Chromosomal Microarray Analysis Results From Pregnancies With Various Ultrasonographic Anomalies

Area of Science:

• Prenatal diagnostics
• Genetics
• Fetal medicine

Background:

• Ultrasonographic anomalies are common indications for prenatal genetic testing.
• Chromosomal microarray analysis (CMA) offers higher resolution than conventional karyotyping for detecting copy number variants (CNVs).

Purpose of the Study:

• To evaluate CMA results in pregnancies with various ultrasonographic anomalies.
• To characterize CNVs in fetuses with diverse phenotypes and compare their prevalence with low-risk pregnancies.

Main Methods:

• Retrospective analysis of nationwide amniocentesis samples (n=5,750) performed for fetal ultrasonographic anomalies (January 2013–September 2017).
• Comparison of abnormal CMA findings rates between different fetal phenotypes and a control group (n=15,225) with normal ultrasonographic findings.

Main Results:

• Clinically significant CMA aberrations were found in 4.7% of pregnancies with fetal anomalies.
• CNVs, including 22q11.21 deletions (0.4%) and gains (0.2%), were up to 20-fold more prevalent than in low-risk pregnancies.
• Specific CNVs were associated with particular phenotypes, such as 22q11.21 microdeletions with cardiovascular defects.

Conclusions:

• CMA identifies clinically significant genetic aberrations in nearly 5% of fetuses with ultrasonographic anomalies.
• The diagnostic yield of CMA is approximately double that of karyotyping for these pregnancies.
• CMA is a valuable tool for characterizing genetic causes of diverse fetal phenotypes.