Performance of Chromosomal Microarray Analysis for Detection of Copy Number Variations in Fetal Echogenic Bowel

Abstract

Background Fetal echogenic bowel (FEB) is associated with an increased risk of poor pregnant outcomes; however, karyotyping fails to detect copy number variations (CNVs) in FEB. This study aimed to evaluate the performance of chromosomal microarray analysis (CMA) for detection of FEB. Methods The medical records of 147 pregnant women with FEB recruited during December 2015 to December 2018 were retrospectively reviewed, and prenatal samples were collected for karyotyping and CMA. The detection of chromosomal abnormality was compared between karyotyping and CMA. Results Karyotyping identified eight cases with abnormal karyotypes (5.44% prevalence), including four fetuses with pathogenic aneuploidy, three with chromosome polymorphism and one with balanced chromosome translocation. CMA identified 13 abnormal CNVs (8.84% prevalence), including 4 fetuses with pathogenic aneuploidy as detected by karyotyping and 9 additional CNVs with normal karyotypes; however, CMA failed to detect chromosome polymorphism and balanced chromosome translocation. In fetuses with isolated FEB, no cases presented pathogenic findings and CMA detected two cases with variants of uncertain significance (VOUS). In cases presenting FEB along with other ultrasound abnormalities, CMA detected three cases with pathogenic CNVs and four cases with VOUS in addition to four cases with aneuploidy. There was no significant difference in the detection of abnormal CNVs between the fetuses with echogenic bowel alone and along with other ultrasound abnormalities (10% vs 8.67%, P > 0.05). Except 9 fetuses lost to the follow-up, the other 138 fetuses with echogenic bowel were successfully followed up. Pregnancy was terminated in 5 fetuses with chromosomal abnormality, 2 with pathogenic CNVs and 1 with VOUS, and other 16 with normal karyotypes and CMA findings but showing ultrasound abnormalities or multiple malformations. Conclusion Isolated FEB is associated with a good prognosis, and a satisfactory pregnant outcome is expected for fetuses with echogenic bowel that are negative for chromosomal anomalies and other severe structure abnormalities. CMA shows an important value in the genetic diagnosis of FEB. As a supplement to karyotyping, CMA may improve the accuracy of prenatal diagnosis of fetal intestinal malformations in pregnant women with FEB.

Hyperechogenic fetal bowel: Current evidence‐based prenatal diagnosis and management

“…27 Among the aneuploidies, hyperechogenic bowel could be related to trisomy 13, trisomy 18, monosomy X, Klinefelter's syndrome, chromosomal mosaicism trisomy, but trisomy 21 is the most common. [28][29][30][31][32] Literature data about chromosomal microarray analysis (CMA) anomalies are contrasting: Singer et al 33 34 In conclusion, the importance of CMA for prenatal diagnosis in fetal hyperechogenic bowel is still debated, and its use it is not mandatory.…”

“…Of these nine fetuses, in six cases CMA identified variants of uncertain significance (VOUS), and in the other cases pathological CNVs were diagnosed, related to the development of neurological and mental disorders and Hirschsprung's disease. The use of CMA in addition to karyotype plays an important role in the improvement of genetic prenatal diagnosis, although CMA could often find VOUS, but anyway both VOUS and pathological CNVs could present several manifestations among family members, ranging from completely normal phenotypes to full‐blown disease 34 …”

The Sonographic Features of Malformation in Fetal Echogenic Bowel and Its Relationship With Chromosome Abnormalities

“…However, the results of the studies evaluating the significance of FEB were contradictory. [9][10][11] Several studies have suggested that FEB seemed to be a benign variant and the association between isolated FEB and fetal infection was uncommon. 9,12 However, most of those studies were carried out in isolated FEB, and the risk factors for poor pregnancy outcomes were not evaluated.…”

“…[9][10][11] Several studies have suggested that FEB seemed to be a benign variant and the association between isolated FEB and fetal infection was uncommon. 9,12 However, most of those studies were carried out in isolated FEB, and the risk factors for poor pregnancy outcomes were not evaluated. Risk assessment of FEB is a prerequisite to carry an appropriate course of management.…”

“…However, the results of the studies evaluating the significance of FEB were contradictory 9–11 . Several studies have suggested that FEB seemed to be a benign variant and the association between isolated FEB and fetal infection was uncommon 9,12 .…”