High-resolution microarray in the assessment of fetal anomalies detected by ultrasound

The main aim of this study was to determine the feasibility of using high-resolution microarray to assist with prenatal diagnosis of ultrasound-detected fetal abnormality and to describe the frequency of abnormal results in different categories of fetal anomalies.

Prospective cross-sectional study was conducted on women diagnosed with a fetal anomaly (ies) between February 2009 and December 2011 who were offered testing by microarray analysis (Affymetrix 2.7M SNP) and fluorescent in situ hybridisation (FISH) instead of standard karyotyping. Fetal anomalies were categorised according to organ system involvement.

One hundred and eighteen women consented to testing with microarray. Eleven of one hundred eighteen (9.3%) cases had aneuploidy detected by FISH. Of the remaining 107, 23 (21.5%) had an abnormality detected on microarray, only three of which would have been detected using the combination of six-probe FISH and banded karyotype. The maximum expected yield for six-probe FISH and karyotype was thus 14/118 (11.8%), compared to 34/118 (28.8%), P < 0.0001. Of the 23 abnormalities detected with microarray, 10 (43%) were pathogenic, six (26%) were long continuous stretches of homozygosity and seven (30%) were of uncertain significance. The maximum yield was in cases with cardiovascular (100%); multiple (40%); central nervous system (CNS) (25%) and skeletal (9%) abnormalities.

This study has confirmed the feasibility of translation of microarray into clinical practice. 11.8% (14/118) of the cases would have a genetic basis of an abnormality with a FISH and banded karyotype. This figure is approximately tripled to 28.8% (34/118) if we offer FISH and microarray. High yield for imbalances are multiple, cardiovascular, CNS and skeletal abnormalities.