Screening for fetal and chromosomal abnormalities

What is it about ?

With every pregnancy comes a low risk of birth defects. These anomalies can be so much physical (for example, a sixth toe) that chromosomal (for example, trisomy 21 or Down syndrome).

Chromosomes

Chromosomes are the carriers of hereditary characteristics. The human being has 23 pairs of them. They make up the scenario of a person’s development from conception to adulthood. Each chromosome is involved in the formation of one or more “parts” of the body. Two of them are the sex chromosomes: they determine, among other things, whether the fetus will become male or female. A child receives half of its genetic information from its mother and the other half from its father. Parents pass on their characteristics to their children.

Sometimes a piece of chromosome is missing or, on the contrary, a chromosome has an extra piece (as in the Down syndrome). It is then a question of a congenital anomaly. When screening, the doctor uses a number of tests to look for such abnormalities before birth.

What is its frequency?

In 2018, 117,800 babies were born in Belgium. Between 3 and 5% of them had an anomaly¹ whose nature was not always genetic, far from it.

Down Syndrome

The risk of having a child with Down’s syndrome (Down syndrome) depends onmother’s age. The risk is 1 in 1,000 if the mother is under 30, and increases to 1 in 100 when the mother is over 40. On average, the risk is about 1 in 700.

Other anomalies

a open back (spina bifida) is observed in 4.5 births out of 10,000. If there have already been cases in the family, the risk explodes to 45 out of 10,000. trisomy 18 (Edwards syndrome) and of trisomy 13 (Patau syndrome) is 1 in 8,000 and 1 in 12,000 respectively

What screening methods can the doctor suggest?

Early serum screening

This screening is done by means of a blood test. During the first trimester (weeks 8 to 13) of pregnancy, the risk of chromosomal abnormalities is assessed by measuring the amount of PAPP-A protein (placental plasma protein A) and beta-hCG hormone (human chorionic gonadotropic hormone) present in the blood. Fetuses carrying Down syndrome have a higher level of PAPP-A and a lower level of beta-hCG than healthy fetuses.

Nuchal translucency measurement

A ultrasound allows to measure the nuchal translucency (fold of the neck) of the fetus between the 10^e and the 13^e week of pregnancy. If it is thicker than normal, there is an increased risk that the child will have a chromosomal abnormality. In these fetuses, the risk of congenital heart defects is also higher (5-10% of babies).

Combination of tests

A combination of the nuchal translucency measurement in the fetus and a serum screening in the mother can be carried out during the first trimester. The age of the mother and the size of the fetus (cranio-caudal length) are taken into account, in addition to the two tests, to assess the likelihood of a Down’s syndrome.

Non-invasive prenatal screening (PNID)

This is a non-invasive screening test aimed at detecting trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome) in babies by measuring the baby’s DNA in the mother’s blood. This blood test is performed no earlier than 12 weeks and examines the baby’s DNA (= genetic material), which is found in the mother’s blood.

This test has a sensitivity of over 99% for the detection of Down syndrome, which means that more than 99 in every 100 children with Down’s syndrome are identified by this test. The chance that the test will indicate an increased risk even though your baby does not have Down syndrome is less than 1%.

The DPNI has been reimbursed since 1^er July 2017 for all pregnant women.²

Ultrasound screening for structural abnormalities

The structural anomalies are abnormalities in the composition of parts of the body. For example, a missing limb or organ, a head that is too large or too small, a cleft lip, an open back …ultrasound allows you to visualize these structural “errors”. If the doctor finds such a structural abnormality, a chromosome analysis may be done to see if there is also a chromosomal abnormality. Ultrasound findings that may suggest these abnormalities are, for example, a thickened nuchal translucency or absence of the nasal bone (visible on the first trimester ultrasound).

Screening for twin pregnancy

When a woman is expecting twins, a ultrasound is performed to see if there are 1 or 2 amniotic sacs (water bags or choria). The number of water pockets is important because, if there is only one, the twins are always monozygous (“identical twins”), while 90% of twin pregnancies are dizygotic in the presence of 2 water pockets. .

Fetal chromosome analyzes

This screening can be done when the previous tests give a suspicion of chromosomal abnormalities. These analyzes are very reliable and provide a definitive result in 99% of cases.

