Gastroesophageal Reflux: Management Guidance for the Pediatrician Jenifer R

Guidance for the Clinician in Rendering Pediatric Care

CLINICAL REPORT Gastroesophageal Reﬂux: Management Guidance for the Pediatrician

Jenifer R. Lightdale, MD, MPH, David A. Gremse, MD, and abstract SECTION ON GASTROENTEROLOGY, HEPATOLOGY, AND Recent comprehensive guidelines developed by the North American NUTRITION Society for Pediatric Gastroenterology, Hepatology, and Nutrition define KEY WORDS fl fl fl gastroesophageal re ux, gastroesophageal re ux disease, the common entities of gastroesophageal re ux (GER) as the physio- pediatrics, guidelines, review, global consensus, reflux-related logic passage of gastric contents into the esophagus and gastroesoph- disease, vomiting, regurgitation, rumination, extraesophageal ageal reflux disease (GERD) as reflux associated with troublesome symptoms, Barrett esophagus, proton pump inhibitors, diagnostic imaging, impedance monitoring, gastrointestinal symptoms or complications. The ability to distinguish between GER endoscopy, lifestyle changes and GERD is increasingly important to implement best practices in ABBREVIATIONS the management of acid reflux in patients across all pediatric age GER—gastroesophageal reflux groups, as children with GERD may benefit from further evaluation GERD—gastroesophageal reflux disease and treatment, whereas conservative recommendations are the only GI—gastrointestinal — fl H2RA histamine-2 receptor antagonist indicated therapy in those with uncomplicated physiologic re ux. This MII—multiple intraluminal impedance clinical report endorses the rigorously developed, well-referenced PPI—proton pump inhibitor North American Society for Pediatric Gastroenterology, Hepatology, This document is copyrighted and is property of the American and Nutrition guidelines and likewise emphasizes important concepts Academy of Pediatrics and its Board of Directors. All authors fi fl for the general pediatrician. A key issue is distinguishing between clin- have led con ict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through ical manifestations of GER and GERD in term infants, children, and ado- a process approved by the Board of Directors. The American lescents to identify patients who can be managed with conservative Academy of Pediatrics has neither solicited nor accepted any treatment by the pediatrician and to refer patients who require con- commercial involvement in the development of the content of this publication. sultation with the gastroenterologist. Accordingly, the evidence basis The guidance in this report does not indicate an exclusive presented by the guidelines for diagnostic approaches as well as treat- course of treatment or serve as a standard of medical care. ments is discussed. Lifestyle changes are emphasized as first-line ther- Variations, taking into account individual circumstances, may be apy in both GER and GERD, whereas medications are explicitly indicated appropriate. only for patients with GERD. Surgical therapies are reserved for children with intractable symptoms or who are at risk for life-threatening complications of GERD. Recent black box warnings from the US Food and Drug Administration are discussed, and caution is underlined when using promoters of gastric emptying and motility. Finally, atten- tion is paid to increasing evidence of inappropriate prescriptions for proton pump inhibitors in the pediatric population. Pediatrics 2013;131:e1684–e1695

www.pediatrics.org/cgi/doi/10.1542/peds.2013-0421 INTRODUCTION doi:10.1542/peds.2013-0421 ﬂ All clinical reports from the American Academy of Pediatrics Gastroesophageal re ux (GER) occurs in more than two-thirds of automatically expire 5 years after publication unless reafﬁrmed, otherwise healthy infants and is the topic of discussion with pedia- revised, or retired at or before that time. tricians at one-quarter of all routine 6-month infant visits.1,2 In addition PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). to seeking guidance from their pediatricians, parents often request Copyright © 2013 by the American Academy of Pediatrics evaluation by pediatric medical subspecialists.3 It is, therefore, not surprising that strongly evidence-based guidelines incorporating

