title: Angiogenic and fibrinolytic factors in blood during the first half of pregnancy and adverse pregnancy outcomes.
abstract: OBJECTIVE
  To estimate whether the imbalance of angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor) and fibrinolytic factors (plasminogen activator inhibitor-2 [PAI-2]) might affect placentation in early pregnancy.
  
  
  METHODS
  We studied the associations of maternal soluble fms-like tyrosine kinase-1, placental growth factor, and PAI-2 concentrations in the first trimester (before 18 weeks of gestation) and soluble fms-like tyrosine kinase-1 and placental growth factor concentrations in the second trimester (18-25 weeks of gestation) with placental function and adverse pregnancy outcomes. This study was embedded in a population-based prospective cohort study. Data were used from 7,519 women. Biomarker concentrations were divided into deciles and evaluated in multivariable linear and logistic regression models.
  
  
  RESULTS
  First-trimester high soluble fms-like tyrosine kinase-1 was associated with a 5.2% lower uterine artery index in the second-trimester and a 1.6% higher birth weight (55 g, confidence interval [CI] 15-95). Neither in the first nor in the second trimester were soluble fms-like tyrosine kinase-1 concentrations significantly associated with preeclampsia. First-trimester low placental growth factor was associated with a 6.1% higher uterine artery index and a 3.4% lower birth weight (-115 g, CI -157 to -74). First-trimester low placental growth factor was associated with fetal growth restriction (odds ratio [OR] 2.62, CI 1.68-4.08) and preeclampsia (OR 2.46, CI 1.49-4.08). First-trimester low PAI-2 was associated with a 1.9% higher uterine artery index and a 2.7% lower birth weight (-94 g, CI -136 to -51). First-trimester low PAI-2 was associated with a higher risk of fetal growth restriction (OR 2.22, CI 1.39-3.55).
  
  
  CONCLUSIONS
  First-half-of-pregnancy concentrations of soluble fms-like tyrosine kinase-1, placental growth factor, and PAI-2 are associated with uteroplacental vascular resistance, placental weight, and birth weight. Moreover, first-trimester placental growth factor and PAI-2 are associated with an increased risk of adverse pregnancy outcomes.
  
  
  METHODS
  II.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, The Netherlands. mcmariannecoolman@gmail.com
authors.forename: Marianne
authors.initials: M
authors.lastname: Coolman
authors.forename: Sarah
authors.initials: S
authors.lastname: Timmermans
authors.forename: Christianne J M
authors.initials: CJ
authors.lastname: de Groot
authors.forename: Henk
authors.initials: H
authors.lastname: Russcher
authors.forename: Jan
authors.initials: J
authors.lastname: Lindemans
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: Geurts-Moespot
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Vincent V W
authors.initials: VV
authors.lastname: Jaddoe
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood; D006801:Humans; D008297:Male; D010920:Placenta / Q000098:blood supply; D000072483:Placenta Growth Factor; D017396:Plasminogen Activator Inhibitor 2 / Q000097:blood*; D011225:Pre-Eclampsia / Q000097:blood; D011247:Pregnancy; D011256:Pregnancy Outcome; D011257:Pregnancy Proteins / Q000097:blood*; D011261:Pregnancy Trimester, First / Q000097:blood; D011262:Pregnancy Trimester, Second / Q000097:blood; D011446:Prospective Studies; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D014655:Vascular Resistance / Q000502:physiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000608036:PGF protein, human; D017396:Plasminogen Activator Inhibitor 2; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1