FETAL AND NEONATAL Third Edition Richard A Polin, MD Professor of Pediatrics Columbia University College of Physicians and Surgeons Director, Division of Neonatology Morgan Stanley Children’s Hospital of New York–Presbyterian New York, New York Alan R Spitzer, MD Senior Vice President for Research, Education, and Quality Pediatrix Medical Group Sunrise, Florida 1600 John F Kennedy Blvd Ste 1800 Philadelphia, PA 19103-2899 FETAL AND NEONATAL SECRETS, THIRD EDITION Copyright © 2014, 2007, 2001 by Saunders, an imprint of Elsevier Inc ISBN: 978-0-323-09139-8 All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notices Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein Library of Congress Cataloging-in-Publication Data Fetal and neonatal secrets / [edited by] Richard A Polin, Alan R Spitzer 3rd ed p ; cm (Secrets series) Includes bibliographical references and index ISBN 978-0-323-09139-8 (pbk.) I Polin, Richard A (Richard Alan), 1945- II Spitzer, Alan R III Series: Secrets series [DNLM: Fetal Diseases Examination Questions Fetal Diseases Outlines Infant, Newborn, Diseases Examination Questions Infant, Newborn, Diseases Outlines WQ 18.2] RJ254 618.92’01 dc23 2013004157 Content Strategy Director: Madelene Hyde Senior Content Strategist: James Merritt Content Development Specialist: Kimberly Hodges Publishing Services Manager: Patricia Tannian Project Manager: Amanda Mincher Design Direction: Steven Stave Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1 To my wife, Helene; my children, Allison and her husband Ted, Mitchell, Jessica and her husband Zac, and Gregory; and my beautiful grandchildren, Lindsey, Eli, Willa, Jasper, and Casey Without their love and support I could never have accomplished as much as I have as a physician and a teacher Richard A Polin, MD This book is dedicated to better outcomes for neonates everywhere and to my amazing grandchildren, Jacob, Matthew, Brianna, Molly, and Morgan, and their equally marvelous parents, Steve, Jen, Kevin, Sara, Jeff, and Lauren I am also eternally indebted to my incredible wife of 42 years, Elaine, who knows more about children and how to make them smile than anyone else I know Alan R Spitzer, MD CONTRIBUTORS Saima Aftab, MD Robert Ryan Clancy, MD Assistant Professor, Department of Pediatrics and Neonatology, Perelman School of Medicine, University of Pennsylvania; Attending Neonatologist, Department of Neonatology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Professor of Neurology and Pediatrics, University of Pennsylvania School of Medicine; Senior Attending Physician, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania K.J.S Anand, MBBS, DPhil Professor, Department of Pediatrics, Anesthesiology, Anatomy, and Neurobiology, Division Chief, Pediatric Critical Care Medicine, Department of Pediatrics, The University of Tennessee Health Science Center; Medical Director, Pediatric Intensive Care Unit, Le Bonheur Children’s Hospital, Memphis, Tennessee Victoria R Barrio, MD, FAAD, FAAP Associate Clinical Professor, Department of Pediatrics and Medicine—Dermatology, University of California, San Diego; Rady Children’s Hospital, San Diego, California Marisa Censani, MD Pediatric Endocrinology Fellow, Department of Pediatric Endocrinology, Columbia University Medical Center, New York, New York Michael F Chiang, MD Knowles Professor, Department of Ophthalmology and Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon Robert D Christensen, MD Research Director, Department of Women and Newborns, Intermountain Healthcare, Salt Lake City, Utah Wendy K Chung, MD, PhD Assistant Professor, Department of Pediatrics and Medicine, Columbia University; Director of Clinical Genetics, New York Presbyterian Hospital, New York, New York Reese H Clark, MD Vice President and Co-Director, the Center for Research, Education, and Quality, Pediatrix Medical Group, Sunrise, Florida Mitchell I Cohen, MD, FACC, FHRS Clinical Associate Professor, Department of Pediatrics, University of Arizona School of Medicine—Phoenix Campus; Section Chief, Pediatric Cardiology, Phoenix Children’s Hospital, Phoenix, Arizona C Andrew Combs, MD, PhD Associate Director of Research, Center for Research, Education, and Quality, Obstetrix Medical Group, Mednax, Inc., San Jose, California Lawrence F Eichenfield, MD, FAAD, FAAP Professor of Pediatrics and Medicine—Dermatology, University of California, San Diego School of Medicine; Chief, Pediatric and Adolescent Dermatology, Rady Children’s Hospital, San Diego, California Jacquelyn R Evans, MD Professor of Clinical Pediatrics, Department of Pediatrics and Neonatology, Perelman School of Medicine, University of Pennsylvania; Associate Division Chief, Department of Pediatrics and