title: Angiogenic factors at diagnosis of late-onset small-for-gestational age and histological placental underperfusion.
abstract: OBJECTIVE
  This study was designed to explore the association between angiogenic factors levels at diagnosis of small-for-gestational age (SGA) and placental underperfusion (PUP).
  
  
  METHODS
  In a cohort of SGA singleton pregnancies, each delivered at >34 weeks, uterine (UtA), umbilical (UA), and middle cerebral (MCA) arteries were evaluated by Doppler upon diagnosis of SGA status. In addition, maternal circulating concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by ELISA, and each placenta was evaluated for histologic signs of PUP using a hierarchical and standardized classification system. Logistic regression was applied to analyze independent relationships (at diagnosis) between angiogenic factors and Doppler parameters.
  
  
  RESULTS
  A total of 122 suspected SGA pregnancies were studied, 70 (57.4%) of which ultimately met PUP criteria. In this group, 85 placental findings qualified as PUP. Both mean UtA pulsatility index z-values (1.26 vs. 0.84; p = 0.038) and PlGF multiples of normal median (0.21 vs. 0.55; p = 0.002) differed significantly in pregnancies with and without PUP, respectively. By logistic regression, PlGF alone was independently predictive of PUP (OR = 0.11 [95% CI 0.025-0.57]; p = 0.008).
  
  
  CONCLUSIONS
  Histologic placental abnormalities in term SGA neonates reflect latent insufficiency in uteroplacental blood supply. The heightened risk of adverse perinatal outcomes in this context underscores a need for new Doppler or biochemical prenatal markers of placental disease. Angiogenic factors may be pivotal identifying SGA neonates.
  
  
  CONCLUSIONS
  Diminished circulating levels of placental growth factor, determined upon discovery of SGA status, are associated with histologic evidence of PUP.
authors.affiliation: BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain; Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: S
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, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain; Frauenklinik und Poliklinik, Technische Universität München, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lobmaier
authors.affiliation: BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain; Maternal-Fetal Unit, CEDIFETAL, Centro de Diagnóstico de Ultrasonido e Imágenes, CEDIUL, Colombia.
authors.forename: M
authors.initials: M
authors.lastname: Parra-Saavedra
authors.affiliation: BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and 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: F
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, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Peguero
authors.affiliation: Department of Pathology, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: A
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, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: E
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, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain. Electronic address: ffiguera@clinic.ub.es.
authors.forename: F
authors.initials: F
authors.lastname: Figueras
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D010920:Placenta / Q000098:blood supply* / Q000473:pathology; D010922:Placenta Diseases / Q000175:diagnosis*; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011673:Pulsatile Flow; D016216:Ultrasonography, Prenatal; D014469:Umbilical Arteries / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D055988:Uterine Artery / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Doppler; Fetal growth restriction; Placental growth factor; Placental lesions; Placental underperfusion; Soluble fms-like tyrosine kinase-1