Preface

On April 15 to 16, 2005 we had the privilege of hosting the 3rd International NEC Symposium at the Children's Hospital, Columbus, Ohio, where 145 health care professionals, including physician scientists, pediatric surgeons, neonatologists, gastroenterologists, pharmacologists, neonatal nurses, and nurse practitioners, gathered to address the pathophysiology and current medical and surgical therapy of this devastating disease (Figure 1). This issue of Seminars in Pediatric Surgery highlights eight presentations from the symposium, providing a glimpse of the basic science research into the etiology of NEC, hopeful strategies for preventive and therapeutic applications of novel agents, and state-of-the-art surgical treatment for affected neonates.

View Large Image Download to PowerPoint

Figure 1. Participants in the 3rd International NEC Symposium, Children's Hospital, Columbus, Ohio. Standing left to right: Brad Warner, Moritz Ziegler, Donna Caniano, Kristina Reber, and Jane Balint. Seated left to right: Josef Neu, Henri Ford, Michael Caplan, Philip Nowicki, Gail Besner, and Larry Moss.

Ross Laboratories sponsored a research conference in 1974 that focused primarily on the clinical recognition of necrotizing enterocolitis, its epidemiology, and its causative factors. Fifteen years later, in 1989, Children's Hospital and the Wexner Institute for Pediatric Research in Columbus, Ohio convened a second conference that aimed to provide a detailed examination of the pathophysiologic mechanisms operational in NEC.

Another decade and a half have passed, and we remain confronted by the challenges of this entity and the suffering that it exacts from its fragile victims.

We understand that prematurity, especially extreme low birth weight, represents the single greatest risk factor for developing NEC. In countries with low rates of prematurity, such as Sweden and Japan, NEC is a rare disease, while in the United States it affects between 1% and 8% of neonatal intensive care unit admissions. NEC is predicted to surpass pulmonary disorders as the leading cause of mortality in premature infants.

Presently, we do not understand how to assess any given infant's risk for developing NEC, and therefore, we are unable to embark on an evidence-based preventive strategy. Dr. Neu and colleagues review the role of intestinal immaturity in premature infants as an underlying feature in altered microbial colonization, response to nutritional factors, and propensity to inflammatory injury. In their paper, Drs. Caplan and Jilling elaborate on the accumulating evidence of an imbalance between an activated proinflammatory response and an inadequate antiinflammatory protection in the immature gut, leading to the histologic findings of intestinal necrosis. Dr. Nowicki offers an elegant description of the unique microvascular derangements in immature neonatal intestine, with specific elucidation of the balance between the endothelial production of the vasoconstrictor peptide-1 and the endothelial production of the vasodilator free radical nitric oxide.

The critical role of nitric oxide, as postulated by Dr. Ford and colleagues, may be central to the molecular signaling pathway for gut barrier failure as seen in NEC. Their work examines various genetic and biochemical molecular markers that may offer ways to stratify infants at risk for NEC. Dr. Besner and colleagues provide compelling evidence for a cytoprotective, and potentially therapeutic, role for heparin-binding EGF-like growth factor in intestinal recovery from ischemia/reperfusion injury. Drs. Warner and Warner review the role of epidermal growth factor in intestinal development and mucosal repair, and postulate that deficient production of this trophic agent may be involved in the development of NEC.

As noted by Drs. Henry and Moss, the surgical treatment for NEC has proceeded without a systematic and rigorous evaluation of optimal interventions. They evaluate the role of meta-analysis in defining “best treatments” for surgical diseases, finding that prospective, randomized clinical trials are rare in pediatric surgery. The current NIH-funded clinical trial for infants with NEC with its two treatment arms of laparotomy versus primary peritoneal drainage is expected to be completed by mid-2005, with the hope of shedding light on the most efficacious therapeutic approach. Drs. Petty and Ziegler summarize the various operative strategies that may be employed for minimizing intestinal loss in NEC, for maximizing intestinal surface area in short bowel syndrome, and for enhancing peristaltic function in dysmotile residual intestine.

The success of the 3rd International NEC Symposium was realized by outstanding presentations in the plenary and poster sessions and by lively audience participation. We are indebted to the staff of the Children's Hospital Institute for Pediatric Education for their assistance in all aspects of the planning, funding, and organization of the symposium. We thank Ross Products Division of Abbott Laboratories and Mead Johnson Nutritionals for providing educational grant support. To Dr. Jay L. Grosfeld we offer our profound thanks for giving us this issue of Seminars in Pediatric Surgery to showcase the basic science and clinical work of these dedicated and talented individuals.