OBJECTIVE: To evaluate the clinical and economic impact of adopting noninvasive prenatal testing (NIPT) using circulating cell-free DNA as a first-line screening method for trisomy 21, 18, and 13 in the general pregnancy population. METHODS: A decision-analytical model was developed to assess the impact of adopting NIPT as a primary screening test compared to conventional screening methods. The model takes the Belgium perspective and includes only the direct medical cost of screening, diagnosis, and procedure-related complications. NIPT costs are EUR 260. Clinical outcomes and the cost per trisomy detected were assessed. Sensitivity analysis measured the impact of NIPT false-positive rate (FPR) on modelled results. RESULTS: The cost per trisomy detected was EUR 63,016 for conventional screening versus EUR 66,633 for NIPT, with a difference of EUR 3,617. NIPT reduced unnecessary invasive tests by 94.8%, decreased procedure-related miscarriages by 90.8%, and increased trisomies detected by 29.1%. Increasing the FPR of NIPT (from < 0.01 to 1.0%) increased the average number of invasive procedures required to diagnose a trisomy from 2.2 to 4.5, respectively. CONCLUSION: NIPT first-line screening at a reasonable cost is cost-effective and provides better clinical outcomes. However, modelled results are dependent on the adoption of an NIPT with a low FPR.

Center for Perinatal and Reproductive Medicine University of Perugia Perugia Italy

Department of Obstetrics and Gynecology CHR Citadelle Liège Belgium

GfK Waltham Massachusetts USA

La Paz Hospital Madrid Spain

Roche Sequencing Solutions Inc Prague Czechia

Roche Sequencing Solutions Inc San Jose California USA

Roche Sequencing Solutions Inc Vilvoorde Belgium

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Neyt M, Hulstaert F, Gyselaers W. Introducing the non-invasive prenatal test for trisomy 21 in Belgium: a cost-consequences analysis. BMJ Open. 2014;4 e005922. PubMed PMC

European Surveillance of Congenital Anomalies (EUROCAT) EUROCAT Special Report: Prenatal Screening Policies in Europe 2010. EUROCAT Central Registry, University of Ulster. 2010

Verloes A, Gillerot Y, van Maldergem L, Schoos R, Herens C, Jamar M, Dideberg V, Lesenfants S, Koulischer L. Major decrease in the incidence of trisomy 21 at birth in south Belgium: mass impact of triple test? Eur J Hum Genet. 2001;9:1–4. PubMed

Hulstaert F, Neyt M, Gyselaers W. The non-invasive prenatal test (NIPT) for trisomy 21 – health economic aspects. Health Technology Assessment (HTA) Brussels, Belgian Health Care Knowledge Centre (KCE) 2014

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. PubMed PMC

Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC, Brar H, Tomlinson MW, Pereira L, Spitz JL, Hollemon D, Cuckle H. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015;372:1589–1597. PubMed

Nicolaides KH, Syngelaki A, Ashoor G, Birdir C, Touzet G. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am J Obstet Gynecol. 2012;207:374.e1–374.e6. PubMed

Gil MM, Quezada MS, Bregant B, Ferraro M, Nicolaides KH. Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies. Ultrasound Obstet Gynecol. 2013;42:34–40. PubMed

Verweij EJ, Jacobsson B, Scheltema PA, Boer MA, Hoffer MJ, Hollemon D, Westgren M, Song K, Oepkes D. European Non-Invasive Trisomy Evaluation (EU-NITE) study: a multicenter prospective cohort study for non-invasive fetal trisomy 21 testing. Prenat Diagn. 2013;33:996–1001. PubMed

American College of Obstetricians and Gynecologists Committee Opinion No. 640: Cell-free DNA screening for fetal aneuploidy. Obstet Gynecol. 2015;126:e31–e37. PubMed

Benn P, Borrell A, Chiu RW, Cuckle H, Dugoff L, Faas B, Gross S, Huang T, Johnson J, Maymon R, Norton M. Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat Diagn. 2015;35:725–734. PubMed

Gregg AR, Skotko BG, Benkendorf JL, Mon­aghan KG, Bajaj K, Best RG, Klugman S, Watson MS. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;18:1056–1065. PubMed

Publication of the Superior Health Council No. 8912 (HGR-CSS, report. 2014) Implementation of non-invasive prenatal genetic screening for trisomy 21 (Down Syndrome) in the practice of health care in Belgium. 2014 May 7

Health Council of the Netherlands Prenatal screening. The Hague, Health Council. 2016 publication No. 2016/19, ISBN 978-94-6281-088-4.

