Cost-effectiveness of exome sequencing and chromosomal microarray for low-risk pregnancies
Michal Rosenberg Friedman1, Yariv Yogev1, Sharon Maslovitz1
1Lis Hospital for Women's Health, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel (Friedman, Yogev, Maslovitz, and Reicher).
Background:
Chromosomal microarray analysis (CMA) has been central to prenatal genetic diagnosis, detecting copy number variants with a ∼1% yield in low-risk cases. Next-generation sequencing (NGS), including exome sequencing (ES), enhances diagnostic capabilities with higher yields (8.5-10%) but at greater cost and complexity. While ES's cost-effectiveness is studied in high-risk pregnancies, data for low-risk pregnancies remain lacking. This study evaluates the cost-effectiveness of ES in low-risk pregnancies.
Objective:
This study aimed to investigate the cost-effectiveness of exome sequencing compared with chromosomal microarray analysis.
Study Design:
Costs, utilities, and quality-adjusted life years were modeled for prenatal testing with chromosomal microarray analysis or chromosomal microarray analysis + exome sequencing. Average costs and utilities were discounted at 3%. In addition, 2 strategies for screening were compared using the Markovian decision analysis model: (1) chromosomal microarray analysis only (an abnormal result leads to a termination of pregnancy, and a normal test has a 1 to 160 chance of developing into a severe disorder) and (2) exome sequencing after a normal chromosomal microarray analysis (a positive result leads to a termination of pregnancy). Of note, 1-way sensitivity analysis was performed for all variables. The outcome measures included quality-adjusted life years after abortion, costs of chromosomal microarray analysis and exome sequencing, and health expenses of a critically ill infant. The time horizon of the model was 20 years.
Results:
The total costs were $1348 for chromosomal microarray analysis and $3108 for chromosomal microarray analysis + exome sequencing. The quality-adjusted life years with a time horizon of 20 years were 14.15 for chromosomal microarray analysis and 14.19 for chromosomal microarray analysis + exome sequencing, with an incremental cost-effectiveness ratio of $46,383 per quality-adjusted life years. Sensitivity analysis revealed that the time horizon and the disutility of moderate/severe disability of the genetic disorder have an effect on the incremental cost-effectiveness ratio. For example, the incremental cost-effectiveness ratios are $84,291 per quality-adjusted life years for a relatively small disutility of moderate/severe disability and $94,148 per quality-adjusted life years for a shorter time horizon of 10 years.
Conclusion:
Exome sequencing has the potential to be cost-effective compared with chromosomal microarray analysis alone. Our research provides data regarding the cost-effectiveness of exome sequencing without a specific indication, which will become increasingly important in the near future as whole exome sequencing becomes the first-tier test in prenatal diagnosis.
