Necrotizing Enterocolitis: Research Agenda for a Disease of Unknown Etiology and Pathogenesis


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Abstract

INTRODUCTIONNecrotizing enterocolitis (NEC) is a significant neonatal public health problem that affects low-birth weight infants in neonatal intensive care units throughout the country. As the survival rate of low-birth weight infants continues to increase and as the number of low-birth weight births remains unchanged, we can anticipate that NEC will continue to be a cause of significant morbidity and mortality in the future.Despite many reports about NEC that describe demographic risk factors and short-term or long-term outcome, there is a paucity of basic science information about neonatal gastrointestinal physiology and pathophysiology in human preterm and even full-term infants. It has become increasingly evident that we need a much better understanding about the developmental aspects of gastrointestinal function in health and disease before we can achieve further advances in our understanding of and thus rational therapy for and prevention of NEC.The purpose of the National Institute of Child Health and Human Development conference “Necrotizing Enterocolitis: Basic Science Approaches to Gut Maturation and Pathogenesis” was to bring together basic science investigators, clinical epidemiologists, and clinical scientists to identify important areas of research that need to be applied to the problem of NEC. The concept of applying the “bench to bedside” type of collaborative research was emphasized and encouraged because many clinical neonatologists may have little scientific interaction with basic scientists. In addition, many basic scientists may be unaware of NEC and the implications for targeted research related to this disease. Finally, there have been major advances in our ability to study diseases of unknown etiology, as witnessed by recent discoveries of the microbiologic agents that cause AIDS, non A-non B hepatitis, roseola, and Whipple disease, and various agents that cause infectious diarrhea.Invited participants represented a broad spectrum of basic science and clinical disciplines and included investigators with expertise in adult gastroenterology, animal physiology, cell biology, molecular virology, host defense, inflammatory mediators, vascular physiology, surgery, pathology, and neonatology. The goals of the participants were to address the gaps in our knowledge about NEC, to reconcile basic science observations about gastrointestinal disease with those in the clinical disease, and to recommend promising areas of investigation worthy of further study. This report summarizes the current concepts of neonatal gastrointestinal physiology and pathophysiology that were presented by experts in the areas relevant to NEC. The report then presents recommendations for future areas of collaborative research initiatives to fill the gaps in our knowledge about NEC. This research agenda is also the basis of a request for applications from the National Institute of Child Health and Human Development to address the next stage of investigations. The names of the participants are included in the acknowledgement.

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