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.
Originalsprog | Engelsk |
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Tidsskrift | Ultrasound in Obstetrics & Gynecology |
Vol/bind | 51 |
Udgave nummer | 4 |
Sider (fra-til) | 480-486 |
Antal sider | 7 |
ISSN | 0960-7692 |
DOI | |
Status | Udgivet - apr. 2018 |
Udgivet eksternt | Ja |