Cost-effectiveness of exome sequencing and chromosomal microarray for low-risk pregnancies: Cost-effectiveness of Prenatal Exome Sequencing.

Objective: To investigate the cost -effectiveness of exome and genome sequencing (ES), compared to Chromosomal microarray (CMA) METHODS: costs, utility and quality adjusted life years (QALYs) were modeled for prenatal testing with CMA or CMA+ES. Average costs and utilities were discounted at 3%. Two strategies for screening were compared using Markovian decision analysis model: (1) CMA only- abnormal result culminating in termination of pregnancy and normal test has with 1/160 chance for severe disorders. (2) ES after a normal CMA, for positive result a termination of pregnancy (TOP) was conducted. One - way sensitivity analysis for all variables. Outcome measures included the QALYs after abortion, cost of CMA and ES test and the health expenses of a critically ill infant. The time horizon of the model was 20 years.

Results: Total costs were $1,348 and $3,108 for CMA and CMA+ES strategies respectively. The QALYs with time horizon of 20 years were 14.15 and 14.19 QALYs for CMA and CMA+ES strategies respectively with incremental cost-effectiveness ratio (ICER) of 46,383$/QALYs. Sensitivity analysis revealed that the time horizon and the dis-utility of moderate/severe disability of the genetic disorder has an impact on the ICER. For example, with a relatively small disutility of moderate/sever disability, the ICER is 84,291$/QALYs and for a shorter time horizon of 10 years, the ICER is 94,148$/QALYs.

Conclusion: Exome has the potential to be cost-effective compared with CMA alone. Our research provides data regarding the cost-effectiveness of ES without specific indication that will become increasingly important in the near future as whole exome sequencing becomes the first-tier test in prenatal diagnosis.