e1684 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from www.aappublications.org/news by guest on September 24, 2021 FROM THE AMERICAN ACADEMY OF PEDIATRICS state-of-the-art approaches to the contents via a coordinated autonomic rarely Barrett esophagus and adeno- evaluation and management of pedi- and voluntary motor response. Re- carcinoma. atric GER have been welcomed by both gurgitation and vomiting can be fur- Although the reported prevalence of general pediatricians and pediatric ther differentiated from rumination, in GERD in patients of all ages world- medical subspecialists and surgical which recently ingested food is ef- wide is increasing,5 GERD is never- specialists. GER, defined as the passage fortlessly regurgitated into the mouth, theless far less common than GER. of gastric contents into the esophagus, masticated, and reswallowed. Rumi- Population-based studies suggest is distinguished from gastroesophageal nation syndrome has been identified reflux disorders are not as common reflux disease (GERD), which includes as a relatively rare clinical entity that in Eastern Asia, where the prevalence troublesome symptoms or complica- involves the voluntary contraction of is 8.5%,19 compared with Western tions associated with GER.4 Differen- abdominal muscles.9 In contrast, both Europe and North America, where the tiating between GER and GERD lies at regurgitation and vomiting can be current prevalence of GERD is esti- the crux of the guidelines jointly de- considered common and often non- mated to be 10% to 20%.20 New epi- veloped by the North American Soci- pathologic manifestations of GER. demiologic and genetic evidence ety for Pediatric Gastroenterology, Symptoms or conditions associated suggests some heritability of GERD Hepatology, and Nutrition and the with GERD are classified by the prac- and its complications, including ero- European Society for Pediatric Gas- tice guidelines as being either sive esophagitis, Barrett esophagus, – troenterology, Hepatology, and Nutri- esophageal or extraesophageal.4 Both and esophageal adenocarcinoma.21 23 tion.4 These definitions have further classifications can be used to define A few pediatric populations at high been recognized as representing a the disease, which can be further risk of GERD have also been identi- 5 fi global consensus. Therefore, it is characterized by findings of mucosal ed, including children with neuro- important that all practitioners who injury on upper endoscopy. Esopha- logic impairment, certain genetic fl 24,25 treat children with re ux-related dis- geal conditions include vomiting, poor disorders, and esophageal atresia orders are able to identify and dis- weight gain, dysphagia, abdominal (Table 1). The prevalence of severe, tinguish those children with GERD, or substernal/retrosternal pain, and chronic GERD is much higher in pe- fi “ who may bene t from further eval- esophagitis. Extraesophageal con- diatric patients with these GERD- ” uation and treatment, from those ditions have been subclassified promoting conditions. These patients maybemorepronetoexperienc- with simple GER, in whom conser- according to both established and ing complications of severe GERD vative recommendations are more proposed associations; established than patients who are otherwise appropriate. extraesophageal manifestations of GERD healthy.26 GER is considered a normal physio- can include respiratory symptoms, in- logic process that occurs several cluding cough and laryngitis, as well Population trends hypothesized to times a day in healthy infants, children, as wheezing in infancy.10,11 Although contribute to a general increase in and adults. GER is generally associated older studies from the 1990s sug- the prevalence of GERD include glo- with transient relaxations of the lower gested that GERD may aggravate bal epidemics of both obesity and esophageal sphincter independent of asthma, recent publications have asthma. In some instances, GERD can swallowing, which permits gastric suggested that the impact of GERD on be implicated as either the underlying contents to enter the esophagus. Epi- asthma control is considerably less etiology (ie, recurrent pneumonia in sodes of GER in healthy adults tend to than previously thought.10,12–18 Other occur after meals, last less than 3 extraesophageal manifestations in- TABLE 1 Pediatric Populations at High Risk minutes, and cause few or no symp- clude dental erosions, and proposed for GERD and Its Complications toms.6 Less is known about the nor- associations include pharyngitis, si- Neurologic impairment mal physiology of GER in infants and nusitis, and recurrent otitis media. Obese children, but regurgitation or spitting Patients can be described clinically by History of esophageal atresia (repaired) up, as the most visible symptom, is Hiatal hernia their symptoms or by the endoscopic Achalasia reported to occur daily in 50% of all description of their esophageal mu- Chronic respiratory disorders infants.7,8 cosa. GERD-associated esophageal in- Bronchopulmonary dysplasia fi fl Idiopathic interstitial brosis In both infants and children, re ux can juries and complications found on Cystic fibrosis also be associated with vomiting, de- endoscopy include reflux esophagitis, History of lung transplantation fined as a forceful expulsion of gastric less commonly peptic stricture, and Preterm infants

