Grand Rounds

Is Chromosomal Microarray Analysis Beneficial in the Setting of Isolated Growth Restriction?

BACKGROUND AND PURPOSE:

Whether chromosomal microarray analysis (CMA) is clinically useful in the context of isolated fetal growth restriction (FGR) isn’t well understood
Monier et al. (AJOG, 2021) examined the incremental yield of CMA vs standard karyotype in the detection of genetic abnormalities in fetuses with isolated FGR

Retrospective observational study
Participants
- Singleton fetuses diagnosed with FGR
- No structural ultrasound anomalies
- Invasive genetic testing with both karyotype and CMA
Study design
- Fetal growth restriction was defined as an EFW <10th percentile for gestational age
- CNVs were classified into 5 groups based on ACMG guidelines
  - Pathogenic
  - Likely pathogenic
  - Variant of unknown significance
  - Likely benign
  - Benign
- The primary outcome was calculated as the proportion of fetuses detected with pathogenic and likely pathogenic CNVs among fetuses with normal karyotype
Primary outcome
- Diagnostic yield of CMA compared to karyotype

146 fetuses with FGR had karyotype and CMA
Overall detection rate of genetic anomalies: 7.5% (95% CI, 3.3 to 11.8)
- Pathogenic: 10 CNVs
- Likely pathogenic: 1 CNV
Among the 139 fetuses with normal karyotype
- 5 were detected with pathogenic and likely pathogenic copy number variants in CMA compared to karyotype
- Incremental yield: 3.6% (95% CI, 0.5 to 6.6)
All fetuses detected with pathogenic or likely pathogenic copy number variants resulted in terminations of pregnancy
2.1% of fetuses with normal karyotype were detected with a variant of unknown significance (VUS)
CMA did not detect low level (13%) fetal mosaicism for trisomy 18

Compared to karyotype, testing with CMA improved the detection of genetic anomalies in fetuses with FGR
The authors conclude

CMA provides substantial additional genetic information compared with karyotype and should be performed in case of isolated FGR

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