Fetal DNA testing is a very accurate screening test for Down syndrome and some other chromosomal abnormalities. However, is it the right test for you? Some factors to take into account:
Advantages of Fetal DNA testing:
- It is the most accurate screening test for trisomy 21 (the most common cause of Down syndrome).
- It is a very sensitive test (>99%), meaning that it would miss fewer cases of trisomy 21 than any other screening test, although it still does not provida a 100% guarantee.
- It is a very specific test (>99.9%), meaning that there is fewer false positive results occur, with less unwarranted anxiety and fewer unnecessary invasive tests such as chorionic villus sampling or amniocentesis.
- Fetal DNA testing can be performed from 10 weeks until the end of the pregnancy.
Disadvantages of fetal DNA testing:
- Fetal DNA testing gives less information than a full chromosome analysis on fetal cells obtained by chorionic villus sampling or amniocentesis. If there are factors that suggest a chromosomal abnormality other than trisomy 21 (the most common cause of Down syndrome), a full chromosome analysis if preferred. These factors include a structural abnormality on ultrasound, a family history of a chromosome abnormality or recurrent miscarriages.
- Fetal DNA testing does not replace a good (first trimester) ultrasound examination which provides information on conditions that are far more common and sometimes more serious than trisomy 21 and which are not detected by Fetal DNA testing. First trimester ultrasound screening also provides information on the risk of pre-eclampsia and growth restriction; risks which can be reduced if one is aware of it.
Conditions other than Down syndrome which are detected by Fetal DNA testing:
- Fetal DNA testing is also accurate at detecting trisomy 18 (the most common cause of Edward syndrome) and trisomy 13 (Pateau syndrome). These are, next to Down syndrome, the most common serious chromosomal abnormalities. These conditions are rare, and few afflicted infants survive for long.
- Sex chromosome abnormalities (such as Turner syndrome or Klinefelter syndrome) can also be detected by Fetal DNA testing. Using Fetal DNA testing to detect these abnormalities increases the chances of a false positive finding, and the implications of Turner or Klinefelter syndrome are very different from the significant mental disability associated with trisomy 21.Using Fetal DNA testing for this purpose is therefore not recommended routinely.
- Some rare conditions (such as DiGeorge syndrome) can also be detected. Using Fetal DNA testing to detect these abnormalities also increases the chances of a false positive finding and significantly adds to the cost of the test, and is therefore not recommended routinely.
If nothing is found is everything all right?
- A low risk screen on Fetal DNA testing does not rule out trisomy 21 (or the other conditions) completely, but makes it extremely unlikely, depending on the starting risk. (For example, if you have a risk of Down syndrome of 1:100 and a negative or low risk fetal DNA test, the residual risk is around 1:100,000.)
If there is a high risk, does it mean that my baby is affected?
- The positive predictive value depends on the starting risk. False positive results (where the test indicates an abnormality, but the baby is actually normal) may be due to a problem confined to the placenta (confined placental mosaicism), a vanishing twin or other maternal factors.
- Confirming the test result with a diagnostic test is therefore recommended to exclude a false positive finding, and to determine the risk in a future pregnancy (or in other family members’ pregnancies).
- It is also good to consider what you would do in case of a high risk finding (whether you would, for example, consider a pregnancy termination if Down syndrome is confirmed in your baby.)
Are all Fetal DNA tests equal?
- Different tests use different methods. Some are more accurate in cases of donor IVF or twins, and others more accurate when screening for abnormalities other than Down syndrome.
- Fetal DNA tests which indicate the fetal fraction (the fraction of total DNA originating from the fetus) are preferred, as the test is less accurate if the fetal fraction is low.
When should the fetal DNA test be done?
- The fetal DNA test can be done from 10 weeks. We recommend first performing a first trimester ultrasound. This excludes serious structural problems in the baby, allow us to estimate the risk of developing pregnancy complications such as pre-eclampsia or fetal growth restriction, and gives a logical base for making the decision on whether to do fetal DNA testing:
- If the risk is of Down syndrome is higher than 1:10 based on first trimester ultrasound, an invasive test (chorionic villus sampling or amniocentesis) is recommended. This allows the quickest, most complete answer.
- If the risk is between 1:10 and 1:100, either an invasive test or fetal DNA test can be appropriate.
- If the risk is between 1:100 and 1:1000, the fetal DNA test is often recommended, but an invasive test might still be preferable.
- If the risk is below 1:1000, further testing is generally not recommended. Fetal DNA testing can of course still be done, but it is important to realize that at such low risks of Down syndrome, the fetal problems which are not detected by fetal DNA testing are much more common than Down syndrome. The relative importance of a false positive test is then also much higher.
What are the practical aspects of fetal DNA testing?
- The test is done by a blood sample of yourself, and not dangerous to the pregnancy.
- The results are usually available in less than two weeks.
- In about 5% of the time, the test does not give an answer. The risk of such a test failure is higher if you are overweight (> 120 kg), or if the test is done too early (before ten weeks). If there is a test failure, the laboratory does not charge for the test, or the sample can be resent.
- The test is expensive, and not all medical aids (fully) reimburse the test.