Cell-free DNA analysis for noninvasive examination of trisomy

Mary E. Norton, Bo Jacobsson, Geeta K. Swamy, Louise C. Laurent, Angela C. Ranzini, Herb Brar, Mark W. Tomlinson, Leonardo Pereira, Jean L. Spitz, Desiree Hollemon, Howard Cuckle, Thomas J. Musci, Ronald J. Wapner

Research output: Contribution to journalArticle

338 Citations (Scopus)

Abstract

BACKGROUND: Cell-free DNA (cfDNA) testing for fetal trisomy is highly effective among high-risk women. However, there have been few direct, well-powered studies comparing cfDNA testing with standard screening during the first trimester in routine prenatal populations. METHODS: In this prospective, multicenter, blinded study conducted at 35 international centers, we assigned pregnant women presenting for aneuploidy screening at 10 to 14 weeks of gestation to undergo both standard screening (with measurement of nuchal translucency and biochemical analytes) and cfDNA testing. Participants received the results of standard screening; the results of cfDNA testing were blinded. Determination of the birth outcome was based on diagnostic genetic testing or newborn examination. The primary outcome was the area under the receiver-operating-characteristic curve (AUC) for trisomy 21 (Down's syndrome) with cfDNA testing versus standard screening. We also evaluated cfDNA testing and standard screening to assess the risk of trisomies 18 and 13. RESULTS: Of 18,955 women who were enrolled, results from 15,841 were available for analysis. The mean maternal age was 30.7 years, and the mean gestational age at testing was 12.5 weeks. The AUC for trisomy 21 was 0.999 for cfDNA testing and 0.958 for standard screening (P = 0.001). Trisomy 21 was detected in 38 of 38 women (100%; 95% confidence interval [CI], 90.7 to 100) in the cfDNA-testing group, as compared with 30 of 38 women (78.9%; 95% CI, 62.7 to 90.4) in the standard-screening group (P = 0.008). False positive rates were 0.06% (95% CI, 0.03 to 0.11) in the cfDNA group and 5.4% (95% CI, 5.1 to 5.8) in the standard-screening group (P

Original languageEnglish (US)
Pages (from-to)1589-1597
Number of pages9
JournalNew England Journal of Medicine
Volume372
Issue number17
DOIs
StatePublished - Apr 23 2015

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Trisomy
DNA
Down Syndrome
Confidence Intervals
Area Under Curve
Nuchal Translucency Measurement
Maternal Age
Genetic Testing
Aneuploidy
First Pregnancy Trimester
ROC Curve
Gestational Age
Multicenter Studies
Pregnant Women
Parturition
Newborn Infant
Pregnancy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Norton, M. E., Jacobsson, B., Swamy, G. K., Laurent, L. C., Ranzini, A. C., Brar, H., ... Wapner, R. J. (2015). Cell-free DNA analysis for noninvasive examination of trisomy. New England Journal of Medicine, 372(17), 1589-1597. https://doi.org/10.1056/NEJMoa1407349

Cell-free DNA analysis for noninvasive examination of trisomy. / Norton, Mary E.; Jacobsson, Bo; Swamy, Geeta K.; Laurent, Louise C.; Ranzini, Angela C.; Brar, Herb; Tomlinson, Mark W.; Pereira, Leonardo; Spitz, Jean L.; Hollemon, Desiree; Cuckle, Howard; Musci, Thomas J.; Wapner, Ronald J.

In: New England Journal of Medicine, Vol. 372, No. 17, 23.04.2015, p. 1589-1597.

Research output: Contribution to journalArticle

Norton, ME, Jacobsson, B, Swamy, GK, Laurent, LC, Ranzini, AC, Brar, H, Tomlinson, MW, Pereira, L, Spitz, JL, Hollemon, D, Cuckle, H, Musci, TJ & Wapner, RJ 2015, 'Cell-free DNA analysis for noninvasive examination of trisomy', New England Journal of Medicine, vol. 372, no. 17, pp. 1589-1597. https://doi.org/10.1056/NEJMoa1407349
Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC, Brar H et al. Cell-free DNA analysis for noninvasive examination of trisomy. New England Journal of Medicine. 2015 Apr 23;372(17):1589-1597. https://doi.org/10.1056/NEJMoa1407349
Norton, Mary E. ; Jacobsson, Bo ; Swamy, Geeta K. ; Laurent, Louise C. ; Ranzini, Angela C. ; Brar, Herb ; Tomlinson, Mark W. ; Pereira, Leonardo ; Spitz, Jean L. ; Hollemon, Desiree ; Cuckle, Howard ; Musci, Thomas J. ; Wapner, Ronald J. / Cell-free DNA analysis for noninvasive examination of trisomy. In: New England Journal of Medicine. 2015 ; Vol. 372, No. 17. pp. 1589-1597.
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