PEDIATRICS Volume 131, Number 5, May 2013 e1685 Downloaded from www.aappublications.org/news by guest on September 24, 2021 the premature infant exacerbated by infants can also be associated with pneumonia, sore throat, hoarseness, GERD) or a direct repercussion (ie, extraesophageal symptoms of cough- chronic sinusitis, laryngitis, or dental obesity leading to GERD) of such ing, choking, wheezing, or upper re- erosions. In a pediatric patient with conditions. In the great majority of spiratory symptoms.7 The incidence of GERD and dental erosions, the pro- cases, however, GERD and comorbid- GERD is reportedly lower in breastfed gression of tooth structure loss may ities are known to occur simulta- infants than in formula-fed infants.27 be indicative that existing therapy for neously in patients without a clear In line with the natural history of GERD is not effective. Conversely, sta- causal relationship. regurgitation, GERD in infants is con- bility of dental erosions is 1 measure sidered to have a peak incidence of of adequacy of GERD management. CLINICAL FEATURES OF GERD approximately 50% at 4 months of age and then to decline to affect only Troublesome symptoms or complica- DIAGNOSTIC STUDIES tions of pediatric GERD are associated 5% to 10% of infants at 12 months of For most pediatric patients, a history 7,8 with a number of typical clinical pre- age. and physical examination in the ab- sentations in infants and children, Common symptoms of GERD in chil- sence of warning signs are sufficient depending on patient age5 (Table 2). dren 1 to 5 years of age include re- to reliably diagnose uncomplicated Reflux may occur commonly in pre- gurgitation, vomiting, abdominal pain, GER and initiate treatment strategies. term newborn infants but is generally anorexia, and feeding refusal.28 Gen- Generally speaking, diagnostic testing nonacidic and improves with matura- erally, GERD causes troublesome is not necessary. The reliability of tion. A full discussion of reflux in symptoms without necessarily in- symptoms to make the clinical di- neonates and preterm infants is be- terfering with growth; however, chil- agnosis of GERD is particularly high in yond the scope of this report. dren with clinically significant GERD adolescents, who often present with – Guidelines have distinguished between or endoscopically diagnosed esoph- heartburn typical of adults.29 31 Nev- manifestations of GERD in full-term agitis may also develop an aversion ertheless, dedicating at least part of infants (younger than 1 year) from to food, presumably because of a a clinical visit to obtaining a clinical those in children older than 1 year and stimulus-response association of eating history and performing a physical adolescents. Common symptoms of with pain. This aversion, combined with examination are also essential to ex- GERD in infants include regurgitation feeding difficulties associated with re- clude more worrisome diagnoses that or vomiting associated with irritability, peated episodes of regurgitation, as can present with reflux or vomiting anorexia or feeding refusal, poor well as potential and substantial nu- (Table 3). weight gain, dysphagia, presumably trient losses resulting from emesis, To date, no single symptom or cluster painful swallowing, and arching of mayleadtopoorweightgainoreven of symptoms can reliably be used the back during feedings. Relying on malnutrition. to diagnose esophagitis or other a symptom-based diagnosis of GERD Older children and adolescents are complications of GERD in children or to can be difficult in the first year of life, most likely to resemble adults in their predict which patients are most likely especially because symptoms of GERD clinical presentation with GERD and to in infants do not always resolve with TABLE 3 Concerning Symptoms and Signs complain of heartburn, epigastric (“Warning Signs” in