Sex chromosome aneuploidy detection by noninvasive prenatal testing: helpful or hazardous?

Abstract

Sex chromosome aneuploidy was frequently suspected on NIPT. False positive rate for monosomy X was surprisingly high (91%). Prediction of other SCA was more accurate. Diagnostic fetal chromosome analysis should be offered after abnormal NIPT or in the presence of cystic hygromas despite normal NIPT. NIPT limitations should be explained in pretest counseling. © 2017 John Wiley & Sons, Ltd.

Clinical experience with sex chromosome aneuploidies detected by noninvasive prenatal testing (NIPT): Accuracy and patient decision‐making

“…The majority of the published data regarding positive and negative predictive values comes from commercial labs in addition to a few retrospective studies from clinical practices . These prior case series have shown that inclusion of SCAs on NIPT platforms doubles the overall positive screening rate and increases the false positive rate . The true positive rate for monosomy X especially is much lower as compared to autosomal trisomies most likely because of maternal and placental mosaicism …”

“…These prior case series have shown that inclusion of SCAs on NIPT platforms doubles the overall positive screening rate and increases the false positive rate . The true positive rate for monosomy X especially is much lower as compared to autosomal trisomies most likely because of maternal and placental mosaicism …”

“…Noninvasive prenatal testing (NIPT) for sex chromosome aneuploidies (SCAs) became clinically available in the United States in 2012. Initially, little information was available regarding the performance of these tests; however, clinical uptake was swift . Prevalence, lack of other screening modalities, and patient desire for earlier information on fetal sex were driving factors for inclusion of SCAs on NIPT platforms.…”

“…While SCAs as a group are as common as autosomal aneuploidies in low‐risk populations, NIPT performance is not as good for SCAs as compared to trisomies 21, 18, and 13 because of fetal mosaicism, confined placental mosaicism, underlying maternal X chromosome variation, and/or fetal aneuploidy diagnoses outside the scope of NIPT validation . The majority of the published data regarding positive and negative predictive values comes from commercial labs in addition to a few retrospective studies from clinical practices . These prior case series have shown that inclusion of SCAs on NIPT platforms doubles the overall positive screening rate and increases the false positive rate .…”

Current controversies in prenatal diagnosis 2: Cell‐free DNA prenatal screening should be used to identify all chromosome abnormalities

“…What about the detection of SCAs? Several studies report sensitivities of between 50 and 100% for 45,X and 47,XXX, 47,XXY, and 47,XYY, but as negative cases are not karyotyped and follow‐up is generally poor, the true sensitivity is not known . These and other studies report false‐positive rates of 0.12 to 1.1% and PPVs of between 9 and 40% for 45,X, the most common sex chromosome anomaly, and 7 to 70% for the others.…”