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PraenaTest in brief
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PraenaTest® with shortest delivery times
Introduction
PraenaTest® is a non-invasive molecular genetic prenatal
test for fetal trisomy 13, 18 and 21 as well as for
gonosomal aneuploidy (Turner, Triple X, Klinefelter and
XYY syndrome) using next generation sequencing and zscore calculation following DNA isolation from maternal
plasma.
Scientific basis
The PraenaTest® method centres on the analysis of cellfree DNA (cfDNA) in the pregnant woman’s blood. These
small fragments of genetic material are not contained
within cells, but circulate freely in the mother’s
bloodstream; they include maternal DNA as well as
between 2-40% (on average around 10%) fetal DNA (cellfree fetal DNA, or cffDNA). The genetic material stems
from dead placental cells, and is continually released into
the pregnant woman’s bloodstream.
Reasons to perform the PraenaTest®
To undergo the PraenaTest®, a pregnant woman must
have received explanations and human genetic
counseling in accordance with national legislation and
has consented to the genetic examination
be in the 10th week of pregnancy (gestational week
9+0) or later
exhibit one of the following indications for performing the
PraenaTest®:
• Age 35 years and over at the time of the birth of the
child
• Prior pregnancy with fetal aneuploidy
• Ultrasound anomalies of the fetus
• Hereditary risk of fetal aneuploidy
• Increased risk of aneuploidy based on screening methods
for prenatal risk determination
PraenaTest® portfolio and prices
WM-1049-EN-002 / Mai 2015
PraenaTest® Option 1
Determination of fetal trisomy 21
EUR 440
PraenaTest® Option 2
EUR 550
Determination of fetal trisomies 21, 18, 13
PraenaTest® Option 3
EUR 660
Determination of fetal trisomies 21, 18, 13
as well as gonosomal aneuploidy
Seite 1 von 2 The PraenaTest® result is generally available
in 8-10 working days (standard)
in 6 working days (express service)
The express service is available for all three test options. Gender
determination is optional. Gonosomal aneuploidy can be
determined for singleton pregnancy only.
The ordered PraenaTest® option can be upgraded at any time
(e.g. from option 2 to option 3), should the doctor wish to
determine more aneuploidies at a later point of time. The patient
pays for the difference between the test options plus a handling
fee of EUR 95.
The prices are incl. VAT and shipping (as of July 2014).
Additional costs associated with the medical consultation
(examination, education and genetic counseling) are
charged separately by the doctor.
Diagnostic value of the PraenaTest®
Singleton pregnancy: The clinical studies comprised 808
blood samples in total: Sensitivity is 99 %, false positive rate
0,1 %
Trisomy 21: Sensitivity 99 % [74/75 cases],
false positive rate 0 %
Trisomy 18: 14 of 14 cases detected,
one sample was false positive
Trisomy 13: 8 of 8 cases detected,
no sample was false positive
Multiple pregnancy: The clinical study comprised 60
blood samples of twin pregnancies and two samples of
triplet pregnancies.
All positive trisomy 21 cases were correctly classified (1x
monochorial, concordant; 5x dichorial, discordant). The other
multiple pregnancy specimens yielded unremarkable results.
LifeCodexx AG also analyses samples for triplet or other multiple
pregnancies. Since the amount of data existing to date is not yet
sufficient for a validation, we are preliminarily offering this
analysis free of charge as part of our research and development
work. Please contact us in such a case.
Gonosomal aneuploidy: The PraenaTest® for gonosomal
aneuploidy (Turner, Triple X, Klinefelter and XYY syndrome) was
tested on a total of 434 specimens from single pregnancies.
During this testing, 11 out of 12 affected fetuses, that is 92 %,
were correctly determined. Moreover, five discordant, „false
positive“ results were obtained. At present, based on the low
number of cases examined, LifeCodexx AG will not separately
report any sensitivities and specificities for gonosomal
aneuploidy.
7.
This is followed by sequencing using state-of-the-art
analysis equipment (random massively parallel sequencing;
rMPS)
8.
The sequences are evaluated using the proprietary
and CE-marked data analysis software PraenaTest®
DAP.plus.
9.
The test result is then scientifically interpreted and
documented in the result report.
Fetal gender determination is optional. If the case of a multiple
pregnancy a –male- report means that at least one of the fetuses
is male.
10. The result report is faxed and sent by post to the
responsible doctor.
Limitations of the PraenaTest®
Regulatory requirements for NIPT-based aneuploidy
testing in Europe
In general, the PraenaTest® is not suitable for statements
regarding structural chromosomal changes or mosaics. The cellfree fetal DNA examined in the PraenaTest® originates from the
trophoblast cells and 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 are not recognisable. In
the event of a fetoplacental discrepancy, this can also mean that
the PraenaTest® result is not representative for the unborn child.
Undisclosed vanished twins can contribute a sufficient proportion
to the total cffDNA fraction to cause discordant NIPT results,
being not representative for the continuing singleton pregnancy.
PraenaTest® process
1.
LifeCodexx AG provides special blood collection tubes
to the doctor.
2.
After the patient has received genetic counselling and
granted consent, the doctor draws 2x10ml venous
blood.
3.
The blood samples are sent by courier to the
LifeCodexx AG diagnostic laboratory in Konstanz,
Germany.
4.
Laboratory work begins by isolating the blood plasma.
5.
Next, the cell-free genetic material (cfDNA) is extracted
from the plasma. The cfDNA is not further separated
into maternal and fetal DNA – further analysis is
always performed using the mixture of maternal and
fetal cell-free DNA. For the analysis to be successful,
the mixture must contain more than 4% fetal cell-free
DNA mixed in with the maternal DNA. Should fetal
DNA comprise less than 4% of the cell-free DNA
mixture, it is recommended that new blood samples be
taken later on in the pregnancy.
6.
The recovered DNA is present in only minute
quantities; after determining its percentage of fetal
DNA, a so-called genomic library is generated and
reproduced so that it can be analysed.
Seite 2 von 2 NIPT-based aneuploidy tests for trisomy 21 fall under the European
Union Directive on In-Vitro-Diagnostics 98/79/EG (List B, Appendix
II, IVD products), and under the corresponding national laws.
This means:
The data analysis pipeline must be CE-marked under the
supervision of a Notified Body.
The company offering the test must have a comprehensive
quality assurance system in place (EN ISO 13485).