Neonatology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Karin M Fuchs, MD Assistant Clinical Professor, Department of Obstetrics and Gynecology, Columbia University; Attending Physician, Division of Maternal Fetal Medicine, Columbia University Medical Center, New York, New York vii viii CONTRIBUTORS Mary Pat Gallagher, MD Joel E Lavine, MD, PhD Assistant Professor of Clinical Pediatrics, Department of Pediatrics, Columbia University; Assistant Attending, Pediatrics, Morgan Stanley Children’s Hospital of New York–Presbyterian, New York, New York Professor, Department of Pediatrics, Columbia University; Chief, Pediatric Gastroenterology, Hepatology, and Nutrition, Morgan Stanley Children’s Hospital of New York–Presbyterian, New York, New York Alejandro Garcia, MD Christopher L Lindblade, MD Resident, General Surgery, Columbia University Medical Center, New York, New York Co-Director of Fetal Cardiology, Department of Cardiology, Phoenix Children's Hospital, Phoenix, Arizona Thomas J Garite, MD Vice President and Co-Director of Obstetrics and Gynecology, University of California, Irvine, Orange, California; Editor in Chief, American Journal of Obstetrics and Gynecology; Director of Research and Education, Obstetrics, Pediatrix Medical Group, Sunrise, Florida Daniel A Greninger, MD Instructor, Pediatric Ophthalmology and Strabismus, Department of Ophthalmology, Oregon Health and Science University, Portland, Oregon R Whit Hall, MD Professor, Department of Pediatrics and Neonatology, University of Arkansas for Medical Sciences; Professor, Neonatology, Department of Pediatrics and Neonatology, Arkansas Children’s Hospital, Little Rock, Arkansas Qusai Hammouri, MBBS, MD Director, Pediatric Orthopedics, North Shore Long Island Jewish, Staten Island University Hospital, Staten Island, New York Karen D Hendricks-Muñoz, MD, MPH Professor and Chair of Neonatal Medicine, Pediatrics, Medical College of Virginia, Virginia Commonwealth University; Chief of Neonatal Medicine, Pediatrics, Children’s Hospital of Richmond at Virginia Commonwealth Health Systems, Richmond, Virginia John M Lorenz, MD Professor of Clinical Pediatrics, Department of Pediatrics, College of Physicians and Surgeons, Columbia University; Attending Neonatologist, Department of Pediatrics, Morgan Stanley Children’s Hospital of New York–Presbyterian, New York, New York William Middlesworth, MD Assistant Professor, Department of Surgery and Pediatrics, Columbia University; Assistant Attending Surgeon, Morgan Stanley Children’s Hospital of New York–Presbyterian, New York, New York Kimberly D Morel, MD, FAAD, FAAP Associate Professor of Clinical Dermatology and Clinical Pediatrics, Departments of Dermatology and Pediatrics, Columbia University and Morgan Stanley Children’s Hospital of New York– Presbyterian, New York, New York Sharon E Oberfield, MD Professor and Director of Pediatrics, Department of Pediatrics, Division of Pediatric Endocrinology, Diabetes, and Metabolism, Columbia University, New York, New York Carol C Prendergast, EdD Institutional Advancement, Syracuse University, Syracuse, New York Joshua E Hyman, MD Fabio Savorgnan, MD Associate Professor, Orthopedic Surgery, Columbia University College of Physicians and Surgeons; Attending, Orthopedic Surgery, Morgan Stanley Children’s Hospital of New York–Presbyterian, New York, New York Fellow, Department of Pediatrics, University of Tennessee, Memphis, Tennessee Beatriz Larru, MD, PhD Fellow, Division of Infectious Diseases, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Sarah A Taylor, MD Fellow, Department of Pediatrics, Columbia University; Fellow, Pediatric Gastroenterology, Hepatology, and Nutrition, Morgan Stanley Children’s Hospital of New York–Presbyterian, New York, New York CONTRIBUTORS ix Patricia L Weng, MD Theoklis E Zaoutis, MD, MSCE Assistant Professor of Clinical Pediatrics, Department of Pediatrics, Columbia University; Department of Pediatrics, Morgan Stanley Children’s Hospital of New York–Presbyterian, New York, New York Professor, Department of Pediatrics and Epidemiology, Perelman School of Medicine, University of Pennsylvania; Associate Chief, Division of Infectious Diseases, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Courtney J Wusthoff, MD Assistant Professor, Department of Neurology and Neurological Sciences, Stanford University; Co-Director, Neonatal Neuro-Intensive Care Unit, Pediatric Neurology, Lucile Packard Children’s Hospital, Palo Alto, California PREFACE TO THE THIRD EDITION Although “secrets” is used in the title of our book, this word belies the book’s purpose and content Throughout much of history, the traditional way of learning medicine was to obtain an apprenticeship with a skilled medical practitioner for an ill-defined