Abstract
Fetal hypoxic episodes may occur antepartum with the potential to induce systemic and cerebral inflammatory responses thereby contributing to brain injury. We hypothesized that intermittent umbilical cord occlusions (UCOs) of sufficient severity but without cumulative acidosis will lead to a fetal inflammatory response. Thirty-one chronically instrumented fetal sheep at ∼0.85 of gestation underwent four consecutive days of hourly UCOs from one to three minutes duration for six hours each day. Maternal and fetal blood samples were taken for blood gases/pH and plasma interleukin (IL)-1β and IL-6 levels. Animals were euthanized at the end of experimental study with brain tissue processed for subsequent counting of microglia and mast cells. Intermittent UCOs resulted in transitory fetal hypoxemia with associated acidemia which progressively worsened the longer umbilical blood flow was occluded, but with no cumulative blood gas or pH changes over the four days of study. Fetal arterial IL-1β and IL-6 values showed no significant change regardless of the severity of the UCOs, nor was there any evident impact on the microglia and mast cell counts for any of the brain regions studied. Accordingly, intermittent UCOs of up to three minutes duration with severe, but limited fetal hypoxemia and no cumulative acidemia, do not result in either a systemic or brain inflammatory response in the pre-term ovine fetus. However, fetal IL-1B and IL-6 values were found to be well correlated with corresponding maternal values supporting the placenta as a primary source for these cytokines with related secretion into both circulations. Female fetuses were also found to have higher IL-1β levels than males, indicating that gender may impact on the fetal inflammatory response to various stimuli.
Highlights
Study in the ovine fetus with repetitive umbilical cord occlusions (UCOs) leading to severe acidemia as might be seen clinically during human labour, has shown an inflammatory response with an increase in plasma IL-1 b levels at the time of maximal acidosis, and an increase in microglia and mast cells within the brain as measured 24 hours thereafter [1]
Intermittent UCOs as studied resulted in transitory fetal hypoxemia with associated acidemia which was most pronounced in the severe UCO group as expected with umbilical blood flow occluded the longest
While UCO insults resulted in moderate to severe degrees of fetal hypoxia and hypercapnia, for the most part there was complete recovery post occlusion with no cumulative blood gas or pH changes observed throughout the 4 days of study either at baseline pre-occlusion or during the UCOs
Summary
Study in the ovine fetus with repetitive umbilical cord occlusions (UCOs) leading to severe acidemia as might be seen clinically during human labour, has shown an inflammatory response with an increase in plasma IL-1 b levels at the time of maximal acidosis, and an increase in microglia and mast cells within the brain as measured 24 hours thereafter [1]. Variable fetal heart rate (FHR) decelerations suggesting umbilical cord compression and resultant fetal hypoxemia are seen clinically in 2% to 10% of antenatal FHR recordings nearterm [9,10,11] and have been associated with increased risk for nuchal cord at delivery and adverse neonatal outcome In this regard, the association of infants with a symptomatic and/or tight nuchal cord at delivery and the later development of subclinical neurodevelopmental deficits [12] and cerebral palsy [13] implicate a role for chronic intermittent UCO insults antenatally in longerterm injury to the brain. We have previously shown in the ovine fetus that intermittent UCO over a four day period does lead to a low level of necrotic appearing cells in the gray matter [14] and a marginal increase in apoptotic appearing cells in the hippocampus [15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
