The clinical, morphologic, and molecular changes in the ileum associated with early postnatal dexamethasone administration: from the baby's bowel to the researcher's bench.
Focal small bowel perforation (FSBP) is a life-threatening event that predominantly affects extremely low birth weight (ELBW) infants. Histopathology from surgical specimens of ileum with FSBP shows a healthy mucosa overlying a thinned muscularis with segmental degeneration. Clinical data strongly support an association between early postnatal administration of dexamethasone (EPD) and FSBP. Additional risk factors, including gestational age, administration of prophylactic indomethacin, and severity of illness, may be synergistic with EPD for the pathogenesis of perforations. Animal models of dexamethasone administration show morphologic changes in the ileum, similar to those seen in ELBW infants, including increased mucosal maturation and thinning of the muscularis. These tissue-specific differences may be mediated by a perturbation in growth factor expression or accumulation. In support of this hypothesis, dexamethasone has been associated with increased IGF-I immunolocalization in the mucosa and decreased immunolocalization in the muscularis. The known growth-promoting functions of IGF-I are consistent with the observed dexamethasone-associated changes within both the mucosa and the muscularis. Ongoing studies in this animal model are exploring the potential mechanisms by which dexamethasone might affect IGF-I availability.
Gordon
P V
PV
Division of Neonatalogy, University of Virginia, Charlottesville, Virginia 22908, USA. PVG4N@virginia.edu
Marshall
D D
DD
Stiles
A D
AD
Price
W A
WA
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D007082:Ileum / Q000002:abnormalities* / Q000187:drug effects* / Q000196:embryology*; D007213:Indomethacin / Q000627:therapeutic use; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D051379:Mice; D008954:Models, Biological; D012965:Sodium Chloride / Q000494:pharmacology
D012965:Sodium Chloride; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D007213:Indomethacin