title: Association of first-trimester low PAPP-A levels with preterm birth.
abstract: OBJECTIVE
  To determine the association of, and predictive ability of, pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin (beta-hCG), and nuchal translucency (NT) with preterm birth (PTB).
  
  
  METHODS
  A 5-year retrospective cohort study of women who underwent first-trimester combined screening was performed. Maternal medical, antepartum, and pregnancy outcome data were obtained. PAPP-A and beta-hCG were converted to multiples of the median (MoM), and primary exposure was defined as < or =10th percentile MoM for PAPP-A. Secondary exposures were defined as > or = 90th percentile MoM for beta-hCG and NT values of > or = 20 and 25 mm. The primary outcome was PTB before 35 weeks and the secondary outcome was PTB before 32 weeks. Univariate, bivariate, multivariate, and receiver-operator analyses were used.
  
  
  RESULTS
  Of the 2231 patients meeting inclusion criteria with complete outcome data available, 222 had a PAPP-A level < or =10th percentile MoM. Abnormally low PAPP-A was associated with an increased risk for PTB < 35 weeks [adjusted odds ratio (aOR) 2.0, 1.0-3.8] and < 32 weeks (aOR 2.7, 1.1-6.4), even after adjusting for prior PTB, tobacco exposure, chronic hypertension, and body mass index. PAPP-A < or =10th percentile was not sufficiently predictive of PTB < 35 weeks (area under curve = 0.63, 95% CI 0.53-0.72). Neither abnormally high beta-hCG nor increased NT was associated with an increased risk for PTB.
  
  
  CONCLUSIONS
  PAPP-A < or =10th percentile is associated with an increased risk for PTB, but is not sufficiently predictive to be used clinically.
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, 4911 Barnes-Jewish Hospital Plaza, St. Louis, MO 63110, USA. goetzingerk@wudosis.wustl.edu
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Goetzinger
authors.forename: Alison G
authors.initials: AG
authors.lastname: Cahill
authors.forename: George A
authors.initials: GA
authors.lastname: Macones
authors.forename: Anthony O
authors.initials: AO
authors.lastname: Odibo
mesh_terms: D000328:Adult; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D005260:Female; D006801:Humans; D048208:Nuchal Translucency Measurement; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D047928:Premature Birth / Q000097:blood* / Q000000981:diagnostic imaging; D012189:Retrospective Studies
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A