Non-Invasive Chromosomal Evaluation (NICE) Study: Results of a Multicenter, Prospective, Cohort Study for Detection of Fetal Trisomy 21 and Trisomy 18

Non-Invasive Chromosomal Evaluation (NICE) Study: Results of a Multicenter, Prospective, Cohort Study for Detection of Fetal Trisomy 21 and Trisomy 18

• Mary E. Norton, MD
,
• Herb Brar, MD
,
• Jonathan Weiss, MD
,
• Ardeshir Karimi, MD
,
• Louise C. Laurent, MD, Ph.D.
,
• Aaron B. Caughey, MD, Ph.D.
,
• M. Hellen Rodriguez, MD
,
• John Williams III, MD
,
• Michael E. Mitchell, MD
,
• Charles D. Adair, MD
,
• Hanmin Lee, MD
,
• Bo Jacobbson, MD
,
• Mark W. Tomlinson, MD
,
• Dick Oepkes, MD, Ph.D.
,
• Desiree Hollemon, M.S.N., M.P.H.
,
• Andrew B. Sparks, Ph.D.
,
• Arnold Oliphant, Ph.D.
,
• Ken Song, MD

Received 24 April 2012; received in revised form 17 May 2012; accepted 24 May 2012. published online 04 June 2012.
Accepted Manuscript

• Abstract
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Abstract 

Objective

To evaluate performance of a non-invasive prenatal test for fetal trisomy 21 (T21) and trisomy 18 (T18).

Study Design

A multicenter cohort study was performed whereby cell-free DNA (cfDNA) from maternal plasma was analyzed. Chromosome-selective sequencing on chromosomes 21 and 18 was performed with reporting of an aneuploidy risk (High Risk or Low Risk) for each subject.

Results

Of the 81 T21 cases, all were classified as High Risk for T21 and there was one false positive among the 2888 normal cases, for a sensitivity of 100% (95% CI: 95.5-100%) and a false-positive rate of 0.03% (95% CI: 0.002-0.20%). Of the 38 T18 cases, 37 were classified as High Risk and there were 2 false positives among the 2888 normal cases, for a sensitivity of 97.4% (95% CI: 86.5%-99.9%) and a false-positive rate of 0.07% (95% CI: 0.02-0.25%).

Conclusion

Chromosome-selective sequencing of cfDNA and application of an individualized risk algorithm is effective in the detection of fetal T21 and T18.

Keywords:  Non-invasive prenatal diagnosis , aneuploidy detection , trisomy , Down syndrome , cell free fetal DNA