Limitations of non-invasive prenatal tests (NIPT)
In the case of structural chromosomal changes, fetal and maternal mosaics, in case of a
polyploidy, of a vanishing twin, a fetoplacental discrepancy or maternal gonosomal
aneuploidy
Due to the examination method non-invasive prenatal testing has certain limits. Therefore please
inform your patients about these limitations as follows:
Structural chromosomal changes, mosaics and polyploidy
In general, no statements regarding structural chromosomal changes, mosaics or polyploidy can be
made with the PrenaTest®. Also, chromosomal disorders in which other chromosomes than 13, 18,
21, X and Y are affected, as well as other genetic diseases, are not the subject of the present
examination.
Fetal mosaics, fetoplacental discrepancies
The examined fetal DNA is primarily derived from the cytotrophoblast and is released by apoptosis
and necrosis of trophoblast cells of the placenta. As such, it is only possible to achieve a level of
diagnostic certainty close to that attained via direct chorionic villus sampling. Consequently,
mosaics or fetoplacental discrepancies in trisomies 21, 18 or 13 resp. gonosomal aneuploidy are
not recognisable. In the event of a fetoplacental discrepancy, this can also mean that the PrenaTest ®
result is not representative for the unborn child.
Vanishing Twin
Undisclosed vanished twins can contribute a sufficient proportion to the total cffDNA fraction to
cause a positive PrenaTest® result being not representative for the continuing singleton pregnancy.
Maternal mosaic
An existing maternal mosaic can lead to a conspicuous PrenaTest ® result which may not
representative for the unborn child. These mosaics primarily affect gonosomal aneuploidy. For
example, positive cases of pregnant women with Turner syndrome were based on mosaic findings
(45,X/46,XX). For example, cases of pregnancies in women affected with Turner syndrome were
based on mosaic findings (45, X/46, XX) in the women.
Maternal gonosomal aneuploidy
An existing maternal gonosomal aneuploidy as the Triple X syndrome can lead to a conspicuous
PrenaTest® result which may not representative for the unborn child. This means, for example, that
a positive PrenaTest® result with a reference to a chromosome disorder 47, XXY does not
necessarily represent a fetal chromosomal abnormality. Rather, it should be examined whether and
how the pregnant woman has a triple X syndrome.
Please note – a predictive value of 100% cannot be expected
LifeCodexx AG work is state of the art in terms of science and technology. LifeCodexx AG notes that
a validity of 100% in the use of the PrenaTest® at the practice cannot be expected. There are risks
that can never be fully excluded, no matter how meticulous the genetic analysis is. Nevertheless, all
possible measures and safety precautions are undertaken to avoid these risks and other errors.
Fetoplacental discrepancies
Mosaics limited to the placenta associated with intrauterine growth disorders
Depending on when and in which stage of embryonic development faulty chromosomal division
occurs, different tissues (fetal and/or extra-fetal) are affected by it. Fig. 1a shows an example of a
mosaic limited to the placenta which can lead to a false-positive or, rather, a discordant test result:
here, the fetus is not affected by the chromosomal disorder and invasive diagnostic procedures
would reveal an unremarkable karyogram. However, mosaics limited to the placenta can also be
medically relevant, since they may be associated with intrauterine growth disorders1. Fig. 1b
shows the mosaic distribution of a chromosomal disorder which only affects the fetus, however not
the placenta. In such a case, the test result would probably be false-negative. There are still few
data about the frequency with which such fetoplacental discrepancies occur. Wegner and Stumm
report that in 1–2 % of chorionic villi examined, mosaics limited to the placenta were able to be
detected
Fig. 1a
Fig. 1b
Despite a high degree of accuracy of NIPT, there will always be discordant test results. While
invasive diagnostic procedures can, as a general rule, be avoided in the case of an unremarkable
test result – in the context of all relevant clinical findings and after appropriate explanation
provided to the pregnant woman – positive test results must be diagnostically clarified using
invasive methods, according to the recommendations of professional associations.
Original text from official Lifecodexx site: http://lifecodexx.com/en/for-physicians/methodstechnology/fetoplacental-discrepancies/