Neonatal mice that are missing a gene encoding a growth factor important in the body’s response to cellular injury are more likely to develop necrotizing enterocolitis (NEC), a severely damaging gastrointestinal disease common in premature infants. Yet, adding the growth factor into daily feedings reverses this susceptibility. These are the findings from the Center for Perinatal Research at The Research Institute at Nationwide Children’s Hospital.
“Necrotizing enterocolitis, NEC, is the most common acquired intraabdominal emergency in infants and the most common surgical emergency in the neonatal intensive care unit,” said Gail Besner, MD, principal investigator in the Center for Perinatal Research and the study’s lead author. “Although evidence suggests that neonatal risk factors including prematurity, asphyxia, , reduced intestinal microvascular blood flow, and formula feeding all contribute to the occurrence of NEC, the pathogenesis of this disease remains unclear.”
Heparin-binding epidermal-like growth factor (HB-EGF) is a protein expressed in a large number of tissues and plays a role in the earliest cellular responses to injury. Previous studies from the Center for Perinatal Research have shown that adult mice that are lacking the HB-EGF gene are increasingly susceptible to intestinal injury when they experience decreased levels of blood flow and oxygen. However this current study, which appears in the Journal of Pediatric Surgery, examines the effect in a neonatal model.
To demonstrate the role HB-EGF plays in neonatal intestinal injury, Dr. Besner and colleagues examined newborn mice born with or without the HB-EGF gene that were inflicted with NEC. An additional group of mice born without the HB-EGF gene received HB-EGF added to each of their feeds. The team examined the gastrointestinal tract of all groups and found that mice born without the gene had a significantly increased incidence of NEC. However, those that received HB-EGF-fortified formula showed a significant decrease in the incidence of NEC, with decreased severity.
“These data support the theory that HB-EGF expression is important in protecting the intestines from NEC,” said Dr. Besner, who is also a surgeon at Nationwide Children’s. “A unique finding was that administering HB-EGF-fortified-formula can compensate for the lack of naturally-occurring HB-EGF. This supports the concept of clinical administration of HB-EGF to patients with or at-risk for developing NEC to prevent the progression or development of the disease.”Radulescu A, Yu X, Orvets ND, Chen Y, Zhang HY, Besner GE. Deletion of the heparin-binding epidermal growth factor-like growth factor gene increases susceptibility to necrotizing enterocolitis. J Pediatr Surg. 2010 Apr;45(4):729-34.