period of time In that way, one learned the “secrets”—useful or not; correct or incorrect—that a single practitioner had acquired over many years of practice In the United States, that system remained in place until the early-1900s when modern medical schools were developed Our current system of education has evolved considerably since that time, but it has never abandoned the idea of students learning from wise clinicians Although modern students and trainees now have nearly unlimited access to a broad range of information, that does not diminish the value of “great clinicians,” whose wisdom is now passed on through seminars, books, and journals, many of which are available electronically Fetal and Neonatal Secrets is an up-to-date collection of questions and answers that deals with a wide variety of common and uncommon neonatal diseases In essence, it brings the great clinician—in this case, many outstanding clinicians and educators—directly to the reader so that he or she can learn the “secrets” from these talented individuals, as if the reader were an apprentice on their rounds As in the previous editions, we have included facts that would qualify as trivia because of the enjoyment value they bring to learning If used appropriately—and gently—by students and trainees, they are perfect for challenging teachers with information in areas that may be outside of their expertise In summary, the book is meant to be both useful and fun It is not meant to be encyclopedic, but we hope it will spur all students to challenge existing dogma and to search for better ways to care for critically ill neonates Richard A Polin, MD Alan R Spitzer, MD xi PREFACE TO THE FIRST EDITION From the time we become physicians until the time we retire from medicine, we are guided by the phrase widely attributed to Hippocrates: primum non nocere, “first no harm.” Although the origins of that exact phrase are unclear, Hippocrates certainly conveyed that meaning in his oath: “I will prescribe regimen for the good of my patients according to my ability and my judgment and never harm to anyone.” Fundamental to the concept of “doing good” is the acquisition of medical knowledge that allows each of us to practice according to the highest possible standards In the first two years of medical school, knowledge is transferred predominantly by large group lectures and required readings Once we enter the clinical years, the process of acquiring new information begins to change We continue to read textbooks, but journal articles become increasingly important sources of the newest information, and much information is transmitted to us through “personal communications” by individuals who are further along in their training For the medical student, that often means an intern or resident, and for the senior resident, a fellow or an attending This apprenticeship aspect of medicine has been an intrinsic part of the field since its inception Even in this era of rapidly intensifying technologic advances, “see one, one, teach one” remains a cornerstone of bedside medical education With this concept in mind, Fetal and Neonatal Secrets is designed to serve as a primer for the bedside teaching that remains such an important part of medical education While it can be read from cover to cover (e.g., to prepare for a certifying examination), we believe that the information in the book should be shared wherever health care providers congregate to provide care (inpatient service, clinics, operating room) to the fetus and newborn infant Although the word “secrets” connotes a sense of privacy, we hope that this book reveals rather than obscures secrets, and that the cumulative wisdom shared by the many experienced contributors serves to enlighten the reader Furthermore, we would love to see these secrets used by the youngest members of the health care team to challenge those more experienced, as well as by professors to make their residents and students think We fear that we may need to tote around a copy of this book on rounds ourselves, as our house staff, fellows, and nurse practitioners may throw down the gauntlet to test us on a daily basis! Although we have tried to make this book as comprehensive and practical as possible, the reader will encounter many facts that might be considered trivial (e.g., what is the ductus of Botallo?), but we hope that the reader is forgiving in this respect The retention of important information has always seemed to be enhanced by its association with interesting, but less essential information (the Mary Poppins approach—“a spoonful of sugar helps the medicine go down”) Where would medicine be without mnemonics? In any event, we hope you find this book useful in your daily practice, but more