NIPT

What is it?

NIPT, or non-invasive prenatal testing, is a very reliable blood test for pregnant woman to detect trisomy 21 (Down's Syndrome), trisomy 13 and trisomy 18. The last two conditions are more rare than Down's Syndrome, and not compatible with life. Non-invasive prenatal testing can be administered starting from the 12th week of pregnancy, after the 12-week ultrasound.

How does NIPT work?

For NIPT, it is essentially genetic material from the placenta that is tested. This genetic material is generally the same as that of your baby, though it sometimes differs. This is why an abnormal NIPT result does not give absolute certainty about a possible abnormality in your baby. You can only know that after an amniocentesis has been performed. An amniocentesis carries a small risk of miscarriage (0.5% = 1 out of 200). If an abnormal NIPT result is confirmed by the amniocentesis, it is important that you are well informed about the possible consequences of the detected condition for your baby.

In addition to the 12-week ultrasound and NIPT, there are other tests that can detect conditions in the foetus. The 20-week ultrasound is also important.

Non-invasive prenatal testing was developed to detect major abnormalities in DNA, such as a (partial) chromosomal deletion or an extra (partial) chromosomal addition. Many hereditary diseases, such as haemophilia and mucoviscidosis, are caused by very small errors in certain genes and cannot (currently) be detected with NIPT.

In addition, there are many conditions that are not based on an abnormality in the genetic material, and, for this reason, cannot be detected with NIPT (nor with an ultrasound, in certain cases). These conditions include diabetes, epilepsy, autism, etcetera.

Non-invasive prenatal testing can only be performed after you have signed a written consent form, found on the reverse side of the request form. You must indicate your three choices regarding your non-invasive prenatal testing on the request form. By signing this written consent, you state that you have understood all the information about your non-invasive prenatal testing, and that your gynaecologist has been able to answer all your questions.

First choice: targeted or whole genome

On the front side of the request form, you must indicate whether you are selecting 'targeted' NIPT or 'whole-genome' (extensive) NIPT.

In order to help you with this choice, we have listed a few characteristics of both types of NIPT:

Targeted NIPT

‘Targeted' non-invasive prenatal testing is able to detect the following syndromes:

Down's Syndrome is detected in approximately 1 out of every 700 pregnancies. Trisomy 13 and 18 are
far more rare. These last two conditions are more serious and are not compatible with life.

Non-invasive prenatal testing is very sensitive screening that can detect specific conditions. It is almost 99% accurate for trisomy 13, 18 and 21. That means that, out of 100 pregnancies where one baby has Down's Syndrome, non-invasive prenatal testing can correctly detect this in 99 of them. There is, however, a very small chance of a false negative result.

On the other hand, an abnormal NIPT result does not automatically mean that your baby has a chromosomal abnormality. The NIPT result may also be a false positive. Only an amniocentesis provides 100% certainty.

The table below gives a rough estimate of the cases where the amniocentesis confirms the
NIPT result. Please note that these percentages depend on the presence of the certain condition in a certain population group and fluctuate with age (the chance of detection increases with age):

The non-invasive prenatal testing shows increased risk of:	Amniocentesis can confirm NIPT for:	NIPT gives a false result:
Trisomy 21 (Down's Syndrome)	99% of the cases	1% of the cases
Trisomy 18	86% of the cases	14% of the cases
Trisomy 13	72% of the cases	28% of the cases

Whole-Genome NIPT

‘Whole-genome' NIPT is the more extensive version of non-invasive prenatal testing, which
has been used in all laboratories in Flanders since 2018. This NIPT test can detect trisomies 21, 18 and 13, as well as abnormalities of other chromosomes (other than chromosome 21, 18 and 13):

It can also detect small pieces of chromosomes that break off or mosaics of other chromosomes other than 13, 18 and 21. A mosaic means that a portion of the baby's cells have the abnormality, while the other portion of the baby's cells do not. These abnormalities can have serious consequences for the baby.
Sometimes, abnormalities are detected that we do not yet understand well, or that are not that important for the baby.
In addition, we see relatively often that, with certain abnormalities, the abnormality is only found in the placenta and not in the baby. An amniocentesis is necessary to know with certainty. We know from experience that these findings can cause concerns in many expecting parents.
In rare cases (1 out of every 5000), the whole-genome NIPT can detect a malignant condition (
cancer, for example) in the mother.

