Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: A cohort study of 3171 pregnancies: Editorial comment

摘要

The mainstay for prenatal diagnosis of fetuses with abnormal ultrasound is karyotyping. Array comparative genomic hybridization (CGH) has been used as an adjunct to conventional karyotyping for detection of chromosomal anomalies beyond the standard aneuploidy. Previous studies have reported that the detection rate with array CGH for submicro-scopic chromosomal abnormalities is highly variable, ranging from 1.3% to 16%. One major concern for the use of microarray CGH is that of uninterpretable copy number variations (CNVs), which will lead to parental anxiety and potentially unnecessary pregnancy terminations. Prospective data from a large cohort of fetuses who have undergone both karyotyping and CGH analysis are needed to demonstrate the diagnostic benefits of chromosomal array for prenatal identification of chromosomal abnormalities.This cross-sectional study evaluated the clinical value of array CGH as a prenatal screening tool for submicroscopic genomic imbalances. Between 2008 and 2011, 3171 women underwent prenatal array CGH testing and karyotyping at a tertiary referral center in Taiwan. Indications for invasive prenatal diagnosis included advanced maternal age, parental anxiety, abnormal ultrasound, and abnormal karyotype. Of the 3171 fetuses, 2497 samples were screened with 1-Mb resolution bacterial artificial chromosome array-based CGH, and 674 by 60-K oligonucleotide array-based CGH. The primary study outcome measure was CNVs.Array CGH successfully identified 84 fetuses with pathological anomalies, including 37 (1.2%) with numerical chromosome anomalies, 34 (1.1%) with microdeletion or duplications, and 13 (0.4%) with large deletion/duplication. Benign copy number changes were identified in 13 fetuses (0.4%) and variations of unknown clinical significance in 5 fetuses (0.2%). Array CGH identified submicroscopic genomic imbalance in 2 (1.8%) of 17 fetuses with de novo balanced translocations, 3 (50%) of 6 fetuses with supernumerary marker chromosomes, and 33 (17.0%) of 194 fetuses with abnormal prenatal ultrasound findings. Use of array CGH was effective in detecting microdeletions/ duplications in 15 normal fetuses (0.52%) without prenatal risk factors as determined by normal standard karyotyping and prenatal ultrasound.These findings show that prenatal array CGH is effective for screening of submicroscopic genomic imbalance. The technique identifies genetic abnormalities not detected with conventional karyotyping and may be especially useful in fetuses with karyotypic balanced translocation or supernumerary marker chromosomes. It may also be quite useful in patients with anatomic abnormalities on ultrasound, particularly those with a normal karyotype.