title: First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in pregnant women with and without preeclampsia.
abstract: BACKGROUND
  First trimester Pregnancy Associated Plasma Protein A (PAPP-A) levels, routinely measured for aneuploidy screening, may predict development of preeclampsia. This study tests the hypothesis that first trimester PAPP-A levels correlate with soluble fms-like tyrosine kinase-1 (sFlt-1) levels, an angiogenic marker associated with preeclampsia, throughout pregnancy.
  
  
  METHODS
  sFlt-1 levels were measured longitudinally in 427 women with singleton pregnancies in all three trimesters. First trimester PAPP-A and PAPP-A Multiples of Median (MOM) were measured. Student's T and Wilcoxon tests compared preeclamptic and normal pregnancies. A linear mixed model assessed the relationship between log PAPP-A and serial log sFlt-1 levels.
  
  
  RESULTS
  PAPP-A and PAPP-A MOM levels were significantly lower in preeclamptic (n = 19), versus normal pregnancies (p = 0.02). Although mean third trimester sFlt-1 levels were significantly higher in preeclampsia (p = 0.002), first trimester sFlt-1 levels were lower in women who developed preeclampsia, compared with normal pregnancies (p = 0.03). PAPP-A levels correlated significantly with serial sFlt-1 levels. Importantly, low first trimester PAPP-A MOM predicted decreased odds of normal pregnancy (OR 0.2, p = 0.002).
  
  
  CONCLUSIONS
  Low first trimester PAPP-A levels suggests increased future risk of preeclampsia and correlate with serial sFlt-1 levels throughout pregnancy. Furthermore, low first trimester PAPP-A status significantly predicted decreased odds of normal pregnancy.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. asaxena@partners.org
authors.forename: Aditi R
authors.initials: AR
authors.lastname: Saxena
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Seely
authors.forename: Janet W
authors.initials: JW
authors.lastname: Rich-Edwards
authors.forename: Louise E
authors.initials: LE
authors.lastname: Wilkins-Haug
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: Thomas F
authors.initials: TF
authors.lastname: McElrath
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D016017:Odds Ratio; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013997:Time Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D011266:Pregnancy-Associated Plasma Protein-A
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