title: Evidence of an imbalance of angiogenic/antiangiogenic factors in massive perivillous fibrin deposition (maternal floor infarction): a placental lesion associated with recurrent miscarriage and fetal death.
abstract: OBJECTIVE
  Massive perivillous fibrin deposition (MPFD) is associated with serious complications of pregnancy including recurrent spontaneous abortion, fetal growth restriction, and fetal demise. The aim of this study was to determine whether maternal plasma concentrations of angiogenic/antiangiogenic factors in MPFD differ from those of uncomplicated pregnancies.
  
  
  METHODS
  This retrospective longitudinal case-control study included MPFD cases (n = 10) and control patients (n = 175) with uncomplicated pregnancies who were enrolled in a longitudinal study and delivered at term. Serial plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor (sVEGFR)-1 and -2 were determined by an enzyme-linked immunosorbent assay (cases, n = 28 samples; controls, n = 723 samples). Individual analyte concentrations were averaged across gestational age at specimen collection intervals. Linear mixed models were used to test for differences in log-transformed mean analyte concentrations both overall and as a function of time.
  
  
  RESULTS
  The following results were found: (1) patients with MPFD had a lower mean plasma PlGF concentration (P = .03) and higher mean plasma concentrations of sVEGFR-1 and sEng (both P < .01) than controls, adjusted for potential confounders; (2) the mean plasma concentration of PlGF differed further among cases and controls as a function of gestational age interval (P < .0001); however, mean sVEGFR-1 and sEng group differences as a function of gestational age interval approached but did not reach significance (P = .09 and P = .11, respectively); (3) patients with MPFD had lower mean plasma concentrations of PlGF/sVEGFR-1 (P < .0001) and PlGF/sEng (P < .001): both of these relationships differed further as a function of gestational age interval (both P < .0001); and (4) differences in mean sVEGFR-1, sEng, and the ratios of PlGF to sVEGFR-1 and PlGF to sEng were observed before 20 weeks of gestation.
  
  
  CONCLUSIONS
  An imbalance of angiogenic/antiangiogenic factors is present in patients with MPFD prior to the diagnosis. We propose that these changes participate in the mechanisms responsible for adverse pregnancy outcomes in patients with MPFD.
authors: Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD, USA.
authors: Amy E
authors: AE
authors: Whitten
authors: Roberto
authors: R
authors: Romero
authors: Steven J
authors: SJ
authors: Korzeniewski
authors: Adi L
authors: AL
authors: Tarca
authors: Alyse G
authors: AG
authors: Schwartz
authors: Lami
authors: L
authors: Yeo
authors: Zhong
authors: Z
authors: Dong
authors: Sonia S
authors: SS
authors: Hassan
authors: Tinnakorn
authors: T
authors: Chaiworapongsa
mesh_terms: D000026:Abortion, Habitual / Q000097:blood / Q000209:etiology; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D020533:Angiogenesis Inhibitors / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005313:Fetal Death / Q000097:blood / Q000209:etiology; D005337:Fibrin / Q000032:analysis; D006801:Humans; D008137:Longitudinal Studies; D010922:Placenta Diseases / Q000097:blood* / Q000175:diagnosis*; D011247:Pregnancy; D055815:Young Adult
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D005337:Fibrin