Economic evaluation of multiplex ligation-dependent probe amplification and karyotyping in prenatal diagnosis: a cost-minimization analysis.

PURPOSE: To assess the cost-effectiveness of Multiplex Ligation-dependent Probe Amplification (MLPA, P095 kit) compared to karyotyping. METHODS: A cost-minimization analysis alongside a nationwide prospective clinical study of 4,585 women undergoing amniocentesis on behalf of their age (≥36 years), an increased risk following first trimester prenatal screening or parental anxiety. RESULTS: Diagnostic accuracy of MLPA (P095 kit) was comparable to karyotyping (1.0 95% CI 0.999-1.0). Health-related quality of life did not differ between the strategies (summary physical health: mean difference 0.31, p = 0.82; summary mental health: mean difference 1.91, p = 0.22). Short-term costs were lower for MLPA: mean difference 315.68 (bootstrap 95% CI 315.63-315.74; -44.4%). The long-term costs were slightly higher for MLPA: mean difference 76.42 (bootstrap 95% CI 71.32-81.52; +8.6%). Total costs were on average 240.13 (bootstrap 95% CI 235.02-245.23; -14.9%) lower in favor of MLPA. Cost differences were sensitive to proportion of terminated pregnancies, sample throughput, individual choice and performance of tests in one laboratory, but not to failure rate or the exclusion of polluted samples. CONCLUSION: From an economic perspective, MLPA is the preferred prenatal diagnostic strategy in women who undergo amniocentesis on behalf of their age, following prenatal screening or parental anxiety.

Aiming at multidisciplinary consensus: what should be detected in prenatal diagnosis?

OBJECTIVE: To determine expert consensus on which chromosomal abnormalities should and should not be detected in prenatal diagnosis, and for which abnormalities disagreement remains after structured discussion. METHODS: An expert panel of 24 prenatal experts (8 clinical cytogeneticists, 8 clinical geneticists and 8 obstetricians) rated 15 chromosomal abnormalities sampled from a nationwide study on rapid aneuploidy detection (RAD). In two individual anonymous rating rounds and one group meeting, the participants rated PRO or AGAINST detection and stated their main argument. The 15 chromosomal abnormalities were described in detail by a stylized vignette containing an obstetrical history, the indication for prenatal diagnosis and the range of possible outcomes of the chromosomal abnormality. Consensus was defined to be present if at least 80% of the experts agreed. RESULTS: Consensus was reached in 12 out of 15 cases. In ten cases, there was agreement PRO detection and in two cases experts agreed AGAINST detection. At the end of the third round, dissensus remained on three abnormalities. CONCLUSION: Experts largely agreed on detecting chromosomal abnormalities with severe consequences and AGAINST detection in case of irrelevant clinical consequences. For chromosomal abnormalities with mild or uncertain outcomes, dissensus remained. None of the currently available tests corresponds to these demands.

Multiplex ligation-dependent probe amplification versus karyotyping in prenatal diagnosis: the M.A.K.E. study.

BACKGROUND: In the past 30 years karyotyping was the gold standard for prenatal diagnosis of chromosomal aberrations in the fetus. Traditional karyotyping (TKT) has a high accuracy and reliability. However, it is labor intensive, the results take 14-21 days, the costs are high and unwanted findings such as abnormalities with unknown clinical relevance are not uncommon. These disadvantages challenged the practice of karyotyping. Multiplex ligation-dependent probe amplification (MLPA) is a new molecular genetic technique in prenatal diagnosis. Previous preclinical evidence suggests equivalence of MLPA and traditional karyotyping (TKT) regarding test performance. METHODS/DESIGN: The proposed study is a multicentre diagnostic substitute study among pregnant women, who choose to have amniocentesis for the indication advanced maternal age and/or increased risk following prenatal screening test. In all subjects, both MLPA and karyotyping will be performed on the amniotic fluid sample. The primary outcome is diagnostic accuracy. Secondary outcomes will be maternal quality of life, women's preferences and costs. Analysis will be intention to treat and per protocol analysis. Quality of life analysis will be carried out within the study population. The study aims to include 4500 women. DISCUSSION: The study results are expected to help decide whether MLPA can replace traditional karyotyping for 'low-risk' pregnancies in terms of diagnostic accuracy, quality of life and women's preferences. This will be the first clinical study to report on all relevant aspects of the potential replacement. TRIAL REGISTRATION: The protocol is registered in the clinical trial register number ISRCTN47252164.