(829) Cost-effectiveness of exome and genome sequencing for low-risk pregnancies

Chromosomal microarray (CMA) is positive in about 1% of fetuses without a specific indication, even with apparent normal anatomy scans. Hence, CMA has become a widely accepted practice upon "parental request". However, it is evident that normal CMA analysis cannot exclude a single nucleotide variant (SNV) that is below the detection limit of CMA. Among low risk pregnancies with normal CMA 1/160 will have pathogenic variant for a severe disorder in exome sequencing (ES). We assessed the cost-effectiveness of ES in low-risk pregnancies

Study Design:

Costs, utility and quality adjusted life years (QALY) were modelled for prenatal testing with CMA or CMA+ES.  Two strategies were compared using Markovian decision analysis model: (1) CMA only- abnormal result culminating in termination of pregnancy and normal test has a 1/160 chance for severe disorder. (2) ES after a negative CMA, for positive result a termination of pregnancy is conducted. 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:

Testing costs were $1,479 and $3,108 for CMA and CMA+ES strategies respectively. The QALY with time horizon of 20 years were 18.768 and 18.819 QALY for CMA and CMA+ES strategies respectively with incremental cost-effectiveness ratio (ICER) of 32,368$/QALY. The commonly accepted threshold for cost-effectiveness in many healthcare systems is an ICER of less than $50,000/QALY. Sensitivity analysis revealed that the time horizon and the dis-utility of moderate/sever disability of the genetic disorder has an impact on the ICER. For example, with a relatively small disutility of moderate/sever disability, the ICER is 58,822$/QALY and for a shorter time horizon of 10 years, the ICER is 80,024$/QALY

Conclusion:

ES has the potential to be cost-effective compared with CMA alone. Our research provides data regarding the cost-effectiveness of ES in low-risk pregnancies that will become increasingly important in the near future as whole genome sequencing becomes the first-tier test in prenatal diagnosis