Figures) for acid-suppression therapy.5,27 GERD in pain, chest pain, nocturnal pain, dys- Primary Etiologies Presenting With phagia, and sour burps. When eliciting Vomiting TABLE 2 Common Presenting Symptoms of GERD in Pediatric Patients a history in school-aged children with Bilious vomiting GI tract bleeding Infant Older Child/Adolescent suspected GERD, it may be important to directly ask patients themselves Hematemesis Feeding refusal Abdominal pain/ Hematochezia heartburn about their symptoms rather than Consistently forceful vomiting Recurrent Recurrent vomiting relying strongly on parent report. In 1 Fever vomiting study, adolescents were significantly Lethargy Poor weight Dysphagia Hepatosplenomegaly gain more likely than their parents to re- Bulging fontanelle Irritability Asthma port themselves to be experiencing Macro/microcephaly Sleep Recurrent pneumonia symptoms of sour burps or nausea.1 Seizures disturbance Abdominal tenderness or distension Respiratory Upper airway symptoms Extraesophageal symptoms in older Documented or suspected genetic/metabolic symptoms (chronic cough, children and adolescents can include syndrome hoarse voice) nocturnal cough, wheezing, recurrent Associated chronic disease

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to respond to therapy.21 Nonetheless, cause GERD-like symptoms and evaluate burn in adults. Esophageal pH metrics a number of GERD symptom ques- for esophageal injury attributable to generally include an absolute number tionnaires have been validated and GERD.4 of reflux episodes detected during may be useful in the detection and monitoring, the duration of reflux epi- surveillance of GERD in affected chil- Upper GI Tract Series sodes detected, and the reflux index, which is calculated as the percentage dren of all ages. Kleinman et al de- Upper GI tract contrast radiography of a study period during which esoph- veloped a questionnaire for infants generally involves obtaining a series of ageal pH is <4.0. Although esophageal that was validated for documentation fluoroscopic images of swallowed pH monitoring may be useful for asso- and monitoring of parent-reported barium until the ligament of Treitz is 30 ciating a temporal relationship between GERD symptoms. Another question- visualized. According to the new 32 asymptomandacidreflux and to naire by Størdal et al for pediatric guidelines, the routine performance of evaluate the efficacy of pharmacologic patients 7 to 16 years of age com- upper GI tract radiographic imaging to therapy on acid suppression, mounting pared favorably with results of pH diagnose GER or GERD is not justified,4 evidence suggests poor reproducibility monitoring. As yet another example, because upper GI tract series are too of pH testing, as well as a clear con- the GERD Symptom Questionnaire de- brief in duration to adequately rule tinuum between pH findings in physio- veloped by Deal et al33 appears valid out the occurrence of pathologic re- logic GER and pathologic GERD. In turn, for differentiating children with GERD flux, and the high frequency of non- esophageal pH monitoring is losing from healthy controls but has not pathologic reflux during the examination value as a primary modality for di- been compared with objective stand- can encourage false-positive diagnoses. agnosing or managing pediatric GERD.34 ards, such as pH monitoring or en- Additionally, observation of the reflux doscopic findings. of a barium column into the esoph- The strategy of using diagnostic agus during GI tract contrast studies Multichannel Intraluminal Impedance Monitoring testing to diagnose GERD may also may not correlate with the severity be fraught with complexity, because of GERD or the degree of esophageal Multiple intraluminal impedance (MII) there is no single test that can rule it mucosal inflammation in patients with is an emerging technology for detect- in or out. Instead, diagnostic tests reflux esophagitis. It is recognized that ing the movement of both acidic and must be used in a thoughtful and serial upper GI tract series are useful in the nonacidic fluids, solids, and air in the manner to document the presence evaluation of vomiting to screen for esophagus, thereby providing a more of reflux of gastric contents in the possible anatomic abnormalities of the detailed picture of esophageal events esophagus, to detect complications, to upper GI tract.4 For example, in infants than pH monitoring.34 MII can be used establish a causal relationship between with bilious