Prenatal diagnosis of chromosomal aberrations by chromosomal microarray analysis in foetuses with ventriculomegaly

Abstract

Ventriculomegaly is considered to be linked to abnormal neurodevelopment outcome. The aim of this retrospective study was to investigate the current applications of chromosomal microarray analysis (CMA) in foetuses with ventriculomegaly. A total of 548 foetuses with ventriculomegaly detected by prenatal ultrasound underwent single nucleotide polymorphism (SNP) array testing and were subjected to long-term follow-up. The overall prevalence of chromosomal aberrations was 7.30% (40/548), including 4.20% (23/548) with pathogenic/likely pathogenic copy number variants. The incidence of chromosomal aberrations was significantly higher in foetuses with bilateral ventriculomegaly than in those with unilateral ventriculomegaly (10.56% vs. 5.71%, P = 0.040), in foetuses with non-isolated ventriculomegaly than in those with isolated ventriculomegaly (12.99% vs. 2.38%, P < 0.0001), and in foetuses with severe ventriculomegaly than in those with mild-to-moderate ventriculomegaly (23.08% vs. 6.51%, P = 0.005). The outcome in foetuses with mild ventriculomegaly was significantly better than in those with moderate ventriculomegaly (95.60% vs. 84.00%, P = 0.003). Thus, CMA should be regarded as the first-tier test for prenatal diagnosis of foetal ventriculomegaly, especially in foetuses with bilateral or non-isolated ventriculomegaly. The outcome of foetuses with mild ventriculomegaly is favourable; however, there is an increased risk of neurodevelopmental disabilities in foetuses with moderate ventriculomegaly.

Prenatal diagnosis and pregnancy outcomes in fetuses with ventriculomegaly

“…With the development of molecular genetic technology, CMA has been gradually applied to detect these chromosomal submicroscopic imbalances due to higher resolution. For our VM cases, the detection rate of chromosomal abnormality using CMA was 16.5%, slightly lower than some studies reporting 17.9–20.6% ( 2 , 17 ) and higher than other studies reporting 6.2–16.3% ( 3 , 10 , 11 , 18 – 20 ). It has been reported that CMA could yield an additional detection rate as a first-tier diagnostic tool in VM, with an incremental yield ranging from 5 to 26% ( 1 , 8 ).…”

“…Chang et al ( 2 ) reported a 12.1% rate of chromosomal abnormalities in 281 fetuses with VM ( 2 ). Among the abnormal karyotypes in fetuses with VM, trisomy 21 was found to be the most common chromosomal aneuploidy ( 2 , 3 , 10 , 11 ), which was also observed in our VM cases. As known, chromosomal CNVs smaller than 5 Mb could hardly be identified by karyotyping.…”

Potentials and challenges of chromosomal microarray analysis in prenatal diagnosis

“…When assessing the relationship between ultrasonographic soft markers and chromosomal aberrations, it was demonstrated that the overall prevalence of chromosomal aberrations in fetuses with soft markers was 4.3% (107/2,466), comprising 40.2% with numerical chromosomal abnormalities, 48.6% with P CNVs, and 11.2% with LP CNVs ( Hu et al, 2021 ). Various ultrasound results of the fetus, such as ventriculomegaly, short femur, and thickened nuchal translucency, have been evaluated separately, and the advantages of CMA in prenatal diagnosis have been established ( Zhang et al, 2019 ; Wang J et al, 2020 ; Li et al, 2021 ).…”

Counseling in fetal medicine: update on mild and moderate fetal ventriculomegaly

“…In addition to abnormal karyotype, other anomalies are detected on CMA in up to 10–15% of cases 9 . The laterality of the lesion (unilateral vs bilateral), the severity of VM (mild and moderate vs severe) and the presence of additional structural anomalies have been described recently as the main predictors of chromosomal aberrations on CMA 20,21 . Thus, due to the higher rate of fetal aneuploidy and copy‐number variants (CNVs) associated with VM, amniocentesis with CMA should always be offered during the diagnostic workup of fetal VM 9 .…”