title: Angiogenic factors in maternal circulation and preeclampsia with or without fetal growth restriction.
abstract: OBJECTIVE
  To study associations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in maternal circulation with the risk of preeclampsia with and without fetal growth restriction.
  
  
  METHODS
  Nested case-control study.
  
  
  METHODS
  A cohort of 29 948 pregnant women in Norway.
  
  
  METHODS
  Cases were identified through linkage to the Medical Birth Registry of Norway. We selected 69 preterm and 36 term preeclampsia cases with delivery of a small-for-gestational-age (SGA) infant, 83 preterm and 154 term preeclampsia cases without SGA delivery, and 384 normotensive controls.
  
  
  METHODS
  We measured PlGF and sFlt-1 in maternal serum samples from each trimester.
  
  
  METHODS
  Odds ratios of preeclampsia subtypes by tertile categories of PlGF and sFlt-1.
  
  
  RESULTS
  Low (lowest third) PlGF and sFlt-1 levels in the first trimester, and low (lowest third) increase in PlGF and strong (highest third) increase in sFlt-1 from first to second trimester were associated with increased risk of preterm preeclampsia, both with and without SGA offspring. For term preeclampsia with SGA offspring, the associations were similar to the findings for preterm preeclampsia. For term preeclampsia without SGA offspring, low increase in PlGF from first to second trimester and high sFlt-1 in the third trimester were associated with increased risk.
  
  
  CONCLUSIONS
  Low PlGF and high sFlt-1 levels in maternal circulation are associated with subsequent development of preeclampsia, regardless of whether fetal growth is affected or not. For term preeclampsia without fetal growth restriction, the imbalance in angiogenic factors seems to appear later in pregnancy than for preterm preeclampsia.
authors.affiliation: Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Lars J
authors.initials: LJ
authors.lastname: Vatten
authors.forename: Bjørn O
authors.initials: BO
authors.lastname: Åsvold
authors.forename: Anne
authors.initials: A
authors.lastname: Eskild
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001724:Birth Weight; D005260:Female; D005317:Fetal Growth Retardation; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007236:Infant, Small for Gestational Age; D009664:Norway; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011257:Pregnancy Proteins / Q000097:blood*; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011446:Prospective Studies; D012307:Risk Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1