important, we want you to have some fun along the way Richard A Polin, MD Alan R Spitzer, MD xiii ACKNOWLEDGMENTS In my development as a physician, I have been exposed to many wonderful teachers, scientists, and physicians However, because of the enormous influence they have had on my career, I would like to acknowledge four individuals by name: Bill Speck (my lifelong friend—no one has ever cared more about resident and student education), John Driscoll (the master clinician who first excited me about neonatology and who remains my role model for the warm, compassionate physician), Bill Fox (my coeditor for Fetal and Neonatal Physiology, who demonstrated to me the importance and fun in doing clinical research and who periodically reminds me how to stay focused on the important things in life), and Mark Ditmar (my coeditor of Pediatric Secrets, whose combination of humor, knowledge, and compassion has allowed me to achieve a balance in medicine and who has shown me how “academic” and wonderful the practice of general pediatrics can be) I am indebted to all of them Finally, I would like to thank my developmental editor at Elsevier, Kimberly Hodges, for helping with the organization and development of this book, and my friend and senior editor at Elsevier, Linda Belfus, for hooking me on the Secrets series and allowing me to put my love of education into print Richard A Polin, MD A career in medicine is never static, but rather constantly evolving As a result, the people and experiences that influence one’s life in medicine often change in unexpected ways In recent years, I have served as the course director for NEO—the Conference for Neonatology held annually in Orlando As part of this meeting, we initiated the “Legends of Neonatology” awards, which I have the honor of presenting each year In preparing for that evening, I have had the chance to venture back into the history of neonatology, relearning the origins of much of what we today and examining the careers of some of the greatest figures in modern neonatal medicine, whose contributions have saved and enhanced the lives of countless infants The impact of these individuals on my perspective on medicine has been immeasurable, and learning about their lives and the challenges that many of them had to overcome to achieve at the highest levels of our specialty has often left me in awe in ways that I would never have anticipated To date, we have honored the following: Maria DelivoriaPapadopoulos, Mary Ellen Avery, Mildred Stahlman, Lu-Ann Papile, Avroy Fanaroff, Marshall Klaus, Jerrold Lucey, Robert Bartlett, William Norwood, George Gregory, John Clements, Forrest Bird, Stanley Dudrick, Abraham Rudolph, and William Oh Upcoming are Lilly Dubowitz, Jeffrey Maisels, and Jen-Tien Wung Each and every one of these figures faced incredible obstacles along their paths but believed in themselves and believed that their work would profoundly improve outcomes for children Their courage and the quality of their work have been a model that I will always deeply admire and forever aspire to match I would be remiss, however, if I did not also thank several other people for their inspiration as role models Roger Medel, the CEO of MEDNAX, Inc (Pediatrix Medical Group), serves as a wise and understanding leader for those of us in my current position and has provided me xv xvi ACKNOWLEDGMENTS with the opportunity to achieve certain goals in my career that would never have been possible otherwise My current partner, Reese Clark, is the ultimate clinical scientist—thoughtful, insightful, knowledgeable, and scrupulously honest Anyone who reads a paper with his name on it can rest assured that no one has ever provided data and its interpretation in a more ethically precise and clear manner A former mentor, Bill Fox at the Children’s Hospital of Philadelphia, has always been a great friend and huge supporter of my work; without him my career would have been very different and far less successful Lastly, my coeditor of this book, Richard Polin, is without question the consummate clinician, educator, and investigator I was most fortunate to spend a dozen years at the earliest stage of my career in the office next to Rich at CHOP, and if there was ever a perfect learning experience, that was it To all of these people, I will forever be indebted Alan R Spitzer, MD CHAPTER 19  SURGERY 507 disease) Although Hirschsprung disease affects boys four times as often as girls, long-segment disease affects boys and girls equally 47 How patients with Hirschsprung disease typically present? Failure to pass meconium in the first 24 hours after birth is highly suggestive of Hirschsprung disease There is a wide spectrum of presentations, ranging from complete