Analysis of POC specimens by karyotyping fails in 20-40% of cases. SNP-based CMA is a robust platform, with successful results obtained in >90% of cases. SNP-based CMA can identify aneuploidy, polyploidy, whole-genome homozygosity, segmental genomic imbalances, and maternal cell contamination, thus maximizing sensitivity and decreasing false-negative results. Understanding the etiology of fetal loss enables clarification of recurrence risk and assists in determining appropriate management for future family planning.Genet Med 19 1, 83-89.

What's already known about this topic? Current professional guidelines regarding the use of chromosomal microarray analysis (CMA) versus karyotyping in prenatal diagnosis support CMA over karyotype only when fetal structural abnormalities are present.Examination of the clinical utility of these guidelines, given advances in microarray technology and prenatal screening, is largely unaddressed. What does this study add? This study demonstrates the diagnostic superiority of CMA by SNP microarray compared with karyotyping for prenatal diagnosis, regardless of the clinical indication for testing.

(Abstracted from Genet Med 2017;19(1):83–89) High-resolution chromosomal microarray analysis (CMA) with single-nucleotide polymorphism (SNP)–based arrays is increasingly used for pediatric and prenatal diagnoses as they can simultaneously detect aneuploidies, submicroscopic chromosomal imbalances, triploidy, and regions of allelic homozygosity. Overall, 15% to 20% of clinically recognized pregnancies end in miscarriage, and approximately 1% of couples experience recurrent (at least 2) pregnancy losses.

Yatsenko et al., 1 "Maternal Cell-Free DNA-Based Screening for Fetal Microdeletion and the Importance of Careful Diagnostic Follow-Up, " describing a single prenatal case identified by noninvasive prenatal screening as harboring a deletion at 22q11.2. Upon diagnostic postnatal testing, however, a smaller, noncritical deletion at 22q11.21 was identified. As stated by the authors, noninvasive prenatal screening (also referred to as noninvasive prenatal testing (NIPT)) has emerged as a powerful tool in screening for fetal aneuploidies. Major providers of this technology have expanded their test offerings to include screening for common microdeletion syndromes. Despite high sensitivity and specificity for common trisomies, the recent literature suggests a need for extreme caution in interpreting NIPT because of false-positive rates higher than previously reported when compared with invasive testing as well as concerns regarding the potential for overrepresentation of the positive predictive value for specific aneuploidies. 1,2 We wanted to make an important and substantial addition to the observation by Yatsenko et al. 3 based on our analysis of cases evaluated by NIPT over the past year and subsequently referred to our laboratory for diagnostic testing by chromosomal microarrays and/or karyotype analysis. From our analysis of 287 consecutive samples, NIPT results were available for 278 cases, and diagnostic testing results were available for 277 of these cases. Of the 88 cases with normal NIPT results, diagnostic testing was concordant (normal chromosomal microarrays and/or karyotype) in 79 cases; discordant in 4 (2 cases with gender discordance, 1 case with monosomy X, and 1 case with two large duplications at 1q42.13q44 and 22q11.1q12.3); and concordant but with a structural variation in 5 cases (1 case with inversion 7, 3 cases with a small deletion or duplication, 1 case with a deletion and a duplication). For 162 cases with NIPT suggestive of a whole-chromosome aneuploidy, diagnostic testing was concordant in 69.8% cases, with the highest true-positive rate for trisomy 21 (88.4%) and the lowest for monosomy X (28%). Results were discordant in 23.5% of cases, with the highest discordant rates for trisomy 13 and monosomy X (47 and 72%, respectively). In 11 cases (6.7%), diagnostic testing revealed results that were only partially concordant with NIPT.The most significant and recent observation we wish to highlight in this letter is 25 cases for which NIPT results suggested a microdeletion or a segmental aneuploidy ( Table 1). The falsepositive rates were uniformly high for the common microdeletions tested for by some providers using expanded versions of NIPT. Notably, diagnostic testing revealed false-positive NIPT results in five of seven cases with 22q11.21 deletion, five of six cases with 5p deletion, three of four cases with 1p36 deletion, and one of one case with 4p deletion. Diagnostic testing results SAHOO et al | Expanding NIPT to include microdeletions and segmental aneuploidiesLetter to the editor wer...

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