A Retrospective Analysis of 10-Year Data Assessed the Diagnostic Accuracy and Efficacy of Cytogenomic Abnormalities in Current Prenatal and Pediatric Settings

Abstract

Background: Array comparative genomic hybridization (aCGH), karyotyping and fluorescence in situ hybridization (FISH) analyses have been used in a clinical cytogenetic laboratory. A systematic analysis on diagnostic findings of cytogenomic abnormalities in current prenatal and pediatric settings provides approaches for future improvement.Methods: A retrospective analysis was performed on abnormal findings by aCGH, karyotyping, and FISH from 3,608 prenatal cases and 4,509 pediatric cases during 2008–2017. The diagnostic accuracy was evaluated by comparing the abnormality detection rate (ADR) and the relative frequency (RF) of different types of cytogenomic abnormalities between prenatal and pediatric cases. A linear regression correlation between known prevalence and ADR of genomic disorders was used to extrapolate the prevalence of other genomic disorders. The diagnostic efficacy was estimated as percentage of detected abnormal cases by expected abnormal cases from served population.Results: The composite ADR for numerical chromosome abnormalities, structural chromosome abnormalities, recurrent genomic disorders, and sporadic pathogenic copy number variants (pCNVs) in prenatal cases were 13.03%, 1.77%, 1.69%, and 0.9%, respectively, and were 5.13%, 2.84%, 7.08%, and 2.69% in pediatric cases, respectively. The chromosomal abnormalities detected in prenatal cases (14.80%) were significantly higher than that of pediatric cases (7.97%) (p < 0.05), while the pCNVs detected in prenatal cases (2.59%) were significantly lower than that of pediatric cases (9.77%) (p < 0.05). The prevalence of recurrent genomic disorders and total pCNVs was estimated to be 1/396 and 1/291, respectively. Approximately, 29% and 35% of cytogenomic abnormalities expected from the population served were detected in current prenatal and pediatric diagnostic practice, respectively.Conclusion: For chromosomal abnormalities, effective detection of Down syndrome (DS) and Turner syndrome (TS) and under detection of sex chromosome numerical abnormalities in both prenatal and pediatric cases were noted. For pCNVs, under detection of pCNVs in prenatal cases and effective detection of DiGeorge syndrome (DGS) and variable efficacy in detecting other pCNVs in pediatric cases were noted. Extend aCGH analysis to more prenatal cases with fetal ultrasonographic anomalies, enhanced non-invasive prenatal (NIPT) testing screening for syndromic genomic disorders, and better clinical indications for pCNVs are approaches that could improve diagnostic yield of cytogenomic abnormalities.

Clinical Utility of SNP Array Analysis in Prenatal Diagnosis: A Cohort Study of 5000 Pregnancies

“…The detection rate of abnormalities by SNP-array was 12.3%, including 4.1% of cases with numerical chromosome anomalies, 0.4% with LOH and 7.8% with CNV ( Table 2 and Figure 1A ). And the detection rate of clinically significant CNVs (i.e., CNVs classified as P or LP) by SNP-array was 2.6% ( Table 2 ), which is similar to a previous systematic review that overall 295/12362 (2.4%) have CNVs with associated clinical significance ( Callaway et al, 2013 ) and a recent retrospective analysis of 10-year data reported that the abnormality detection rate of pathogenic CNVs by aCGH is 2.59% for prenatal cases ( Chai et al, 2019 ). Moreover, the 5000 samples were categorized into five groups according to the indications for invasive prenatal testing: anomaly on ultrasonography, advanced maternal age, abnormal result on maternal serum screening, abnormal NIPT results and other indications.…”

“…that the abnormality detection rate of pathogenic CNVs by aCGH is 2.59% for prenatal cases (Chai et al, 2019). Moreover, the 5000 samples were categorized into five groups according to the indications for invasive prenatal testing: anomaly on ultrasonography, advanced maternal age, abnormal result on maternal serum screening, abnormal NIPT results and other indications.…”

Cytogenomic Abnormalities in 19 Cases of Salivary Gland Tumors of Parotid Gland Origin

“…aCGH analysis has been used extensively for prenatal and postnatal detection of constitutional copy number variants and showed significantly improved diagnostic efficacy and accuracy [ 19 ]. However, the application of aCGH to detect somatic CNAs in various cancers has been adapted slowly due to the difficulty in dissecting the clonal heterogeneity from CNAs and the deficiency of supporting databases to interpret abnormal findings [ 16 , 17 ].…”

Prenatal diagnosis and pregnancy determination of sex chromosome aneuploidy screened by non-invasive prenatal testing from 52,453 unselected singleton pregnancies: a retrospective analysis of 4-year experience

“…We found out the higher rate of prenatal diagnosis, the change of indications prior to NIPT, the declining trend of termination rate as well as PPV for each SCA by NIPT, However, the limitation of this study is that can not follow-up all false-positive cases, the existence of CPM can not be ruled out. Most of SCA cases can not be diagnosed until childbearing age, and some of them can not be diagnosed throughout lifetimes [32]. Therefore, the sensitivity, false-positive rate and falsenegative rate of NIPT screening for SCA can not be accurately calculated.…”