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

• Published in: Prenatal diagnosis 2017-05, Vol.37 (5), p.515-520
• Main Authors: Reiss, Rosemary E., Discenza, Marie, Foster, Judith, Dobson, Lori, Wilkins‐Haug, Louise
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Amniocentesis; Aneuploidy; Chemical vapor synthesis; Chromosome number; Chromosomes; Cytogenetics; Deoxyribonucleic acid; Diagnostic systems; DNA; Down Syndrome - diagnosis; Down Syndrome - genetics; Female; Fetuses; Gender; Genetic counseling; Genetic screening; Genetic Testing - methods; Humans; Identification methods; Incidence; Karyotyping; Klinefelter's syndrome; Laboratories; Logbooks; Monosomy; Nuchal Translucency Measurement; Patients; Population genetics; Predictions; Pregnancy; Prenatal development; Prenatal diagnosis; Prenatal Diagnosis - adverse effects; Prenatal Diagnosis - methods; Retrospective Studies; Sex; Sex Chromosome Aberrations; Sex Chromosomes; Trisomy; Ultrasound
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.5039

Objectives To assess the incidence of sex chromosome aneuploidy (SCA) predicted by noninvasive prenatal testing (NIPT), assess test performance, and compare it with nuchal translucency (NT) screening among patients seen in our prenatal diagnosis center. Methods We identified suspected cases of SCA by reviewing results from all NIPT samples sent from our center to commercial laboratories offering analysis by cell‐free DNA between 1 December 2012 and 31 July 2015. Records of pregnancies positive for SCA were reviewed for ultrasound findings, NIPT indications, and karyotype results on maternal, fetal, and postnatal samples. Other SCA cases presenting during this period regardless of NIPT status were identified from genetic counseling and cytogenetics laboratory logbooks. Results Noninvasive prenatal testing predicted SCA in 18/2851 patients (0.63%). All had diagnostic testing of fetal or newborn samples. No patients terminated pregnancies on the basis of NIPT. NIPT suggested triple X in five cases, two with elevated NT: all were confirmed on karyotype. Two Klinefelter syndrome cases were also accurately predicted by NIPT. NIPT indicated monosomy X in 11 cases. Only one was a true positive. Ten were false positives, with 46, XX found on fetal or newborn karyotype. Maternal karyotype was mosaic (45, X[4], 46, XX[26]) in one case. Over the same time period, four additional cases of 45, X were confirmed on fetal samples, all with cystic hygromas. One of these had had a false negative NIPT result. The remaining patients pursued only direct testing via CVS or amniocentesis. Conclusions 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. What's Already Known About This Topic? Noninvasive prenatal testing (NIPT) in maternal blood can identify fetal trisomies and assess fetal sex chromosome number. NIPT is less accurate in prediction of sex chromosome aneuploidy than for trisomies 21, 18, and 13. Most patients choosing NIPT for fetal trisomy screening elect to learn fetal gender without knowing they may learn of sex chromosome aneuploidies What Does This Study Add? The false positive rate of NIPT for monosomy X is higher than previous