Pathophysiology 21 (2014) 1–2
Preface
Neonatal Necrotizing Enterocolitis (NEC) is a major cause of mortality and significant morbidity, often in premature infants with an inverse relationship to gestation, and may occur uncommonly in term infants. Despite advances in neonatal intensive care, its incidence, morbidity and mortality has remained unchanged. Some Neonatologists have attributed this to saving smaller and sicker extremely low birth weight premature infants with advances in MaternalFetal Medicine and neonatal care. Complications arising from NEC may lead to prolong or repeated hospitalizations, and on rare occasions require intestinal and/or liver transplantation in patients with short gut syndrome. The financial and emotional burden to families of these patients can be ‘life changing’. As the name indicates, definitive diagnosis is either histopathological with its characteristic findings of inflammatory response, pneumatosis, bacterial overgrowth and coagulation necrosis; or radiological with the findings of intramural gas (pneumatosis intestinalis), hepatic portal gas or pneumoperitoneum which are seen in advanced stage of this disease. It may have an insidious or rapid onset masquerading as ‘feeding intolerance’ (Stage I NEC), Septicemia or as isolated ileo-colic perforation. This problem is compounded by our inability to diagnose NEC in its early stages with a ‘chalice test’ which continues to elude clinical investigators. Thus clinicians face a dilemma whether to deprive enteral nutrition in ‘growing premature infant with feeding intolerance’ with its potential of inhibiting gut development, or place them on antibiotics and altering gut flora possibly resulting in increase of NEC risk, or continue feeding and cause “NEC totalis” and short gut syndrome or death. Although the jury is still out on the definitive management of NEC, several clinical studies have suggested a cautious approach to increasing enteral feeding preferably with breast milk, use of selected probiotics, not administering blood transfusion during or in proximity to enteral feeding, and prudent use of antibiotics and discontinuing them promptly, particularly in premature infants at hi-risk of developing NEC. This approach has arisen from observations of management of at-risk patients in NICUs with very low prevalence 0928-4680/$ – see front matter. Published by Elsevier Ireland Ltd http://dx.doi.org/10.1016/j.pathophys.2014.01.002
of NEC and a unified consistent feeding practice amongst neonatologists. The past decade has been punctuated by elegant research in basic sciences at microbial, molecular, cellular and genetic levels to understand the relationship between gut colonization, inflammation and injury to the developing gut leading to the pathophysiology of NEC. Unfortunately there is no “ideal” animal model of NEC which replicates the variable clinical course of the disease in premature infants, and rarer presentation in term newborn infants. In this issue of the journal, experts with extensive experience in the clinical management and basic research experience in NEC have reviewed their respective topics. Drs. Huda, Pramanik and their colleagues have set the stage with challenges for the clinician in context its pathophysiology. Drs. Phillip Gordan and Jonathan Swenson have outlined its varying presentations and possible modes of preventing NEC by cautiously increasing feeding in the NICU. Dr. Neu a respected researcher in NEC has attempted to ‘decode’ the mysteries of this enigmatic disease. Drs. Clark and Munshi have elaborated on the potential novel role of fermentation of undigested enteral carbohydrates producing organic acids possibly resulting in mucosal injury at cellular level. Dr. Panigrahi has elaborated on the role of pro- and prebiotics in NEC. Dr. Denning has further described how pro and prebiotics play a role in altering the commensal bacteria to prevent NEC. Dr. Peter Minneci has updated the management of short gut syndrome He has also summarized the current status of intestinal transplantation in these patients. Dr. Lawrence Moss, an authoritative Pediatric surgeon on NEC has reviewed the surgical management of NEC. Another reputed Pediatric surgeon, Dr. Gail Bessner and her team have shared their ‘futuristic’ view of using Heparin-BindingEGF like growth factor to possibly prevent intestinal injury based on their extensive animal data. Dr. David Hackam, an expert on toll-like receptor regulation in the developing gut has elaborated its role in the pathogenesis of NEC. Dr. Isabelle De Plane, an expert on NFk and cytokine interaction in inflammatory signaling cascade has discussed her research in the pathophysiology of NEC. Finally, Dr. Jilling and his
2
Preface / Pathophysiology 21 (2014) 1–2
colleagues have extensively reviewed gut development, outlining the inflammatory signals regulating intestinal epithelial renewal, differentiation, migration and cell death with their implication in the pathophysiology of NEC. We wish to thank the editors of Pathophysiology, Drs., Osmo Hanninen, Neil Granger and Steve Alexander for their encouragement and patience. We are indebted to all the authors for sharing their expertise and promptly responding to the queries by the reviewers. Our immense gratitude is extended to Mr. Jaffar Ali Mohideen and Mr. U. Kumar at Elsevier for their editorial assistance and patience during this enduring journey.
