Challenges in non‐invasive prenatal screening for sub‐chromosomal copy number variations using cell‐free DNA. (26th October 2017)

• Record Type: Journal Article
• Authors: Advani, Henna V.; Barrett, Angela N.; Evans, Mark I.; Choolani, Mahesh
• Is Part Of: Prenatal diagnosis. Volume 37:Number 11(2017)
• Page Start: 1067
• Page End: 1075
• Publication Date: 2017-10-26
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.5161
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Non‐invasive prenatal screening (NIPS) has revolutionized the approach to prenatal fetal aneuploidy screening. Many commercial providers now offer analyses for sub‐chromosomal copy number variations (CNVs). Here, we review the use of NIPS in the context of screening for microdeletions and microduplications, issues surrounding the choice of disorders tested for, and the advantages and disadvantages associated with the inclusion of microdeletions to current NIPS. Several studies have claimed benefits; however, we suggest that microdeletions have not demonstrated a low enough false positive rate to be deemed practical or ethically acceptable, especially considering their low positive predictive values. Because a positive NIPS result should be confirmed using diagnostic techniques, and false positive rates are as high as 90% for some microdeletions, diagnostic testing seems preferable when the goal is to maximize the detection of microdeletion or microduplication syndromes. Abstract : What is already known about this topic? Microdeletion testing is included in many commercial NIPS panels. Although individually rare, collectively microdeletions and microduplications are common. What does this study add? More validation studies need to be carried out to properly assess false positive rates, sensitivities, and specificities before implementing NIPS for copy number variations (CNVs) before such can be considered a reasonable routine. NIPS is not a panacea, and patients and physicians need to understand the pros and cons of screening for CNVs. Establishment of an online registry to share information on CNV detection between health care professionals would aid in assessing the accuracy of screening.