Chromosomal microarray vs. NIPS: analysis of 5541 low-risk pregnancies

Area of Science:

• Prenatal diagnostics
• Medical genetics
• Reproductive medicine

Background:

• Normal ultrasound findings do not exclude chromosomal abnormalities.
• Chromosomal microarray (CMA) offers higher resolution than traditional karyotyping for detecting submicroscopic genetic variations.
• Evaluating the utility of CMA in low-risk pregnancies is crucial for optimizing prenatal screening strategies.

Purpose of the Study:

• To determine the diagnostic yield of chromosomal microarray (CMA) in pregnancies presenting with normal ultrasound findings.
• To assess the rate of clinically significant CMA findings across different indications in a cohort with normal ultrasounds.

Main Methods:

• Retrospective cohort analysis of pregnancies undergoing CMA testing between 2010 and 2016.
• Inclusion criteria: pregnancies with normal ultrasound examinations.
• Analysis of CMA results to identify clinically significant findings and their detection rates based on indication.

Main Results:

• Clinically significant findings were detected in 1.4% (78/5541) of all CMA analyses.
• Submicroscopic findings, primarily recurrent syndromes, accounted for a significant portion of CMA-only detections.
• The detection rate of clinically significant CMA findings was lower in pregnancies with no specific indication (0.76%) compared to those with advanced maternal age (1.8%) or sonographic soft markers (4.1%).

Conclusions:

• Chromosomal microarray (CMA) identifies clinically significant genetic aberrations in approximately 1 in 71 pregnancies with normal ultrasounds.
• The diagnostic yield, particularly for submicroscopic findings, supports considering CMA as a first-tier test in pregnancies with normal ultrasounds.
• CMA provides valuable genetic information beyond conventional screening methods, even in the absence of ultrasound abnormalities.