functional distal obstruction with bilious vomiting and a distended abdomen to chronic constipation (in which case the diagnosis is usually not made until after the neonatal period) Sepsis resulting from enterocolitis can occur at any time 48 How is the diagnosis established? The gold standard is a rectal biopsy that typically demonstrates an absence of ganglion cells and hypertrophy of parasympathetic nerve fibers, which stain intensively for acetylcholinesterase This biopsy can be done at the bedside in the neonate A contrast enema is suggestive of Hirschsprung disease if it shows a change in the caliber of the colon at the transition zone (Fig 19-5) It is important that the study be delayed if the baby has had an enema or a digital rectal examination or even if a rectal thermometer was inserted because any rectal manipulation may temporarily obliterate the radiographic appearance of the transition zone The contrast enema may identify a transitional zone, which may be useful for operative planning Figure 19-5.  Contrast enema demonstrating patent colon with narrowing in rectum consistent with Hirschsprung disease 508 CHAPTER 19  SURGERY 49 What is the treatment for Hirschsprung disease? Even in instances in which there is significant abdominal distention, the proximal intestine can almost always be decompressed by rectal irrigation and rectal exams, allowing time for a diagnostic work-up Surgical repair involves resection of the aganglionic segment of bowel Various surgical procedures have been developed to address this The traditional surgical repair is a staged operation with a temporary diverting colostomy constructed above the transition zone, followed several months later by a “pull-through” operation in which the ganglionic bowel is brought down and anastomosed to the anal canal In full-size babies without enterocolitis, the pull-through procedure is performed as a single operation, often with laparoscopic assistance 50 What is Hirschsprung enterocolitis? Patients with Hirschsprung disease may develop enterocolitis, the precise cause of which is not well understood but which involves stasis, bacterial overgrowth, and translocation through the wall of the colon Enterocolitis may be the first recognized manifestation of Hirschsprung disease but may also occur after surgery It can be mild or severe with explosive diarrhea, dehydration, peritonitis, and sepsis Enterocolitis is the most common cause of mortality from Hirschsprung disease Treatment must be immediate and consists of bowel rest, broad-spectrum antibiotics, and thorough colonic irrigations 51 How does one differentiate meconium ileus from meconium plug and small left colon syndrome? Meconium ileus, as previously described, is obstruction of the distal ileum by thick and viscid meconium, which occurs in 10% to 20% of neonates with cystic fibrosis Meconium plug is caused by meconium blocking the left colon in otherwise healthy babies Small left colon syndrome is most common in infants of diabetic mothers and produces an obstruction from a temporarily dysfunctional, small-caliber left colon A contrast enema with barium is usually diagnostic as well as therapeutic for both meconium plug and small left colon syndrome (through its mechanical effect), although subsequent testing for Hirschsprung disease or cystic fibrosis may be indicated ANORECTAL MALFORMATIONS 52 What is an anorectal malformation? Anorectal malformations comprise a spectrum of disorders in which the rectum is deflected anteriorly and fails to reach its normal perineal termination When the rectum and urinary system end in a blind pouch, this is classified as a cloaca When the rectum ends above the levator muscles, the malformation is classified as high; when it passes through these muscles, the malformation is low High lesions are more common in males; low lesions are more common in females 53 How are anorectal malformations diagnosed? The diagnosis is usually obvious on inspection of the perineum, which should be standard procedure for a newborn examination Either no perineal opening is present or an external fistula is visible In male newborns this fistula is usually a small opening anterior to the normal anal location in the perineum or as far forward as the scrotal raphe Female newborns may also have an external fistula draining into the anterior perineum, or else in the posterior vulva behind the hymen (the vaginal “fourchette”) A single perineal opening signifies a cloaca, where the rectum, vagina, and urethra all open into one common chamber 54 What are the steps for the evaluation of a baby with an anorectal malformation? Inspection and urinalysis allow the clinician to determine the anatomy in most cases A perineal fistula always means the