Outcome of publicly funded nationwide first-tier noninvasive prenatal screening.

Aneuploidy; Chromosome Disorders/diagnosis/epidemiology/genetics; Down Syndrome/diagnosis/epidemiology/genetics; Female; Humans; Noninvasive Prenatal Testing; Pregnancy; Prenatal Diagnosis; Trisomy

Abstract :

[en] PURPOSE: Noninvasive prenatal screening (NIPS) using cell-free DNA has transformed prenatal care. Belgium was the first country to implement and fully reimburse NIPS as a first-tier screening test offered to all pregnant women. A consortium consisting of all Belgian genetic centers report the outcome of two years genome-wide NIPS implementation. METHODS: The performance for the common trisomies and for secondary findings was evaluated based on 153,575 genome-wide NIP tests. Furthermore, the evolution of the number of invasive tests and the incidence of Down syndrome live births was registered. RESULTS: Trisomies 21, 18, and 13 were detected in respectively 0.32%, 0.07%, and 0.06% of cases, with overall positive predictive values (PPVs) of 92.4%, 84.6%, and 43.9%. Rare autosomal trisomies and fetal segmental imbalances were detected in respectively 0.23% and 0.07% of cases with PPVs of 4.1% and 47%. The number of invasive obstetric procedures decreased by 52%. The number of trisomy 21 live births dropped to 0.04%. CONCLUSION: Expanding the scope of NIPS beyond trisomy 21 fetal screening allows the implementation of personalized genomic medicine for the obstetric population. This genome-wide NIPS approach has been embedded successfully in prenatal genetic care in Belgium and might serve as a framework for other countries offering NIPS.

Disciplines :

Genetics & genetic processes

Author, co-author :

Van Den Bogaert, Kris

Lannoo, Lore

Brison, Nathalie

Gatinois, Vincent

Baetens, Machteld

Blaumeiser, Bettina

BOEMER, François ; Centre Hospitalier Universitaire de Liège - CHU > Unilab > Laboratoire Biochimie Génétique

Bourlard, Laura

Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique humaine

De Leener, Anne

More authors (22 more)

Language :

English

Title :

Outcome of publicly funded nationwide first-tier noninvasive prenatal screening.

Publication date :

2021

Journal title :

Genetics in medicine : official journal of the American College of Medical Genetics

ISSN :

1098-3600

eISSN :

1530-0366

Volume :

Issue :

Pages :

1137-1142

Peer reviewed :

Peer reviewed

Available on ORBi :

