title: Maternal plasma concentrations of angiogenic/antiangiogenic factors in the third trimester of pregnancy to identify the patient at risk for stillbirth at or near term and severe late preeclampsia.
abstract: OBJECTIVE
  To determine whether maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) at 30-34 weeks of gestation can identify patients at risk for stillbirth, late preeclampsia, and delivery of small-for-gestational-age (SGA) neonates.
  
  
  METHODS
  A prospective cohort study included 1269 singleton pregnant women from whom blood samples were obtained at 30-34 weeks of gestation and who delivered at >34 weeks of gestation. Plasma concentrations of PlGF, sEng, and sVEGFR-1 were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The prevalence of late (>34 weeks of gestation) preeclampsia, severe late preeclampsia, stillbirth, and SGA was 3.2% (n = 40), 1.8% (n = 23), 0.4% (n = 5), and 8.5% (n = 108), respectively. A plasma concentration of PlGF/sEng <0.3 MoM was associated with severe late preeclampsia (adjusted odds ratio, 16); the addition of PlGF/sEng to clinical risk factors increased the area under the receiver-operating characteristic curve from 0.76 to 0.88 (P = .03). The ratio of PlGF/sEng or PlGF/sVEGFR-1 in the third trimester outperformed those obtained in the first or second trimester and uterine artery Doppler velocimetry at 20-25 weeks of gestation for the prediction of severe late preeclampsia (comparison of areas under the receiver-operating characteristic curve; each P ≤ .02). Both PlGF/sEng and PlGF/sVEGFR-1 ratios achieved a sensitivity of 74% with a fixed false-positive rate of 15% for the identification of severe late preeclampsia. A plasma concentration of PlGF/sVEGFR-1 <0.12 MoM at 30-34 weeks of gestation had a sensitivity of 80%, a specificity of 94%, and a likelihood ratio of a positive test of 14 for the identification of subsequent stillbirth. Similar findings (sensitivity 80%; specificity 93%) were observed in a separate case-control study.
  
  
  CONCLUSIONS
  Risk assessment for stillbirth and severe late preeclampsia in the third trimester is possible with the determination of maternal plasma concentrations of angiogenic and antiangiogenic factors at 30-34 weeks of gestation.
authors: Perinatology Research Branch, National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD, USA. tchaiwor@med.wayne.edu
authors: Tinnakorn
authors: T
authors: Chaiworapongsa
authors: Roberto
authors: R
authors: Romero
authors: Steven J
authors: SJ
authors: Korzeniewski
authors: Juan Pedro
authors: JP
authors: Kusanovic
authors: Eleazar
authors: E
authors: Soto
authors: Jennifer
authors: J
authors: Lam
authors: Zhong
authors: Z
authors: Dong
authors: Nandor G
authors: NG
authors: Than
authors: Lami
authors: L
authors: Yeo
authors: Edgar
authors: E
authors: Hernandez-Andrade
authors: Agustín
authors: A
authors: Conde-Agudelo
authors: Sonia S
authors: SS
authors: Hassan
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000097:blood; D020533:Angiogenesis Inhibitors / Q000097:blood; D043924:Angiogenesis Modulating Agents / Q000097:blood*; D015703:Antigens, CD / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D000071063:Endoglin; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000097:blood; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D050497:Stillbirth; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D043924:Angiogenesis Modulating Agents; D015703:Antigens, CD; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1