Prenatal array comparative genomic hybridization in a well-defined cohort of high-risk pregnancies. A 3-year implementation results in a public tertiary academic referral hospital

Objective To find out whether the diagnostic yield of prenatal array comparative genomic hybridization (aCGH) can be improved by targeting preselected high-risk pregnancies. Method All the in-house arrays ordered by the Fetomaternal Medical Center from February 2016 until December 2018 were retrospectively analyzed. The indications for array analysis included fetal structural abnormalities, increased nuchal translucency >= 3.5 mm and a chromosomal abnormality in a parent or a sibling. Common aneuploidies were excluded. Results Diagnostic yield was 15.1% in the entire patient cohort and as high as 20% in fetuses with multiple structural anomalies. The diagnostic yield was lowest in the group with isolated growth retardation. A total of 76 copy number variants (CNVs) were reported from a total of 65 samples, including 16 CNVs associated with a well-described microdeletion/microduplication syndrome, six autosomal trisomies in mosaic form, and three pathogenic single-gene deletions with dominant inheritance and 12 CNVs known to be risk factors for eg developmental delay. Conclusion The diagnostic yield of aCGH was higher than what has previously been reported in less defined patient cohorts. However, the number of CNVs with unclear correlation to the fetal ultrasound findings was still relatively high. The importance of adequate pre- and posttest counseling must therefore be emphasized.

Automated summary

This study retrospectively analyzed the diagnostic yield of prenatal array comparative genomic hybridization (aCGH) in high-risk pregnancies, finding an overall diagnostic yield of 15.1% in the patient cohort, with the potential for higher yields in fetuses with multiple structural anomalies. However, a relatively high number of copy number variants (CNVs) with unclear correlation to fetal ultrasound findings was observed, highlighting the importance of adequate pre- and posttest counseling.