Cost-effectiveness of exome sequencing and chromosomal microarray for low-risk pregnancies.

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.