The aim of this study is to evaluate the role of MLPA in a routine clinical setting for detecting firstly, DS and secondly, the most common chromosomal aberrations compared to TKT (gold standard) in prenatal diagnosis.Is diagnostic accuracy of the…
ID
Source
Brief title
Condition
- Placental, amniotic and cavity disorders (excl haemorrhages)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Diagnostic accuracy is assessed through a blind comparison of MLPA against the
accepted gold standard (TKT)in a clinical setting. Sensitivity and specificity
are calculated and discordant test results are recorded.
Technical performance including technical difficulties (i.e. equipment
malfunction)and missing or inconclusive results are recorded, as well as
missing results due to lack of amniotic fluid.
Turnaround time for laboratory processing and availability of test results of
MLPA versus TKT, known at laboratory level and patientlevel are recorded.
Secondary outcome
1. Anxiety and distress as secondary outcome will be measured by available
standardized questionnaires (STAI, PPC, IES, MOS-SF)which also have been used
for similar studies(PhD Thesis Muller, 2006 in press; screening for irregular
erythrocyte antibodies in pregnancy].
2. Cost as secondary outcome will focus on medical costs (including
implementation and quality control).
If relevant the cost-effectiveness of TKT over MLPA will be calculated.
3. Using acommercially available kit(i.e.P095), trisomy 13, 18, 21 and
sexchromosome abnormalities will be detected. Firstly, we will focus on
detecting trisomy 21 and secondly, chromosomes 13 18, X and Y. The latter can
be of uncertain clinical relevance and cause counselling difficulties. A panel
will assess these findings and will judge whether they are clinically relevant,
irrelevant or of uncertain relevance. This might result in excluding/including
probes from/into the MLPA aneuploidy kit in future testing. Differences
inemerging unexpected or incomprehensible findings will be described
qualitatively taking advantage of a recent study on this issue
[VanZwieten,2004].
4. A standard patientpreference study (so called discrete choice
evaluation)will allow quantification of the balance of all (dis)advantages of
either test[Ryan,2005].
Background summary
For the past 30 years karyotyping is the gold standard in prenatal diagnosis
for the detection of chromosomal aberrations in the fetus, in particular
trisomy 21(Down syndrome). The main indications for traditional karyotyping
(TKT) in the Netherlands are advanced maternal age and increased risk based on
prenatal screening tests (PNS).
The annual numbers of maternal age-based invasive procedures for TKT are
decreasing. The numbers of PNS are increasing, due to a shift of the maternal
age distribution, with a relative increase of elderly pregnant women making use
of PNS, and an increased demand of pregnant women, augmented by a change in
government policy allowing PNS (combined test, triple test) for risk estimation
of Down syndrome (DS).
targeted testing
Prenatal TKT provides genotypic diagnosis of DS and also detects other
chromosomal aberrations. In the patient*s perception, some of thes e other
chromosomal aberrations are unexpected, even after pretest counselling(van
Zwieten 2004). Another problem is the uncertain clinical relevance of some of
these other chromosomal aberrations. Unexpected and/or uncertain findings can
cause patient anxiety, difficult counselling issues and potentially unnecessary
pregnancy terminations(vanZwieten,2004).
MLPA (multiplex ligation-dependent probe amplification)is a new molecular
genetic technique in prenatal diagnosis usingamnioticfluid.It is a potential
alternative test for detecting aneuploidies. Compared to TKT, MLPA has 4
potential advantages:(1)the result is known in 2 days instead of 3 weeks,
(2)the procedure is considerably less labourintensive,(3)the test requires less
amniotic fluid (2-4ml in stead of 20ml)(4)MLPA is suitable for high throughput
testing. Previous preclinical evidence suggests equivalence of MLPA and TKT
regarding test performance (accuracy in detection of common occurring
chromosome aberrations).
Study objective
The aim of this study is to evaluate the role of MLPA in a routine clinical
setting for detecting firstly, DS and secondly, the most common chromosomal
aberrations compared to TKT (gold standard) in prenatal diagnosis.
Is diagnostic accuracy of the MLPA P095 aneuploidy kit equivalent to that of
TKT? In other words: can MLPA fully replace TKT, using amniotic biomaterial in
an unrestricted way?
Does MLPA reduce anxiety for the patient by getting quicker results and less
complex counselling issues?
Does substitution of TKT by MLPA improve cost-effectiveness of prenatal care?
What is the relevance of the differential pattern of unexpected findings in
MLPA versusTKT?
What do pregnant women generally prefer, MLPA or TKT, given the most pertinent
characteristics of both tests (includings equelae of the different availability
of the test result)?
Study design
The study is designed as a diagnostic substitute study.
Study burden and risks
There will be no extra risk, associated with participating as the TKT result
still is the gold standard.
oosterpark 9
1090 HM Amsterdam
Nederland
oosterpark 9
1090 HM Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
pregnant women undergoing amniocentesis
the referral indication for amniocentesis is: 1)advanced maternal age, 2) increased risk after prenatal screening tests
informed consent is given
Exclusion criteria
patients with other referral indications, e.g. ultrasound abnormalities, previous child with chromosomal berration, structural balanced chromosome aberration of one of the parents.
language barrier
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL12992.067.06 |