Italian Ministry of Health Linee guida: screening prenatale non invasive basato sul DNA [guidelines: DNA based noninvasive prenatal testing] 2015 July 3

Belgium Monitor 25.10.2017. http://www.vbs-gbs.org/fileadmin/user_upload/ e-specialist/2017/KB-AR_2017.10.15_-_BS-MB_2017.10.25_NIPT.pdf.

Gil MD, Quezada MS, Bregant B, Syngelaki A, Nicolaides KH. Cell-free DNA analysis for trisomy risk assessment in first-trimester twin pregnancies. Fetal Diagn Ther. 2014;35:204–211. PubMed

Cuckle HS, Wald NJ, Thompson SG. Estimating a woman's risk of having a pregnancy associated with Down's syndrome using her age and serum alpha-fetoprotein level. Br J Obstet Gynaecol. 1987;94:387–402. PubMed

NomenSoft (Belgium) National Institute for Health and Disability Insurance (INAMI) http://www.riziv.fgov.be/nl/themas/kost-te­rugbetaling/door-ziekenfonds/individuele-verzorging/honoraires/Paginas/default.aspx#.Wl5vW6inHIV F (accessed July 2016)

Snijders RJ, Holzgreve W, Cuckle H, Nicolaides KH. Maternal age-specific risks for trisomies at 9–14 weeks' gestation. Prenat Diagn. 1994;14:543–552. PubMed

Gil MM, Revello R, Poon LC, Akolekar R, Nicolaides KH. Clinical implementation of routine screening for fetal trisomies in the UK NHS: cell-free DNA test contingent on results from first-trimester combined test. Ultrasound Obstet Gynecol. 2016;47:45–52. PubMed

Tabor A, Alfirevic Z. Update on procedure-related risks for prenatal diagnosis techniques. Fetal Diagn Ther. 2010;27:1–7. PubMed

Institut national d'assurance maladie invalidité (INAMI) CSS 2017/175 2017 May 29

Institute of Health Economics First and Second Trimester Prenatal Screening for Trisomies 13, 18, and 21 and Open Neural Tube Defects. Edmonton, Institute of Health Economics. 2012 PubMed

Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Deciu C, Grody WW, Nelson SF. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med. 2011;13:913–920. PubMed

Taylor-Phillips S, Freeman K, Geppert J, Agbebiyi A, Uthman OA, Madan J, Clarke A, Quenby S, Clarke A. Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis. BMJ Open. 2016;6:e010002. PubMed PMC

Langlois S, Johnson J, Audibert F, Gekas J, Forest JC, Caron A, Harrington K, Pastuck M, Meddour H, Tétu A, Little J. Comparison of first tier cell-free DNA screening for common aneuploidies with conventional publically funded screening. Prenat Diagn. 2017;37:1238–1244. PubMed

Beulen L, Grutters JP, Faas BH, Feenstra I, van Vugt JM, Bekker MN. The consequences of implementing non-invasive prenatal testing in Dutch national health care: a cost-effectiveness analysis. Eur J Obstet Reprod Biol. 2014;182:53–61. PubMed

Fairbrother G, Burigo J, Sharon T, Song K. Prenatal screening for fetal aneuploidies with cell-free DNA in the general pregnancy population: a cost-effectiveness analysis. J Matern Fetal Neonatal Med. 2016;29:1160–1164. PubMed PMC

Walker BS, Jackson BR, LaGrave D, Ashwood ER, Schmidt RL. A cost-effectiveness analysis of cell free DNA as a replacement for serum screening for Down syndrome. Prenat Diagn. 2015;35:440–446. PubMed

Morris S, Karlsen S, Chung N, Hill M, Chitty LS. Model-based analysis of costs and outcomes of non-invasive prenatal testing for Down's syndrome using cell free fetal DNA in the UK National Health Service. PLoS One. 2014;9:e93559. PubMed PMC

Nshimyumukiza L, Beaumont JA, Duplantie J, Langlois S, Little J, Audibert F, McCabe C, Gekas J, Giguère Y, Gagné C, Reinharz D, Rousseau F. Cell-free DNA-based non-invasive prenatal screening for common aneuploidies in a Canadian province: a cost-effectiveness analysis. J Obstet Gynaecol Can. 2018;40:48–60. PubMed

Crombag NM, Bensing JM, Iedema-Kuiper R, Schielen PC, Visser GH. Determinants affecting pregnant women's utilization of prenatal screening for Down syndrome: a review of the literature. J Matern Fetal Neonatal Med. 2013;26:1676–1681. PubMed