for genetic and other fetal testing. This can be obtained from the fetal umbilical cord after 20 weeks.

Chorionic Villus Sampling (CVS)

What is CVS?

Chorionic Villus Sampling (CVS) is a test for fetal genetic abnormalities that can be performed in early pregnancy and is usually done between 10 and 14 weeks. Under ultrasound guidance, a thin needle is inserted through the abdomen and into the developing placenta. Small samples of placental tissue are collected. The tissue (chorionic villi) is then examined in the laboratory.

Who is offered CVS?

• Women who are 37 years or over at the estimated time of delivery. This is because the chance of having a baby with a chromosomal abnormality increases as the woman ages.
• Women who have had a high risk first trimester prenatal screening test (such as NIPT or CFTS) that has shown an increased probability of chromosomal abnormality.
• Women whose baby is found to have a physical/structural issue or an increased thickness in the fluid behind the baby’s neck (Nuchal Translucency) at the 12-13 weeks ultrasound. Structural abnormalities or increased Nuchal Translucency may suggest an underlying genetic disorder.
• Women who have already had a pregnancy with a condition such as Down syndrome.
• Women who are known to have, or be carriers of, hereditary conditions that might be passed on to their baby, such as cystic fibrosis.

What will happen on the day of the test?

• You will have an ultrasound scan to confirm the fetal age, the position of the placenta, assess for and recheck any previously reported anomalies.
• The abdomen is cleaned with antiseptic solution then the CVS site is injected with local anaesthetic.
• A thin needle is inserted through the abdomen into the placenta. The path of the needle is followed carefully on the ultrasound screen.
• A second finer needle is passed inside the first needle to collect small fragments of placental tissue. The tissue fragments are inserted into a flask of tissue culture fluid and sent for analysis.
• You may feel a strange dragging or drawing sensation in your pelvis. Some women may experience period type cramping afterwards.
• Once the sample is taken, the needle is removed and the fetus is checked again with ultrasound. You can then leave the ultrasound room and get dressed.
• After sitting quietly for 15 minutes or so you may go home.

While most women are quite capable of driving themselves, where possible, it is suggested that someone accompany you so that you can be driven home. We recommend that you take it quietly for the rest of the day and possibly the next day as well, although there is no reason to stay in bed. Strenuous exercise and heavy lifting should be avoided.

What to bring?

Please bring your referral, blood group card and a copy of any abnormal result or ultrasound. You may eat and drink as normal. You do not need a full bladder for the invasive test.

If you are taking Aspirin or on Clexane, please notify our staff when booking the procedure, as you will need to withhold a dose.

If you are a carrier of a blood borne virus such as Hepatitis B, Hepatitis C or HIV please notify our staff.  Amniocentesis may be a better test for you.

If you are having a test for a specific DNA condition such as cystic fibrosis or thalassemia, we will need to notify the laboratory to confirm your screening status. Some DNA tests for rare conditions are done interstate or overseas and prompt transport between laboratories needs to be arranged.

You are welcome to bring a support person to be with you, or you may prefer to attend alone. Either way our staff will look after you from the time you arrive, to caring for you during and after the procedure.

What analysis is done?

Microarray Test
Standard testing for fetal chromosome abnormality is now preformed as a Microarray Test. This can detect extremely small deleted or missing segments of DNA. Microarray uses a microchip that allows many small pieces of DNA to be tested for all at once. It is an automated procedure that allows large numbers of points on the fetal genome to be studied. There are many well understood genetic abnormalities that can now be diagnosed using this technology, but like all new technologies it is not comprehensive yet. Some findings on Microarray are still being studied for their significance in humans. The final microarray result studies all 23 chromosomes and will take 7-10 days.

FISH Test (Fluorescent In Situ Hybridisation)
A FISH Test is a rapid test routinely performed as part of the fetal microarray testing. This test gives a limited preliminary result looking at the 5 major chromosomes involved in fetal abnormality. It counts the number of chromosomes 21, 18, 13, X and Y.
A result is available within one working day.

How do I obtain my results?

As soon as results are available from the laboratory, WUMe will forward them to your doctor.  In case of any abnormal result, your WUMe doctor will personally phone your referring doctor to discuss the finding and expedite you receiving the results.

Sometimes genetic counselling and/or consultation with a geneticist is required and WUMe can help facilitate this next step.

Very rarely, the test may fail either because the laboratory cannot establish a culture or inadequate tissue sample.

What complications can occur?