vomiting, an upper GI tract to measure volume, speed, and physi- reflux and symptoms, to evaluate the series may be useful for evaluating for callengthofbothanterogradeand efficacy of therapies, and to exclude possible malrotation or duodenal web. retrograde esophageal boluses. Com- fi other conditions. The diagnostic meth- Persistent, forceful vomiting in the rst bined pH/MII testing is evolving into the ods most commonly used to evaluate few months of life should be evaluated test of choice to detect temporal rela- fi pediatric patients with GERD symptoms with pyloric ultrasonography to evalu- tionships between speci c symptoms fl are upper gastrointestinal (GI) tract ate for possible pyloric stenosis. An and the re ux of both acid and nonacid contrast radiography, esophageal pH upper GI tract series should be re- gastric contents. In particular, MII has served if the results of the pyloric ul- and/or impedance monitoring, and up- been used in recent years to investigate trasound are equivocal. per endoscopy with esophageal biopsy. how GER and GERD correlate with apnea, cough, and behavioral symptoms.35 Upper GI tract series are useful to According to the new guidelines, MII and delineate anatomy and to occasion- Esophageal pH Monitoring pH electrodes can and should be com- ally document a motility disorder, Continuous intraluminal esophageal bined on a single catheter.4 whereas esophageal pH monitoring pH monitoring can be used to quan- and intraluminal esophageal impedance tify the frequency and duration of represent tools to quantify GER. Up- esophageal acid exposure during Gastroesophageal Scintigraphy per endoscopy with esophageal bi- a study period. The conventional Gastroesophageal scintigraphy scans opsy represents the primary method to definition of acid exposure in the for reflux of 99mTc-labeled solids or investigate the esophageal mucosa to esophagus is a pH <4.0, the pH most liquids into the esophagus or lungs both exclude other conditions that can associated with a complaint of heart- after administration of the test

PEDIATRICS Volume 131, Number 5, May 2013 e1687 Downloaded from www.aappublications.org/news by guest on September 24, 2021 material into the stomach. This nuclear or antral webs, Crohn esophagitis, may be effective strategies to address scan evaluates postprandial reflux and peptic ulcer, Helicobacter pylori in- GERD in many patients. In particular, can also quantitate gastric emptying; fection, and infectious esophagitis. the guidelines emphasize that milk however, the lack of standardized tech- Erosive esophagitis is reported less protein allergy can cause a clinical niques and age-specific normal values oftenininfantsandchildrenwith presentation that mimics GERD in limits the usefulness of this test. GERD than in adults with GERD; how- infants. Therefore, a 2- to 4-week trial Therefore, gastroesophageal scintigra- ever, a normal endoscopic appear- of a maternal exclusion diet that re- phy is not recommended in the routine ance of the esophageal mucosa in stricts at least milk and egg is rec- evaluation of pediatric patients with pediatric patients does not exclude ommended in breastfeeding infants GER.4 histologic evidence of reflux esoph- with GERD symptoms, whereas an ex- agitis.5,8 Esophageal biopsy is beneficial tensively hydrolyzed protein or amino in evaluating for conditions that may – Endoscopy and Esophageal Biopsy acid based formula may be appro- mimic symptoms of GERD, such as eo- priate in formula-fed infants.4,30 It is It is certainly preferable to pursue sinophilic esophagitis, infectious esoph- important to note that this recom- conservative measures for treating agitis (Candida esophagitis or herpetic mendation applies to the subset of GERD in children before considering esophagitis), Crohn disease, or Barrett infants with complications of GER, and the use of more invasive testing. In 24 esophagus. Because endoscopic find- not “happy spitters.” particular, any diagnostic benefits of ings correlate poorly with histologic In 1 study of formula-fed infants, GERD pursuing upper endoscopy in pediatric testing in infants and children, per- symptoms resolved in 24% of infants patients suspected of having GERD forming esophageal biopsies during after a 2-week trial of changing to must also be weighed against minimal, endoscopy is recommended for the a protein hydrolysate formula thick- but not entirely negligible, procedural evaluation of GERD in children.4 and sedation risks.36 Nevertheless, the ened