Discordant noninvasive prenatal testing and cytogenetic results: a study of 109 consecutive cases.

Abstract

PURPOSE:

Recent published studies have demonstrated the incremental value of the use of cell-free DNA for noninvasive prenatal testing with 100% sensitivity for trisomies 21 and 18 and a specificity of ≥99.7% for both. Data presented by two independent groups suggesting positive results by noninvasive prenatal testing were not confirmed by cytogenetic studies.

METHODS:

Concordance of results among cases with noninvasive prenatal testing referred for cytogenetic prenatal and/or postnatal studies by karyotyping, fluorescence in situ hybridization, and/or oligo-single-nucleotide polymorphism microarray was evaluated for 109 consecutive specimens.

RESULTS:

Cytogenetic results were positive for trisomy 21 in 38 of the 41 noninvasive prenatal testing-positive cases (true-positive rate: 93%) and for trisomy 18 in 16 of the 25 noninvasive prenatal testing-positive cases (true-positive rate: 64%). The true-positive rate was only 44% (7/16 cases) for trisomy 13 and 38% (6/16 cases) for sex chromosome aneuploidy.

CONCLUSION:

These findings raise concerns about the limitations of noninvasive prenatal testing and the need for analysis of a larger number of false-positive cases to provide true positive predictive values for noninvasive testing and to search for potential biological or technical causes. Our data suggest the need for a careful interpretation of noninvasive prenatal testing results and cautious transmission of the same to providers and patients.

• Authors: Jia-Chi Wang, Trilochan Sahoo, Steven Schonberg, Kimberly A Kopita, Leslie Ross, Kyla Patek, Charles M Strom
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 17 Issue 3 Pg. 234-6 (Mar 2015) ISSN: 1530-0366 [Electronic] United States
• PMID: 25101914 (Publication Type: Journal Article)

Topics

• Cell-Free System
• Chromosomes, Human, Pair 18
• Cytogenetic Analysis (methods)
• Down Syndrome (diagnosis)
• Female
• Humans
• Pregnancy
• Prenatal Diagnosis (methods)
• Sensitivity and Specificity
• Trisomy (diagnosis)
• Trisomy 18 Syndrome