title: The association between angiogenic markers and fetal sex: Implications for preeclampsia research.
abstract: Current research suggests sexual dimorphism between the male and female fetoplacental units, but with unknown relevance for preeclampsia. We investigated the association between fetal sex and concentrations of the angiogenic markers soluble Fms-like kinase 1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in first and second-third trimester in women with/without preeclampsia, and the impact of fetal sex on the prognostic value of angiogenic markers for preeclampsia.
  
  
  
  Observational study in a prospective, population-based cohort of 2110 singleton pregnancies with 150 preeclampsia cases.
  
  
  
  Higher sFlt-1 concentrations were observed for women carrying female fetuses in first trimester (all, 1107.65 vs. 992.27pg/ml; preeclampsia cases, 1118.79 vs. 934.49pg/ml, p<0.05) and in second-third trimester (all, 1130.03 vs. 1043.15pg/ml; preeclampsia, 1480.30 vs. 1152.86pg/ml, p<0.05), with similar findings for the sFlt-1/PlGF ratio concentrations in first (29.67 vs. 27.39 p<0.05) and second-third trimester (3.56 vs. 3.22, p<0.05). In first trimester, log transformed concentrations of PlGF, sFlt-1 and sFlt-1/PlGF (all participants) and sFlt-1 (preeclampsia cases) associated with fetal sex in adjusted analyses (p<0.05). In second-third trimester, only log(sFlt-1) associated with fetal sex (all, p=0.028; preeclampsia, p=0.067) In receiver operating curve analysis, prediction of early-onset preeclampsia by sFlt-1/PlGF tended to be superior in pregnancies with female vs. male fetuses (p=0.06).
  
  
  
  Sexual dimorphism was observed for concentrations of angiogenic markers. Female fetal sex was associated to higher sFlt-1 and sFlt-1/PlGF ratio concentrations in both healthy pregnancies and women developing preeclampsia. Fetal sex should be considered in research and clinical use of angiogenic markers.
authors.affiliation: HCA Research, Hans Christian Andersen Children's Hospital, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark; Institute for Clinical Research, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark. Electronic address: louise.bjoerkholt.andersen@rsyd.dk.
authors.forename: L B
authors.initials: LB
authors.lastname: Andersen
authors.affiliation: Institute for Clinical Research, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark; Department of Obstetrics and Gynecology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark; Odense Patient data Explorative Network (OPEN), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark; Odense Child Cohort, Hans Christian Andersen Children's Hospital, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.
authors.forename: J S
authors.initials: JS
authors.lastname: Jørgensen
authors.affiliation: Experimental and Clinical Research Center, Max-Delbrueck Center and Charité Berlin and HELIOS Clinic Berlin-Buch, Lindenberger Weg 80, 13125 Berlin, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Herse
authors.affiliation: Department of Endocrinology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.
authors.forename: M S
authors.initials: MS
authors.lastname: Andersen
authors.affiliation: HCA Research, Hans Christian Andersen Children's Hospital, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark; Institute for Clinical Research, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark; Odense Child Cohort, Hans Christian Andersen Children's Hospital, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.
authors.forename: H T
authors.initials: HT
authors.lastname: Christesen
authors.affiliation: Odense Child Cohort, Hans Christian Andersen Children's Hospital, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark; Experimental and Clinical Research Center, Max-Delbrueck Center and Charité Berlin and HELIOS Clinic Berlin-Buch, Lindenberger Weg 80, 13125 Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Dechend
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D047109:Fetal Development; D005786:Gene Expression Regulation; D005865:Gestational Age; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D018919:Neovascularization, Physiologic; D044382:Population Groups; D011225:Pre-Eclampsia / Q000175:diagnosis*; D011247:Pregnancy; D011446:Prospective Studies; D012723:Sex; D012727:Sex Characteristics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; C098069:PIGF protein, human; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: PlGF; Preeclampsia; Prenatal screening; Sexual dimorphism; sFlt-1