Economic evaluation of multiplex ligation-dependent probe amplification and karyotyping in prenatal diagnosis: a cost-minimization analysis Elisabeth M. A. BoormansErwin BirnieMariette J. V. Hoffer • Merryn V. E. MacvilleRobert-Jan GaljaardGijsbertha H. Schuring-Blom • Shama L. BholaKarin HuijsdensArie SmitsJan M. M. van Lith

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 (C36 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). Healthrelated 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. On behalf of the MLPA and karyotyping (MAKE) study group. Members of the MAKE study group are given in the Appendix.