Fetal Aneuploidy Detection by Maternal Plasma DNA Sequencing

Judith Walsh, MD, MPH

CTAF

Introduction

The California Technology Assessment Forum is requested to review the scientific evidence for the use of maternal plasma DNA sequencing for fetal aneuploidy detection. This topic is being addressed because of recent publicationsof studies of diagnostic accuracy of this technology in high risk women. This is the first time that CTAF has addressed this topic.

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Table 1. Studies using cell free fetal DNA to screen for fetal aneuploidy
Author, year	Study Type	N total	N with abnormal karyotype	Trisomy targeted	Test	Inclusion Criteria
Palomaki, 2011¹⁸ Palomaki, 2012¹⁹	Multicenter nested case control	1971	283 212 (T21) 59 (T18) 12 (T13)	21	MPSS	High risk for Down syndrome: maternal age, family history or positive screening test
Sehnert, 2011¹⁶	Multicenter cross sectional validation study	119	53	21 18	MPSS	18 years and older and pregnant
Ehrich, 2011²⁰	Blinded prospective	480	39	21	MPSS	Advanced maternal age, positive screening test, personal or family history of Down Syndrome
Bianchi, 2012²¹	Blinded prospective; multicenter with nested case control	532	221	21 18 13	MPSS	Women undergoing an invasive prenatal procedure; aged 38 and over; positive screening test for aneuploidy or prior aneuploidy fetus
Chiu, 2011¹⁷	Diagnostic accuracy with prospectively collected or archived serum	753	86	21	MPSS	Women with "clinical indications for CVS or amniocentesis"
Ashoor, 2012²²	Nested case control	400	100	21 18	DANSR	Stored plasma High risk women where risk for aneuploidy was >1/300
Sparks, 2012¹⁵	Nested case control with training and validation sets	338	88	21 18	DANSR	At least 18 years of age; at least 10 weeks pregnant; singleton pregnancy (subset of larger prospective group chosen based on ploidy status)

Table 2. Results of studies using cell free fetal DNA to screen for fetal aneuploidyy
Author, year	N Total	N with abnormal karyotype	Main results:T21	Main results: T18	Main results: T13	Comments
Palomaki, 2011¹⁸ Palomaki, 2012¹⁹	1971	212 (T21) 59 (T18) 12 (T13)	98.6% detection rate 99.8% specificity	100% detection rate 99.72 specificity	91.7% detection rate 99.03% specificity	Overall detection rate 98.9% for common aneuploidies 17 samples could not be interpreted: three were Trisomy 18 Very few T13 cases
Sehnert, 2011¹⁶	119	53	100% sensitivity	100% sensitivity	N/A	Training and validation set: Training set 71 samples (26 abnormal karyotypes) and validation set 48 samples (27 abnormal karyotypes) 13 T21 and 8 T18 samples
Ehrich, 2011²⁰	480	39	100% sensitivity 99.7% specificity	N/A	N/A	38 T21 samples
Bianchi, 2012²¹	532	221 Total 89 (T21) 36 (T18) 14 (T13)	100 sensitivity	97.2% sensitivity	78.6% sensitivity	No false positives for autosomal euploides
Chiu, 2011¹⁷	753	86	100% sensitivity 97.9% specificity	N/A	N/A	Two different methods tested (2-plex and 8-plex). 2-plex method had better sensitivity
Ashoor, 2012²²	400	100 50 (T21) 50 (T18)	100% sensitivity 99%	100% sensitivity 99%	N/A	Specificity calculated on total of 300 euploid fetuses although three samples were not available for analysis
Sparks, 2012¹⁵	338	88	100% sensitivity	100% sensitivity	N/A	36 T21 cases in validation set 7 T18 cases in validation set

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Fetal Aneuploidy Detection by Maternal Plasma DNA Sequencing

Introduction

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Tables

References

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Authors and Disclosures

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