Chorioamnionitis: New ideas from experimental models

Chorioamnionitis is defined as the inflammatory response of the membranes, placenta and amniotic fluid to a microbial invasion of the amniotic cavity. Preterm birth is frequently associated with chorioamnionitis which increases the risk of adverse neonatal outcomes. However, many aspects of chorioamnionitis, such as its causes, time of onset and the fetal responses, are still unclear. This short review presents the latest evidence in this field obtained from studies in an animal model (pregnant sheep) where chorioamnionitis was induced by injections of lipopolysaccharide (LPS) or Ureaplasma species into the amniotic cavity under ultrasound guidance.
LPS-induced chorioamnionitis resulted in a cascade of organ injury, inflammation, and remodeling which caused alveolar and microvascular simplification similar to bronchopulmonary dysplasia. Importantly, these organ-specific changes were accompanied by systemic effects determining immune suppression against several Toll-like receptor agonists (cross-tolerance). This may be an interesting mechanism whereby the fetus adapts to inflammation in the amniotic cavity.
Ureaplasma species can be detected in 60–80% of adults. However, the pathogenic importance of Ureaplasma still remains unclear. In the sheep model, intra-amniotic injections of Ureaplasma resulted in chorioamnionitis and a pulmonary inflammatory response. In acute infections, the pulmonary inflammation affected the fetal lung structure, whereas in long-term infection the lung structure was only mildly affected. Overall, the postnatal effects of intra-amniotic exposure to Ureaplasma were mild. This evidence supports the hypothesis that the time of infection has an effect on changes in the fetal lung; however, the effects on the fetal immune system remain to be studied.
In conclusion, experimental and clinical data suggest that chorioamnionitis is a multi-organ disease of the fetus. Animal models can be helpful to understand the mechanisms of disease and to further develop antenatal interventions such as glucocorticoids, vitamin A and IL-1 receptor antagonist. Additional clinical data are necessary to understand the role of chorioamnonitis in the outcome of preterm babies. In particular, the collection of histologic data from the membranes, placenta and cord may be helpful to analyze the neonatal outcomes in the context of antenatal exposure to inflammation.

Top