Chromosome analysis is performed on a sample of cells from the fetus or placenta. There are two ways to get these cells: one placenta puncture (chorionic villus sampling) or a puncture of amniotic fluid (amniocentesis). It is important to note that these tests are not completely safe. 1 in 200 amniocentesis and up to 1 in 100 placenta punctures end in abortion.

• Placenta puncture (chorionic villus sampling)

This test can be performed after the 10^e week of pregnancy. The doctor takes a few placenta cells using a needle. The site of the sample is determined by ultrasound. The placenta is virtually identical to the fetus in terms of genetic information.

• Puncture of amniotic fluid (amniocentesis)

This test is usually performed between the 15^e and the 16^e week of pregnancy. Guided by the ultrasound, the doctor inserts a needle into the amniotic sac. Unlike the placenta puncture, the cells taken do not come from the placenta, but from the amniotic fluid of the fetus. In this test, the doctor can not only examine the cells, but he can also check the amount of AFP protein. This amount is usually increased in the event of a structural abnormality in the fetus.

Who is it suitable for?

Screening for fetal and chromosomal abnormalities is a choice of the pregnant woman and her partner. They may decide to have the tests performed on the fetus after receiving the necessary information about their reliability and their risks.

If you are determined, whatever happens, to keep a (severely) disabled child, there is no point in carrying out screening tests or punctures. These tests always come with a certain risk. If, on the other hand, you are completely convinced that you want a termination of pregnancy if your baby has a severe disability, it is in your best interest to go through prenatal screening.

Reliability

Keep in mind, however, that the results of an exam may sometimes be false-negative or false-positive. In the case of a false-negative result, the test does not detect an abnormality but, at birth, it is revealed that the child does indeed have an abnormality. In the case of a false-positive result, the test detects an anomaly when there is none.

It is therefore extremely important that parents decide in advance what to do in the event that an anomaly is found. In this case, the doctor suggests in principle to carry out Additional tests, namely a puncture of placenta or amniotic fluid.

In addition, it is important to think carefully in advance about the desire to screen for fetal and chromosomal abnormalities. Indeed, studies show that about 1 in three young pregnant women who had an “abnormal” result then regretted having made the “choice” of screening.

When is chromosome analysis indicated?

Chromosome analyzes can be considered in the following situations:

• the pregnant woman is over 40 years ;
• the doctor establishes a increased risk after serum screening alone or the combination of ultrasound and serum screening;
• an ultrasound reveals anomalies fetal;
• a structural anomaly is seen in the baby during an ultrasound, as a thickened nuchal translucency, abnormalities in the intestines, dilation of the renal calyxes, cysts in the brain or a growth retardation ;
• one of the parents, or an older child, has a chromosomal abnormality.

And after the analysis or screening?

Make sure you receive enoughexplanations (genetic counseling) if the results of the chromosome analysis are abnormal. It is important to fully understand what the analysis revealed so that you can plan the next steps.

Continuation of pregnancy

You can decide to continue the pregnancy. In this case, a additional follow-up should be scheduled so that the rest of the pregnancy and childbirth go well and the newborn receives the best care.

Termination of pregnancy

In some cases, you may want to terminate the pregnancy. In Belgium, the termination of pregnancy is legally authorized until the 12^e week. However, it remains permitted at any time during pregnancy in the following circumstances:

• In the event of serious and incurable malformations diagnosed by a doctor and confirmed by another doctor.
• At least 6 days must elapse between the decision to terminate the pregnancy and the procedure for termination of pregnancy. Indeed, the termination of an advanced pregnancy corresponds in reality to a childbirth started prematurely, which requires good preparation, including on the psychological level. In addition, this deadline gives you a little extra time to think about it, so that you can possibly reconsider your decision.
• If, after a termination of pregnancy, the fetus has a birth defect, the exact nature of the defect will be analyzed. To do this, doctors screen the fetus: they examine its body, take pictures and perform genetic tests. This information will allow you, your parents, to consider the future with full knowledge of the facts: after these tests, the doctor will be able to tell you more about the risk of the anomaly repeating in a future pregnancy, as well as about any tests that can then be carried out.

Sources

• Foreign clinical practice guide ‘Screening for fetal chromosomal abnormalities’ (2000), updated on 2/05/2017 – ebpnet
• ¹ ‘Registratie van aangeboren afwijkingen provincie Antwerpen’ Report 1989 – 2012 (2015) – EUROCAT Provincie Antwerpen
• ² ‘Non-invasive prenatal screening (DPNI): price’ – UZLeuven