BACKGROUND AND PURPOSE:

• 20% of congenital heart disease (CHD) detected prenatally is caused by chromosomal anomalies
• ACOG, SMFM and other international bodies recommend or suggest offering microarray analysis in the presence of fetal anomalies detected on ultrasound
• Data is limited on whether there is significant diagnostic yield with microarray vs routine karyotype, including in the setting of prenatal CHD
• Wang et al. (AJOG, 2018) evaluated the clinical utility of chromosomal microarray as the first-tier test for chromosomal abnormalities in fetuses with congenital heart disease (CHD)

METHODS:

• Prospective cohort study (2012-2017)
• Cases of CHD were investigated using SNP microarray
• The detection rates for the following conditions were compared
  • Isolated CHD
  • CHD and additional structural anomalies
  • CHD and intrauterine growth restriction
  • CHD with soft markers (e.g., short long bones, echogenic bowel, thickened nuchal fold)
  • CHD with ventriculomegaly

RESULTS:

• 602 prenatal cases of CHD were included
• Overall diagnostic yield
  • 20.8% if likely pathogenic findings were not included
  • 52.0% of these cases had numerical chromosomal abnormalities
• Detection rate of likely pathogenic copy number variations and VUS were 1.3% and 6.0%, respectively
• The detection rates were significantly increased when compared to isolated CHD
  • Isolated CHD: 14.3%
  • CHD and structural anomalies: 48.9% (P< .0001)
  • IUGR: 50.0% (P= .044)
• The detection rate in CHD with additional structural anomalies group was significantly higher than that in CHD with soft markers group (48.9% vs 19.8%,P< .0001)
• No significant difference was observed in the detection rates between any other group combinations
• The detection rate in fetuses with CHD plus mild ventriculomegaly was significantly higher than in those with other types of soft markers (50.0% vs 15.6%,P< .05)
• Additional yield using microarray vs karyotype
  • Atrioventricular septal defect (AVSD): 0%
  • Conotruncal defect: 16.9%
  • Truncus arteriosus: 44.4%
  • Interrupted aortic arch: 30.8%
  • Double outlet right ventricle: 15.0%
  • Tetralogy of Fallot: 13.6%
• 22q11.2 Deletion/duplication was detected in 20 cases (3.3%)
  • All submicroscopic pathogenic CNVs identified in CHD with facial malformations were 22q11.2 microdeletion

CONCLUSION:

• Chromosomal microarray analysis should be included as a first-tier test for prenatal diagnosis of CHD regardless of type of CHD or whether other ultrasound anomalies are involved
• Consider 22q11.2 deletion syndrome in the case of CHD is accompanies by facial anomalies on prenatal ultrasound

Learn More – Primary Sources:

Prenatal chromosomal microarray analysis in fetuses with congenital heart disease: a prospective cohort study

Related ObG Topics:

The Use of Microarrays in the Prenatal and Postnatal Setting – Current Professional Guidelines

Microarrays and Microdeletions: Key Concepts Summarized

The Chromosome – Structure and Number