title: Unfractionated heparin and placental pathology in high-risk pregnancies: secondary analysis of a pilot randomized controlled trial.
abstract: BACKGROUND
  Heparin is often prescribed during pregnancy with the intention of improving perinatal outcomes on the basis that it exerts an anticoagulant action in the inter-villous space. Accumulating in-vitro and in-vivo evidence indicates that heparin's beneficial effects in pregnancy may result from 'non-anticoagulant' effects including the promotion of angiogenesis.
  
  
  METHODS
  To study the effect of heparin within the placenta, we performed secondary analyses on a pilot trial where 32 women with negative thrombophilia screens and second-trimester evidence of placental insufficiency were randomized to standard care or antenatal self-administration of unfractionated heparin (UFH) 7500 IU twice-daily. Serial placental ultrasound images were reviewed and compared with histo-pathologic findings following delivery.
  
  
  RESULTS
  There were no differences between the two arms in either the evolution of abnormal placental lesions on ultrasound (p = 0.75) or evidence of maternal vascular under-perfusion on histopathology (p = 0.89). In pregnancies considered at increased risk for adverse pregnancy outcomes based on previous history or abnormal serum marker screen, early (second-trimester) placental ultrasound, reflecting developmental pathology had better test characteristics (sensitivity 77.8%; positive predictive value 80.8%) for predicting adverse pregnancy outcomes than third-trimester ultrasound that is reflective of placental thrombotic injury.
  
  
  CONCLUSIONS
  Administration of UFH did not prevent the development or evolution of abnormal placental lesions on placental ultrasound or evidence of maternal vascular underperfusion on placental histo-pathology. Second-trimester placental ultrasound may be of value in predicting those at greatest risk of adverse outcomes.
authors.affiliation: Departments of Obstetrics & Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: D'Souza
authors.affiliation: Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Keating
authors.affiliation: Departments of Obstetrics & Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Walker
authors.affiliation: Departments of Obstetrics & Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Drewlo
authors.affiliation: Departments of Obstetrics & Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. Electronic address: john.kingdom@utoronto.ca.
authors.forename: J
authors.initials: J
authors.lastname: Kingdom
mesh_terms: D000328:Adult; D005260:Female; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010865:Pilot Projects; D010920:Placenta / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology*; D010927:Placental Insufficiency / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second; D018566:Pregnancy, High-Risk; D016896:Treatment Outcome; D016216:Ultrasonography, Prenatal
chemical_list: D006493:Heparin
keywords: Adverse pregnancy outcomes; Placental histopathology; Placental ultrasound; Pregnancy; Unfractionated heparin