Necrotizing Enterocolitis

Contents

Foreword: Necrotizing Enterocolitis Prevention: Art or Science? xiii

Lucky Jain

Preface: Necrotizing Enterocolitis: Hope on the Horizon xvii

Patricia Wei Denning and Akhil Maheshwari

Feeding Practices and Necrotizing Enterocolitis 1

Manimaran Ramani and Namasivayam Ambalavanan

Necrotizing enterocolitis (NEC) is a multifactorial disorder that primarilyaffects premature infants. Human milk compared with formula reducesthe incidence of NEC. Feeding practices do not increase the incidenceof NEC in preterm infants. There is no evidence supporting continuousversus intermittent tube feedings in preterm infants. In a feed-intolerantpreterm infant without any other clinical and radiologic evidence of NEC,minimal enteral nutrition rather than complete suspension of enteral feed-ing may be an alternative. Human milk–based fortifier compared withbovine-based fortifier may reduce the incidence of NEC but additionalstudies are required.

Therapeutic Use of Prebiotics, Probiotics, and Postbiotics to Prevent NecrotizingEnterocolitis:What is the Current Evidence? 11

Ravi Mangal Patel and Patricia Wei Denning

Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidityand mortality, and preventive therapies that are both effective and safeare urgently needed. Current evidence from therapeutic trials suggeststhat probiotics are effective in decreasing NEC in preterm infants, and pro-biotics are currently the most promising therapy for this devastating dis-ease. However, concerns regarding safety and optimal dosing havelimited the widespread adoption of routine clinical use of probiotics in pre-term infants. This article summarizes the current evidence regarding theuse of probiotics, prebiotics, and postbiotics in the preterm infant, includ-ing their therapeutic role in preventing NEC.

AClinical Perspective of Necrotizing Enterocolitis: Past, Present, and Future 27

Renu Sharma and Mark Lawrence Hudak

Necrotizing enterocolitis (NEC) primarily affects premature infants. It is lesscommon in term and late preterm infants. The age of onset is inversely re-lated to the postmenstrual age at birth. In term infants, NEC is commonlyassociated with congenital heart diseases. NEC has also been associatedwith other anomalies. More than 85% of all NEC cases occur in very lowbirth weight infants or in very premature infants. Despite incrementaladvances in our understanding of the clinical presentation and pathophys-iology of NEC, universal prevention of this disease continues to elude useven in the twenty-first century.

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Short Bowel Syndrome in the NICU 53

Sachin C. Amin, Cleo Pappas, Hari Iyengar, and Akhil Maheshwari

Short bowel syndrome (SBS) is the most common cause of intestinalfailure in infants. In neonates and young infants, necrotizing enterocolitis,gastroschisis, intestinal atresia, and intestinal malrotation/volvulus arethe leading causes of SBS. Following an acute postsurgical phase, theresidual gastrointestinal tract adapts with reorganization of the crypt-villushistoarchitecture and functional changes in nutrient absorption and motil-ity. A cohesive, multidisciplinary approach can allow most neonates withSBS to transition to full enteral feeds and achieve normal growth anddevelopment. In this article, the clinical features, management, complica-tions, and prognostic factors in SBS are reviewed.

Necrotizing Enterocolitis in Term Infants 69

Robert D. Christensen, Diane K. Lambert, Vickie L. Baer, and Phillip V. Gordon

This article is an overview of NEC in term neonates and also summarizesdata from 52 cases within Intermountain Healthcare during the last 11years. In all 52, NEC occurred among neonates already admitted to a neo-natal intensive care unit for some other reason; thus, NEC invariably devel-oped as a complication of treatment, not as a primary diagnosis. Theauthors speculate that the incidence of term NEC can be reduced by iden-tifying neonatal intensive care unit patients at risk for NEC and applyingappropriate-volume human milk feeding programs for these patients.

