Single nucleotide polymorphism array in genetic evaluation of fetal ultrasound abnormalities: a retrospective follow-up study

Fetal ultrasound abnormalities may be complicated by cognitive dysfunction or developmental retardation, and ultrasonography cannot detect these problems; therefore, chromosome detection is required in fetuses with ultrasound abnormalities. To examine the effectiveness of single nucleotide polymorphism (SNP) array in genetic diagnosis of fetal ultrasound abnormalities, the prenatal samples of 805 pregnant women with fetal ultrasound abnormalities were collected for SNP array and karyotyping analysis. A 95.5% percentage of normal karyotypes and 4.5% percentage of abnormal karyotypes were observed, and aneuploidy was detected in 28 fetuses with abnormal karyotypes. SNP array identified 89 positives, including 55 cases (6.8%) with pathogenic copy number variation (CNVs) and 34 (4.2%) with variants of unknown significance (VOUS). In addition to 36 cases showing consistent results with karyotyping, SNP array detected 19 additional cases with pathogenic CNVs, including microdeletion/microduplication syndromes in 18 cases and uniparental disomy in one case. The detection rate of pathogenic CNVs was highest in fetuses with structural abnormalities of multiple systems complicated by non-structural abnormalities (13.7%) and lowest in those with structural abnormalities of a single system (4.2%). Presence of pathogenic CNVs was 12.2% in fetuses with structural abnormalities in the urinary system, followed by in the skeletal system (10.3%), while no pathogenic CNVs were identified in fetuses with structural abnormalities in the head and face, the respiratory system or the digestive system. An 89.6% follow-up rate was seen in the study sample, and 55 fetuses with pathogenic CNVs identified by SNP array were all given induction of labor. Our data demonstrate that SNP array improves the detection of genetics aberrations in fetuses with prenatal ultrasound abnormality relative to karyotyping.