Summary

	Targeted NIPT	Whole-Genome NIPT
Pros	The test is very targeted (trisomy 13, 18 and 21), and you can thoroughly prepare for what the result will be.	There is a small chance that, in addition to trisomy 13, 18 and 21, another chromosomal abnormality will be detected, which could have consequences for your baby.
Cons	There is a small chance that you may miss other (possibly serious) chromosomal abnormalities in your baby.	There is a large chance that your abnormal NIPT result is only present in the placenta, and not in your baby. Only an amniocentesis can provide certainty. This carries a minor risk of miscarriage of roughly 0.5%. Something else may be detected, which we still do not understand well. This can bring a certain worry or fear with it.

ATTENTION: if you do not indicate your choice on the request form (front page), targeted NIPT will be performed.

Second choice: sex

The second choice you will make is whether or not you would like to know the sex of your baby. This choice must be indicated on the reverse side of the request form.

Many couples definitely know that they want NIPT to tell them the sex of their baby. This is not the goal of non-invasive prenatal testing, however. It's great that you can know the baby's sex a bit earlier than with ultrasound: you can usually tell with NIPT around 13-14 weeks, or with ultrasound around 16 weeks.

Be careful, because it is possible for NIPT to be wrong when determining the sex of the baby. The sex should be confirmed using ultrasound. This is usually possible around week 16 or 20.

If you do not know whether or not you want to know the baby's sex, or whether you want it to be a surprise, select 'no' on the form. If you change your mind later on during your pregnancy, your gynaecologist will be happy to check the sex of your baby using ultrasound. The chance of not being able to determine the sex of the baby on ultrasound is very small.

ATTENTION: if you do not indicate your choice, the non-invasive prenatal testing will not check for sex.

Third choice: sex chromosome conditions

The third choice that you will need to make is whether or not you would like to be informed of an increased risk for a sex chromosome condition. This choice must be indicated on the reverse side of the request form.

This primarily includes:

The chance is roughly 1 out of 400, though we do not have an exact percentage. There can also be other, even rarer sex chromosome conditions.

If NIPT shows an increased risk for a sex chromosome condition, then that does not indicate any certain diagnosis. Only an amniocentesis can give you 100% certainty. The chance of a false positive result is significantly larger than that for Down's Syndrome, and is most like when screening for Turner's Syndrome.
You are absolutely not obligated to have an amniocentesis performed. You may, if you wish, also wait until the birth of your baby in order to confirm the diagnosis. This would be done by performing a blood test on the baby. This often brings with it a lot of anxiety.
If a sex chromosome condition is confirmed (either during the pregnancy or at birth), you will be extensively informed about the condition by a specialised paediatrician.
Sometimes, a sex chromosome condition is suspected during childhood or puberty. Your paediatrician will definitely speak to you about it. A blood test may be performed during childhood or puberty to confirm the diagnosis.

Just as with Down's syndrome, Triple X and Klinefelter's Sydrome are trisomies, which means that the chance of these conditions increases with the age of the pregnant woman. This is not the case with Turner's Syndrome, for which the pregnant woman's age does not play a role.

Summary about whether or not to know about a sex chromosome condition:

Pros	It can be useful to know that your baby has a sex chromosome condition for taking care of your child and so you can participate in your baby's medical treatment.
Cons	It can be stressful to know about this, during the pregnancy, as well as while your child is growing up. The psychological consequences of an early diagnosis, for the parents as well as the child, have not been sufficiently researched. Based on the limited experience we have had, expecting parents tend to become quite worried. It is often the source of fear and panic.

ATTENTION: if you do not indicate your choice, the NIPT test will not check for sex chromosome conditions.

NIPT when pregnant with multiples

NIPT when pregnant with twins In this case, if there is an abnormal result, a double amniocentesis is necessary to know which baby has the condition. The miscarriage risk is roughly 1%.

Which choices do you have to make for NIPT when pregnant with twins?

The first choice (targeted or whole-gene NIPT) remains the same.
The second choice (sex) is also the same. There are, however, two possible outcomes:
- We may not find any Y chromosomes, which would mean that both are girls.
- We may find one Y chromosome, which means that at least one of the babies is a boy.
The third choice, regarding sex chromosome conditions, cannot be selected. In the event of a twin pregnancy, it is not possible to estimate the risk of a sex chromosome condition.

