TY - JOUR
T1 - Residual risk for clinically significant copy number variants in low-risk pregnancies, following exclusion of noninvasive prenatal screening–detectable findings
AU - Maya, Idit
AU - Salzer Sheelo, Liat
AU - Brabbing-Goldstein, Dana
AU - Matar, Reut
AU - Kahana, Sarit
AU - Agmon-Fishman, Ifaat
AU - Klein, Cochava
AU - Gurevitch, Merav
AU - Basel-Salmon, Lina
AU - Sagi-Dain, Lena
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/4
Y1 - 2022/4
N2 - Background: Chromosomal microarray analysis detects a clinically significant amount of copy number variants in approximately 1% of low-risk pregnancies. As the constantly growing use of noninvasive prenatal screening has facilitated the detection of chromosomal aberrations, defining the rate of abnormal chromosomal microarray analysis findings following normal noninvasive prenatal screening is of importance for making informed decisions regarding prenatal testing and screening options. Objective: To calculate the residual risk for clinically significant copy number variants following theoretically normal noninvasive prenatal screening. Study Design: The chromosomal microarray results of all pregnancies undergoing amniocentesis between the years 2013 and 2021 in a large hospital-based laboratory were collected. Pregnancies with sonographic anomalies, abnormal maternal serum screening, or multiple fetuses were excluded. Clinically significant (pathogenic and likely pathogenic) copy number variants were divided into the following: 3-noninvasive prenatal screening–detectable (trisomies 13, 18, and 21), 5- noninvasive prenatal screening–detectable (including sex chromosome aberrations), 5-noninvasive prenatal screening and common microdeletion-detectable (including 1p36.3–1p36.2, 4p16.3–4p16.2, 5p15.3–5p15.1, 15q11.2–15q13.1, and 22q11.2 deletions), and genome-wide noninvasive prenatal screening–detectable (including variants >7 Mb). The theoretical residual risk for clinically significant copy number variants was calculated following the exclusion of noninvasive prenatal screening–detectable findings. Results: Of the 7235 pregnancies, clinically significant copy number variants were demonstrated in 87 cases (1.2%). The residual risk following theoretically normal noninvasive prenatal screening was 1.07% (1/94) for 3-noninvasive prenatal screening, 0.78% (1/129) for 5- noninvasive prenatal screening, 0.74% (1/136) for 5- noninvasive prenatal screening including common microdeletions, and 0.68% (1/147) for genome-wide noninvasive prenatal screening. In the subgroup of 4048 pregnancies with advanced maternal age, the residual risk for clinically significant copy number variants following theoretically normal noninvasive prenatal screening ranged from 1.36% (1/73) for 3- noninvasive prenatal screening to 0.82% (1/122) for genome-wide noninvasive prenatal screening. In 3187 pregnancies of women <35 years, this residual risk ranged from 0.69% (1/145) for 3- noninvasive prenatal screening to 0.5% (1/199) for genome-wide noninvasive prenatal screening. Conclusion: The residual risk of clinically significant copy number variants in pregnancies without structural sonographic anomalies is appreciable and depends on the noninvasive prenatal screening extent and maternal age. This knowledge is important for the patients, obstetricians, and genetic counselors to facilitate informed decisions regarding prenatal testing and screening options.
AB - Background: Chromosomal microarray analysis detects a clinically significant amount of copy number variants in approximately 1% of low-risk pregnancies. As the constantly growing use of noninvasive prenatal screening has facilitated the detection of chromosomal aberrations, defining the rate of abnormal chromosomal microarray analysis findings following normal noninvasive prenatal screening is of importance for making informed decisions regarding prenatal testing and screening options. Objective: To calculate the residual risk for clinically significant copy number variants following theoretically normal noninvasive prenatal screening. Study Design: The chromosomal microarray results of all pregnancies undergoing amniocentesis between the years 2013 and 2021 in a large hospital-based laboratory were collected. Pregnancies with sonographic anomalies, abnormal maternal serum screening, or multiple fetuses were excluded. Clinically significant (pathogenic and likely pathogenic) copy number variants were divided into the following: 3-noninvasive prenatal screening–detectable (trisomies 13, 18, and 21), 5- noninvasive prenatal screening–detectable (including sex chromosome aberrations), 5-noninvasive prenatal screening and common microdeletion-detectable (including 1p36.3–1p36.2, 4p16.3–4p16.2, 5p15.3–5p15.1, 15q11.2–15q13.1, and 22q11.2 deletions), and genome-wide noninvasive prenatal screening–detectable (including variants >7 Mb). The theoretical residual risk for clinically significant copy number variants was calculated following the exclusion of noninvasive prenatal screening–detectable findings. Results: Of the 7235 pregnancies, clinically significant copy number variants were demonstrated in 87 cases (1.2%). The residual risk following theoretically normal noninvasive prenatal screening was 1.07% (1/94) for 3-noninvasive prenatal screening, 0.78% (1/129) for 5- noninvasive prenatal screening, 0.74% (1/136) for 5- noninvasive prenatal screening including common microdeletions, and 0.68% (1/147) for genome-wide noninvasive prenatal screening. In the subgroup of 4048 pregnancies with advanced maternal age, the residual risk for clinically significant copy number variants following theoretically normal noninvasive prenatal screening ranged from 1.36% (1/73) for 3- noninvasive prenatal screening to 0.82% (1/122) for genome-wide noninvasive prenatal screening. In 3187 pregnancies of women <35 years, this residual risk ranged from 0.69% (1/145) for 3- noninvasive prenatal screening to 0.5% (1/199) for genome-wide noninvasive prenatal screening. Conclusion: The residual risk of clinically significant copy number variants in pregnancies without structural sonographic anomalies is appreciable and depends on the noninvasive prenatal screening extent and maternal age. This knowledge is important for the patients, obstetricians, and genetic counselors to facilitate informed decisions regarding prenatal testing and screening options.
KW - chromosomal aberrations
KW - chromosomal microarray
KW - copy number variants
KW - noninvasive prenatal screening
KW - prenatal diagnosis
KW - prenatal screening
UR - http://www.scopus.com/inward/record.url?scp=85120864679&partnerID=8YFLogxK
U2 - 10.1016/j.ajog.2021.11.016
DO - 10.1016/j.ajog.2021.11.016
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C2 - 34762861
AN - SCOPUS:85120864679
SN - 0002-9378
VL - 226
SP - 562.e1-562.e8
JO - American Journal of Obstetrics and Gynecology
JF - American Journal of Obstetrics and Gynecology
IS - 4
ER -