Gastroesophageal reflux in children

Introduction
Contents
1: Epidemiology of GER
	Introduction
		Epidemiological Pitfalls
		GER and Regurgitation in Infants
			Effect of Feeding
		GERD in Infancy
		GER(D) in Children and Adolescents
	Potential Risk Factors for GERD
		Genetic Factors
		Smoking and Alcohol
		Preterm Infants
		Comorbidity
	Conclusion
	References
2: Pathophysiology of GER
	LES Function
	Other Structural Abnormalities
	Esophageal Mechanisms
		Esophageal Peristalsis
		Esophageal Mucosa Defense
		Mucosal Integrity
		Sensation
	Special Patient Groups
	Conclusion
	References
3: Symptoms of GER
	Introduction
	Clinical Picture of Physiologic GER and GERD in Infants
	Clinical Picture of GERD in Young Children
	Clinical Picture of GERD in Older Children and Adolescents
	Overview on GERD and Respiratory Symptoms
	References
4: Dysphagia and GER
	Introduction
	Pathophysiology of Swallowing
	Genesis of Dysphagia in Patients with GERD
	Clinical Presentation
	Diagnosis
	Treatment
	Conclusion
	References
5: Duodeno-GER
	Introduction
	Mechanism of Bile Injury
	Luminal Factors Responsible of Impaired Mucosal Integrity
	Measurement of Duodenogastroesophageal Reflux
		Esophageal pH Monitoring/Impedance
		Bilirubin Monitoring
		HIDA Scintigraphy
		Aspiration Study
		Other
	Role of Duodenogastroesophageal Reflux in Esophageal Lesions
	Role of Duodenogastroesophageal Reflux in Symptoms
	The Role of Duodenogastroesophageal Reflux in Neoplasia
	Therapeutic Implications
	References
6: GER in Preterm Infants
	Introduction
	Diagnosis
		Clinical Evaluation
		Multichannel Intraluminal Impedance and pH Monitoring (MII-pH)
		Other Diagnostic Tools
		Use of Proton Pump Inhibitors as a Diagnostic Test
		Use of Extensively Hydrolyzed Protein Formula as a Diagnostic Test
	Treatment
		Conservative Approach
			Improvement of Feeding Tolerance
			Use of Hydrolized Protein Formula
		Medications
			First-Line Treatments
			Second-Line Treatments
	References
7: GER and Respiratory Diseases
	Introduction
	Mechanisms of Association Between GER and Respiratory Disease
	GER and Asthma
		Pathogenetic Mechanisms
		The Role of Anti-acid Drugs in Asthma
	GER and Chronic Cough
		Pathogenetic Mechanisms
		The Role of Anti-acid Drugs for Chronic Cough
	GER and Laryngopharyngeal Disease
		The Role of Anti-acid Drugs for Laryngopharyngeal Disease
	Conclusion
	References
8: GER and Apnea
	Introduction
	Pathogenic Links
	Apnoea, ALTE, and GER(D)
	APNOEA and GER(D): Studies in Infants
	ALTE and GER(D)
	Studies in Children
	OSAS and GER
	Conclusion
	References
9: GER in Cystic Fibrosis
	Introduction
	Gastroesophageal Reflux and Gastroesophageal Reflux Disease
	Cystic Fibrosis
	What is the Mechanism of Increased GER in CF?
	Esophageal Motility in CF
	Incidence of GER and GERD in Children with CF
	Incidence of GER in Adults with CF
	Diagnosing GERD in CF
	Relationship Between GER and Worsening Lung Function in People with CF
	Delayed Gastric Emptying and GERD
	Barrett’s Esophagus and Esophageal and Gastroesophageal Junction Adenocarcinoma in CF
	Evidence of Aspiration in Children with CF
	How does GER Differ Between Children with CF and Symptomatic Children Without CF?
	Aging in CF: Impact on GER
	Treatments for GERD in CF
		PPI/H2RA/Prokinetics
		Lifestyle Changes
		Nissen Fundoplication
	What is on the Horizon?
	Conclusion
	References
10: GER and Esophageal Atresia
	Introduction
	GERD is Frequent in Patients with EA
	GERD is Associated with Complications in Neonates and Infants Operated for EA
	GERD Impacts Quality of Life of EA Patients
	What is the Natural History of GERD in EA Patients?
