title: Prediction of preeclampsia and induced delivery at <34 weeks gestation by sFLT-1 and PlGF in patients with abnormal midtrimester uterine Doppler velocimetry: a prospective cohort analysis.
abstract: BACKGROUND
  Women with bilateral abnormal uterine artery Doppler velocimetry (UtADV) are at increased risk for an adverse pregnancy outcome. This study aimed to determine if additional assessment of midtrimester angiogenic factors improves the predictive accuracy of Doppler results for various outcome parameters.
  
  
  METHODS
  Women with a bilateral abnormal UtADV, which was defined as a postsystolic incision and/or an increased pulsatility index greater than the 95th centile, and a singleton pregnancy were prospectively recruited between 19 + 0 and 26 + 6 weeks of gestation. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT-1) were measured with a fully automated immunoassay and their ratio was calculated.
  
  
  RESULTS
  Angiogenic factors could predict the development of preeclampsia (PE), as well as induced delivery at <34 weeks of gestation, but failed to predict the development of normotensive intrauterine growth restriction. Twelve (24.0%) of the 50 recruited women developed PE. Nine of these patients had early-onset disease (<34 + 0 weeks). Six (12.0%) patients were delivered at <34 + 0 weeks. The most useful test results in the prediction of PE and induced delivery at <34 + 0 weeks were observed using the sFLT-1/PlGF >95th centile ratio with a sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 66.7%, 89.5%, 66.7%, and 89.5% for PE, and 85.7%, 86.1%, 50.1%, and 97.4% for induced delivery, respectively. Positive and negative likelihood ratios were 6.33 (95% CI 2.31-17.38) and 0.37 (95% CI 0.17-0.84) for PE, and 6.14 (95% CI 2.76-13.69) and 0.17 (0.03-1.02) for induced delivery, respectively. Corresponding odds ratios were 17.0 (95% CI 3.5-83.0) and 37.0 (95% CI 3.8-363.9), respectively.
  
  
  CONCLUSIONS
  Measurement of angiogenic factors improves the specificity of an abnormal UtADV for prediction of PE. Compared with prediction of PE an abnormal sFLT-1/PlGF ratio revealed higher sensitivity for prediction of induced delivery at <34 + 0 weeks. The NPV of 97% will help to reassure most patients with an abnormal UtADV and a normal sFLT-1/PlGF ratio.
authors.affiliation: Department of Obstetrics and Gynecology, University of Rostock, Suedring 81, 18059 Rostock, Germany. johannes.stubert@uni-rostock.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Stubert
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ullmann
authors.forename: Michael
authors.initials: M
authors.lastname: Bolz
authors.forename: Thomas
authors.initials: T
authors.lastname: Külz
authors.forename: Max
authors.initials: M
authors.lastname: Dieterich
authors.forename: Dagmar-Ulrike
authors.initials: DU
authors.lastname: Richter
authors.forename: Toralf
authors.initials: T
authors.lastname: Reimer
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000175:diagnosis; D005865:Gestational Age; D006801:Humans; D007751:Labor, Induced; D008565:Membrane Proteins / Q000097:blood*; D011225:Pre-Eclampsia / Q000097:blood* / Q000000981:diagnostic imaging*; D011237:Predictive Value of Tests; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood; D011673:Pulsatile Flow; D018608:Ultrasonography, Doppler; D055988:Uterine Artery / Q000000981:diagnostic imaging / Q000502:physiology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C098069:PIGF protein, human; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1