title: Maternal circulating angiogenic factors in twin and singleton pregnancies.
abstract: OBJECTIVE
  The purpose of this study was to compare longitudinally sampled maternal angiogenic proteins between singleton and twin pregnancies.
  
  
  METHODS
  Placental growth factor (PlGF), soluble feline McDonough sarcoma (fms)-like tyrosine kinase (sFlt)-1, and soluble endoglin from healthy pregnant women were quantified at 10, 18, 26, and 35 weeks' gestation (n=91), and during the third trimester (31-39 weeks) and at delivery (33-41 weeks; n=41). Geometric means and 95% confidence intervals were calculated for gestational age-adjusted angiogenic protein concentrations and compared between matched twin and singleton pregnancies.
  
  
  RESULTS
  Maternal sFlt-1 concentrations and the sFlt-1/PlGF ratio were higher in twins than singletons across pregnancy and at delivery, with the greatest differences at week 35 (sFlt-1: 36,916 vs 10,151 pg/mL; P<.0001; sFlt-1/PlGF: 168.4 vs 29.0; P<.0001). Maternal concentrations of soluble endoglin also were higher in the third trimester and delivery. Maternal PlGF concentrations were lower in twin than singleton pregnancies at week 35 only (219.2 vs 350.2 pg/mL; P<.0001). Placental weight appeared to be inversely correlated with maternal sFlt-1/PlGF ratio at the end of pregnancy in both twins and singletons.
  
  
  CONCLUSIONS
  Higher maternal antiangiogenic proteins in twin than singleton pregnancies does not appear to be due to greater placental mass in the former, and may be one explanation for the increased risk of preeclampsia in women carrying multiple gestations. Determining whether women with a history of multiple gestations have an altered cardiovascular disease and breast cancer risk, like those with a history of preeclampsia, is warranted.
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Bethesda, MD; Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Faupel-Badger
authors.affiliation: Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: McElrath
authors.affiliation: Geisel School of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH.
authors.forename: Michele
authors.initials: M
authors.lastname: Lauria
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Houghton
authors.affiliation: Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA.
authors.forename: Kee-Hak
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center, Philadelphia, PA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Parry
authors.affiliation: Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: David
authors.initials: D
authors.lastname: Cantonwine
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lai
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Beth Israel-Deaconess Medical Center, Boston, MA.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD. Electronic address: troisir@mail.nih.gov.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Troisi
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D016022:Case-Control Studies; D000071063:Endoglin; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor; D011247:Pregnancy / Q000097:blood*; D011257:Pregnancy Proteins / Q000097:blood*; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D059285:Pregnancy, Twin / Q000097:blood*; D011956:Receptors, Cell Surface / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: angiogenic balance; endoglin; pregnancy; singletons; soluble fms-like tyrosine kinase-1; twins