There is a small increase in the risk of miscarriage following a CVS.

The additional risk of miscarriage following CVS is estimated to be between 1 in 200 (0.50%) and at 1 in 450 (0.22%) in recent clinical studies. (1)  A recent audit of a large number of women who had a CVS performed by Wume has shown a rate of miscarriage that is at the lower end of this range: 1 loss for each 405 procedures performed. (2)

Most women experience some discomfort during the procedure but it is normally not severe. You may get a small bruise at the injection site.

Following the procedure, if you have any excessive pain or loss of blood or fluid you should contact your referring doctor or present to the Emergency Department of the hospital where you are booked.

Occasionally the placenta is in a position where there is no access to do a CVS. This is often in earlier pregnancy or where the uterus is very retroverted, or tipped backwards. The position of the uterus changes  as the pregnancy grows.  As the uterus grows, it rises higher into the abdomen and the placenta may be safely reached to perform the test.

Some women choose to review again in one week to see if CVS is now possible while others will choose to wait for an amniocentesis.

Your WUMe Doctor will discuss these options with you.

Amniocentesis

What is Amniocentesis?

Amniocentesis is a test for fetal genetic abnormalities that is performed from 15 weeks of pregnancy, when there is enough fluid around the fetus to sample safely. Fetal cells are present in the amniotic fluid which can be separated out and analysed and tested for genetic disorders.

The test involves taking a sample of amniotic fluid by passing a needle through the skin of the abdomen and into the uterus, while carefully watching with ultrasound. A 15-20ml sample of the fluid is collected. The needle does not touch the baby.

Who is offered Amniocentesis?

• Women who are 37 years or over at the estimated time of delivery. This is because the chance of having a baby with a chromosomal abnormality increases as the woman ages.
• Women who have had a high risk prenatal screening test (such as NIPT, CFTS) that has shown an increased probability of chromosomal abnormality.
• Women whose baby is found to have a physical/structural abnormality on ultrasound which increases the probability of an underlying genetic disorder.
• Women who have already had a child with a condition such as Down syndrome.
• Women who are known to have a hereditary condition that might be passed on to their baby.

What will happen on the day of the test?

• You will have an ultrasound to confirm the age and development of the baby and position of the placenta. The presence of any previously reported problems will be reviewed.
• The skin on your abdomen will be cleaned and a thin needle inserted into your uterus while carefully watching with ultrasound. It usually takes less than 30 seconds to draw up the 15-20ml of fluid required into the syringe.
• The needle is then removed. The baby is checked again. You will be able to leave the ultrasound room and sit quietly for 15 minutes or so before leaving.

Almost without exception, women tell us that they experience far less discomfort than they expect and that the discomfort is usually very minor. Most women feel the discomfort is similar to having a blood test.

While most women are quite capable of driving themselves, where possible, it is suggested that someone accompany you so that you can be driven home. We recommend that you take it quietly for the rest of the day and possibly the next day as well, although there is no reason to stay in bed. Strenuous exercise and heavy lifting should be avoided.

What to bring?

Please bring your referral, blood group card and a copy of any abnormal result or ultrasound. You may eat and drink as normal. You do not need a full bladder for the invasive test.

If you are taking Aspirin or on Clexane, please notify our staff when booking the procedure, as you will need to withhold a dose.

If you are a carrier of a blood borne virus such as Hepatitis B, Hepatitis C or HIV please notify our staff.

If you are having a test for a specific DNA condition such as cystic fibrosis or thalassemia, we will need to notify the laboratory to confirm your screening status. Some DNA tests for rare conditions are done interstate or overseas and prompt transport between laboratories needs to be arranged.

You are welcome to bring a support person to be with you, or you may prefer to attend alone. Either way our staff will look after you from the time you arrive, to caring for you during and after the procedure.

What analysis is done?

Microarray Test
Standard testing for fetal chromosome abnormality is now preformed as a microarray test. This can detect extremely small deleted or missing segments of DNA. Microarray uses a microchip that allows many small pieces of DNA to be tested for all at once. It is an automated procedure that allows large numbers of points on the fetal genome to be studied. There are many well understood genetic abnormalities that can now be diagnosed using this technology, but like all new technologies is not comprehensive yet. Some findings on Microarray are still being studied for their significance in humans. The final microarray result studies all 23 chromosomes and will take 7-10 days.

