title: Understanding intestinal vulnerability to perforation in the extremely low birth weight infant.
abstract: Spontaneous intestinal perforation (SIP) occurs commonly in extremely low birth weight (ELBW) infants. Our understanding of its etiologies has improved dramatically over the last decade. Included in this comprehension is an ongoing reconciliation of the iatrogenic risk factors, the microbiology, and the histopathology. The latter shows focal perforations with necrosis of the muscularis externa and no sign of ischemic damage (typically characterized by mucosal necrosis in the preterm bowel). Associations include extreme prematurity, early postnatal steroids (EPS), early use of indomethacin (EUI), and two common pathogens (Candida and Staphylococcus epidermis). Animal models of SIP suggest that all risk factors converge on a common collection of signaling pathways: those of nitric oxide synthases (NOS), insulin-like growth factors (IGFs), and epidermal growth factors (EGFs). Many of these factors skew trophism of the ileum (defined as thinning of the submucosa concomitant with hyperplasia of the muscosa). Global depletion of NOS is associated with disturbed intestinal motility and diminished transforming growth factor-alpha (TGF-alpha) in the muscularis externa. This constellation of insults seems to make the distal intestine vulnerable to perforation during recovery of motility.
authors.affiliation: Department of Pediatrics, Ochsner Health System, New Orleans, Louisiana, 70121, USA. pvgordon@ochsner.org
authors.forename: Phillip V
authors.initials: PV
authors.lastname: Gordon
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D003141:Communicable Diseases / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005769:Gastrointestinal Motility; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007213:Indomethacin / Q000009:adverse effects; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007416:Intestinal Perforation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009336:Necrosis; D011247:Pregnancy; D011248:Pregnancy Complications / Q000382:microbiology / Q000473:pathology; D012307:Risk Factors; D012422:Rupture, Spontaneous; D015398:Signal Transduction; D013256:Steroids / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013256:Steroids; D007213:Indomethacin