	How Should GERD be Diagnosed in EA Patients?
	How Should GERD be Treated in EA Patients?
	Should GERD Systematically be Treated with PPI in all EA Patients?
	How Long Should GERD be Treated and Monitored?
	Is Routine Endoscopy Useful in the Follow-up of EA Patients?
	When do We Perform Fundoplication in EA Patients with GERD?
	What Evaluations Should be Performed Prior to Fundoplication?
	What are the Long-Term Morbidities of GERD in Adults with EA?
	Conclusion
	References
11: GERD and Cow’s Milk Allergy
	Introduction
	The Role of Cow’s Milk Protein (CMP) in GERD
	Diagnosis
	Dietary Management in Proven CMP-Induced GERD
		Breastmilk in the Management of GERD
		Formulas for CMA in the Management of GERD
		Complementary Feeding in Infants with GERD
	Natural History of CMP-Induced GERD
	Conclusion
	References
12: GER and Overweight/Obesity
	Introduction and Epidemiology
	Pathophysiology
	Other Associations
	Specific Treatment Options
	References
13: GER and Eosinophilic Esophagitis
	Conclusion
	References
14: GER and Helicobacter pylori
	Introduction
	Diagnosis of GERD
	Diagnosis of H. pylori
	H. pylori Pathogenesis in Children
	H. pylori and GERD
	The Effects on Children
	H. pylori and Reflux Esophagitis (RE)
	Atrophic Gastritis
	The Effect of H. pylori Eradication on GERD
	Barrett’s Esophagus
	Effects of H. pylori Infection on Gastrin, Ghrelin, and GERD
	GERD, H. pylori and Gastrin
	GERD, H. pylori, and Pepsinogens (PGs)
	GERD, H. pylori, and Ghrelin
	Virulence Factors of H. pylori, and GERD
		Virulence Factors of H. pylori
			Cytotoxin-Associated Gene A (CagA)
			Vacuolation Cytotoxin A (VacA)
			Duodenal Ulcer Promoting Gene A Protein (DupA)
			Outer Inflammatory Protein (OipA)
			Adherence and Outer Membrane Proteins (OMPs)
	Inflammatory Cytokines of H. pylori, and GERD
	H. pylori and Gastric Microbiota in Children
		Limitation
	Conclusion
	References
15: GER and Probiotic
	The Infant with Uncomplicated Recurrent Regurgitation
	The Infant with Recurrent Regurgitation and Poor Weight Gain
	The Child over 18 Months of Age with Chronic Regurgitation or Vomiting
	Role of Probiotics
	Probiotics and PPI
	Possible Effect of Probiotic Treatment
		Microbiota–Gut–Brain Axis
	Conclusion
	References
16: Diagnosis of GERD
	Introduction
	History, Physical Exam, and Questionnaires
		Typical Symptoms
			Infants
			Older Children and Adolescents
		Extra-Esophageal Symptoms
	Diagnostic Tests
		Proton Pump Inhibitor (PPI) Trial
		Endoscopy and Esophageal Biopsies
		Function Tests
			High-Resolution Manometry
			24-Hour Esophageal pH—Monitoring
			24-Hour Esophageal pH-Impedance Monitoring
			Function Testing in Extra-Esophageal Symptoms
		Other Tests
			Imaging
			Non-invasive Tests
	Conclusion
	References
17: Contribution of Histology to the Diagnosis of GER
	Introduction
	Histology of the Esophagus and Reflux Esophagitis
		Normal Esophagus Biopsies
		Histological Lesions in Gastroesophageal Reflux Disease
		Where to Take Biopsies? How Many Biopsies?
	Correlation of Histology to GERD in Children
		Symptoms
			Infants
			Child and Adolescent
		Endoscopy
		pHmetry
		Esophageal Impedance
			Baseline Impedance
			Contractile Segment Impedance
	Contribution of Histology to Diagnostic of GERD
		Identifying the Differential Diagnosis
		Screening for Barrett’s Esophagus
		In Specific Situations
			Esophageal Atresia (EA)
			Neurologically impaired Children
			Cystic Fibrosis (CF)
	Conclusion
	References
18: How to Position pH-Impedance Probes in Pediatric Patients
	Introduction
	Formulas Proposed in Literature
	The KidZ Health Castle Formula
	References
19: Esophageal Clearance in GERD
	Clearance of Gastroesophageal Reflux
	Volume Clearance
	Chemical Clearance
	Esophageal Motility Disorders
	Measuring Esophageal Clearance
	Modifiers of Esophageal Clearance
	References
20: Manometry
	Introduction
	Practicalities of Performing Esophageal HRM Studies in Children
	What Can Esophageal HRM Measure That Is Relevant to GER Disease?