Lactoferrin and Necrotizing Enterocolitis 79

Michael P. Sherman

Lactoferrin (LF) is a multifunctional protein and a member of the transfer-rin family. LF and lysozyme in breast milk kill bacteria. In the stomach,pepsin digests and releases a potent peptide antibiotic called lactoferricinfrom native LF. The antimicrobial characteristics of LF may facilitatea healthy intestinal microbiome. LF is the major whey in human milk; itshighest concentration is in colostrum. This fact highlights early feedingof colostrum and also fresh mature milk as a way to prevent necrotizingenterocolitis.

TheAltered Gut Microbiome and Necrotizing Enterocolitis 93

Roberto Murgas Torrazza and Josef Neu

Current evidence highlights the importance of developing a healthyintestinal microbiota in the neonate. Many aspects that promote healthor disease are related to the homeostasis of these intestinal microbiota.Their delicate equilibrium could be strongly influenced by the interven-tion that physicians perform as part of the medical care of the neonate,especially preterm infants. As awareness of the importance of thedevelopment and maintenance of these intestinal flora increase andnewer molecular techniques are developed, it will be possible to pro-vide better care of infants with interventions that will have long-lastingeffects.

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Inflammatory Signaling in Necrotizing Enterocolitis 109

Isabelle G. De Plaen

The pathogenesis of necrotizing enterocolitis (NEC) is complex and itsspeed of progression is variable. To gain understanding of the disease,researchers have examined tissues resected from patients with NEC; how-ever, as these are obtained at late stages of the disease, they do not yieldclues about the early pathogenic events leading to NEC. Therefore, animalmodels are used and have helped identify a role for several mediators ofthe inflammatory network in NEC. In this article, we discuss the evidencefor the role of these inflammatory mediators and conclude with a currentunifying hypothesis regarding NEC pathogenesis.

Newer Monitoring Techniques to Determine the Risk of Necrotizing Enterocolitis 125

James E. Moore

Necrotizing enterocolitis affects up to 10% of neonates who are bornweighing less than 1500 g. It has a high rate of morbidity and mortality,and predicting infants who will be affected has so far been unsuccessful.In this article, a number of new methods are discussed from the literatureto determine if any currently available techniques may allow for the identi-fication of patients who are at increased risk for developing this potentiallylethal disease.

The Surgical Management of Necrotizing Enterocolitis 135

Zachary J. Kastenberg and Karl G. Sylvester

Necrotizing enterocolitis (NEC), a common cause of neonatal morbidityand mortality, is strongly associated with prematurity and typically oc-curs following initiation of enteral feeds. Mild NEC is adequately treatedby cessation of enteral feeding, empiric antibiotics, and supportive care.Approximately 50% of affected infants will develop progressive intestinalnecrosis requiring urgent operation. Several surgical techniques havebeen described, but there is no clear survival benefit for any single op-erative approach. While debate continues regarding the optimal surgicalmanagement for infants with severe NEC, future progress will likelydepend on the development of improved diagnostic tools and preventivetherapies.

Biomarkers for Prediction and Diagnosis of Necrotizing Enterocolitis 149

Pak C. Ng, Kathy Y.Y. Chan, and Terence C.W. Poon

This article summarizes the commonly used biomarkers currently availablefor diagnosis of necrotizing enterocolitis. The most exciting advances in di-agnostic tests were the use of new nucleic acid sequencing techniques(eg, next-generation sequencing) and molecular screening methods (eg,proteomics and microarray analysis) for the discovery of novel biomarkers.The new technology platform coupled with stringent protocols of bio-marker discovery and validation would enable neonatologists to studybiologic systems at a level never before possible and discover unique bio-markers for specific organ injury and/or disease entity.

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IntestinalTransplantation in Infants with Intestinal Failure 161

Richard S. Mangus and Girish C. Subbarao

Intestinal failure (IF) occurs when a person’s functional intestinal mass isinsufficient. Patients with IF are placed on parenteral nutrition (PN) whileefforts are made to restore intestinal function through surgical or medicalintervention. Patients who fail standard IF therapies may be candidates forintestinal transplantation (IT). Clinical outcomes for IT have improved tomake this therapy the standard of care for patients who develop complica-tions of PN. The timing of referral for IT is critical because accumulatedcomplications of PN can render the patient ineligible for IT or can forcethe patient to await multiorgan transplantation.

Index 175