BACKGROUND AND PURPOSE:

• Current professional guidelines recommend that chromosomal microarray be offered in the setting of a fetal structural abnormality
• Sagi-Dain et al. (Obstetrics & Gynecology, 2018) assessed the chromosomal microarray analysis results in various ultrasonographic anomalies and characterized the copy number variants (CNV) in diverse fetal phenotypes

METHODS:

• Retrospective cohort study
• Chromosomal microarray analyses (amniocenteses) performed for the following fetal indications
  • Structural defects
  • Fetal growth restriction
  • Polyhydramnios
• Rate of abnormal chromosomal microarray findings was compared based on phenotypes and compared to a historical control population (normal prenatal ultrasound)

RESULTS:

• 5,750 pregnancies
  • 272 with chromosomal anomalies
  • Routine karyotype-detectable: 2%
  • Submicroscopic (only on microarray) :2.7%
  • 107 different aberrations | 157 submicroscopic abnormal variants
• Most commonly detected copy number variants
  • 22q11.21 deletions: 0.4% (14.6% of CNVs)
  • 22q11.21 duplication: 0.2% (7.6% of CNVs)
• CNVs were up to 20-fold more prevalent in fetuses with ultrasound anomalies compared to low-risk pregnancies
• Some variants were associated with specific phenotypes
  • 22q11.21 microdeletions: Cardiovascular
  • 17q12 microdeletions: Genitourinary defects
  • 16p11.2 duplications: Gastrointestinal defects
• The 22q11.22 deletion had the highest increased odds ratio in fetuses with anomalies compared with pregnancies with normal ultrasonographic findings
  • OR: 20.4 (95% CI 6.1–67.8)

CONCLUSION:

• The results of this study demonstrated lower rates of CNVs in anomalous fetuses compared to previous studies (4.7% vs 16%), which may be due to
  • First trimester screening and earlier aneuploidy detection
  • Use of chromosomal microarray for all structural anomalies, not just severe findings
  • Inclusion of growth restriction and polyhydramnios
• The authors note that the 6 most common variants only made up 42.7% of the 107 different CNVs and therefore testing for predefined CNVs/syndromes may not be effective
• The authors also state that these data bring in to question

…the advisability of using noninvasive prenatal screening aimed at specific variants in pregnancies with structural anomalies

Learn More – Primary Sources:

Chromosomal Microarray Analysis Results From Pregnancies With Various Ultrasonographic Anomalies

Related ObG Topics:

Microarrays and Microdeletions: Key Technical and Genetic Concepts Summarized

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

Chromosomal Microarray Analysis for Congenital Heart Disease – Clinically Relevant Findings