title: Association of first-trimester angiogenic factors with placental histological findings in late-onset preeclampsia.
abstract: OBJECTIVE
  To explore in women with late-onset preeclampsia (PE) the association between maternal levels of angiogenic/antiangiogenic factors in the first trimester of pregnancy and histological findings attributable to placental underperfusion (PUP).
  
  
  METHODS
  A nested case-control cohort study was conducted in 73 women with pregnancies complicated by late-onset PE (>34 weeks at delivery) matched with controls. First trimester uterine artery Doppler (UtA); maternal levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were retrieved. Placentas were histologically evaluated using a hierarchical and standardized classification system. One-way ANOVA with linear polynomial contrast or linear-by-linear association test was performed to test the hypothesis of a linear association across study groups (controls, PE without PUP and PE with PUP).
  
  
  RESULTS
  In 54 (74%) placentas, 89 placental histological findings qualifying for PUP were found. Across study groups, significant values were observed in maternal levels of decreased PlGF (MoM values: 1.53, 1.41 and 1.37; p < 0.001), increased sFlt-1 (MoM values: 3.11, 3.11 and 3.22; p = 0.002), increased sFlt-1/PlGF ratio (MoM values: 2.3, 2.3 and 2.44; p < 0.001), abnormal UtA Doppler (MoM values: 1, 1.26 and 1.32; p < 0.001), and worse perinatal outcomes in terms of gestational age at delivery, cesarean section for not reassuring fetal status, birth weight and neonatal acidosis.
  
  
  CONCLUSIONS
  In late-onset PE an imbalance of circulating angiogenic and anti-angiogenic factors already present at 8-10 weeks of pregnancy was associated with histological findings reflecting placental insufficiency. An early first trimester screening by angiogenic factors might help to identify patients with placental involvement among late-onset PE cases.
  
  
  CONCLUSIONS
  In late-onset preeclampsia, first-trimester uterine Doppler and circulating levels of angiogenic/antiangiogenic factors are associated with placental underperfusion.
authors.affiliation: BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain. Electronic address: TRIUNFO@clinic.ub.es.
authors.forename: Stefania
authors.initials: S
authors.lastname: Triunfo
authors.affiliation: BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain; Ca' Granda, Ospedale Maggiore Policlinico, Dipartimento Ostetricia e Ginecologia, Università degli Studi di Milano, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Crovetto
authors.affiliation: BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Fatima
authors.initials: F
authors.lastname: Crispi
authors.affiliation: Biochemistry and Molecular Biology Research Centre for Nanomedicine, Hospital Univeritari Vall d'Hebron, Centre for Biomedical Research on Rare Disease (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Rodriguez-Sureda
authors.affiliation: Biochemistry and Molecular Biology Research Centre for Nanomedicine, Hospital Univeritari Vall d'Hebron, Centre for Biomedical Research on Rare Disease (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Dominguez
authors.affiliation: Department of Pathology, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Nadal
authors.affiliation: BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Peguero
authors.affiliation: BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Gratacos
authors.affiliation: BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Figueras
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D000072483:Placenta Growth Factor / Q000097:blood*; D010927:Placental Insufficiency / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D018615:Ultrasonography, Doppler, Color; D016216:Ultrasonography, Prenatal; D055988:Uterine Artery / Q000000981:diagnostic imaging; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: First trimester screening; Histological findings; Placental growth factor; Placental underperfusion; Preeclampsia; Soluble fms-like tyrosine kinase-1