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Grand Rounds

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

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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

METHODS:

  • 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

RESULTS:

  • 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

CONCLUSION:

  • 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

Learn More – Primary Sources:

Should prenatal chromosomal microarray analysis be offered for isolated fetal growth restriction? A French multicenter study

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Related ObG Topics:

Chromosomal Microarray Analysis for Congenital Heart Disease – Clinically Relevant Findings
Can NT Values be Used as an Indication for Prenatal Microarray Analysis?
Chromosomal Microarrays and Abnormal Prenatal Ultrasound Findings
Can Whole-Exome Sequencing Help Diagnose Otherwise Unexplained Fetal Structural Anomalies?

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