title: Placental growth factor and soluble fms-like tyrosine kinase-1 are useful markers for the prediction of preeclampsia but not for small for gestational age neonates: a longitudinal study.
abstract: OBJECTIVE
  To determine maternal serum concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) longitudinally in normal pregnancies, pregnancies that developed preeclampsia and pregnancies that deliver a small for gestational age (SGA) infant, in order to evaluate them as markers for the prediction of preeclampsia.
  
  
  METHODS
  In this case-control study we included 12 singleton pregnancies that developed preeclampsia and 104 randomly selected singleton normal pregnancies. Fourteen of the normal pregnancies gave birth to an SGA infant. Blood samples and ultrasonographic data were collected during the 1st, 2nd and 3rd trimesters of pregnancy.
  
  
  RESULTS
  In preeclamptic pregnancies, PlGF (pg/mL) (median; inter-quartile range) was significantly lower in the 2nd (208; 84-339) (p=0.035) and in the 3rd trimester (202; 109-284) (p=0.002) while sFlt-1 was significantly higher only in the 3rd trimester (2521; 2101-3041) (p=0.011) compared to normal pregnancies (PlGF 2nd: 311; 243-440, PlGF 3rd: 780; 472-1037, sFlt-1 3rd: 1616; 1186-2220). In pregnancies with SGA infants, PlGF and sFlt-1 did not differ significantly from normal pregnancies in any trimester. The sFlt-1 to PlGF ratio was significantly higher in preeclamptic pregnancies than in normal pregnancies, in both the 2nd and 3rd trimesters. The relative difference and the slope of PlGF concentration between 1st and 2nd trimester were significantly reduced in preeclampsia compared to normal pregnancies. A logistic regression model with predictors BMI, 2nd trimester Doppler PI and relative difference of PlGF from the 1st to the 2nd trimester gave 46% sensitivity and 99% specificity for the prediction of preeclampsia, with a very high negative predictive value of 98.3%.
  
  
  CONCLUSIONS
  Our study confirms that maternal serum PlGF concentration is significantly lower, at least after 20th week, while sFlt-1 concentration is significantly higher in 3rd trimester, in pregnancies destined to develop preeclampsia. Pregnancies that gave birth to SGA infants do not have altered angiogenic factor concentrations throughout pregnancy. The relative difference of PlGF from the 1st to the 2nd trimester, uterine artery Doppler PI in the 2nd trimester and BMI are the most powerful markers for the prediction of preeclampsia.
authors.affiliation: Hormone Laboratory, 2nd Department of Obstetrics & Gynecology, Medical School, University of Athens, "Aretaieio" Hospital, Athens, Greece. Electronic address: drizos@aretaieio.uoa.gr.
authors.forename: Demetrios
authors.initials: D
authors.lastname: Rizos
authors.forename: Makarios
authors.initials: M
authors.lastname: Eleftheriades
authors.forename: Gregory
authors.initials: G
authors.lastname: Karampas
authors.forename: Myrto
authors.initials: M
authors.lastname: Rizou
authors.forename: Alexander
authors.initials: A
authors.lastname: Haliassos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Hassiakos
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Vitoratos
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000097:blood*; D008137:Longitudinal Studies; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; 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
keywords: PlGF; Preeclampsia; Pregnancy; SGA; Slope PlGF; Small for gestational age; sFlt-1; sFlt-1 to PlGF ratio