Chromosomal Microarray versus Karyotyping for Prenatal Diagnosis

Abstract

Background Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. Methods Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray. Results We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down’s syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results. Conclusions In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.)

ACOG and SMFM guidelines for prenatal diagnosis: Is karyotyping really sufficient?

“…Our data show that at least 4.7% of patients with 1 or more fetal structural abnormalities have a clinically significant microarray abnormality that would have been missed by karyotype analysis, similar to previous reports 3, 5, 6, 7. Additionally, at least 2.5% of patients whose indication did not include a structural fetal abnormality had a CSCA detected by CMA that would have been missed by karyotyping alone.…”

“…Additionally, at least 2.5% of patients whose indication did not include a structural fetal abnormality had a CSCA detected by CMA that would have been missed by karyotyping alone. It may be worth noting that the above data do reflect an increase in detection over previously reported and comparable data (a 47.1% increase compared with previous estimates of 1.7%) 3. Bornstein et al recently reported the prevalence of pathogenic CNVs in 1980 high‐risk versus low‐risk patients who had undergone prenatal diagnosis by CMA.…”

“…Wapner et al3 reported a VOUS rate of 3.4% in their landmark study comparing CMA by aCGH to karyotyping. As we have learned more about incompletely penetrant CNVs, the VOUS category has broadened.…”

Balanced reciprocal translocation at amniocentesis: cytogenetic detection and implications for genetic counseling

“…It is at least as good at identifying aneuploidies and unbalanced rearrangements as karyotyping. However, it is not able to identify balanced translocations or triploidies (Wapner et al, 2012). Instead, it can detect small microdeletions/microduplications (copy number variations) with unknown functional roles and difficult genotype/phenotype correlations.…”

“…These technologies are, however, limited to detecting the most common aneuploidies such as trisomies 13, 18, and 21, and do not detect balanced translocations (Wapner et al, 2012;Novelli et al, 2013;Konialis and Pangalos, 2015).…”