lesion is low and a colostomy is not necessary If such a fistula cannot be detected initially, there should always be a 16- to 24-hour waiting period to allow increased luminal pressure to force meconium through a possible fistula so that it becomes visible on examination If there is meconium in the urine, an internal fistula to the urinary tract is confirmed If there is no visible fistula, a cross-table lateral film with the baby in the prone position can be used to measure CHAPTER 19  SURGERY 509 the most distal aspect of the rectum relative to the perineal skin The work-up should also include a search for other possible components of the VACTERL association (see answer to Question 23) 55 When is a colostomy not necessary as the initial operative procedure? Is surgery always necessary? If there is an external fistula to the perineum, or bucket-handle deformity in a male (i.e., a vertical raphe in the perineum with indentations on both sides), the lesion is low, and a primary anoplasty can be performed in the neonatal period Otherwise, the lesion is probably high or intermediate, and an initial colostomy is recommended, followed by a pull-through procedure within the next several months If there is a large fistulous opening only slightly anterior to the normal anal location (“anterior anus”), function may be normal and surgery may be unnecessary 56 How are anorectal malformations surgically corrected? Alberto Peña devised the posterior sagittal anorectoplasty (PSARP) in which the anal and rectal sphincter muscles are divided posteriorly in the midline; this operative approach has become the standard procedure for the pull-through procedure because it allows for excellent visualization Recently, a laparoscopic pull-through operation has become feasible 57 What is the main determination of continence in persons who have had an imperforate anus? What should parents be told? Continence depends on the coordinated actions of the external sphincter, internal sphincter, and levator muscles Because the levators are most important, infants with low lesions in whom the bowel has descended normally within the levator sling have an excellent functional outlook Children with high anomalies frequently have underdeveloped sphincter muscles, and their results are mixed, with many having at least occasional soiling Finally, children with a flat bottom (which implies very poorly developed muscles) without a developed gluteal fold and those having sacral anomalies on radiograph have the worst prospects for normal continence These patients require a structured bowel management program, including daily enemas, to achieve “functional” continence All children with anorectal malformations suffer from constipation, and parents must be informed of bowel regimens NECROTIZING ENTEROCOLITIS (NEC) 58 What is NEC? NEC is a condition that most commonly affects premature infants after the institution of oral feedings; however, it also occurs in term babies who have other comorbidities (e.g., congenital heart disease) It is a hemorrhagic necrosis that initially affects the mucosa but may progress to involve full-thickness injury Manifestations vary considerably, from mild abdominal distention with hematochezia to fulminant sepsis with necrosis of the entire intestinal tract 59 What are the factors that are believed to predispose a patient to the development of NEC? Although the precise etiology is unknown, three factors seem to act in concert in promoting the development of NEC: n Damage to the intestinal mucosa, which may result from ischemia caused by perinatal hypoxia, low-flow states (e.g., premature infants with patent ductus arteriosus), or reperfusion injury n The combination of intestinal immaturity and the presence of feedings in the intestinal tract, which acts as a substrate for bacterial proliferation (NEC is highly uncommon among infants who have not received enteral feeds.) n Impaired host defense mechanisms, as is the case in premature infants, allowing intestinal bacteria to invade the wall of the intestine (It is believed that the excessive immature inflammatory response associated with abnormal intestinal microbiota is the most likely basis for the pathogenesis of NEC.) (Fig 19-6) Neu J, Walker WA Necrotizing enterocolitis N Engl J Med 2011;364:255–64 Intestinal necrosis Intact intercellular junction Commensals IgA TLR Mucus Intestinal epithelium Genetics Polymorphisms in TLRs Immature intestinal barrier Decreased mucus Decreased IgA Low intercellular junction integrity and increased permeability Exaggerated inflammation and tissue injury Figure 19-6.  