Category: Prenantal testing

It is important to understand why prenatal testing is offered specifically for Down syndrome (Trisomy 21). This emphasis on Down syndrome is not because it is the worst condition a child can have. It is also not because people living with Down syndrome do not have a good quality of life or a ‘life worth living’. In fact, many people who have first-hand experience with Down syndrome do not consider it to be something that needs to be avoided.

• • • The first reason testing for Down syndrome is offered is that it is possible. The genetic basis of Down syndrome (3 rather than 2 chromosomes 21) is easy to identify and it is well researched and understood. This is not the case with most other causes of intellectual disability or other congenital anomalies. There are other conditions that are easy to diagnose during pregnancy, such as neural tube defectsneural tube defectsNeural tube defects (NTDs) are birth defects that develop in the first month of pregnancy and affect the brain and/or spinal cord of the fetus. They occur in about 1 in 750 newborns. Symptoms vary depending on the specific condition and range from no symptoms to stillbirth or death soon after birth. The most common NTDs are spina bifida and anencephaly. Spina bifida is a spinal cord defect. Depending on the type of spina bifida, people with this condition can have no symptoms, while others can have physical symptoms, such as paralysis, and/or intellectual disabilities. Anencephaly is a brain defect where some or all of the brain is missing. Anencephaly can cause stillbirth. Newborns with this condition generally stay unconscious and die soon after birth. Other NTDs include encephalocele and iniencephaly., Edwards syndrome, or trisomy 18Edwards syndrome, or trisomy 18Edwards syndrome, or trisomy 18, is caused by having three chromosomes 18 instead of two. It occurs in about 1 in 5000 live births. Newborns with Edwards syndrome usually have a low birth weight because of slow growth in the mother’s womb. Individuals with Edwards syndrome have physical malformations and birth defects, most commonly heart and kidney defects. They also have a delayed physical and intellectual development and severe intellectual disability. About 5 to 10% of children with Edwards syndrome live beyond the age of 1. In very rare cases, individuals with less severe Edwards syndrome can live into early adulthood. Those who survive with Edwards syndrome may learn to smile, sit and stand and they may build meaningful relationships with friends and family., and Patau syndrome, or trisomy 13Patau syndrome, or trisomy 13Patau syndrome, or trisomy 13, is caused by having three chromosomes 13 instead of two. It occurs in about 1 in 16 000 live births. Patau syndrome can lead to pregnancy loss or stillbirth. Individuals with Patau syndrome have severe intellectual disability as well as many physical malformations and birth defects, such as heart and kidney defects. About 5 to 10% of children who have Patau syndrome live beyond the age of 1. In extremely rare cases they can live up to the age of 5 or a little older. Those who survive with Patau syndrome may learn to smile, sit, and walk with assistance and they may build meaningful relationships with friends and family. . These conditions are often screened for at the same time as Down syndrome.
    • The second reason for the emphasis on Down syndrome is that of all the known causes of intellectual disability, it is the most common. Yet, if we consider all the other causes taken together (combined), then they are responsible for 92-94% of the cases of intellectual disability. In other words, Down syndrome is responsible for about 6-8% of intellectual disability cases. This means that terminating a pregnancy on the basis of Down syndrome does not eliminate the probability of having a child with an intellectual disability.

The purpose of prenatal testing is to identify the presence of Down syndrome in the fetus. Parents may choose to use this information for various reasons:

• • • They may want to have this information because it involves an increased risk of complications during delivery. They may want to change their plans for the birth (for example, have the baby at the hospital rather than at home).
    • They may want to have this information to prepare in advance for the birth of a child with Down syndrome (for example, read about Down syndrome, find out about available services, and connect with support groups).
    • They may want to have this information because they prefer not to have a child with Down syndrome and would choose to terminate the pregnancy if the fetus is diagnosed with it.
    • They may want to have this information because they would continue the pregnancy but would like to make plans for the child to be adopted.

To learn more about the possible pregnancy decisions after a positive diagnosis, click here.

Whatever the reason, pregnant patients should always be offered prenatal testing. They should never be pressured or guilted into doing or not doing it.

