title: First trimester screening for Down syndrome using nuchal translucency, maternal serum pregnancy-associated plasma protein A, free-β human chorionic gonadotrophin, placental growth factor, and α-fetoprotein.
abstract: OBJECTIVE
  The aim of this study was to assess the screening performance for Down syndrome using first trimester combined screening (FTS) and two additional markers, serum placental growth factor (PlGF) and α-fetoprotein (AFP).
  
  
  METHODS
  This is a retrospective case-control study of 137 pregnancies affected by Down syndrome and 684 individually matched unaffected pregnancies. Stored serum samples were tested for all four markers, and results were expressed as multiples of the gestation-specific median (MoM). Multivariate Gaussian modeling was used to calculate risks for different combinations of markers and to predict the detection rate (DR) and false positive rate (FPR). The predicted performance of enhanced FTS (FTS plus PlGF and AFP) was compared with FTS; the performance without nuchal translucency (first trimester quad) was assessed.
  
  
  RESULTS
  For affected pregnancies, the median PlGF level was 0.622 MoM and median AFP 0.764 MoM. Adding PlGF and AFP improved the screening performance. At 3% FPR, DR increased by 4.4% from 83.8% to 88.2% using enhanced FTS; at 95% DR, FPR decreased by 8.3%, from 19.3% to 11.0%. At 3% FPR, DR using first trimester quad test was 76.4%.
  
  
  CONCLUSIONS
  The performance of FTS can be enhanced by adding PlGF and AFP. Even without nuchal translucency, the test would perform well.
authors.affiliation: Genetics Program, North York General Hospital, Toronto, Ontario, Canada.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Huang
authors.affiliation: Genetics Program, North York General Hospital, Toronto, Ontario, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Dennis
authors.affiliation: Genetics Program, North York General Hospital, Toronto, Ontario, Canada.|Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Meschino
authors.affiliation: Genetics Program, North York General Hospital, Toronto, Ontario, Canada.
authors.forename: Shamim
authors.initials: S
authors.lastname: Rashid
authors.affiliation: Genetics Program, North York General Hospital, Toronto, Ontario, Canada.
authors.forename: Ellen
authors.initials: E
authors.lastname: Mak-Tam
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Cuckle
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D062145:Maternal Serum Screening Tests; D015233:Models, Statistical; D015999:Multivariate Analysis; D016011:Normal Distribution; D048208:Nuchal Translucency Measurement; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011261:Pregnancy Trimester, First / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D012189:Retrospective Studies; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000509:alpha-Fetoproteins; D000072483:Placenta Growth Factor; D011266:Pregnancy-Associated Plasma Protein-A