title: Chromosome abnormalities investigated by non-invasive prenatal testing account for approximately 50% of fetal unbalances associated with relevant clinical phenotypes.
abstract: During the past 20 years non-invasive screening tests have been increasingly utilized in prenatal diagnosis (PD) practice. Considerable effort has been exerted by multicenter consortia to evaluate the reliability of non-invasive screening tests in detecting those women with an increased risk of having a pregnancy affected by trisomies 21, 18, and 13, monosomy X, and triploidies. To what extent this group of abnormal karyotypes accounts for the total number of phenotypically relevant fetal chromosome abnormalities has, however, never been investigated. The present report is an attempt aimed to quantify this proportion. A retrospective analysis of a homogeneous survey of 115,128 consecutive invasive prenatal tests was undertaken. All cases were classified in accordance with the indication given for the invasive testing. Cytogenetic results regarding 96,416 karyotype analyses performed because of advanced maternal age (>or=35 years) or gestational anxiety (<35 years) were considered since these are the patients who usually undergo non-invasive screening tests. We calculated the number of cases (T21, T18, T13, 45,X, and triploidy) that would have been detected by prenatal screening on the basis of the published detection rate of the combined-2 test or the quadruple test. Our findings indicate that the chromosomal abnormalities investigated by screening tests represent <50% of the fetal chromosomal abnormalities associated with an abnormal outcome ranging from intermediate-to-severe in women <35 years (45.8% and 39.6% in the first and second trimesters, respectively), and sensitivity >50% in women >or=35 years (65.1% and 61.8%, respectively). To conclude, approximately 50% of the phenotypically relevant abnormal karyotypes cannot be detected by non-invasive prenatal screening tests.
authors.affiliation: Ricerca e Sviluppo, Citogenetica e Biologia Molecolare, TOMA Advanced Biomedical Assays S.p.A., Busto Arsizio, Varese, Italy. fgrati@tomalab.com
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Grati
authors.forename: Andrea
authors.initials: A
authors.lastname: Barlocco
authors.forename: Beatrice
authors.initials: B
authors.lastname: Grimi
authors.forename: Silvia
authors.initials: S
authors.lastname: Milani
authors.forename: Giuditta
authors.initials: G
authors.lastname: Frascoli
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Meco
authors.forename: Rosaria
authors.initials: R
authors.lastname: Liuti
authors.forename: Anna
authors.initials: A
authors.lastname: Trotta
authors.forename: Sara
authors.initials: S
authors.lastname: Chinetti
authors.forename: Francesca
authors.initials: F
authors.lastname: Dulcetti
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Ruggeri
authors.forename: Simona
authors.initials: S
authors.lastname: De Toffol
authors.forename: Maurizio
authors.initials: M
authors.lastname: Clementi
authors.forename: Federico
authors.initials: F
authors.lastname: Maggi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Simoni
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D005188:False Negative Reactions; D005260:Female; D005333:Fetus / Q000002:abnormalities*; D006801:Humans; D008423:Maternal Age; D009006:Monosomy / Q000175:diagnosis; D011123:Polyploidy; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D014314:Trisomy / Q000175:diagnosis