title: First trimester PAPP-A in the detection of non-Down syndrome aneuploidy.
abstract: Combined first trimester screening using pregnancy associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotrophin, and nuchal translucency (NT), is currently accepted as probably the best combination for the detection of Down syndrome (DS). Current first trimester algorithms provide computed risks only for DS. However, low PAPP-A is also associated with other chromosome anomalies such as trisomy 13, 18, and sex chromosome aneuploidy. Thus, using currently available algorithms, some chromosome anomalies may not be detected. The purpose of the present study was to establish a low-end cut-off value for PAPP-A that would increase the detection rates for non-DS chromosome anomalies. The study included 1408 patients who underwent combined first trimester screening. To determine a low-end cut-off value for PAPP-A, a Receiver-Operator Characteristic (ROC) curve analysis was performed. In the entire study group there were 18 cases of chromosome anomalies (trisomy 21, 13, 18, sex chromosome anomalies), 14 of which were among screen-positive patients, a detection rate of 77.7% for all chromosome anomalies (95% CI: 55.7-99.7%). ROC curve analysis detected a statistically significant cut-off for PAPP-A at 0.25 MoM. If the definition of screen-positive were to also include patients with PAPP-A<0.25 MoM, the detection rate would increase to 88.8% for all chromosome anomalies (95% CI: 71.6-106%). This low cut-off value may be used until specific algorithms are implemented for non-Down syndrome aneuploidy.
authors.affiliation: Prenatal Diagnosis Unit, Genetic Institute, Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Ochshorn
authors.forename: M J
authors.initials: MJ
authors.lastname: Kupferminc
authors.forename: I
authors.initials: I
authors.lastname: Wolman
authors.forename: A
authors.initials: A
authors.lastname: Orr-Urtreger
authors.forename: A J
authors.initials: AJ
authors.lastname: Jaffa
authors.forename: Y
authors.initials: Y
authors.lastname: Yaron
mesh_terms: D000328:Adult; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D005260:Female; D006801:Humans; D009333:Neck / Q000000981:diagnostic imaging; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011296:Prenatal Diagnosis / Q000592:standards*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012730:Sex Chromosomes; D014314:Trisomy / Q000175:diagnosis*; D014463:Ultrasonography
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A