title: Improving the Positive Predictive Value of Non-Invasive Prenatal Screening (NIPS).
abstract: We evaluated performance characteristics of a laboratory-developed, non-invasive prenatal screening (NIPS) assay for fetal aneuploidies. This assay employs massively parallel shotgun sequencing with full automation. GC sequencing bias correction and statistical smoothing were performed to enhance discrimination of affected and unaffected pregnancies. Maternal plasma samples from pregnancies with known aneuploidy status were used for assay development, verification, and validation. Assay verification studies using 2,085 known samples (1873 unaffected, 69 trisomy 21, 20 trisomy 18, 17 trisomy 13) demonstrated complete discrimination between autosomal trisomy (Z scores >8) and unaffected (Z scores <4) singleton pregnancies. A validation study using 552 known samples (21 trisomy 21, 10 trisomy 18, 1 trisomy 13) confirmed complete discrimination. Twin pregnancies showed similar results. Follow-up of abnormal results from the first 10,000 clinical samples demonstrated PPVs of 98% (41/42) for trisomy 21, 92% (23/25) for trisomy 18, and 69% (9/13) for trisomy 13. Adjustment for causes of false-positive results identified during clinical testing (eg, maternal duplications) improved PPVs to 100% for trisomy 21 and 96% for trisomy 18. This NIPS test demonstrates excellent discrimination between trisomic and unaffected pregnancies. The PPVs obtained in initial clinical testing are substantially higher than previously reported NIPS methods.
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Strom
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Ben
authors.initials: B
authors.lastname: Anderson
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Tsao
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Kayla
authors.initials: K
authors.lastname: Livingston
authors.affiliation: Athena Diagnostics, Marlborough, Massachusetts, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Elzinga
authors.affiliation: Athena Diagnostics, Marlborough, Massachusetts, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Evans
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Quoclinh
authors.initials: Q
authors.lastname: Nguyen
authors.affiliation: Celera Diagnostics, Alameda, California, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Wolfson
authors.affiliation: Celera Diagnostics, Alameda, California, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Rowland
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Paula
authors.initials: P
authors.lastname: Kolacki
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Megan
authors.initials: M
authors.lastname: Maxwell
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Jia-Chi
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Douglas
authors.initials: D
authors.lastname: Rabin
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Catanese
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Renius
authors.initials: R
authors.lastname: Owen
authors.affiliation: Athena Diagnostics, Marlborough, Massachusetts, United States of America.
authors.forename: Corey
authors.initials: C
authors.lastname: Braastad
authors.affiliation: Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
authors.forename: Weimin
authors.initials: W
authors.lastname: Sun
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics*; D005189:False Positive Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics*