The role of chromosomal microarray analysis among fetuses with normal karyotype and single system anomaly or nonspecific sonographic findings.

INTRODUCTION Chromosomal microarray analysis is recommended as the first-tier test for the evaluation of fetuses with structural anomalies. This study aims to investigate the incremental diagnostic yield of chromosomal microarray over conventional karyotyping analysis in fetuses with anomalies restricted to one anatomical system and those with nonspecific anomalies detected by sonography. MATERIAL AND METHODS This is a retrospective cohort analysis of 749 fetuses undergoing prenatal diagnosis for abnormal ultrasound findings isolated to one anatomical system and normal karyotype, utilizing chromosomal microarray. Overall, 495 (66%) fetuses had anomalies confined to one anatomical system and 254 (34%) had other nonspecific anomalies including increased nuchal translucency (≥3.5mm), cystic hygroma, intra-uterine growth restriction, and hydrops fetalis. RESULTS Fetuses with ultrasound anomalies restricted to one anatomical system had 3.0% risk of carrying a pathogenic copy number variants, this risk varied depending on the anatomical system affected. Fetuses with confined anomalies of the cardiac system had the highest diagnostic yield of at 4.6% and none in the urogenital system. Fetuses with nonspecific ultrasound anomalies had the highest diagnostic yield in fetuses with intrauterine growth restriction at 5.9%. Overall, fetuses with a nonspecific ultrasound anomaly were affected with pathogenic copy number variants in 1.6% in the cases. CONCLUSIONS The diagnostic yield of chromosomal microarray in fetuses with normal karyotype and ultrasound abnormality defect confined to a single anatomical system was highest if it involved cardiac defects or intrauterine growth restriction. This diagnostic yield ranges from 0-4.6% depending on the anatomical system involved. Chromosomal microarray has considerable diagnostic value in these pregnancies.