Choosing to use prenatal testing or not to use it, is a personal decision. Pregnant patients may want to make this decision alone, or with their partner. They may wish to discuss it with friends, family members and/or health care providers. The role of health care providers in prenatal testing is to provide all the information and counseling necessary for the pregnant patient/couple to make their decision.

The fact that prenatal testing is routinely offered and the fact that some tests are paid for by the Canadian public healthcare system (or by the government or insurance in other countries) does not mean that it is better to use them than not to use them. Prenatal tests are tools that are made available to pregnant patients to help them make choices that suit their needs and preferences. Choosing not to use these tools is as valid as choosing to use some of them or all of them.

Prenatal screening methods used together or separately, give a chance of the fetus having Down syndrome. This chance is described as ‘high’ or ‘low’. The cut-off between ‘high’ and ‘low’ varies between programs but it is generally around 1/300.

To understand probabilities better, it can be useful to present them in various forms.

For example:

• • • A 1/300 probability that the fetus has Down syndrome means that in a group of 300 pregnant patients, one will have a fetus with Down syndrome.
    • A 1/300 probability that the fetus has Down syndrome also means a 299/300 probability that it does not have Down syndrome. Therefore, it means that that in a group of 300 pregnant patients, 299 will not have a fetus with Down syndrome.
    • A 1/300 probability that the fetus has Down syndrome means a 0,3% probability that it has Down syndrome and a 99,7% probability that it does not.

The cut-off points for probabilities to be considered ‘high’ or ‘low’ are set with the intention of maximizing detection rates while minimizing false-positive rates. The detection rate is the proportion of babies with Down syndrome that are given a “high-chance” result. The false-positive rate is the proportion if babies without Down syndrome that are given a “high-chance” result.

It is useful to understand this because many people experience anxiety when they hear that they have a “high chance” after screening. Calling the result “high chance/risk/probability” can be misleading. Most people would consider that if an event has a 1 in 250 or 1 in 300, or even a 1 in 100 chance of occurring, it is not “highly likely” that this event will occur. Indeed, a large majority of those who get a “high chance” result after nuchal translucency scan or serum screening do not carry a baby with Down syndrome. Less than 5% of fetuses with a positive serum screen actually have Down syndrome. This is called the “positive predictive value” (PPV).

A 5% positive predictive value means that a pregnant patient who has received a “high chance” result that the fetus has Down Syndrome has a 5% chance that the fetus does have Down Syndrome and 95% chances that the fetus does not have Down Syndrome.

Interpreting a risk/chance level is very subjective and personal. Different people may have very different understandings and feelings about what is an acceptable risk for them.

Individual patients may decide for themselves what they consider to be high chance/risk/probability. Based on this, they may pursue follow-up options (diagnostic testing) or not, depending on their own tolerance of risk. However, public prenatal testing programs do set eligibility criteria. Consider the following examples.

• • • Mary’s fetus has been identified as having a 1 in 30 chance of having Down syndrome. Mary finds this probability quite high. The public health system in her province has a cut-off point at 1 in 300. Mary will be eligible for further testing in the public system and will pursue it. Depending on the province she lives in, she may have free access to NIPT before she is offered diagnostic testing (amniocentesis).
    • Lucy’s fetus has been identified as having a 1 in 350 chance of having Down syndrome. Lucy finds this probability quite high. The public healthcare system in her province has a cut-off point at 1 in 300. Lucy will not be eligible for further testing in the public system, but she will pursue further testing privately and pay for it out-of-pocket.
    • Chloe’s fetus has been identified as having a 1 in 250 probability of having Down syndrome. Chloe finds this probability quite low. The public healthcare system in her province has a cut-off point at 1 in 300. Chloe would be eligible for further testing in the public system, but she chooses not to do any more tests.

It is also important to consider that the type of results provided by screening never completely eliminates the probability of the fetus having Down syndrome. For instance, when the screening result is 1 in 25 000, it still means that out of 25 000 pregnant patients with this result, 1 is indeed carrying a fetus with Down syndrome.

