Exome Sequencing for Prenatal Detection of Genetic Abnormalities in Fetal Ultrasound Anomalies: An Economic Evaluation

Abstract

Introduction: In light of the prospective Prenatal Assessment of Genomes and Exomes (PAGE) study, this paper aimed to determine the additional costs of using exome sequencing (ES) alongside or in place of chromosomal microarray (CMA) in a fetus with an identified congenital anomaly. Methods: A decision tree was populated using data from a prospective cohort of women undergoing invasive diagnostic testing. Four testing strategies were evaluated: CMA, ES, CMA followed by ES ("stepwise"); CMA and ES combined. Results: When ES is priced at GBP 2,100 (EUR 2,407/USD 2,694), performing ES alone prenatally would cost a further GBP 31,410 (EUR 36,001/USD 40,289) per additional genetic diagnosis, whereas the stepwise would cost a further GBP 24,657 (EUR 28,261/USD 31,627) per additional genetic diagnosis. When ES is priced at GBP 966 (EUR 1,107/USD 1,239), performing ES alone prenatally would cost a further GBP 11,532 (EUR 13,217/USD 14,792) per additional genetic diagnosis, whereas the stepwise would cost a further additional GBP 11,639 (EUR 13,340/USD 14,929) per additional genetic diagnosis. The sub-group analysis suggests that performing stepwise on cases indicative of multiple anomalies at ultrasound scan (USS) compared to cases indicative of a single anomaly, is more cost-effective compared to using ES alone. Discussion/Conclusion: Performing ES alongside CMA is more cost-effective than ES alone, which can potentially lead to improvements in pregnancy management. The direct effects of test results on pregnancy outcomes were not examined; therefore, further research is recommended to examine changes on the projected incremental cost-effectiveness ratios.

The Diagnostic Yield of Prenatal Genetic Technologies in Congenital Heart Disease: A Prospective Cohort Study

“…The aetiology of CHD is complex and further research using CHD models to explore the interaction between genetic and epigenetic modifications and cardiac embryology and morphology is needed [11]. Whole-genome sequencing aids not only in gene discovery but can also assess for the presence of aneuploidy and structural variation as well as single nucleotide changes, hence, can potentially serve as an “all-in-one-test” in the future once turnaround times and costs reduce [37, 38].…”

The role of next‐generation sequencing in the investigation of ultrasound‐identified fetal structural anomalies

“…severe skeletal dysplasia associated with osteogenesis imperfecta) may provide opportunities for antenatal therapy (such as mesenchymal stem cell transplantation); as in the pan‐EU Brittle Bone Before Birth (BOOSTB4) study 65 . However, as well as a robust, relatively conservative infrastructure for clinical delivery of this service, there is a need to continue to debate the societal, moral and ethical issues surrounding the implementation of such science so as to provide additional prognostic information to parents while attempting to limit unnecessary emotional burden on parents and society 51–66 …”

“…When ES is priced at GBP 966 (EUR 1,107/USD 1,239), performing ES alone prenatally would cost a further GBP 11,532 (EUR 13,217/USD 14,792) per additional genetic diagnosis, whereas stepwise ES would cost a further GBP 11,639 (EUR 13,340/USD 14,929) per additional genetic diagnosis. The sub‐group analysis suggests that performing stepwise ES on cases indicative of multiple anomalies at ultrasound scan versus cases indicative of a single anomaly, is more cost‐effective compared with using ES alone 62 . It is likely that these are conservative costs and different healthcare economies will need to evaluate their costs and make decisions as to whether it is possible to implement prenatal exome sequencing within their healthcare systems.…”

Diagnosis of hepatic glycogen storage disease patients with overlapping clinical symptoms by massively parallel sequencing: a systematic review of literature

“…Therefore, the best diagnostic strategy to identify hepatic GSDs can be starting with a TGS method, as a more cost-effective method than the ES, but with the high coverage and a wide range of the panel. If there is no definite result, then analysis with a more comprehensive method, such as an ES, should be performed [40]. ES should particularly be the diagnostic tool of choice when an accurate diagnosis of more complex cases is necessary.…”