Use of array comparative genomic hybridization for prenatal diagnosis of fetuses with sonographic anomalies and normal metaphase karyotype

OBJECTIVE: To prospectively study the addition of array comparative genomic hybridization (CGH) to the prenatal evaluation of fetal structural anomalies. METHODS: Pregnant women carrying fetuses with a major structural abnormality were recruited at the time of invasive procedure for chromosome analysis. Only women whose fetuses had a normal karyotype (n = 50) were subsequently evaluated by array CGH using one of two arrays (1887 clones covering 622 loci or subsequently 4685 clones covering 1500 loci). RESULTS: The mean gestational age of the fetuses was 24.5 weeks (range 11-38 weeks). The most prevalent anomalies were cardiac, central nervous system, skeletal, and urogenital. The median turnaround time for culturing and array CGH diagnosis was 18 days (range 2-72). Four of 50 fetuses had abnormal array results. One (2%) was clinically significant and three (6%) were inherited or benign variants. CONCLUSIONS: Array CGH studies in fetuses with sonographic anomalies and normal metaphase karyotype detected clinically significant copy number alterations in 1 of 50 cases. This percentage (2%) is consistent with prior prenatal reports. Further studies are warranted to more precisely identify which fetal anomalies are associated with copy number alterations of clinical significance.