since 12 October 2021

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Bibliography

Vermeesch, J. R., Voet, T. & Devriendt, K. Prenatal and pre-implantation genetic diagnosis. Nat. Rev. Genet. 17, 643–656 (2016). DOI: 10.1038/nrg.2016.97
Fan, H. C., Blumenfeld, Y. J., Chitkara, U., Hudgins, L. & Quake, S. R. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc. Natl. Acad. Sci. U. S. A. 105, 16266–16271 (2008). DOI: 10.1073/pnas.0808319105
Chiu, R. W. K. et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc. Natl. Acad. Sci. U. S. A. 105, 20458–20463 (2008). DOI: 10.1073/pnas.0810641105
Gil, M. M., Accurti, V., Santacruz, B., Plana, M. N. & Nicolaides, K. H. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstet. Gynecol. 50, 302–314 (2017). DOI: 10.1002/uog.17484
Taylor-Phillips, S. et al. 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 6, e010002 (2016). DOI: 10.1136/bmjopen-2015-010002
Badeau, M. et al. Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women. Cochrane Database Syst. Rev. 11, CD011767 (2017).
Gregg, A. R. et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet. Med. 18, 1056–1065 (2016). DOI: 10.1038/gim.2016.97
Committee opinion no. 640: cell-free DNA screening for fetal aneuploidy. Obstet. Gynecol. 126, e31–e37 (2015).
Society for Maternal-Fetal Medicine (SMFM) Publications Committee. SMFM statement: clarification of recommendations regarding cell-free DNA aneuploidy screening. Am. J. Obstet. Gynecol. 213, 753–754 (2015).
Benn, P. et al. Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat. Diagn. 35, 725–734 (2015). DOI: 10.1002/pd.4608
Bianchi, D. W. & Chiu, R. W. K. Sequencing of circulating cell-free DNA during pregnancy. N. Engl. J. Med. 379, 464–473 (2018). DOI: 10.1056/NEJMra1705345
Gadsbøll, K. et al. Current use of noninvasive prenatal testing in Europe, Australia and the USA: a graphical presentation. Acta Obstet. Gynecol. Scand. 99, 722–730 (2020). DOI: 10.1111/aogs.13841
Van Elslande, J. et al. The sudden death of the combined first trimester aneuploidy screening, a single centre experience in Belgium. Clin. Chem. Lab. Med. 57, e294–e297 (2019). DOI: 10.1515/cclm-2019-0231
FPS Public Health. Opinion no. 66 of 9 May 2016—non-invasive prenatal testing (NIPT).https://www.health.belgium.be/en/opinion-no-66-non-invasive-prenatal-testing-nipt (2016).
Belgium Society of Human Genetics prenatal working group. Belgian Guidlines for managing incidental findings detected by NIPT. https://www.college-genetics.be/assets/recommendations/fr/guidelines/BELGIAN%20GUIDELINES%20FOR%20MANAGING%20INCIDENTAL%20FINDINGS%20DETECTED%20BY%20NIPT%20(2019).pdf.
Kalia, S. S. et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet. Med. 19, 249–255 (2017). DOI: 10.1038/gim.2016.190
Bayindir, B. et al. Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management. Eur. J. Hum. Genet. 23, 1286–1293 (2015). DOI: 10.1038/ejhg.2014.282
Dheedene, A. et al. Implementation of non-invasive prenatal testing by semiconductor sequencing in a genetic laboratory. Prenat. Diagn. 36, 699–707 (2016). DOI: 10.1002/pd.4841
Raman, L., Dheedene, A., De Smet, M., Van Dorpe, J. & Menten, B. WisecondorX: improved copy number detection for routine shallow whole-genome sequencing. Nucleic Acids Res. 47, 1605–1614 (2019). DOI: 10.1093/nar/gky1263
Engel, E. A fascination with chromosome rescue in uniparental disomy: Mendelian recessive outlaws and imprinting copyrights infringements. Eur. J. Hum. Genet. 14, 1158–1169 (2006). DOI: 10.1038/sj.ejhg.5201619
Brison, N. et al. Accuracy and clinical value of maternal incidental findings during noninvasive prenatal testing for fetal aneuploidies. Genet. Med. 19, 306–313 (2017). DOI: 10.1038/gim.2016.113
Ammon Avalos, L., Galindo, C. & Li, D.-K. A systematic review to calculate background miscarriage rates using life table analysis. Birth Defects Res. A Clin. Mol. Teratol. 94, 417–423 (2012). DOI: 10.1002/bdra.23014
Gyselaers, W., Hulstaert, F. & Neyt, M. Contingent non-invasive prenatal testing: an opportunity to improve non-genetic aspects of fetal aneuploidy screening. Prenat. Diagn. 35, 1347–1352 (2015). DOI: 10.1002/pd.4704
Yaron, Y. The implications of non-invasive prenatal testing failures: a review of an under-discussed phenomenon. Prenat. Diagn. 36, 391–396 (2016). DOI: 10.1002/pd.4804
van der Meij, K. R. M. et al. TRIDENT-2: national implementation of genome-wide noninvasive prenatal testing as a first-tier screening test in the Netherlands. Am. J. Hum. Genet. 105, 1091–1101 (2019). DOI: 10.1016/j.ajhg.2019.10.005
Pertile, M. D. et al. Rare autosomal trisomies, revealed by maternal plasma DNA sequencing, suggest increased risk of feto-placental disease. Sci. Transl. Med. 9, eaan1240 (2017).
Scott, F. et al. Rare autosomal trisomies: Important and not so rare. Prenat. Diagn. 38, 765–771 (2018). DOI: 10.1002/pd.5325
Brison, N. et al. Predicting fetoplacental chromosomal mosaicism during non-invasive prenatal testing. Prenat. Diagn. 38, 258–266 (2018). DOI: 10.1002/pd.5223
Amant, F. et al. Presymptomatic identification of cancers in pregnant women during noninvasive prenatal testing. JAMA Oncol. 1, 814–819 (2015). DOI: 10.1001/jamaoncol.2015.1883
Brison, N. et al. Maternal copy-number variations in the DMD gene as secondary findings in noninvasive prenatal screening. Genet. Med. 21, 2774–2780 (2019).
Robson, S. J. & Hui, L. National decline in invasive prenatal diagnostic procedures in association with uptake of combined first trimester and cell-free DNA aneuploidy screening. Aust. N. Z. J. Obstet. Gynaecol. 55, 507–510 (2015). DOI: 10.1111/ajo.12380
Larion, S. et al. Association of combined first-trimester screen and noninvasive prenatal testing on diagnostic procedures. Obstet. Gynecol. 123, 1303–1310 (2014). DOI: 10.1097/AOG.0000000000000275
Platt, L. D. et al. Impact of noninvasive prenatal testing in regionally dispersed medical centers in the United States. Am J Obstet. Gynecol. 211, 368.e1–7 (2014). DOI: 10.1016/j.ajog.2014.03.065
van Schendel, R. V. et al. Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening. Eur. J. Hum. Genet. 22, 1345–1350 (2014). DOI: 10.1038/ejhg.2014.32
Hill, M. et al. Has noninvasive prenatal testing impacted termination of pregnancy and live birth rates of infants with Down syndrome? Prenat. Diagn. 37, 1281–1290 (2017). DOI: 10.1002/pd.5182
Dondorp, W. et al. Noninvasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. Eur. J. Hum. Genet. 23, 1438–1450 (2015). DOI: 10.1038/ejhg.2015.57
Grati, F. R. et al. Outcomes in pregnancies with a confined placental mosaicism and implications for prenatal screening using cell-free DNA. Genet. Med. 22, 309–316 (2020).
Malvestiti, F. et al. Interpreting mosaicism in chorionic villi: results of a monocentric series of 1001 mosaics in chorionic villi with follow-up amniocentesis. Prenat. Diagn. 35, 1117–1127 (2015). DOI: 10.1002/pd.4656
Toutain, J., Goutte-Gattat, D., Horovitz, J. & Saura, R. Confined placental mosaicism revisited: impact on pregnancy characteristics and outcome. PLoS One 13, e0195905 (2018). DOI: 10.1371/journal.pone.0195905
van Schendel, R. V. et al. What do parents of children with Down syndrome think about non-invasive prenatal testing (NIPT)? J. Genet. Couns. 26, 522–531 (2017). DOI: 10.1007/s10897-016-0012-4
Crombag, N. M., Page-Christiaens, G. C., Skotko, B. G. & de Graaf, G. Receiving the news of Down syndrome in the era of prenatal testing. Am. J. Med. Genet. A 182, 374–385 (2020). DOI: 10.1002/ajmg.a.61438