Chromosomal microarray as primary diagnostic genomic tool for pregnancies at increased risk within a population‐based combined first‐trimester screening program. (4th March 2018)

• Record Type: Journal Article
• Authors: Vogel, I.; Petersen, O. B.; Christensen, R.; Hyett, J.; Lou, S.; Vestergaard, E. M.
• Is Part Of: Ultrasound in obstetrics & gynecology. Volume 51:Number 4(2018)
• Page Start: 480
• Page End: 486
• Publication Date: 2018-03-04
• Subjects: array comparative genomic hybridization -- chromosomal microarray -- genomic imbalance -- pathogenic CNV -- prenatal diagnosis -- risk above 1:300; Ultrasonics in obstetrics -- Periodicals; Generative organs, Female -- Diseases -- Diagnosis -- Periodicals; Diagnosis, Ultrasonic -- Periodicals; Genital Diseases, Female -- ultrasonography -- Periodicals; Ultrasonography, Prenatal -- Periodicals; 618.047543
• DOI: 10.1002/uog.17548
• Languages: English
• ISSNs: 0960-7692

Abstract

ABSTRACT: Objective: To evaluate the performance of high‐resolution chromosomal microarray (CMA) as the standard diagnostic approach for genomic imbalances in pregnancies with increased risk based on combined first‐trimester screening (cFTS). Methods: This was a retrospective study of genomic findings in a cohort of 575 consecutive pregnancies undergoing invasive testing because of a cFTS risk ≥ 1:300 on a publicly funded population‐based screening program in the Central and Northern Regions of Denmark, between September 2015 and September 2016. Women with fetal nuchal translucency thickness ≥ 3.5 mm or opting for non‐invasive prenatal testing (NIPT) were excluded. Comparative genomic hybridization was performed using a 180‐K oligonucleotide array on DNA extracted directly from chorionic villus/amniocentesis samples. Genomic outcomes were reported in relation to cFTS findings. Results: Of the 575 pregnancies that underwent invasive testing, CMA detected 22 (3.8% (95% CI, 2.5–5.7%)) cases of trisomies 21, 18 and 13, 14 (2.4% (95% CI, 1.4–4.0%)) cases of other types of aneuploidy and 15 (2.6% (95% CI, 1.5–4.3%)) cases with a pathogenic or probably pathogenic copy number variant (CNV). Of the 15 CNVs, three were > 10 Mb and would probably have been detected by chromosomal analysis, but the other 12 would most probably not have been detected using conventional cytogenetic techniques; therefore, the overall detection rate of CMA (8.9% (95% CI, 6.8–11.5%)) was significantly higher than that estimated for conventional cytogenetic analysis (6.8% (95% CI, 5.0–9.1%)) ( P = 0.0049). Reducing the cFTS risk threshold for invasive diagnostic testing to 1 in 100 or 1 in 50 would have led, respectively, to 60% or 100% of the pathogenic CNVs being missed. Conclusions: CMA is a valuable diagnostic technique that can identify an increased number of genomic aberrations in pregnancies at increased risk on cFTS. Limiting diagnostic testing to pregnancies with a risk above 1 in 100 or 1 in 50, as proposed in contingent NIPT/invasive testing models, would lead to a significant proportion of pathogenic CNVs being missed at first‐trimester screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.