title: Placental Features of Late-Onset Adverse Pregnancy Outcome.
abstract: OBJECTIVE
  Currently, no investigations reliably identify placental dysfunction in late pregnancy. To facilitate the development of such investigations we aimed to identify placental features that differ between normal and adverse outcome in late pregnancy in a group of pregnancies with reduced fetal movement.
  
  
  METHODS
  Following third trimester presentation with reduced fetal movement (N = 100), placental structure ex vivo was measured. Placental function was then assessed in terms of (i) chorionic plate artery agonist responses and length-tension characteristics using wire myography and (ii) production and release of placentally derived hormones (by quantitative polymerase chain reaction and enzyme linked immunosorbant assay of villous tissue and explant conditioned culture medium).
  
  
  RESULTS
  Placentas from pregnancies ending in adverse outcome (N = 23) were ~25% smaller in weight, volume, length, width and disc area (all p<0.0001) compared with those from normal outcome pregnancies. Villous and trophoblast areas were unchanged, but villous vascularity was reduced (median (interquartile range): adverse outcome 10 (10-12) vessels/mm2 vs. normal outcome 13 (12-15), p = 0.002). Adverse outcome pregnancy placental arteries were relatively insensitive to nitric oxide donated by sodium nitroprusside compared to normal outcome pregnancy placental arteries (50% Effective Concentration 30 (19-50) nM vs. 12 (6-24), p = 0.02). Adverse outcome pregnancy placental tissue contained less human chorionic gonadotrophin (20 (11-50) vs. 55 (24-102) mIU/mg, p = 0.007) and human placental lactogen (11 (6-14) vs. 27 (9-50) mg/mg, p = 0.006) and released more soluble fms-like tyrosine kinase-1 (21 (13-29) vs. 5 (2-15) ng/mg, p = 0.01) compared with normal outcome pregnancy placental tissue.
  
  
  CONCLUSIONS
  These data provide a description of the placental phenotype of adverse outcome in late pregnancy. Antenatal tests that accurately reflect elements of this phenotype may improve its prediction.
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, M13 9WL, United Kingdom; Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, United Kingdom.
authors.forename: Lucy E
authors.initials: LE
authors.lastname: Higgins
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, M13 9WL, United Kingdom; Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, United Kingdom.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rey de Castro
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, M13 9WL, United Kingdom; Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, United Kingdom.
authors.forename: Naa
authors.initials: N
authors.lastname: Addo
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, M13 9WL, United Kingdom; Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Wareing
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, M13 9WL, United Kingdom; Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, United Kingdom.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Greenwood
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, M13 9WL, United Kingdom; Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, United Kingdom.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Jones
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, M13 9WL, United Kingdom; Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, United Kingdom.
authors.forename: Colin P
authors.initials: CP
authors.lastname: Sibley
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, M13 9WL, United Kingdom; Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, United Kingdom.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Johnstone
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, M13 9WL, United Kingdom; Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, United Kingdom.
authors.forename: Alexander E P
authors.initials: AE
authors.lastname: Heazell
mesh_terms: D000328:Adult; D004703:Endocrine System / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology; D005324:Fetal Movement; D006801:Humans; D010920:Placenta / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011263:Pregnancy Trimester, Third / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050497:Stillbirth
chemical_list: D012333:RNA, Messenger