SIP histopathology is associated with robust mucosa, with or without submucosal hemorrhage, and segmental/focal necrosis or absence of muscularis externa. These findings are not consistent with an ischemic insult. While some cases of SIP (especially in larger infants) can be associated with congenital deficits in the muscularis layer of the bowel, theories have been developed for the unique association of SIP with perinatal stress and postnatal early steroids and indomethacin exposure. The following sequence of events has been proposed: Steroids promote mucosal growth at the expense of bowel wall integrity with thinning of the submucosal layer. Indomethacin, in combination with steroids, causes a transient ileus due to depletion of nitric oxide synthase. Swallowing of air and return of bowel motility at about 7 days' age leads to increased intraluminal pressure in the bowel leading to bowel perforation.