		Excluding Achalasia
		Ineffective Esophageal Motility
		Mucosal Impedance
		Additive Value Multiple Rapid Swallows
		Transient LES Relaxation
		Esophago-Gastric Junction Morphology
		Esophago-gastric Junction Contractility
	Pre-operative HRM to Identify Pediatric Patients at Risk Postoperative Dysphagia
	Use of Manometry with Impedance to Investigate Rumination Syndrome
	Conclusion
	References
21: Nuclear Scintigraphy and GER
	References
22: Acid-Lowering Drugs for the Treatment of Gastro-esophageal Reflux Disease
	Introduction
	Medical Management of GERD
	Antacid and Alginate Formulations
		Pharmacology
		Clinical Efficacy
	Antisecretory Drugs
		Regulation of Gastric Acid Secretion
		Pharmacology of H2-Receptor Antagonists
	Formulations of H2-Receptor Antagonists
		Pharmacology of Proton Pump Inhibitors
		Pharmacogenetics of Proton Pump Inhibitors
		Formulations of Proton Pump Inhibitors
	Non-Antisecretory Effects of H2-Receptor Antagonists and Proton Pump Inhibitors
		Clinical Efficacy of H2-Receptor Antagonists
		Clinical Efficacy of Proton Pump Inhibitors
	Overuse and Misuse of Antisecretory Therapy
	Acid Suppression Drugs: What Is New?
	Conclusions
	References
23: Anti-Acid Drugs: Adverse Effects
	Introduction
	Antacids
		Magnesium Hydroxide and Aluminum Hydroxide
		Sodium and/or Magnesium Alginates
	Acid Suppressive Drugs
		H2-Receptor Antagonist
		Proton Pomp Inhibitors
		Potassium-Competitive Acid Blockers
	Conclusion
	References
24: GER and Prokinetics
	Metoclopramide
	Bromopride
	Bethanechol
	Cisapride
	Domperidone
	Drugs Acting on Lower Esophageal Sphincter
	References
25: Adverse Effects of GER Medication Except Anti-Acid Drugs
	Introduction
	Prokinetics
		Metoclopramide
		Domperidone
		Cisapride
	Erythromycin
	Bethanechol
	Baclofen
	Conclusion
	References
26: GER and Hypnotherapy
	Introduction
	What Is Hypnosis?
	Hypnosis and Gastric Functioning
	Hypnotherapy and Gastric Symptoms
	Future Directions
	References
27: Alternative Medicine and Lifestyle Changes in GERD
	Introduction
	Weight Loss in Obesity
	Massage Therapy
	Acupuncture
	Mind–Body Therapies
	Herbs and Dietary Supplements
	Summary
	References
28: GERD and Endoscopic Therapeutic Approach
	Introduction
	Endoscopic Suturing Devices
	Full Thickness Plicator®
	EsophyX®
	Delivery of Radiofrequency Energy (Stretta® System)
	Gastro-esophageal Biopolymer Injection
	Conclusion
	References
29: Surgical Options to Treat GERD
	Introduction
		For a Successful Surgical Treatment, Three Conditions Need to be Fulfilled: Careful Selection of the Candidates for Surgery After a Complete Pre-Operative Work-Up, and a Technically Correct Operation
			Preoperative Work-Up for Anti-reflux Surgery
			Indications for Anti-Reflux: Surgery
			Surgical Technique
				The History of Anti-Reflux Surgery [15]
				Laparoscopic Fundoplication (Nissen Procedure)
				Partial Fundoplication
				Esophagogastric Disconnection
				Additional (Concomitant) Procedures
			Complications of Anti-reflux Surgery
				Intra-Operative Complications
				Postoperative Complications
			Results of Anti-reflux Surgery
	Conclusion
	References
Index