title: Association of extreme first-trimester free human chorionic gonadotropin-beta, pregnancy-associated plasma protein A, and nuchal translucency with intrauterine growth restriction and other adverse pregnancy outcomes.
abstract: OBJECTIVE
  The purpose of this study was to determine the association between first-trimester trisomy 21 screening markers (free human chorionic gonadotropin-beta [hCG], pregnancy-associated plasma protein A [PAPP-A], and nuchal translucency) and adverse pregnancy outcome.
  
  
  METHODS
  This was a cohort study of 8012 patients enrolled in a National Institute of Child Health and Human Development-sponsored study of first-trimester trisomy 21 and 18 screening. Trisomy 21 and 18 risk results and individual marker levels in unaffected pregnancies and pregnancies with adverse outcomes were evaluated.
  
  
  RESULTS
  PAPP-A <1st percentile (OR 5.4, 95% CI 2.8-10.3) and PAPP-A <5th percentile (OR 2.7, 95% CI 1.9-3.9) and free beta-hCG <1st percentile (OR 2.7, 95% CI 1.3-5.9) were associated with increased risk of intrauterine growth restriction (IUGR) with positive predictive values of 24.1%, 14.1%, and 14.3%, respectively. PAPP-A <5th percentile (OR 2.3 95% CI 1.1-4.7) and nuchal translucency >99th percentile (OR 3.5, 95% CI 1.1-11.3) were associated with increased risk of preterm delivery before 34 weeks. Increased risk at screening for trisomy 21 and 18 identified 16 of the 29 other chromosomal abnormalities (55%). Low free beta-hCG, low PAPP-A, and increased nuchal translucency were all associated with an increased rate of fetal abnormality.
  
  
  CONCLUSIONS
  Extreme values of first-trimester free beta-hCG, PAPP-A, and nuchal translucency are all associated with adverse outcomes. The especially high predictive value for IUGR of PAPP-A levels below the 1st percentile suggests that patients within this group may benefit from increased surveillance for this condition.
authors.affiliation: NTD Laboratories Inc., 403 Oakwood Road, Huntington Station, NY 11746, USA. dakrantz@ntdlabs.com
authors.forename: David
authors.initials: D
authors.lastname: Krantz
authors.forename: Laura
authors.initials: L
authors.lastname: Goetzl
authors.forename: Joe Leigh
authors.initials: JL
authors.lastname: Simpson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thom
authors.forename: Julia
authors.initials: J
authors.lastname: Zachary
authors.forename: Terrence W
authors.initials: TW
authors.lastname: Hallahan
authors.forename: Richard
authors.initials: R
authors.lastname: Silver
authors.forename: Eugene
authors.initials: E
authors.lastname: Pergament
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Platt
authors.forename: Karen
authors.initials: K
authors.lastname: Filkins
authors.forename: Anthony
authors.initials: A
authors.lastname: Johnson
authors.forename: Maurice
authors.initials: M
authors.lastname: Mahoney
authors.forename: W Allen
authors.initials: WA
authors.lastname: Hogge
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Wilson
authors.forename: Patrick
authors.initials: P
authors.lastname: Mohide
authors.forename: Douglas
authors.initials: D
authors.lastname: Hershey
authors.forename: Ronald
authors.initials: R
authors.lastname: Wapner
mesh_terms: D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood*; D006801:Humans; D048208:Nuchal Translucency Measurement; D016017:Odds Ratio; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011446:Prospective Studies; D012680:Sensitivity and Specificity
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A