title: Levels of maternal serum angiogenic factors in third-trimester normal pregnancies: reference ranges, influence of maternal and pregnancy factors and fetoplacental Doppler indices.
abstract: OBJECTIVE
  To establish normal ranges of maternal placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and sFlt-1/PlGF ratio at 32-41 weeks' gestation and to evaluate the influence of maternal characteristics, and of fetoplacental Doppler.
  
  
  METHODS
  Serum levels of PlGF, sFlt-1 and sFlt-1/PlGF ratio were measured in 300 noncomplicated pregnancies (30 at each gestational week between 32 and 41). Quantile regression analysis was used to derive gestational age (GA)-adjusted normal ranges, and to account for characteristics that might influence serum levels. The relationship with Doppler indices was tested, including umbilical artery pulsatility index and middle cerebral artery pulsatility index.
  
  
  RESULTS
  PlGF decreased with GA from 32 weeks, while sFlt-1 and sFlt-1/PlGF ratio increased steadily. None of the factors evaluated showed any significant influence on the levels of angiogenic factors. PlGF multiple of the median significantly correlated with mean uterine artery Doppler (R -0.17; p = 0.029).
  
  
  CONCLUSIONS
  In normal pregnancies during the third trimester, serum PlGF decreases, sFlt-1 increases and sFlt-1/PlGF ratio increases with GA. Angiogenic factor levels needed no adjustment for factors such as smoking, body mass index, blood pressure or parity.
authors.affiliation: Fetal i+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Silvia Martina
authors.initials: SM
authors.lastname: Lobmaier
authors.forename: Francesc
authors.initials: F
authors.lastname: Figueras
authors.forename: Imma
authors.initials: I
authors.lastname: Mercade
authors.forename: Francesca
authors.initials: F
authors.lastname: Crovetto
authors.forename: Anna
authors.initials: A
authors.lastname: Peguero
authors.forename: Miguel
authors.initials: M
authors.lastname: Parra-Saavedra
authors.forename: Javier U
authors.initials: JU
authors.lastname: Ortiz
authors.forename: Fatima
authors.initials: F
authors.lastname: Crispi
authors.forename: Eduard
authors.initials: E
authors.lastname: Gratacós
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008423:Maternal Age; D000072483:Placenta Growth Factor; D021041:Placental Circulation / Q000502:physiology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011263:Pregnancy Trimester, Third / Q000097:blood*; D012016:Reference Values; D016216:Ultrasonography, Prenatal / Q000639:trends; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1