Rapid aneuploidy detection in prenatal diagnosis : the clinical use of multiplex ligation-dependent probe amplication

Abstract

The aim of prenatal diagnosis is to provide information on chromosomal abnormalities, in order to allow parents an informed choice on the course of pregnancy. Karyotyping is the diagnostic test used to detect chromosomal abnormalities. It is highly accurate, but labour-intense, costly and slow. Karyotyping detects chromosomal abnormalities with no, mild, or unclear clinical consequences. Rapid aneuploidy detection (RAD) techniques can detect the most common chromosomal abnormalities (trisomies 13, 18, 21, X and Y). Multiplex Ligation-dependent Probe Amplification (MLPA) is a RAD test. Its diagnostic accuracy, tested on 4585 amniotic fluid samples in routine clinical practice, is comparable to that of karyotyping (P<0.001) and it reduces waiting time with 14.5 days at lower costs (-__240 per sample). Patient quality of life does not differ significantly. While caregivers prefer RAD, experts prefer a test detecting all severe chromosomal abnormalities. Patients' preferences are equally divided; they value the detection of severe chromosomal abnormalities most. Since RAD and karyotyping both detect the most common chromosomal abnormalities with severe consequences, both tests are appropriate for prenatal diagnosis. Based on decision analytic considerations and our study results, women should be offered a choice, since they will bear the responsibility of raising the child.