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.
OBJECTIVE
To evaluate the clinical performance of non-invasive prenatal testing for trisomy 21, 18, and 13 using targeted cell-free DNA (cfDNA) analysis.


METHODS
Targeted cfDNA analysis using DANSR™ and FORTE™ with microarray quantitation was used to evaluate the risk of trisomy 21, 18, and 13 in blinded samples from 799 singleton, twin, natural, and IVF pregnancies. Subjects either had fetal chromosome evaluation by karyotype, FISH, QF-PCR, or karyotype for newborns with suspected aneuploidy at birth. The results of targeted cfDNA analysis were compared to clinical genetic testing outcomes to assess clinical performance.


RESULTS
Targeted cfDNA analysis with microarray quantification identified 107/108 trisomy 21 cases (99.1%), 29/30 trisomy 18 cases (96.7%), and 12/12 trisomy 13 cases (100%). The specificity was 100% for all three trisomies. Combining this data with all published clinical performance studies using DANSR/FORTE methodology for greater than 23 000 pregnancies, the sensitivity of targeted cfDNA analysis was calculated to be greater than 99% for trisomy 21, 97% for trisomy 18, and 94% for trisomy 13. Specificity for each trisomy was greater than 99.9%.


CONCLUSIONS
Targeted cfDNA analysis demonstrates consistently high sensitivity and extremely low false positive rates for common autosomal trisomies in pregnancy across quantitation platforms.
Ariosa Diagnostics, Inc., San Jose, CA, USA.
Renee
R
Stokowski
Ariosa Diagnostics, Inc., San Jose, CA, USA.
Eric
E
Wang
Ariosa Diagnostics, Inc., San Jose, CA, USA.
Karen
K
White
Ariosa Diagnostics, Inc., San Jose, CA, USA.
Annette
A
Batey
Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Bo
B
Jacobsson
Prenatal Diagnostic and Perinatal Center, Riverside, CA, USA.
Herb
H
Brar
Ariosa Diagnostics, Inc., San Jose, CA, USA.
Madhumitha
M
Balanarasimha
Ariosa Diagnostics, Inc., San Jose, CA, USA.
Desiree
D
Hollemon
Ariosa Diagnostics, Inc., San Jose, CA, USA.
Andrew
A
Sparks
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
Kypros
K
Nicolaides
Ariosa Diagnostics, Inc., San Jose, CA, USA.
Thomas J
TJ
Musci
D000328:Adult; D018849:Controlled Clinical Trials as Topic; D005260:Female; D006801:Humans; D062145:Maternal Serum Screening Tests / Q000592:standards / Q000706:statistics & numerical data*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D017422:Sequence Analysis, DNA