title: Altered hemodynamics and hyperuricemia accompany an elevated sFlt-1/PlGF ratio before the onset of early severe preeclampsia.
abstract: OBJECTIVE
  Early identification of women at risk of developing early-onset severe preeclampsia (sPE) is a key objective in obstetrics. An elevated ratio of serum soluble fms-like tyrosine kinase (sFlt-1) to placenta-like growth factor (PlGF) (sFlt-1/PlGF ratio) precedes overt hypertension. The longitudinal relationship between this biomarker, maternal hemodynamics, and maternal serum uric acid during the pre-clinical phase is unknown.
  
  
  METHODS
  We followed 20 normotensive women at high risk of developing sPE from 20 weeks until delivery or 34 weeks' gestation. Non-invasive hemodynamic monitoring using bioreactance technology was performed at 20 to 22, 24 to 26, 28 to 30, and 32 to 34 weeks' gestation. Serum uric acid, sFlt-1, and PlGF were measured simultaneously.
  
  
  RESULTS
  Six of 20 women (30%) delivered before 33 weeks with sPE and had significantly higher mean total peripheral resistance (TPR), higher serum uric acid, and higher sFlt-1/PlGF ratios at 24 weeks' gestation than unaffected individuals. The area under the curve, cut-off values, and sensitivity and specificity to predict sPE at 24 weeks were as follows: TPR 0.84, 1250 dyne.s.cm-5, 80%, 93%; sFlt-1/PlGF ratio 0.94, 55, 100%, 93%; and serum uric acid 0.99, 255 μmol/L, 100%, 93%. TPR and sFlt-1 were positively correlated in the sPE group before antihypertensive treatment (r = 0.65, P = 0.01). Serum uric acid correlated with both sFlt-1 (r = 0.65, P = 0.003) and sFlt-1/PlGF ratio (r = 0.54, P = 0.02).
  
  
  CONCLUSIONS
  A combination of non-invasive determination of TPR together with measurement of serum uric acid may identify a subset of clinically high-risk women with evolving sPE, independent of the determination of the sFlt-1/PlGF ratio. The predictive ability of this integrated approach needs to be assessed in a larger cohort of women to further confirm its utility.
authors.affiliation: Department of Anesthesia, Mount Sinai Hospital, University of Toronto, Toronto ON.
authors.forename: Anne
authors.initials: A
authors.lastname: Doherty
authors.affiliation: Department of Anesthesia, Mount Sinai Hospital, University of Toronto, Toronto ON; Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto ON.
authors.forename: Jose C A
authors.initials: JC
authors.lastname: Carvalho
authors.affiliation: Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto ON; The Lunenfeld-Tannenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto ON.
authors.forename: Sascha
authors.initials: S
authors.lastname: Drewlo
authors.affiliation: Department of Neonatology, Mount Sinai Hospital, University of Toronto ON.
authors.forename: Afif
authors.initials: A
authors.lastname: El-Khuffash
authors.affiliation: Department of Anesthesia, Mount Sinai Hospital, University of Toronto, Toronto ON.
authors.forename: Kristi
authors.initials: K
authors.lastname: Downey
authors.affiliation: Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto ON.
authors.forename: Madelaine
authors.initials: M
authors.lastname: Dodds
authors.affiliation: Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto ON; The Lunenfeld-Tannenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto ON.
authors.forename: John
authors.initials: J
authors.lastname: Kingdom
mesh_terms: D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006439:Hemodynamics; D006801:Humans; D033461:Hyperuricemia / Q000097:blood*; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; 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: NICOM; PlGF; bioreactance; early severe preeclampsia; sflt -1; uric acid; vascular resistance