Pathophysiology of Necrotizing Enterocolitis Factors conferring a predisposition to necrotizing enterocolitis include genetic factors and several immature characteristics of the fetal intestine, including altered microbiota, inadequate intestinal barrier function, and an excessive inflammatory response These factors contribute to the severe necrosis of the small intestine that is characteristic of this disease TLR denotes toll-like receptor (From Neu J, Walker WA Necrotizing enterocolitis New Engl J Med 2011;364:255–64.) 510 CHAPTER 19  SURGERY Altered microbiota (low diversity caused by antibiotics) CHAPTER 19  SURGERY 511 60 Which portion of the gastrointestinal tract is affected by NEC? NEC may involve any portion of the gastrointestinal tract, but the ileocecal region is the most commonly affected 61 Is there a specific type of bacteria associated with NEC? No Although affected patients may be clustered in place and time, no consistent agent has been isolated from all reported epidemics, and it is considered that a variety of the enteric flora may contribute to NEC’s pathogenesis 62 How babies with NEC typically present? Clinical signs are initially nonspecific and may consist of lethargy, apnea, temperature instability, and feeding intolerance Gastrointestinal manifestations follow and include vomiting, bloody stools, abdominal distention, and abdominal tenderness Generalized sepsis may supervene 63 How is the diagnosis of NEC established? Although the diagnosis may be strongly suspected by the clinical findings outlined in the previous passages, the presence of bubbly lucencies in the intestinal wall on x-ray, called pneumatosis intestinalis, is pathognomonic Pneumatosis represents gas in the bowel wall produced by enteric organisms and is seen in 80% of NEC cases (Fig 19-7) Other radiographic features may include irregularly dilated air-filled loops of bowel and the visualization of branching lucencies in the liver, which may signify gas in the portal venous system 64 Do all infants who develop NEC require surgery? No Most infants with NEC will respond to medical treatment consisting of withholding all enteral feeds, nasogastric decompression, broad-spectrum systemic antibiotics, and general supportive measures to optimize tissue oxygenation and perfusion Frequent clinical examinations are mandatory, and serial abdominal radiographs are obtained to assess for static loops or perforation 65 When is surgery indicated in an infant with NEC? Absolute indications for surgical intervention include pneumoperitoneum and intestinal gangrene (as demonstrated by abdominal wall erythema, unchanging bowel gas pattern, or failure to respond to medical therapy) Relative indications include progressive clinical deterioration, abdominal wall erythema, tender abdomen, metabolic acidosis, ventilatory failure, oliguria, thrombocytopenia, and portal vein gas KEY POINTS: INDICATIONS FOR SURGERY IN INFANTS WITH NEC Absolute indication: free air in the abdomen on radiograph Relative indications: clinical deterioration with erythema of the abdominal wall, a distended and tense abdomen, portal venous gas, static loops on abdominal x-ray, refractory metabolic acidosis, and thrombocytopenia 66 What are the surgical options for patients with NEC that require surgical intervention? Traditionally, a laparotomy is performed with inspection of the entire intestinal tract Necrotic or perforated segments are resected, and an ostomy is performed Bedside placement of an abdominal drain has been shown to have similar outcomes with regard to mortality, dependence on total parenteral nutrition, and length of hospital stay compared with laparotomy Peritoneal drainage can be used as a temporizing procedure followed by subsequent operation Close observation is required after any operative intervention Moss RL, Dimmitt RA, Barnhart DC, et al Laparotomy versus peritoneal drainage for necrotizing enterocolitis and perforation N Engl J Med 2006;354:2224–34 512 CHAPTER 19  SURGERY A C B D E Figure 19-7.  Features of Necrotizing Enterocolitis A, Tense abdominal distension B, Pneumaosis intestinalis C, Portal venous gas and thickened bowel wall D, Featureless, fixed loop of bowel E, Pneumoperitoneum, or free air 67 When should the stoma be closed? Ideally, stomas are reversed months later, when the patient is thriving and the elective procedure is very low risk In reality, malabsorption or skin breakdown often necessitates earlier closure A distal contrast study should always be obtained before reversing an ostomy to ensure that there is no silent stricture in the defunctionalized bowel Approximately 10% to 15% of patients with NEC who not develop full-thickness necrosis and perforation will develop an obstructive intestinal stricture 68 How does spontaneous intestinal perforation (SIP) differ from NEC? Babies with SIP are generally younger (