OC21.04: Chromosomal microarray as a primary diagnostic genomic tool for pregnancies defined as being at increased risk within a population‐based combined first trimester screening program

Abstract

Objective To evaluate the impact of using high-resolution chromosomal microarray (CMA) as the standard diagnostic approach to examine for genomic imbalances in pregnancies with increased risk (≥1 in 300) defined through combined first trimester screening (cFTS). Methods A cohort of 575 consecutive pregnancies that had cFTS risk ≥1:300 through a publicly funded population based screening program in the Central and Northern Regions of Denmark between September 2015 and September 2016. Women with an NT ≥3.5 mm or opting for NIPT were excluded. Comparative genomic hybridization was performed using a 180 K oligonucleotide array on DNA extracted directly from samples. Genomic outcomes are reported in relation to cFTS findings. Results 22 cases (22/575, 3.8%; 95% CI: 2.5-5.7%) of trisomy 21, 18 and 13 were detected. A further 14 cases (14/575, 2.4%; 95% CI: 1.4-4.0%) of other types of aneuploidy were detected as well as 15 (15/575, 2.6%: 95% CI: 1.5-4.3%) cases with a pathogenic or likely pathogenic copy number variant (CNV). 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. Conclusion CMA is a valuable diagnostic technique that can identify an increased number of genomic aberrations in pregnancies at increased risk after cFTS. Limiting diagnostic testing to pregnancies with a risk above 1:100 or 1:50, as proposed in contingent NIPT/invasive testing models, will lead to a significant proportion of pathogenic CNVs being missed at first trimester screening.