The use of chromosome microarray analysis as a first-line test in pregnancies with a priori low risk for detection of submicroscopic chromosomal abnormalities

Francesco Fiorentino1*, Stefania Napoletano1, Fiorina Caiazzo1, Mariateresa Sessa1, Sara Bono1, Letizia Spizzichino1, Silvia Michiorri1, Anthony Gordon2, Andrea Nuccitelli1, Giuseppe Rizzo1, Marina Baldi1.


1 GENOMA”- Molecular Genetics Laboratory, Via Po, 102 00198 Rome – Italy

2 Bluegnome Ltd, Cambridge CB22 5LD, UK

Objectives: In this study we aimed to explore the usefulness of chromosome microarray analysis (CMA) in groups of pregnancies with a priori low risk for detection of submicroscopic chromosome abnormalities, usually not considered an indication for testing, in order the assess if CMA improves the prenatal detection rate of chromosomal aberrations.

Method: A total of 2800 prenatal samples were processed in parallel using both CMA and conventional karyotyping. The indications for prenatal testing included: advanced maternal age (AMA), abnormal results of maternal serum screening tests (MSS), abnormal ultrasound findings (AUS), known abnormal fetal karyotype (AFK), parental anxiety (PA), family history of a genetic condition (FIS), cell culture failure (CCF).

Results: the use of CMA resulted in an increased detection rate regardless of the indication for analysis. This was evident in high-risk groups (AUS-AFK), in which the percentage of detection was 6.1%(7/114), and also in low risk groups, such as AMA (7/1033, 0.7%) and PA (10/1569, 0.6%). A total of 24(0.9%) fetal conditions would have remained undiagnosed if only a standard karyotype had been performed. Importantly, 17(0.6%) of such findings would have otherwise been overlooked offering CMA to high risk pregnancies only.

Conclusions: The results of this study demonstrate that more widespread testing by CMA in fetuses would result in a higher detection of chromosome abnormalities prenatally, also in low risk pregnancies. Our findings provide substantial evidence for the utility of using CMA as a first-line diagnostic test to all pregnant women undergoing invasive prenatal testing, regardless of risk factors.