Objectives: To assess the accuracy of non-invasive prenatal testing (NIPT) for sex chromosome aneuploidy (SCA) in routine clinical practice and to review counselling and sonographic issues arising in SCA cases. Methods: Three specialist Australian obstetric ultrasound and prenatal diagnosis practices offering NIPT after 10 weeks' gestation participated in this study. NIPT was reported for chromosomes 21, 18, 13, X, and Y. Results: NIPT screening was performed in 5,267 singleton pregnancies. The odds of being affected given a positive screening result (OAPR) was lowest for SCAs, most notably for monosomy X (20%). Fewer women underwent invasive prenatal testing when counselled regarding a high risk for SCA (65.5%) compared with those who had a high risk for another aneuploidy (85%). The positive screening rate of NIPT including SCA was 2.3%, but 1.2% if only the autosomal trisomies were included in the panel. Conclusion: The addition of SCA testing to NIPT doubles the positive screening rate. The OAPR for SCAs (most notably for monosomy X) is reduced compared with the autosomal trisomies. Clinicians need a more extensive discussion with women prior to the inclusion of the X and Y chromosomes in the NIPT panel, given the complexity in counselling regarding further management and the additional anxiety that these abnormal results may cause. A benefit of sex chromosome analysis is an improvement in antenatal diagnosis of some disorders of sexual development.

Taylor-Phillips S, Freeman K, Geppert J, Agbebiyi A, Uthman O, Madan J, Clarke A, Quenby S, Clarke A: Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis. BMJ Open 2016;6:e010002.
Russo ML, Blakemore KJ: A historical and practical review of first trimester aneuploidy screening. Semin Fetal Neonatal Med 2014;19:183-187.
Hui L, Teoh M, da Silva Costa F, Ramsay P, Palma-Dias R, Richmond Z, Piessens S, Walker S; Australian NIPT collaboration: Clinical implementation of cell-free DNA-based aneuploidy screening: perspectives from a national audit. Ultrasound Obstet Gynecol 2015;45:10-15.
Gil MM, Quezada MS, Revello R, Akolekar R, Nicolaides KH: Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol 2015;45:249-266.
Menuti MT, Chandrasekaran S, Khalek N, Dugoff L: Cell-free DNA screening and sex chromosome aneuploidies. Prenat Diagn 2015;35:980-985.
Wright D, Spencer K, Kagan K, Tørring KN, Petersen OB, Christou A, Kallikas J, Nicolaides KH: First trimester combined screening for trisomy 21 at 7-14 weeks' gestation. Ultrasound Obstet Gynecol 2010;36:404-411.
Sparks AB, Struble CA, Wang ET, Song K, Oliphant A: Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012;206:319.e1-e9.
McLennan A, Palma-Dias R, da Silva Costa F, Meagher S, Nisbet D, Scott F: Noninvasive prenatal testing in routine clinical practice - an audit of NIPT and combined first trimester screening in an unselected Australian population. Aust NZ J Obstet Gynecol 2016;56:22-28.
Mansfield N, Boogert A, McLennan A: Prenatal diagnosis of a 46,XX male following noninvasive prenatal testing. Clin Case Rep 2015;3:849-853.
Raymond CS, Parker ED, Kettlewell JR, Brown LG, Page DC, Kusz K, Jaruzelska J, Reinberg Y, Flejterg WL, Bardwell VJ, Hirsch B, Zarkower D: A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators. Hum Mol Genet 1999;8:989-996.
Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC, Brar H, Tomlinson MW, Pereira L, Spitz JL, Hollemon D, Cuckle H, Musci TJ, Wapner RJ: Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med 2015;372:1589-1597.
Porreco RP, Garite TJ, Maurel K, Marusiak B; Obstetrix Collaborative Research Network, Ehrich M, van den Boom D, Deciu C, Bombard A: Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA. Am J Obstet Gynecol 2014;211:365.e1-e12.
Nicolaides KH, Musci TJ, Struble CA, Singelaki A, Gil MM: Assessment of fetal sex chromosome aneuploidy using directed cell-free DNA analysis. Fetal Diagn Ther 2014;35:1-6.
Mazloom AR, Džakula Ž, Oeth P, Wang H, Jensen T, Tynan J, McCullough R, Saldivar JS, Ehrich M, van den Boom D, Bombard AT, Maeder M, McLennan G, Meschino W, Palomaki GE, Canick JA, Deciu C: Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma. Prenat Diagn 2013;33:591-597.
Samango-Sprouse C, Banjevic M, Ryan A, Sigurjonsson S, Zimmermann B, Hill M, Hall MP, Westemeyer M, Saucier J, Demko Z, Rabinowitz M: SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy. Prenat Diagn 2013;33:643-649.
Bourke E, Snow P, Herlihy A, Amor D, Metcalfe S: A qualitative exploration of mothers' and fathers' experiences of having a child with Klinefelter syndrome and the process of reaching this diagnosis. Eur J Hum Genet 2014;22:18-24.
Lewis C, Hill M, Skirton H, Chitty L: Non-invasive prenatal diagnosis for fetal sex determination: benefits and disadvantages from the service users' perspective. Eur J Hum Genet 2012;20:1127-1133.
Kalafat E, Seval MM, Turgay B, Koc A: Non-invasive prenatal testing for sex chromosome abnormalities: a source of confusion. BMJ Case Rep 2015;2015:bcr2014207309.
Chitty L, Chatelain P, Wolffenbuttel KP, Aigrain Y: Prenatal management of disorders of sex development. J Pediatr Urol 2012;8:576-584.
Dickinson JE, de Costa CM: Non invasive prenatal testing: the new era in reproductive medicine. Med J Aust 2015;203:57-58.
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