European Non-invasive Trisomy Evaluation (EU-NITE Study): Evaluation of a targeted analysis of cell free fetal DNA in maternal blood for prenatal diagnosis of fetal trisomies.

Since the 1970s, pregnant women are offered prenatal screening or prenatal
diagnostic testing for Down*s syndrome. The standard diagnostic test,
karyotyping on cultured fetal or placental cells, also reveals, if present,
other chromosomal aberrations such as trisomy 18, 13 or sex chromosome
anomalies. The main aim to test for genetic diseases is to provide reassurance
to parents with an increased risk of an abnormal fetus, and for the minority
who receives an unfavourable outcome, to provide the option of terminating the
pregnancy. This option is chosen by more than 90% of parents when confronted
with the diagnosis of Down*s syndrome.
To check for fetal chromosomal aberrations, fetal cells can be acquired by
chorionic villus sampling or amniocentesis. Traditionally, microscopic visual
assessment of the shape and number of the fetal chromosomes, called karyotyping
is then performed. This assessment is only possible in dividing cells, which
means that a chromosome culture is necessary. Because of this culture time, it
can take up to 14-21 days before a reliable test result can be reported to the
patient. The currently available tests, chorionic villus sampling and
amniocentesis, are highly reliable with practically 100% sensitivity and
specificity for the detection of fetal trisomies. The main disadvantage however
is the invasive nature of the diagnostic tests. Both tests are associated with
a procedure-related fetal loss rate of 0.5-1%.
Recently real-time polymerase chain reaction (PCR) techniques have allowed the
identification and quantification of fetal DNA in the maternal blood. Fetal sex
determination with Y-chromosome-PCR and Rhesus-D typing has been found to have
a specificity of 100% and a sensitivity of 96%. Both of these diagnostic tests
have important clinical applications, for X-linked genetic disorders and
Rh-disease respectively, and have already been implemented in clinical care.
However, these tests rely on the absence of a copy gene in the mother, and are
not suitable for trisomy detection.

Recently, new approaches have been introduced aimed at detection of fetal
trisomies (and potentially many other genetic diseases) using a maternal blood
sample. Some methods utilize a targeted analysis of circulating DNA in maternal
blood. In one pilot study whereby tandem SNPs were used for the targeted
analysis, the accuracy of trisomy 21 detection was 100%.

our primary aim is to validate a targeted analysis of circulating DNA in
maternal blood by assessing the diagnostic accuracy for fetal trisomy 21. In
addition, test characteristics for fetal trisomy 18 detection will be
evaluated.

In a prospective, consecutive cohort of pregnant women scheduled to undergo
invasive diagnostic testing, a blood sample will be taken prior to invasive
procedure.

venous puncture