Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies

Objective To evaluate the clinical value of prenatal array comparative genomic hybridisation (CGH) in screening for submicroscopic genomic imbalances. Design Cross-sectional study. Setting Tertiary referral centre. Population From June 2008 to February 2011, 3171 fetuses underwent prenatal array CGH testing and karyotyping at the National Taiwan University Hospital. Indications for invasive prenatal diagnosis included abnormal karyotype, abnormal ultrasound, advanced maternal age and parental anxiety. Methods In all, 2497 fetuses were screened with 1-Mb resolution bacterial artificial chromosome array-based CGH, and 674 fetuses with 60-K oligonucleotide array-based CGH. Multiplex ligationdependent probe amplification, fluorescence in situ hybridization, or 105-K oligonucleotide array CGH provided further confirmation. Main outcome measure Copy number variations identified by array CGH. Results Array CGH detected numerical chromosome anomalies in 37 (1.2%) fetuses, microdeletion/duplication in 34 (1.1%) fetuses, large deletion/duplication in 13 (0.4%) fetuses, benign copy number changes in 13 (0.4%) fetuses and variation of unknown clinical significance in five (0.2%) fetuses. Array CGH was effective in identifying submicroscopic genomic imbalance in fetuses with de novo balance translocations (2/17, 1.8%), supernumerary marker chromosomes (3/6, 50%), and abnormal prenatal ultrasound findings (33/194, 17.0%). Array CGH detected microdeletions/duplications in 12 fetuses with normal karyotype. Conclusion Prenatal array CGH is effective in screening for submicroscopic genomic imbalance. Array CGH may add 8.2% to the diagnostic field, compared with conventional karyotyping, for fetuses with abnormal ultrasound results, and is particularly useful in fetuses with karyotypic balanced translocation or marker chromosomes. There is a 0.52% baseline risk of submicroscopic genomic imbalance, even in women with an uneventful prenatal examination.