Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov 23;20(1):713.
doi: 10.1186/s12884-020-03394-w.

Prenatal screening for trisomy 21: a comparative performance and cost analysis of different screening strategies

Tianhua Huang  1   2   3 , Clare Gibbons  4   5 , Shamim Rashid  4 , Megan K Priston  4 , H Melanie Bedford  4   6 , Ellen Mak-Tam  4 , Wendy S Meschino  4   6
Affiliations

Prenatal screening for trisomy 21: a comparative performance and cost analysis of different screening strategies

Tianhua Huang et al. BMC Pregnancy Childbirth. .

Abstract

Background: Prenatal screening for chromosome aneuploidies have constantly been evolving, especially with the introduction of cell-free fetal DNA (cfDNA) screening in the most recent years. This study compares the performance, costs and timing of test results of three cfDNA screening implementation strategies: contingent, reflex and primary.

Methods: We modelled enhanced first trimester screening (eFTS) as the first-tier test in contingent or reflex strategies. cfDNA test was performed contingent on or reflex from eFTS results. A comparison was made between cfDNA screening using sequencing technology and Rolling Circle Amplification (RCA)/imaging solution. All model assumptions were based on results from previous publications or information from the Ontario prenatal screening population.

Results: At an eFTS risk cut-off of ≥1/1000, contingent and reflex cfDNA screening have the same detection rate (DR) (94%) for trisomy 21. Reflex cfDNA screening using RCA/Imaging solution provided the lowest false positive rate and cost. The number of women requiring genetic counselling and diagnostic testing was significantly reduced and women received their cfDNA screening result 9 days sooner compared with the contingent model. While primary cfDNA screening improved the trisomy 21 DR by 3-5%, it was more costly and more women required diagnostic testing.

Conclusion: Reflex cfDNA screening is the most cost-effective prenatal screening strategy. It can improve the efficiency of prenatal aneuploidy screening by reducing the number of patient visits and providing more timely results.

Keywords: Cell-free fetal DNA screening; Cost and performance; Multiple marker prenatal screening; Non-invasive prenatal screening; Trisomy 21.

PubMed Disclaimer

Conflict of interest statement

The authors (Tianhua Huang, Wendy S. Meschino, Shamim Rashid and Ellen Mak-Tam) had received reagent kits for previous studies on multiple marker screening from PerkinElmer. The authors (Tianhua Huang, Melanie Bedford, Shamim Rashid and Ellen Mak-Tam) have received a funding for study on pre-eclampsia screening from Thermo Fisher Scientific. The authors (Clare Gibbons and Wendy S. Meschino) are part of Validation of a Low Cost Aneuploidy Screening (VALUE) study and received funds for study activities (recruitment and sample collection). PerkinElmer and Thermo Fisher had no role in the design, data collection and analysis, and decision to publish the current study.

Figures

Fig. 1
Fig. 1
Prenatal screening pathway using different screening strategries. eFTS: Enhanced first trimester screening; cfDNA screening: cell free fetal DNA screening; Amnio: Amniocentesis, CVS: Chorionic villus sampling
See this image and copyright information in PMC

References

    1. Snijders RJ, Noble P, Sebire N, Souka A, Nicolaides KH. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation. Fetal Medicine Foundation first trimester screening group. Lancet. 1998;352(9125):343–346. doi: 10.1016/S0140-6736(97)11280-6. - DOI - PubMed
    1. Summers AM, Farrell SA, Huang T, Meier C, Wyatt PR. Maternal serum screening in Ontario using the triple marker test. J Med Screen. 2003;10:107–111. doi: 10.1177/096914130301000302. - DOI - PubMed
    1. Chiu RW, Akolekar R, Zheng YW, et al. Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ. 2011;342:c7401. doi: 10.1136/bmj.c7401. - DOI - PMC - PubMed
    1. Stokowski R, Wang E, White K, Batey A, Jacobsson B, Brar H, Balanarasimha M, Hollemon D, Sparks A, Nicolaides K, Musci TJ. Clinical performance of non-invasive prenatal testing (NIPT) using targeted cell-free DNA analysis in maternal plasma with microarrays or next generation sequencing (NGS) is consistent across multiple controlled clinical studies. Prenat Diagn. 2015;35:1243–1246. doi: 10.1002/pd.4686. - DOI - PMC - PubMed
    1. Ericsson O, Ahola T, Dahl F, et al. Clinical validation of a novel automated cell-free DNA screeningassay for trisomies 21, 13, and 18 in maternal plasma. Prenat Diagn. 2019. 10.1002/pd.5528 [Epub ahead of print] PubMed PMID: 31429096. - PMC - PubMed

Substances