with 1 tablespoon rice cereal per performance of upper endoscopy al- ounce, avoiding overfeeding, avoiding lows direct visualization of the esoph- MANAGEMENT seated and supine positions, and avoiding 3 ageal mucosa to determine the presence The new guidelines describe several environmental tobacco smoke. Feeding and severity of injury from the reflux of treatment options for treating children changes can also be recommended gastric contents into the esophagus.26 with GER and GERD. In particular, life- in breastfed infants, because it is Esophageal biopsies allow evaluation style changes are emphasized, because well known that small amounts of of the microscopic anatomy.24 Upper they can effectively minimize symptoms cow milk protein ingested by the endoscopy with esophageal biopsy may of both in infants and children. For mother may be expressed in human be useful to evaluate inflammation in patients who require medication, op- milk. Indeed, several studies have the esophageal mucosa attributable to tions include buffering agents, acid found that breastfed infants may GERD and to exclude other associated secretion suppressants, and promoters benefit from a maternal diet that conditions with symptoms that can of gastric emptying and motility. Finally, restricts cow milk and eggs.38,39 mimic GERD, such as eosinophilic surgical approaches are reserved for The feeding management strategy that esophagitis. Recent data confirm that children who have intractable symp- involves the use of thickened feedings, approximately 25% of infants younger toms unresponsive to medical therapy either by adding up to 1 tablespoon of than 1 year will have histologic evi- or who are at risk for life-threatening dry rice cereal per 1 oz of formula30 or dence of esophageal inflammation.37 complications of GERD. changing to commercially thickened This test is indicated in patients with (added rice) formulas for full-term GERD who fail to respond to pharma- infants who are not cow milk protein LIFESTYLE CHANGES cologic therapy or as part of the ini- intolerant, is recognized as a reason- tial management if symptoms of poor Lifestyle Modifications for Infants able management strategy for other- weight gain, unexplained anemia or Lifestyle changes to treat GERD in wise healthy infants with both GER and fecal occult blood, recurrent pneumo- infants may involve a combination GERD.4 On the other hand, all pediatric nia, or hematemesis exist. of feeding changes and positioning clinicians should be aware of a possible Upper endoscopy may also be helpful therapy. Modifying maternal diet if in- association between thickened feedings in the assessment of other causes of fants are breastfed, changing formulas, and necrotizing enterocolitis in preterm abdominal pain and vomiting in pe- and reducing the feeding volume while infants.40 The Food and Drug Adminis- diatric patients, such as esophageal increasing the frequency of feedings tration issued a warning regarding a

e1688 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from www.aappublications.org/news by guest on September 24, 2021 FROM THE AMERICAN ACADEMY OF PEDIATRICS common commercially available thick- that prone positioning should be postprandial chewing of sugarless ening agent in 2011, suggesting that considered acceptable only if the in- gum.45–47 “parents, caregivers and health care fant is observed and awake.4 Prone ‘ ’ positioning is suggested to be benefi- providers not...feed SimplyThick to PHARMACOTHERAPEUTIC AGENTS cial in children older than 1 year with infants born before 37 weeks gestation FOR PEDIATRIC GERD who are currently receiving hospital either GER or GERD, because the risk care or have been discharged from the of sudden infant death syndrome is Several medications may be used to hospital in the past 30 days.” greatly decreased in older age groups. treat GERD in infants and children. The 2 major classes of pharmacologic Thickened feedings appear to de- Perceived and actual benefits of seated agents for treatment of GERD are acid crease observed regurgitation rather or semisupine positioning are also suppressants and prokinetic agents than the actual number of reflux epi- explored in the new guidelines. (Table 4). Growing evidence that de- sodes. Little is known about the effect Semisupine positioning, particularly monstrates the former to be more of thickening formula on the natural in an infant carrier or car seat, may effective than the latter has led to an history of infantile reflux or