FISH Test (Fluorescent In Situ Hybridisation)
A FISH Test is a rapid test routinely performed as part of the fetal microarray testing. This test gives a limited preliminary result looking at the 5 major chromosomes involved in fetal abnormality. It counts the number of chromosomes 21, 18, 13, X and Y. A result is available within one working day.

How do I obtain my results?

As soon as results are available from the laboratory, WUMe will forward them to your doctor.  In case of any abnormal result, your WUMe doctor will personally phone your referring doctor to discuss the finding and expedite you receiving the results.

Sometimes genetic counselling and/or consultation with a geneticist is required and WUMe can help facilitate this next step.

Very rarely, the test may fail because the laboratory cannot establish a culture.

What complications can occur?

There is a small increase in the risk of miscarriage following an Amniocentesis.

The additional risk of miscarriage found in recent clinical studies varies from approximately 1 in 200 (0.50%) to 1 in 900 (0.11%). (1)

Rarely, women may have some fluid leakage following the procedure. Mostly this will stop on its own and will not necessarily progress to a miscarriage. Bed rest may be recommended if you experience fluid leakage following Amniocentesis.

When Amniocentesis is done later in pregnancy (more than 20 weeks) there is a small increase in the chance of premature birth or preterm premature rupture of the membranes (PPROM).

Apart from the above risks, Amniocentesis does not appear to be associated with any other complications to the baby or to the pregnancy.

Rarely, the test may fail either because of sample quality or because the laboratory cannot produce a result. Depending on the circumstances, you may be offered a repeat procedure.

What should I look for after the test?

After the test, it is very rare to have any problems at all. Occasionally, there may be some mild discomfort or a little bruising under the skin. Following the procedure, if you have any excessive pain or loss of blood or fluid you should contact your referring doctor or present to the Emergency Department of the hospital where you are booked.

References:

1. Ghi T et al. ISUOG Practice Guidelines: invasive procedures for prenatal diagnosis in obstetrics. Ultrsaound Obstet Gynecol 2016, 48: 256-268.

2. Kane SC, Reidy KL, Norris F, Kornman LH, Nisbet DL, Palma-Dias R: The impact of the introduction of cfDNA screening on CVS testing. Oral communication at the 15th World Congress in Fetal Medicine, Greece, 2015.

CVS or Amniocentesis?

The decision about which test to have often depends on what stage of pregnancy a potential problem is identified.

Whichever test is chosen, it will take approximately 7-10 days from sampling to get a definitive result. The sample taken will be sent to a cytogenetic laboratory where a Microarray Test will be performed on the sample. This targets many genes in the fetal tissue and can detect many genetic abnormalities. It cannot detect everything that could be wrong with the fetus.

Most women who choose a CVS do so because it is performed earlier in pregnancy and so results can be obtained sooner. Other women choose it because the placenta is the preferred tissue for DNA testing especially where specific genetic abnormality is being tested for.

There are some conditions where an amniocentesis is preferred. Amniocentesis gathers cells shed directly from the fetus making it more accurate for some conditions. This is especially so when there is suspicion of a mosaic or “mixed cell line condition. In around 1% or 1:100 of CVS, a mosaic result is returned. This frequently reflects a placental rather than fetal issue, but requires a second test by amniocentesis to confirm.

Amniocentesis  is also preferred with a high risk NIPT result for Turner syndrome (XO) while the fetal ultrasound appears normal.

Other considerations:

The risk of miscarriage-

This is very low with either procedure. The reported risk from recent large international studies varies widely from study to study. The reported pregnancy loss rates for amniocentesis vary from 1:200 to as low as 1:900. In contrast, CVS procedure loss rates vary from 1:200 to 1: 450. (1)  The CVS loss rate for WUMe as published in our own large series is 1:405. (2)

For those women where the lowest risk of miscarriage is paramount, they may prefer to wait and have an amniocentesis.

Timing of procedure-

Some women may consider a termination of pregnancy should their pregnancy be affected with a chromosome or other genetic abnormality. CVS allows diagnosis at the earliest stage of pregnancy. In early pregnancy, a termination is a surgical procedure, while later on it may require an induction of labour.

References:

1. Ghi T et al. ISUOG Practice Guidelines: Invasive procedures for prenatal diagnosis in obstetrics. Ultrsaound Obstet Gynecol 2016 (al.); 48: 256-268.

2. Kane SC, Reidy KL, Norris F, Kornman LH, Nisbet DL, Palma-Dias R: The impact of the introduction of cfDNA screening on CVS testing. Oral communication at the 15th World Congress in Fetal Medicine, Greece, 2015.