Clinical utility of chromosomal microarray analysis in prenatal diagnosis of fetuses with ultrasound soft markers: A retrospective single-center comparative study with karyotyping.

OBJECTIVE

Cardiac soft markers are subtle mid-trimester sonographic findings that may indicate an increased risk of chromosomal abnormalities. While conventional karyotyping remains the standard for detecting aneuploidies and balanced rearrangements, chromosomal microarray analysis (CMA) offers higher resolution for submicroscopic copy number variations (CNVs). However, the incremental diagnostic value of CMA in fetuses with cardiac soft markers, particularly in Chinese populations, remains underexplored. This study aimed to compare the diagnostic yield of CMA and karyotyping in fetuses with cardiac soft markers and evaluate the association between marker type and CMA outcomes.

METHODS

We conducted a retrospective analysis of 42 singleton pregnancies (gestational age: 18+3-23+6 weeks) with fetal cardiac soft markers who underwent amniocentesis at Putian First Hospital between June 2022 and December 2023. Both G-banding karyotyping and Affymetrix CytoScan 750K SNP-array CMA were performed. CNVs were classified according to ACMG guidelines. Postnatal follow-up was conducted until September 2024.

RESULTS

CMA identified pathogenic or likely pathogenic (P/LP) copy number variations (CNVs) in 4.8% (2/42) of cases, specifically two 17q12 deletions. Additionally, variants of uncertain significance (VOUS) were found in 19.0% (8/42). In contrast, karyotyping detected chromosomal abnormalities of potential clinical significance in 2.4% (1/42, a de novo translocation t (3;19) (p14;q12)), with the remaining two findings (a common inversion polymorphism and likely maternal cell contamination) considered unlikely to be of clinical relevance to the fetus.

CONCLUSION

CMA detected pathogenic CNVs that were missed by karyotyping, demonstrating its incremental value. However, karyotyping remains essential for identifying balanced chromosomal rearrangements. Our findings support the complementary use of CMA and karyotyping in prenatal diagnosis of fetuses with ≥2 cardiac soft markers, although larger prospective studies are warranted to validate these observations.