Non-invasive diagnosis of fetal Down syndrome using fetal DNA or RNA present in the maternal blood

To study the presence or absence of fetal Down syndrome, invasive diagnostic
procedures, such as amniocenteses or chorionic villus biopsy, are necessary.
Such procedures carry a risk of pregnancy loss, which is estimated to be
0.3-0.5%. Well-defined inclusion criteria are therefore needed to avoid
unnecessary procedure-related risks. Using noninvasive methods, such as
examination of several factors in the maternal blood in combination with
ultrasound scanning, only a risk of carrying a child with Down syndrome can be
established, not a certainty.

For more than 15 years now researchers have explored the use of fetal cells,
DNA or RNA in the maternal blood for fetal Down syndrome detection. Recently,
important progress has been made by the group of prod dr Lo from Hong Kong, as
they described a method with which the presence or absence of fetal Down
syndrome can be established using maternal blood only, i.e. without an invasive
procedure. Worldwide, several groups are working on this challenging field,
leader in this being the American company Sequenom. Together with the grop of
Dennis Lo, they further developed a test, which is now being validated. So far,
the results are informative in 95% of the US population, and for those pregnant
women for whom it can be used, the sensitivity and specificity for the
detection of fetal Down syndrome is 100%.

The final aim of the study is the implementation of a test for the detection of
fetal Down syndrome via noninvasive procedures, with the same characteristics
as the tests that are currently being used (sensitivity and specificity). This
test can then replace the present combination of noninvasive screening followed
by an invasive diagnostic test. As worldwide much effort is put into the
development of such a test, we expect a test becoming commercially available in
2009. Thus, the aim of the present study is not the development of such a test,
but the validation of it once a test has become available.

Therefore, a study has to be conducted which can be divided into three phases:
Phase 1: in this phase, there is no commercially available test. Only blood
from pregnant women will be collected and stored in such a way that, once a
test becomes available, they can be used to validate the test in our own
laboratory. Phase 2: a test is commercially available. In this phase the test
will be validated on our own lab with the materials that we collected in phase
1. Furthermore, collection of material will continu during phase 2.
Phase 3: this phase will only follow when the test has proven to be potentially
suitable for diagnostic use. In this phase, the test will be performed on large
numbers of samples, collected in all centres of the Nijmegen Network of
Prenatal Diagnosis.

The present project only concerns phases 1 and 2.

As mentioned above, in phase 1, blood of pregnant women will be collected and
stored in such a way that fetal DNA / RNA can be isolated from it and tested,
once the test becomes available (phase 2, estimation: second part of 2009).

The risk of venous blood sampling is negligable.