Evaluation of array comparative genomic hybridisation in prenatal diagnosis of fetal anomalies: a multicentre cohort study with cost analysis and assessment of patient, health …

Background Current pathways for testing fetuses at increased risk of a chromosomal anomaly because of an ultrasound anomaly involve karyotyping after rapid aneuploidy exclusion. Chromosomal microarray (CMA) may detect more clinically significant chromosomal imbalances than karyotyping but evidence to guide UK health service providers on whether or not CMA should replace karyotyping is limited. Objectives (1) To compare detection rates of copy number variants (CNVs) and laboratory turnaround times (TATs) by karyotyping and CMA in fetuses with ultrasound anomalies, (2) to calculate test costs and the cost per additional pathogenic CNV detected by CMA relative to karyotyping and (3) to determine what factors influence parents’ and health professionals’ choice and decision-making about CMA. Design A multicentre experimental research cohort study with an additional cost analysis. Setting A total of 20 fetal medicine units and nine cytogenetic laboratories across England and Wales. Participants Women with a fetus undergoing quantitative fluorescent polymerase chain reaction (QF-PCR) and karyotyping for clinical indications with (1) one or more structural anomalies identified on ultrasound or (2) an isolated nuchal translucency (NT) of ≥ 3.5 mm. Interventions Karyotyping and CMA after exclusion of major chromosomal anomalies by QF-PCR. The array design consisted of 8-plex 60,000 60-mer oligonucleotides with a backbone resolution of ≈75 kb. Main outcome measures Rates of abnormal karyotypes and pathogenic CNVs and variants of unknown significance on CMA. Laboratory TATs for karyotyping and CMA …