title: Circulating angiogenic factors in early pregnancy and the risk of preeclampsia, intrauterine growth restriction, spontaneous preterm birth, and stillbirth.
abstract: OBJECTIVE
  To estimate the relationship between maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in early pregnancy with the risk of subsequent adverse outcome.
  
  
  METHODS
  A nested, case-control study was performed within a prospective cohort study of Down syndrome screening. Maternal serum levels of sFlt-1 and PlGF at 10-14 weeks of gestation were compared between 939 women with complicated pregnancies and 937 controls. Associations were quantified as the odds ratio for a one decile increase in the corrected level of the analyte.
  
  
  RESULTS
  Higher levels of sFlt-1 were not associated with the risk of preeclampsia but were associated with a reduced risk of delivery of a small for gestational age infant (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.88-0.96), extreme (24-32 weeks) spontaneous preterm birth (OR 0.90, 95% CI 0.83-0.99), moderate (33-36 weeks) spontaneous preterm birth (OR 0.93, 95% CI 0.88-0.98), and stillbirth associated with abruption or growth restriction (OR 0.77, 95% CI 0.61-0.95). Higher levels of PlGF were associated with a reduced risk of preeclampsia (OR 0.95, 95% CI 0.90-0.99) and delivery of a small for gestational age infant (OR 0.95, 95% CI 0.91-0.99). Associations were minimally affected by adjustment for maternal characteristics.
  
  
  CONCLUSIONS
  Higher early pregnancy levels of sFlt-1 and PlGF were associated with a decreased risk of adverse perinatal outcome.
authors.affiliation: Department of Obstetrics and Gynaecology, Cambridge University, Cambridge, United Kingdom. gcss2@cam.ac.uk
authors.forename: Gordon C S
authors.initials: GC
authors.lastname: Smith
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Crossley
authors.forename: David A
authors.initials: DA
authors.lastname: Aitken
authors.forename: Nicola
authors.initials: N
authors.lastname: Jenkins
authors.forename: Fiona
authors.initials: F
authors.lastname: Lyall
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cameron
authors.forename: J Michael
authors.initials: JM
authors.lastname: Connor
authors.forename: Richard
authors.initials: R
authors.lastname: Dobbie
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005317:Fetal Growth Retardation / Q000453:epidemiology*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007236:Infant, Small for Gestational Age; D016017:Odds Ratio; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000453:epidemiology*; D011247:Pregnancy / Q000097:blood; D011256:Pregnancy Outcome; D011257:Pregnancy Proteins / Q000097:blood*; D011261:Pregnancy Trimester, First / Q000097:blood; D047928:Premature Birth / Q000453:epidemiology*; D011446:Prospective Studies; D012307:Risk Factors; D050497:Stillbirth / Q000453:epidemiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1