Guest Editor Arun K. Pramanik (MD) ∗ Professor of Pediatrics, LSU Health, Shreveport, LA, United States Guest Editor David Clark (MD) Professor and Chairman of Pediatrics, Albany Medical College, Albany, NY, United States ∗ Corresponding author. E-mail addresses: [email protected] (A.K. Pramanik), [email protected] (D. Clark)
Preface
Neonatal Necrotizing Enterocolitis (NEC) is a major cause of mortality and significant morbidity, often in premature infants with an inverse relationship to gestation, and may occur uncommonly in term infants. Despite advances in neonatal intensive care, its incidence, morbidity and mortality has remained unchanged. Some Neonatologists have attributed this to saving smaller and sicker extremely low birth weight premature infants with advances in MaternalFetal Medicine and neonatal care. Complications arising from NEC may lead to prolong or repeated hospitalizations, and on rare occasions require intestinal and/or liver transplantation in patients with short gut syndrome. The financial and emotional burden to families of these patients can be ‘life changing’. As the name indicates, definitive diagnosis is either histopathological with its characteristic findings of inflammatory response, pneumatosis, bacterial overgrowth and coagulation necrosis; or radiological with the findings of intramural gas (pneumatosis intestinalis), hepatic portal gas or pneumoperitoneum which are seen in advanced stage of this disease. It may have an insidious or rapid onset masquerading as ‘feeding intolerance’ (Stage I NEC), Septicemia or as isolated ileo-colic perforation. This problem is compounded by our inability to diagnose NEC in its early stages with a ‘chalice test’ which continues to elude clinical investigators. Thus clinicians face a dilemma whether to deprive enteral nutrition in ‘growing premature infant with feeding intolerance’ with its potential of inhibiting gut development, or place them on antibiotics and altering gut flora possibly resulting in increase of NEC risk, or continue feeding and cause “NEC totalis” and short gut syndrome or death. Although the jury is still out on the definitive management of NEC, several clinical studies have suggested a cautious approach to increasing enteral feeding preferably with breast milk, use of selected probiotics, not administering blood transfusion during or in proximity to enteral feeding, and prudent use of antibiotics and discontinuing them promptly, particularly in premature infants at hi-risk of developing NEC. This approach has arisen from observations of management of at-risk patients in NICUs with very low prevalence 0928-4680/$ – see front matter. Published by Elsevier Ireland Ltd http://dx.doi.org/10.1016/j.pathophys.2014.01.002
of NEC and a unified consistent feeding practice amongst neonatologists. The past decade has been punctuated by elegant research in basic sciences at microbial, molecular, cellular and genetic levels to understand the relationship between gut colonization, inflammation and injury to the developing gut leading to the pathophysiology of NEC. Unfortunately there is no “ideal” animal model of NEC which replicates the variable clinical course of the disease in premature infants, and rarer presentation in term newborn infants. In this issue of the journal, experts with extensive experience in the clinical management and basic research experience in NEC have reviewed their respective topics. Drs. Huda, Pramanik and their colleagues have set the stage with challenges for the clinician in context its pathophysiology. Drs. Phillip Gordan and Jonathan Swenson have outlined its varying presentations and possible modes of preventing NEC by cautiously increasing feeding in the NICU. Dr. Neu a respected researcher in NEC has attempted to ‘decode’ the mysteries of this enigmatic disease. Drs. Clark and Munshi have elaborated on the potential novel role of fermentation of undigested enteral carbohydrates producing organic acids possibly resulting in mucosal injury at cellular level. Dr. Panigrahi has elaborated on the role of pro- and prebiotics in NEC. Dr. Denning has further described how pro and prebiotics play a role in altering the commensal bacteria to prevent NEC. Dr. Peter Minneci has updated the management of short gut syndrome He has also summarized the current status of intestinal transplantation in these patients. Dr. Lawrence Moss, an authoritative Pediatric surgeon on NEC has reviewed the surgical management of NEC. Another reputed Pediatric surgeon, Dr. Gail Bessner and her team have shared their ‘futuristic’ view of using Heparin-BindingEGF like growth factor to possibly prevent intestinal injury based on their extensive animal data. Dr. David Hackam, an expert on toll-like receptor regulation in the developing gut has elaborated its role in the pathogenesis of NEC. Dr. Isabelle De Plane, an expert on NFk and cytokine interaction in inflammatory signaling cascade has discussed her research in the pathophysiology of NEC. Finally, Dr. Jilling and his
2
Preface / Pathophysiology 21 (2014) 1–2
colleagues have extensively reviewed gut development, outlining the inflammatory signals regulating intestinal epithelial renewal, differentiation, migration and cell death with their implication in the pathophysiology of NEC. We wish to thank the editors of Pathophysiology, Drs., Osmo Hanninen, Neil Granger and Steve Alexander for their encouragement and patience. We are indebted to all the authors for sharing their expertise and promptly responding to the queries by the reviewers. Our immense gratitude is extended to Mr. Jaffar Ali Mohideen and Mr. U. Kumar at Elsevier for their editorial assistance and patience during this enduring journey.
Guest Editor Arun K. Pramanik (MD) ∗ Professor of Pediatrics, LSU Health, Shreveport, LA, United States Guest Editor David Clark (MD) Professor and Chairman of Pediatrics, Albany Medical College, Albany, NY, United States ∗ Corresponding author. E-mail addresses: [email protected] (A.K. Pramanik), [email protected] (D. Clark)
