title: Integrated ultrasound and biochemical screening for trisomy 21 using fetal nuchal translucency, absent fetal nasal bone, free beta-hCG and PAPP-A at 11 to 14 weeks.
abstract: BACKGROUND
  Screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A) at 11 to 14 weeks of gestation is associated with a detection rate of 90% for a false-positive rate of 5%. Recent evidence suggests that in about 70% of fetuses with trisomy 21, the nasal bone is not visible at the 11th- to 14th-week scan (Cicero et al., 2001). The aim of this study was to examine whether fetal NT thickness and the level of maternal serum biochemical markers is independent of the presence or absence of the nasal bone, and to estimate the performance of a screening test that integrates the two sonographic and the two biochemical markers.
  
  
  METHODS
  This was a retrospective case-control study comprising 100 trisomy 21 and 400 chromosomally normal singleton pregnancies at 11 to 14 weeks of gestation. Ultrasound examination was carried out for measurement of fetal NT and assessment of the presence or absence of the fetal nasal bone. Maternal serum free beta-hCG and PAPP-A were measured using the Kryptor rapid random-access immunoassay analyser (Brahms Diagnostica GmbH, Berlin). The distribution of fetal NT, maternal serum free beta-hCG and PAPP-A in trisomy 21 fetuses with absent and present nasal bone was examined.
  
  
  RESULTS
  The nasal bone was absent in 69 and present in 31 of the trisomy 21 fetuses. There were no significant differences in median maternal age, median gestational age, NT delta, free beta-hCG MoM and PAPP-A MoM in trisomy 21 fetuses with and without a visible nasal bone. For a false-positive rate of 5%, it was estimated that screening with the four markers in combination with maternal age would be associated with a detection rate of 97%. For a false-positive rate of 0.5%, the detection rate was 90.5%.
  
  
  CONCLUSIONS
  An integrated sonographic and biochemical test at 11 to 14 weeks can potentially identify about 90% of trisomy 21 fetuses for a false-positive rate of 0.5%.
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, Denmark Hill, London, UK.
authors.forename: Simona
authors.initials: S
authors.lastname: Cicero
authors.forename: Renu
authors.initials: R
authors.lastname: Bindra
authors.forename: Georgios
authors.initials: G
authors.lastname: Rembouskos
authors.forename: Kevin
authors.initials: K
authors.lastname: Spencer
authors.forename: Kypros H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis* / Q000453:epidemiology; D005189:False Positive Reactions; D005260:Female; D005865:Gestational Age; D006801:Humans; D008297:Male; D008423:Maternal Age; D009295:Nasal Bone / Q000002:abnormalities / Q000000981:diagnostic imaging*; D009333:Neck / Q000002:abnormalities / Q000000981:diagnostic imaging*; D011247:Pregnancy / Q000097:blood; D011261:Pregnancy Trimester, First; D018566:Pregnancy, High-Risk; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D012189:Retrospective Studies; D016216:Ultrasonography, Prenatal; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A