A diagnostic test is required if a person wishes to completely eliminate the uncertainty regarding Down syndrome. In this case, the probability of the fetus having Down syndrome needs to be weighed against the risk of a miscarriage occurring because of the diagnostic test. Statistically, this risk of such a miscarriage is estimated between 1 in 200 (0.5%) and 1 in 500 (0.2%). In addition to the probability of each event, people may consider which event they wish to avoid the most – a miscarriage or the birth of a child with Down syndrome. There is no right or wrong answer to this question. It is very personal.

Other body features of the fetus also provide useful information at this point. For instance, the absence of a nose bone is also an indicator for a higher probability of trisomies. In addition, some organs can be visualized, the heartbeat can be heard, and the fetus can be measured to monitor fetal development.

Different screening programs and different physicians offer various combinations of the first and/or second trimester serum screening with NT scan and/or NIPT. Using the second trimester serum screening has the advantage of making the results more accurate, and the disadvantage of delaying the results of screening.

A few examples:

A combination called “Enhanced First Trimester Prenatal Screening” uses the first trimester serum screening and the NT scan. It gives a result in the first trimester with an 83% detection rate83% detection rateAn 83% detection rate means that 83 out of 100 fetuses with Down syndrome will be correctly given a “high chance” result. This means that 17 out of 100 fetuses with Down syndrome will not be identified by this screening. and 5% false-positive rate5% false-positive rateA 5% false-positive rate means that 5 out of 100 fetuses without Down syndrome will be incorrectly given a “positive screen” even if they don’t have the condition.. If a pregnant patient ‘screens positive’, it means that she is given a ‘high chance’ result based on this screening combination. In this case, the patient may access NIPT or prenatal diagnosis in the first trimester or early in the second trimester. This screening combination is offered by the Ontario and Saskatchewan public programs, as well as in private clinics across Canada.

Another combination called “Serum Integrated Prenatal Screening” uses the serum screening from the first and second trimesters. It gives a probability result in the second trimester with an 85% detection rate85% detection rateAn 85% detection rate means that 85 out of 100 fetuses with Down syndrome will be correctly given a “high chance” result. This means that 15 out of 100 fetuses with Down syndrome will not be identified by this screening. and a 4% false-positive rate4% false-positive rateA 4% false-positive rate means that 4 out of 100 fetuses without Down syndrome will be incorrectly given a “positive screen” even if they don’t have the condition.. If a pregnant patient ‘screens positive’, it means that she is given a ‘high chance’ result based on this combination. In this case, the patient may access NIPT or diagnostic tests later in the second trimester. The Serum Integrated Screen is offered by the Quebec and British Columbia public program and by private clinics across Canada.

A third combination called “Integrated Prenatal Screening” uses the serum screening from the first and second trimesters with the NT scan. It gives a probability result in the second trimester with an 87% detection rate87% detection rateAn 87% detection rate means that 87 out of 100 fetuses with Down syndrome will be correctly given a “high chance” result. This means that 13 out of 100 fetuses with Down syndrome will not be identified by this screening. and a 2% false-positive rate2% false-positive rateA 2% false-positive rate means that 2 out of 100 fetuses without Down syndrome will be incorrectly given a “positive screen” even if they don’t have the condition.. If a pregnant patient ‘screens positive’, it means that she is given a ‘high chance’ result based on this combination. In this case, the patient access NIPT or diagnostic tests later in the second trimester. The Integrated Screen is offered by the Quebec and British Columbia public program, in locations where nuchal translucency is available, and by private clinics across Canada.

In addition to Down syndrome, NIPT can also test for other conditions where the fetus has an extra chromosome, including Patau syndrome and Edwards syndrome. It can also test for conditions caused by a nontypical (extra or missing) numbers of sex chromosomes: Klinefelter syndrome, Turner syndrome and triple X syndrome.

Typically, females have two X chromosomes (XX) and males have one X chromosome and one Y chromosome (XY). Any other number of sex chromosomes will lead to syndromes in the fetus that vary from mild to life-threatening. People who receive a “positive screen” for one of these less-common syndromes will be offered follow-up prenatal diagnosis and medical information specific to that condition. NIPT cannot find neural tube defects (NTDs) that can be found by serum screening. Most neural tube defects are identified by ultrasound in the second trimester.

