Development of the MLPA technique as a non-invasive prenatal diagnostic test to detect foetal chromosomal abnormalities in the maternal circulation in the first trimester of pregnancy

Prenatal diagnosis includes invasive techniques (chorionic villus sampling or amniocentesis), which are used to detect chromosomal abnormalities in pregnancy. The major disadvantage of this technique is the procedure-related risk of abortion. Currently, no safe, non-invasive prenatal diagnostic tool exists to detect foetal chromosomal abnormalities. It is therefore challenging to develop a new non-invasive diagnostic prenatal test. Optimal test characteristics should include high efficiency, high reliability and low costs. Our goal is to develop such a prenatal diagnostic test on cell-free foetal DNA present in maternal plasma, using the innovative “Multiplex Ligation-dependent Probe Amplification” (MLPA) technique, to detect trisomy 13, 18 and 21 in early pregnancy. The MLPA technique is highly specific, fast, cheap and applicable for high through put analysis. The Department of Clinical Genetics of the University Hospital Maastricht has a unique position in the Netherlands because we have large experience with single cell analysis for the purpose of pre-implantation genetic diagnosis (PGD), and we are thus used to work with very small amounts of DNA. After optimising the MLPA method on cell-free foetal DNA, we aim to test this new technique in prenatal practice. Therefore, pregnant women in the South-East region of The Netherlands who undergo prenatal screening are invited to collaborate in this study. We will compare the results of MLPA on cell-free foetal DNA present in maternal plasma with the MLPA results of invasively obtained foetal DNA, with conventional karyotyping; the “Gold Standard” and with clinical follow-up results of newborns. When validated, the MLPA test on cell-free foetal DNA can be rapidly implemented using the excellent dynamic management resources available through the “RIVM” in The Netherlands. If successful, this would mean an innovative break-through in the international field of prenatal diagnosis.