title: Quantitative assessment of placental morphology may identify specific causes of stillbirth.
abstract: BACKGROUND
  Stillbirth is frequently the result of pathological processes involving the placenta. Understanding the significance of specific lesions is hindered by qualitative subjective evaluation. We hypothesised that quantitative assessment of placental morphology would identify alterations between different causes of stillbirth and that placental phenotype would be independent of post-mortem effects and differ between live births and stillbirths with the same condition.
  
  
  METHODS
  Placental tissue was obtained from stillbirths with an established cause of death, those of unknown cause and live births. Image analysis was used to quantify different facets of placental structure including: syncytial nuclear aggregates (SNAs), proliferative cells, blood vessels, leukocytes and trophoblast area. These analyses were then applied to placental tissue from live births and stillbirths associated with fetal growth restriction (FGR), and to placental lobules before and after perfusion of the maternal side of the placental circulation to model post-mortem effects.
  
  
  RESULTS
  Different causes of stillbirth, particularly FGR, cord accident and hypertension had altered placental morphology compared to healthy live births. FGR stillbirths had increased SNAs and trophoblast area and reduced proliferation and villous vascularity; 2 out of 10 stillbirths of unknown cause had similar placental morphology to FGR. Stillbirths with FGR had reduced vascularity, proliferation and trophoblast area compared to FGR live births. Ex vivo perfusion did not reproduce the morphological findings of stillbirth.
  
  
  CONCLUSIONS
  These preliminary data suggest that addition of quantitative assessment of placental morphology may distinguish between different causes of stillbirth; these changes do not appear to be due to post-mortem effects. Applying quantitative assessment in addition to qualitative assessment might reduce the proportion of unexplained stillbirths.
authors: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL UK ; Maternal and Fetal Health Research Centre, 5th floor (Research), St Mary's Hospital, Oxford Road, Manchester, M13 9WL UK.
authors: Imogen
authors: I
authors: Ptacek
authors: Department of Histopathology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL UK.
authors: Anna
authors: A
authors: Smith
authors: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL UK ; Maternal and Fetal Health Research Centre, 5th floor (Research), St Mary's Hospital, Oxford Road, Manchester, M13 9WL UK.
authors: Ainslie
authors: A
authors: Garrod
authors: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL UK ; Maternal and Fetal Health Research Centre, 5th floor (Research), St Mary's Hospital, Oxford Road, Manchester, M13 9WL UK.
authors: Sian
authors: S
authors: Bullough
authors: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL UK ; Maternal and Fetal Health Research Centre, 5th floor (Research), St Mary's Hospital, Oxford Road, Manchester, M13 9WL UK.
authors: Nicola
authors: N
authors: Bradley
authors: Department of Histopathology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL UK.
authors: Gauri
authors: G
authors: Batra
authors: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL UK ; Maternal and Fetal Health Research Centre, 5th floor (Research), St Mary's Hospital, Oxford Road, Manchester, M13 9WL UK.
authors: Colin P
authors: CP
authors: Sibley
authors: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL UK ; Maternal and Fetal Health Research Centre, 5th floor (Research), St Mary's Hospital, Oxford Road, Manchester, M13 9WL UK.
authors: Rebecca L
authors: RL
authors: Jones
authors: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL UK ; Maternal and Fetal Health Research Centre, 5th floor (Research), St Mary's Hospital, Oxford Road, Manchester, M13 9WL UK.
authors: Paul
authors: P
authors: Brownbill
authors: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL UK ; Maternal and Fetal Health Research Centre, 5th floor (Research), St Mary's Hospital, Oxford Road, Manchester, M13 9WL UK.
authors: Alexander E P
authors: AE
authors: Heazell
keywords: Avascular villi; Fetal Growth Restriction; Placental Morphometry; Stillbirth; Unexplained Stillbirth; Villous vascularity