Comparison of Multiplex Ligation-Dependent Probe Amplification and Karyotyping in Prenatal Diagnosis

To estimate whether multiplex ligation-dependent probe amplification (MLPA), a molecular technique used for detecting the most common chromosomal aneuploidies, is comparable with karyotyping for the detection of aneuploidies of chromosomes X, Y, 13, 18, and 21 in routine clinical practice and to estimate the costs differences of both techniques.In this prospective, nationwide cohort study, we consecutively included 4,585 women who had an amniocentesis because of their age (36 years or older), increased risk after prenatal screening, or maternal anxiety. Amniotic fluid samples were tested independently with both MLPA and karyotyping. The primary outcome was diagnostic accuracy of MLPA to detect aneuploidies of chromosomes X, Y, 13, 18, and 21. Secondary outcome measures were turnaround time for test results and costs. A sample size was calculated using a critical noninferiority margin of 0.002; therefore, at least 4,497 paired test results were needed (one-sided alpha 0.05, power 0.90).Diagnostic accuracy of MLPA was 1.0 (95% confidence interval [CI] 0.99-1.0), sensitivity was 100% (95% CI 0.96-1.0) and specificity was 100% (95% CI 0.999-1.0). Diagnostic accuracy of MLPA was statistically similar (noninferior) to that of karyotyping (P