MLPA And Karyotyping, an Evaluation (M.A.K.E.).

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 decreasing1, in contrast to the numbers of PNS. This is due to a shift of the maternal age distribution, with a relative increase of elderly pregnant women making use of PNS, 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).
MLPA (multiplex ligation-dependent probe amplification) is a new molecular genetic technique in prenatal diagnosis using amniotic fluid. It is a potential alternative test for detecting aneuploidies.
Compared to TKT, MLPA has four potential advantages:
(1) The result is known in 2-4 days instead of 3 weeks
(2) The procedure is considerably less labour intensive
(3) The test requires less amniotic fluid (2-4 ml instead of 20 ml)
(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).

The present study will establish the suggested equivalent preclinical diagnostic accuracy of MLPA in a clinical setting.

Both MLPA and Karyotyping are carried out.
MLPA (multiplex ligation-dependent probe amplification) is a molecular genetic technique in prenatal diagnosis using amniotic fluid. In this study a commercially available kit, P095 is used (produced by MRC Holland and widely tested).
The MLPA-result is known in 2-4 days. To perform MLPA 2-4ml of amniotic fluid is required. Such an amount is available since routinely 15-20 ml of amniotic fluid is obtained. If there is too little amniotic fluid (<12ml), MLPA will not be carried out in the study.
Karyotyping is carried out without any changes. The result is known in 2-3 weeks.