Gastroesophageal Reflux in Children Yvan Vandenplas Editor Second Edition 123 Gastroesophageal Reflux in Children Yvan Vandenplas Editor Gastroesophageal Reflux in Children Second Edition Editor Yvan Vandenplas Vrije Universitiet Brussel (VUB) UZ Brussel KidZ Health Castle Brussels, Belgium ISBN 978-3-030-99066-4 ISBN 978-3-030-99067-1 (eBook) https://doi.org/10.1007/978-3-030-99067-1 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2017, 2022 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. 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This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Introduction Dear reader, Thank you for reading this book on gastroesophageal reflux (disease) in children. This second edition was made possible thanks to the success of the first edition. The second edition was extensively revised but still provides a comprehensive overview of almost all aspects of Gastroesophageal Reflux (Disease) in children. There are chapters on the epidemiology and pathophysiology of the condition. Multiple diag- nostic methods and treatment techniques are also covered. Profoundly revised chap- ters discuss several aspects associated with GER in defined patient populations. The chapters on diagnosis and management are also extensively updated. New chapters cover new knowledge on the microbiome, how nutrition can be key to treatment. Much attention is also given to adverse effects of medical treatment. Attention is also given to colic and new developments in eosinophilic esophagitis are also described. GER in preterm infants, neurologic patients, and children with cystic fibrosis is discussed as well. An important part of the book is dedicated to therapeu- tic approaches from medication to surgery and alternative approaches such as com- plementary medicine and hypnotherapy. This Second Edition on Gastroesophageal Reflux in Children was made possible thanks to all co-authors who realized outstanding contributions. Without their tre- mendous work, this book would not have been possible. Thanks to their work, this book offers you an up-to-date overview of all aspects of Gastroesophageal Reflux disease in children. This book has the intention to be a critical resource for pediatri- cians, gastroenterologists to pulmonologists, otolaryngologists, and neurologists Me and all co-authors do hope that you will enjoy the content of our book. Yvan Vandenplas v Contents 1 Epidemiology of GER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Silvia Salvatore and Yvan Vandenplas 2 Pathophysiology of GER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Samuel Nurko 3 Symptoms of GER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Paolo Quitadamo and Annamaria Staiano 4 Dysphagia and GER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 Valeria Dipasquale and Claudio Romano 5 Duodeno-GER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Ilse Hoffman 6 GER in Preterm Infants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 Francesco Cresi, Domenico Umberto De Rose, and Elena Maggiora 7 GER and Respiratory Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 Valeria Dipasquale and Claudio Romano 8 GER and Apnea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Silvia Salvatore and Yvan Vandenplas 9 GER in Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 Frederick W. Woodley, Rosara Bass, Don Hayes Jr, and Benjamin T. Kopp 10 GER and Esophageal Atresia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Frederic Gottrand, Audrey Nicolas, Rony Sfeir, and Madeleine Aumar 11 GERD and Cow’s Milk Allergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Rosan Meyer 12 GER and Overweight/Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Karolien Van De Maele 13 GER and Eosinophilic Esophagitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Jorge Amil Dias vii viii Contents 14 GER and Helicobacter pylori . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Oya Yücel 15 GER and Probiotic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 Flavia Indrio and Fernanda Cristofori 16 Diagnosis of GERD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 Michiel van Wijk 17 Contribution of Histology to the Diagnosis of GER. . . . . . . . . . . . . . . . 217 Chloé Girard and Christophe Faure 18 How to Position pH-Impedance Probes in Pediatric Patients . . . . . . . . 229 Yvan Vandenplas, Kris Van De Maele, Caroline Ernst, Astrid Leus, and Koen Huysentruyt 19 Esophageal Clearance in GERD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237 Stefano Nobile and Giovanni Vento 20 Manometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251 Taher Omari 21 Nuclear Scintigraphy and GER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267 Yvan Vandenplas and Bruno Hauser 22 Acid-Lowering Drugs for the Treatment of Gastro-esophageal Reflux Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 Carmelo Scarpignato 23 Anti-Acid Drugs: Adverse Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307 Elvira Ingrid Levy, Sebastien Kindt, Melina Simon, and Yvan Vandenplas 24 GER and Prokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319 Mário C. Vieira 25 Adverse Effects of GER Medication Except Anti-Acid Drugs . . . . . . . 