TY - JOUR
T1 - Cost-effectiveness of exome sequencing and chromosomal microarray for low-risk pregnancies
AU - Friedman, Michal Rosenberg
AU - Yogev, Yariv
AU - Maslovitz, Sharon
AU - Leshno, Moshe
AU - Reicher, Lee
N1 - Publisher Copyright:
© 2024 Elsevier Inc.
PY - 2025
Y1 - 2025
N2 - 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.
AB - 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.
KW - chromosomal microarray analysis
KW - cost-effectiveness analysis
KW - exome sequencing
KW - quality-adjusted life years
UR - http://www.scopus.com/inward/record.url?scp=85215087479&partnerID=8YFLogxK
U2 - 10.1016/j.ajogmf.2024.101512
DO - 10.1016/j.ajogmf.2024.101512
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C2 - 39424276
AN - SCOPUS:85215087479
SN - 2589-9333
JO - American Journal of Obstetrics and Gynecology MFM
JF - American Journal of Obstetrics and Gynecology MFM
M1 - 101512
ER -