title: Changes in uterine artery Doppler velocimetry and circulating angiogenic factors in the first half of pregnancies delivering a small-for-gestational-age neonate.
abstract: OBJECTIVE
  To assess the relationship between longitudinal changes in placental Doppler indices and maternal circulating angiogenic factors in the first half of pregnancy and delivery of a small-for-gestational-age (SGA) neonate, and ascertain whether longitudinal evaluation of these variables improves the prediction achieved by second-trimester cross-sectional evaluation.
  
  
  METHODS
  From a prospective cohort of unselected singleton pregnancies undergoing first-trimester screening for aneuploidy, 138 were included in this study. Of these, 46 were complicated by SGA (delivering after 34 weeks' gestation with a birth weight < 10thcentile) and 92 were appropriate-for-gestational-age (AGA) pregnancies, which were included as controls (ratio 1:2). First-to-second trimester longitudinal changes in uterine artery (UtA) Doppler indices and maternal circulating levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were analyzed.
  
  
  RESULTS
  Compared with the AGA group, SGA pregnancies had significantly higher UtA impedance in the first (Z-score: 0.46 vs -0.57; P < 0.001) and second (Z-score: 1.71 vs -0.75; P < 0.001) trimesters. Likewise, the sFlt-1/PlGF ratio was significantly higher in SGA than in AGA pregnancies in the first (98.0 vs 67.9; P = 0.01) and early second (22.4 vs 8.8; P < 0.001) trimesters. The predictive performance of the longitudinal changes in UtA Doppler indices for SGA was significantly lower than that of second-trimester cross-sectional values (area under receiver-operating characteristics curve (AUC), 60.8% vs 84.3%; P = 0.0035). The detection rate of SGA, at a 10% false-positive rate (FPR), was 17.7% by longitudinal changes in UtA Doppler and 56.2% by second-trimester cross-sectional UtA Doppler values. Similarly, the predictive performance of the longitudinal changes in PlGF was significantly lower than that of early second-trimester cross-sectional values (AUC, 71.4% vs 76.5%; P = 0.008). The detection rate of SGA at a 10% FPR was 40.6% when screening by longitudinal changes in PlGF and 52.1% when screening by early second-trimester cross-sectional values.
  
  
  CONCLUSIONS
  First- and second-trimester UtA Doppler velocimetry and maternal circulating angiogenic markers have clinical utility as a cross-sectional assessment for the identification of pregnancies at high risk of delivering a SGA neonate, however, they do not improve prediction when their longitudinal changes are used. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: Fetal i+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Center for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Triunfo
authors.affiliation: Fetal i+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Center 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: Biochemistry and Molecular Biology Research Centre for Nanomedicine, Hospital Univeritari Vall d'Hebron, Barcelona, and Centre for Biomedical Research on Rare Disease (CIBER-ER), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Rodriguez-Sureda
authors.affiliation: Obstetrics, Gynecology and Reproductive Medicine Department, Institut Universitari Dexeus, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Scazzocchio
authors.affiliation: Fetal i+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Center for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Crispi
authors.affiliation: Biochemistry and Molecular Biology Research Centre for Nanomedicine, Hospital Univeritari Vall d'Hebron, Barcelona, and Centre for Biomedical Research on Rare Disease (CIBER-ER), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Dominguez
authors.affiliation: Fetal i+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Center for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Gratacos
authors.affiliation: Fetal i+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Center for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Figueras
mesh_terms: D000328:Adult; D000782:Aneuploidy; D003430:Cross-Sectional Studies; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D007236:Infant, Small for Gestational Age / Q000378:metabolism*; D008423:Maternal Age; D008565:Membrane Proteins / Q000097:blood; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood; D011262:Pregnancy Trimester, Second; D011446:Prospective Studies; D018608:Ultrasonography, Doppler / Q000379:methods*; D016216:Ultrasonography, Prenatal / Q000379:methods*; D055988:Uterine Artery / Q000000981:diagnostic imaging*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D008565:Membrane Proteins; C098069:PIGF protein, human; D011257:Pregnancy Proteins; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: early second trimester; first trimester; placental growth factor; small-for-gestational age; soluble fms-like tyrosine kinase-1; uterine  artery Doppler