Physiologic and histologic changes in near-term fetal lambs exposed to asphyxia by partial umbilical cord occlusion

Am J Obstet Gynecol. 1998 Jan;178(1 Pt 1):24-32. doi: 10.1016/s0002-9378(98)70621-0.


Objectives: Our purpose was to characterize the histologic changes in the asphyxiated fetal lamb brain and to correlate the severity of these changes with fetal physiologic parameters during and after asphyxia.

Study design: Seventeen near-term fetuses were used for analysis: control group without manipulation (n = 4, 132 +/- 1.1 days of gestation at autopsy, mean +/- SEM), sham-asphyxia control group (n = 3, 132 +/- 1.3 days), and asphyxiated group, which successfully survived 72 hours after asphyxia (n = 10, 130 +/- 1.0 days). Asphyxia was produced by umbilical cord occlusion lasting for approximately 60 minutes until fetal arterial pH diminished to < 6.9 and base excess to < -20 mEq/L. Fetal heart rate, blood pressure, and electrocorticographic activity were continuously monitored. The fetuses were killed 72 hours after asphyxia, and the brains were fixed in formalin and processed for histologic and immunocytochemical studies.

Results: Neuropathologic changes varied from case to case, ranging from almost total infarction of cortical and subcortical structures to extremely subtle and patchy white matter alterations characterized by slight vacuolization of the white matter or slight to moderate increases in cellularity confined to the junction of cerebral cortex and white matter. Even fetuses that showed full recovery of all physiologic parameters, including electrocorticographic activity, demonstrated subtle but distinct white matter lesions. The gray matter, including the hippocampal neurons, was generally spared in these cases. Electrocorticographic parameters, duration of hypotension during asphyxia, and delayed recovery of blood lactate concentrations correlated well with the histologic grading of brain damage.

Conclusions: Asphyxia by partial umbilical cord occlusion in near-term fetal lambs produces variable neuropathologic changes. The mildest change is a white matter lesion characterized by vacuolization and loss of myelin or by increased cellularity in the damaged regions.

MeSH terms

  • Animals
  • Asphyxia / embryology*
  • Asphyxia / pathology
  • Asphyxia / physiopathology
  • Blood Glucose / analysis
  • Carbon Dioxide / blood
  • Cerebral Cortex / pathology*
  • Female
  • Fetal Diseases / embryology
  • Fetal Diseases / pathology*
  • Fetal Diseases / physiopathology*
  • Hydrogen-Ion Concentration
  • Lactates / blood
  • Oxygen / blood
  • Pregnancy
  • Sheep
  • Time Factors
  • Umbilical Arteries / physiology
  • Umbilical Cord / pathology
  • Umbilical Cord / physiopathology*


  • Blood Glucose
  • Lactates
  • Carbon Dioxide
  • Oxygen