Although there are many genetic diseases that can be diagnosed prenatally, there is only a limited amount of prenatal tests that are frequently carried out.
Besides the screening test in maternal blood there are 3 important prenatal tests: ultrasound, amniocentesis and chorionic villi sampling (chorion biopsy).
A normal result for a specific prenatal test only means that one (or a few) genetic diseases were excluded, but this does not guarantee that the child will have no congenital or genetic disease, and is healthy. There always remains a risk that there exists a disease, for which no test was performed.
A routine procedure in each pregnancy to detect malformations of the foetus (such as spina bifida). A fetal ultrasound to detect structural anomalies can best be performed around week 18-20.
Prenatal test using amniotic fluid taken around the 16nd week of gestation . Routinely cytogenetic anomalies (including Down syndrome) and Spina Bifida, and in some cases specific monogenic disorders (eg. cystic fibrosis), are tested for. This test is usually performed when there is a slightly increased risk (1-5%) for cytogenetic anomalies.
Chorionic villi sampling (chorion biopsy or CVS)
CVS is a prenatal test using chorionic villi sampled around the 11 nd week of gestation. This test is performed in case of a high risk (> 5%). In case of a monogenic disorder there might be an increased risk of 25% (eg. cystic fibrosis) or even 50% (eg. Huntington disease). Usually cytogenetic anomalies are also performed when CVS is performed, but Spina Bifida cannot be excluded as AFP is not detectable in chorionic villi.
Second trimester maternal screening - triple test
The triple test is a screening test with determination of biochemical parameters in blood of the mother sampled between week 14-18 in order to estimate the risk on Down syndrome.
First trimester maternal screening
A screening test between week 9-13 to estimate the risk on Down syndrome and some other anomalies. The biochemical parameters in the blood of the mother are combined with the results of the fetal ultrasound.
Ultrasound uses ultrasonic waves to make a picture of the fetus. The echo apparatus sends out sound waves to the body of mother and child, and catches the echos (hence the denomination echography) of these sound waves. These echos are then converted into a picture of the fetus. Ultrasound is very frequently used in medicine to visualise internal structures, just like CT scan and MRI. The ultrasonic sound waves are harmless for mother and fetus.
With ultrasound it is possible to visualise structural anomalies of the fetus such as growth retardation, neural tube defects (spina bifida), hydrocephalus, heart malformations, etc. Because ultrasound only visualises the form and not the function, ultrasound cannot exclude functional defects (eg mental retardation, epilepsy, etc). A fetal ultrasound to visualise the fetus and its organs is called a structural fetal ultrasound; it is best performed around week 18-19 of gestation. Ultrasound is the most important prenatal screening test, and should therefore be performed in each pregnancy, certainly when there is an increased risk for a child with a congenital or genetic anomaly. This is the case if there is (was) a previous child with such anomaly, or if of the parents themselves have such an anomaly. Some malformations can be visualised already very early in pregnancy (from week 12 on).
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With an amniocentesis approximately 10-20ml amniotic fluid is absorbed with a needle introduced into the amniotic cavity through the abdomen. Amniocentesis causes little discomfort or pain for mother and foetus (to compare with an injection of medicines). The procedure has only a small risk for the pregnancy. In approximately 1 on 200 cases (0,5%) miscarriage results because of haemorrhage, infection or leaking of amniotic fluid after the puncture. Of course, not every miscarriage after an amniocentesis is the consequence of this test, because also women without amniocentesis can have a miscarriage. The risk of touching the fetus with the needle is very small.
An amniocentesis is performed to obtain amniotic fluid and foetal cells that float in the amniotic fluid. These cells are fetal cells from the skin and internal membranes of the fetus. Both amniotic fluid and amniotic cells can be used for prenatal testing.
Tests that can be performed are cytogenetic analysis, molecular tests, metabolic tests and determination of alpha-foetoproteine (AFP). Usually specific genetic tests are performed to exclude specific syndromes for which there exists an increased risk. Whatever the indication for the amniocentesis routinely cytogenetic analysis (to exclude Down syndrome and other chromosome anomalies), and AFP determination (to exclude a neural tube defect) are performed. Sometimes a rapid screening chromosome analysis is performed to exclude some frequent chromosome disorders such as Down syndrome, trisomy 13 and trisomy 18 (this test is called the fast FISH test or QF-PCR test). In some countries also cystic fibrosis is screened for routinely.
The most frequent indication for amniocentesis is a slightly increased risk (1-5%) for cytogenetic anomalies. The test is carried out preferentially between week 15-16. The result of the AFP tests and the fast FISH test or QF-PCR test are already ready after 3 days. Additional tests (complete cytogenetic test, molecular and biochemical tests) usually take longer (2-4 weeks).
When an anomaly is detected, the parents have to discuss the consequences of this anomaly with the clinical geneticist. At this time the pregnancy is already advanced (16-18 weeks). When the parents decide to terminate the pregnancy because of the seriousness of the fetal anomalies, this is not possible anymore by suction curettage, but is performed by induction of (premature) labour with drugs.
Chorionic villi sampling (chorion biopsy or CVS)
During chorionic villi sampling a needle is introduced through the abdominal wall or vagina/cervix into in the placenta, and a number of chorionic villi are absorbed. These villi contain fetal cells that can be studied in the laboratory. The risk of a miscarriage due to the CVS varies between 1 and 2%, and is slightly higher than that of amniocentesis because CVS is performed earlier (week 11), and the foetus is more sensitive for an intervention then in the 16th week when amniocentesis generally is performed.
Tests that can be performed after CVS are cytogenetic analysis, molecular tests, metabolic tests. Only alpha-foetoproteine (AFP) cannot be tested as it is not present in chorionic villi. But CVS has also some advantages compared to amniocentesis. CVS is preferred test for molecular tests because chorionic villi contain more DNA than amniotic fluid. The most important advantage of CVS is that it can be performed a month earlier than amniocentesis (11th versus 16th week). The result of the CVS test is usually available in week 12-13, whereas the result of the amniocentesis is only ready in week 17-19. When the parents decide to terminate the pregnancy because of the seriousness of the fetal anomalies, this usually can be performed by suction curettage after CVS, which is less stressful than induction of (premature) labour with drugs after amniocentesis.