Limitations of NIPT

Non-invasive prenatal testing may provide an unclear result in the following situations:

In women who are overweight (BMI >30)
If there was physical exertion during the hour before the blood draw
If there are certain autoimmune diseases
If certain anticoagulation medications are taken

In these cases, the reporting of the NIPT results may take longer than normal because extra tests are required. Another blood draw may be necessary.

To properly perform non-invasive prenatal testing, there must not have been any procedures such as a blood transfusion, stem cell therapy, organ transplant, radiation therapy or immunotherapy performed in the last three months.

In the future, it may be possible to detect an ever-increasing number of abnormalities with NIPT. You must understand that any non-invasive prenatal testing you have performed now is not only limited to the type of NIPT that you select, but also limited insofar as what medical genetics (hereditary sciences) currently knows.

There is no single test that can detect everything: some chromosomal or genetic abnormalities cannot be detected with NIPT.

Practical information

Reimbursement

As of the 12th week of pregnancy, NIPT is reimbursed. The co-payment (that is what you must pay) for the NIPT is €8.68.
If you are not registered with a Belgian health insurer, the cost of NIPT is €260.00.

Blood draw

The blood draw for NIPT takes place at the hospital:

An appointment will have to be scheduled for this.
You must be fasting.
Avoid physical exertion during the hour before the blood draw.
Bring the request form and the signed informed consent form, as well as your indicated selections. Otherwise, the blood draw cannot be performed.

Location	Address	Weekdays	Saturday
Maria Middelares General Hospital	Buitenring Sint-Denijs 309000 Ghent	8am to 7pm, registration 6.45pm	8am to 12pm, registration 11.45am
Maria Middelares Medical Centre	Kliniekstraat 27, 9050 Ghent-Bruges	8am to 12.30pm 1pm to 5pm register at 4.45pm	closed
St Vincent General Hospital in Deinze	Schutterijstraat 34, 9800 Deinze	8am to 8pm	closed

Results

Normal NIPT result

A normal NIPT result will appear on the NIPT report as 'Low risk'.
A letter with the NIPT result will be sent by post to your home address. This takes about ten workdays. Due to privacy laws (GDPR), it is not permitted to send the result by e-mail.
You may have an appointment with CoZo to discuss the result (go to www.cozo.be or use the CoZo app). You may find the results in your personal chart. The results are available more quickly when using CoZo than when sending them by post.

Abnormal NIPT result

An abnormal NIPT result will appear as 'Increased risk' on the NIPT report.
If the NIPT result is abnormal, your gynaecologist will inform you by telephone. In this case, you will not be sent a letter. The result will also be published on CoZo once you have spoken over the phone with your gynaecologist.

Ending the pregnancy

After a diagnosis (e.g. amniocentesis), you will be referred to a specialised paediatrician and/or clinical geneticist, who will inform you about the possible consequences.

The extent of a result may be so serious, for you, as well as for the baby, that you may decide to end the pregnancy. This can only be done after an amniocentesis, since this is the test that provides 100% certainty. Non-invasive prenatal testing can sometimes give a false result.

If you wish to end the pregnancy, a conversation with a paediatrician and psychologist is required.

If it is a question of a condition that is non-compatible with life, such as trisomy 13 and 18, it is possible to end the pregnancy (without participation of the ethical committee).
For all other conditions, a discussion within the hospital's ethical committee is required first. This committee consists of two gynaecologists (your own gynaecologist and the gynaecologist who performed the amniocentesis), the paediatrician, the psychologist with whom you spoke, a humanist and the main midwife. Your own gynaecologist will inform you of the committee's recommendation.
- If the ethical committee is in agreement, your gynaecologist will oversee the process.
- If the ethical committee is not in agreement, you will be referred to another centre. This may be another centre in Flanders or outside of Belgium (the Netherlands or England, for example).
This tends to be the case more when there are sex chromosome conditions:
- Ending the pregnancy for Triple X or for Klinefelter's Syndrome is not allowed in many Flemish hospitals, which is also the case in our hospital.
- For Turner's Syndrome there are sometimes abnormalities on ultrasound, and, in that case, the necessary specialists are consulted, along with the hospital's ethical committee.

For a sex chromosome condition, you should keep in mind that you may be referred to a foreign institution (in the Netherlands or England, for example).

Every care provider (physician or midwife) has the right to refuse to end a pregnancy if the decision to end the pregnancy does not agree with his/her ethical point of view. In this case, however, there is an obligation to refer you to another centre where you would be able to end the pregnancy.