Although NIPT can be performed as early as week 9 or 10, many professional associations recommend using it only in pregnancies with high probability of having a condition. A pregnancy is considered “high probability” (sometimes referred to as “high risk”) when:

• • • Another screening test, such as screening serum and/or a nuchal scan gave a “high-probability” result.

Or

• • • The pregnant woman will be 40 years old or more at the expected time of delivery.

Or

• • • There is a personal or family history of a condition that can be found by NIPT.

Some Canadian provinces currently do not cover the cost of NIPT through public healthcare. Ontario, Manitoba, British Columbia, Quebec, Nova Scotia and Newfoundland and Labrador have added NIPT to their prenatal screening programs for high probability pregnancies. NIPT is available in private clinics across Canada for high probability and low probability pregnancies. It may also be available as part of clinical trials in some locations.

NIPT gives results that are more reliable than nuchal scans and serum screening. In high probability pregnancies, NIPT detects 99 out of 100 fetuses that have trisomy 21, 18 or 13.

However, NIPT is not as certain as a diagnostic test. This means that it can give a “positive result” even if the baby does not have the condition. This is called a “false-positive”. False-positives happen frequently, especially in low probability pregnancies. Because of this, a diagnostic test (CVS or amniocentesis) is recommended for:

1. 1. 1. People who want to be as sure as possible about the result.
      2. People considering terminating the pregnancy after a positive NIPT.

However, false-negatives (a negative screen when the fetus actually has a trisomy) are rare with NIPT.

In about 1% to 8% of cases the test does not give a result. In these cases, the chance of a chromosomal trisomy, especially trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) is increased and the NIPT should be repeated or other tests can be used.

Amniocentesis is the most common type of prenatal diagnostic test. It involves collecting a small sample of amniotic fluid from the uterus, using a fine needle that is inserted through the pregnant patient’s abdomen, under ultrasound guidance. This fluid contains fetal cells from which chromosomes, or DNA, can later be analyzed. Amniocentesis can be done from week 15 of the pregnancy.

Advantages:
Amniocentesis provides a diagnosis (definite result), as opposed to a probability, or a likelihood/chance. It is more widely available than CVS and it fails in less cases than CVS.

Disadvantages:
Discomfort can be felt from the needle insertion. Amniocentesis involves an increased risk of miscarriage estimated at 0.2-0.5% (1 in 500 to 1 in 200). Other possible complications include pain, cramps, bleeding, fever, and loss of amniotic fluid.

Compared to CVS, the test is done later in the pregnancy, and analyzing the sample may take longer (2 to 4 weeks), although results can be obtained faster (4-6 days). This leaves less time for decision-making. If someone chooses to terminate the pregnancy because of the results of amniocentesis, the termination would occur later in the pregnancy.
After the amniocentesis, it is recommended to rest for 24 hours.

Chorionic villi are little branches in placental tissue that reach out in the wall of the mother’s womb to help the flow of blood between the mother and fetus. Therefore, villi are the placental structures that are most easily accessible from the outside. CVS consists of collecting a small piece of villi with a needle or catheter. The procedure is guided by ultrasound and may be done through the abdomen or vagina. The actual procedure takes less than one minute but it takes overall approximately 10-20 minutes including the preparation. It is performed between weeks 11 and 14 of pregnancy.

Advantages:
CVS provides definitive results, as opposed to a probability or a likelihood/chance, early in the pregnancy, which leaves more time for decision-making about the pregnancy. Results are usually provided within 2 weeks.

Disadvantages:
There is an increased risk of miscarriage estimated at 0.5-1% (1 in 200 to 1 in 100). Discomfort or pain can be felt from the needle insertion. Other possible complications include pain, cramps, bleeding, fever, and loss of amniotic fluid. Test failure: in 1 to 2% of cases, the results may be inconclusive due to the presence of maternal tissue in the collected sample or other technical problems. In these cases, either a new CVS or an amniocentesis could be offered.

After the procedure, it is recommended to rest for 24 hours.

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