327 Melina Simon, Elvira Ingrid Levy, and Yvan Vandenplas 26 GER and Hypnotherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335 A. M. Vlieger 27 Alternative Medicine and Lifestyle Changes in GERD . . . . . . . . . . . . . 339 Yvan Vandenplas 28 GERD and Endoscopic Therapeutic Approach . . . . . . . . . . . . . . . . . . . 345 Shishu Sharma and Mike Thomson 29 Surgical Options to Treat GERD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361 Antoine De Backer Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371 Epidemiology of GER 1 Silvia Salvatore and Yvan Vandenplas Abstract The real prevalence of gastro-esophagel reflux (GER) and GER-disease (GERD) is difficult to estimate, particularly in infants and young children, because of caregiver’s interpretation, lack of specific symptoms, proper investigation and a gold standard test, over-the-counter medications, and limited prospective stud- ies. GER episodes may physiologically happen several times per day, especially in postprandial period, without causing any manifestations. In many reports, the terms GER and GERD, that is GER with troublesome symptoms or complica- tions, are often erroneously interchangeably used, hampering the confusion about the real prevalence of these two different conditions. Regurgitation is a common manifestation of GER, occurring in at least 25% of infants, naturally disappearing before the first year of life and representing a functional disorder in the vast majority of cases. Despite it being neither sufficient nor specific, regur- gitation is often considered a reliable symptom for the diagnosis of GERD. Conversely, heartburn shows an adequate specificity for GERD in older children and adolescents although sensitivity is poor particularly for extra- esophageal manifestations. Few studies assessed the prevalence of GERD per- forming upper endoscopy and esophageal pH-impedance and even in these studies, recruitment and diagnostic criteria are heterogeneous. Prospective data off and on GER treatment are also limited in pediatric ages and the rate of pro- gression from GER to GERD is still unclear. S. Salvatore (*) Pediatric Department, Hospital “F. Del Ponte”, University of Insubria, Varese, Italy e-mail: [email protected] Y. Vandenplas Vrije Universitiet Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium © The Author(s), under exclusive license to Springer Nature 1 Switzerland AG 2022 Y. Vandenplas (ed.), Gastroesophageal Reflux in Children, https://doi.org/10.1007/978-3-030-99067-1_1 2 S. Salvatore and Y. Vandenplas Nevertheless, a number of studies demonstrated an increased prevalence of GERD in children with neurological impairment, cystic fibrosis, and esophageal atresia. However, individual sensitivity, esophageal clearance, and mucosal resistance determine the severity of symptoms and the presence of complications. Keywords Reflux · GER · GERD · Regurgitation · Natural history · Esophagitis · Infants Children Introduction The exact prevalence of gastroesophageal reflux (GER) and GER-disease (GERD) which is defined as GER causing troublesome symptoms or complications [1] is unclear in all pediatric ages. The caregiver’s interpretation of symptoms, the lack of a specific manifestation of GERD, the complementary diagnostic role of upper endoscopy and esophageal pH-impedance (pH-MII) with no gold standard test, the limited investigations performed in young children, the high heterogeneity of the literature data and the over-the-counter medications determine the difficulty in the epidemiological estimation. Epidemiological Pitfalls GER, that is the return of gastric contents into the esophagus, physiologically occurs several times per day in every individual, particularly in postprandial periods and in the first months of life [1–3]. Most reflux episodes are brief and do not cause any manifestation. Regurgitation is the involuntary and effortless progression of GER into and eventually outside the oral cavity [1] and has a peak incidence at 3–4 months of life occurring in more than 25% of healthy infants. The spectrum of GERD pre- sentation is wide and unspecific, including gastrointestinal (regurgitation, vomiting, heartburn, and epigastric pain), respiratory and general (feeding and sleeping prob- lems, crying, irritability, failure to thrive) symptoms. Because these manifestations are age-related and overlap many other functional and organic conditions, the preva- lence of GERD cannot accurately rely on a clinical diagnosis except in the case of heartburn that is considered a highly sensitive and specific symptom [1, 4]. Moreover, none of the above symptoms is predictive of esophagitis but only a minority of children are submitted to upper endoscopy and esophageal biopsies. An impaired quality of life is sufficient to make the passage from GER to GERD in adults but is difficult to report in childhood because it is mainly related to parental perception. The absence of a gold standard test for the diagnosis of GERD, the limited inves- tigations in infants and children, the heterogeneity of diagnostic criteria used in different studies and the lack of large prospective trials hamper the difficulty to clarify the prevalence of GERD.