Residual risk for clinically significant copy number variants in low-risk pregnancies, following exclusion of noninvasive prenatal screening–detectable findings

Clinical utility of expanded non‐invasive prenatal screening compared with chromosomal microarray analysis in over 8000 pregnancies without major structural anomaly

“…This noticeable residual risk for clinically significant CMA findings, following omission of 5-NIPS residual findings, was also shown in our previous studies 9,10 . In our previous study on pregnancies with normal MSS, the residual risk of a CMA finding following normal NIPS was estimated as 0.60% (19/3182) in women younger than 35 years and as 0.92% (37/4022) in older patients 10 .…”

Chromosomal Microarray Analysis Compared With Noninvasive Prenatal Testing in Pregnancies With Abnormal Maternal Serum Screening

“…This finding probably reflects the a priori increased risk for abnormal chromosomal microarray analysis results in pregnant women with advanced maternal age, 11 and suggests that invasive testing might be performed in all pregnancies of women older than 35 years, regardless of the results of maternal serum screening. As the baseline risk for trisomy 21 at the age of 35 years approximates 1:380, 19,20 the threshold for invasive testing in the authors' country, maternal serum screening can either increase or decrease this risk. It was interesting to note that all abnormal microarray results in the advanced-maternal-age group with known maternal serum screening risk were found only in pregnancies in which the maternal serum screening had increased the baseline risk by maternal age only.…”

“…18,19 Relative risk (RR) for clinically significant chromosomal microarray analysis findings (with 95% CIs) was calculated using comparison with the recently described baseline rate of abnormal chromosomal microarray analysis results in normal pregnancies. 20 This control cohort of 7,235 pregnancies with normal maternal serum screening and ultrasonogram results, undergoing amniocentesis in the same clinical laboratory, included 4,048 chromosomal microarray analysis analyses in pregnant women with advanced maternal age, as well as 3,187 pregnancies of women younger than 35 years (undergoing invasive testing at parental request). In this control group, 87 (1.2%) clinically significant chromosomal microarray analysis findings were noted: 63 (1.56%) in the advanced-maternal-age cohort, including seven cases of trisomy 21, one case of trisomy 18, 18 sex chromosome anomalies, three 22q11.2 microdeletions, and one additional genome-wide NIPT-detectable finding (ie, sized greater than 7 Mb); and 24 (0.75%) in the younger cohort, including two cases of trisomy 21, two sex chromosome anomalies, and three additional genome-wide NIPT-detectable findings.…”

Reclassification of DMD Duplications as Benign: Recommendations for Cautious Interpretation of Variants Identified in Prenatal Screening

“…NIPS is an effective method for detecting aneuploidies, and expanded NIPS panels and fetal fraction amplification within NIPS can detect 1-Mb deletions and 2-Mb duplications [ 24 , 25 ]. Chromosomal copy number variations (CNVs) are frequently detected in fetuses during prenatal screening and can be inherited from a parent who is unaffected, has mild clinical symptoms, or may also occur de novo [ 26 ].…”