the po- exacerbate GER and should be increased use of acid suppressants to tential allergenicity of commercial avoided when possible, especially manage suspected GERD in pediatric thickening agents. Excessive energy after feeding.43 More recent data patients4,39; however, there is also sig- intake may occur with long-term use of obtained with esophageal imped- nificant concern for the overprescription feedings thickened with rice cereal or ance–pH monitoring have confirmed of acid suppressants, particularly proton corn. To this point, it is important to that postprandial reflux occurs pump inhibitors (PPIs), and it is im- realize that thickening a 20-kcal/oz similarly when infants are in car seats as when they are supine but portant to understand the new guide- infant formula with 1 tablespoon of lines for medication indications. rice cereal per ounce increases the also suggests that being in a car energy density to 34 kcal/oz. Com- seat for 2 hours after a feeding Acid Suppressants mercially available antiregurgitant reduces reflux-related respiratory formulae contain processed rice, corn, events.44 The main classes of acid suppressants or potato starch; guar gum; or locust are antacids, histamine-2 receptor bean gum and may present an option Lifestyle Modifications for Children antagonists (H2RAs), and PPIs. The that does not involve excess energy and Adolescents principles of using these medications intake by infants when consumed in in the treatment of pediatric GERD are Lifestyle changes that may benefit normal volumes. To date, there has similar to those in adults, other than GERD in older children and adoles- been little investigation into any re- the need to prescribe weight-adjusted cents are more akin to recommen- lationship between use of added rice doses and the need to consider the dations made for adult patients, form of the drug prescribed (ie, for cereal or antiregurgitant formulae and including the importance of weight childhood obesity. ease of ingestion in infants and chil- loss in overweight patients, cessation dren). Dosage ranges for drugs com- Lifestyle changes that may also benefit of smoking, and avoiding alcohol use. monly prescribed for pediatric patients infants with GERD include keeping Recommendations for conservatively with GERD are listed in Table 4. them in the completely upright posi- managing GERD in older children and tion or even placing them prone. In- adolescents, likewise, may involve di- deed, a number of recent studies that etary modification and positioning Antacids used impedance and pH monitoring changes, although the effectiveness of Antacids are a class of medications have confirmed older studies that used the latter as a treatment of GERD in that can be used to directly buffer pH monitoring to demonstrate signif- older children has not been as well gastric acid in the esophagus or stom- icantly less GER in infants in the flat studied as in infants. In terms of di- ach to reduce heartburn and ideally prone position compared with the etary changes, older children and allow mucosal healing of esophagitis. flat supine position.41,42 However, the adolescents are advised to avoid caf- There is limited historical evidence guidelines are unequivocal that the feine, chocolate, alcohol, and spicy that on-demand use of antacids can risk of sudden infant death syndrome foods as potential symptom triggers. lead to symptom relief in infants and in sleeping infants outweighs the The guidelines also point out that 3 children.48 Instead, although antacids benefits of prone positioning in the independent studies have demonstrated are generally seen as a relatively be- management of GERD and, therefore, decreased reflux episodes with nign approach to treating pediatric

PEDIATRICS Volume 131, Number 5, May 2013 e1689 Downloaded from www.aappublications.org/news by guest on September 24, 2021 TABLE 4 Pediatric Doses of Medications Prescribed for GERD Medications Doses Formulations Ages Indicated by the Food and Drug Administration Cimetidine 30–40 mg/kg/d, divided in 4 doses Syrup ≥16 y Ranitidine 5–10 mg/kg/d, divided in 2 to 3 doses Peppermint-flavored syrup; Effervescent tablet 1 mo–16 y Famotidine 1 mg/kg/d, divided in 2 doses Cherry-banana-mint–flavored oral suspension 1–16 y Nizatidine 10 mg/kg/d, divided in 2 doses Bubble gum–flavored solution ≥12 y Omeprazole 0.7–3.3 mg/kg/d Sprinkle contents of capsule onto soft foods 2–16 y Lansoprazole 0.7–3 mg/kg/d Sprinkle contents of capsule onto soft foods or select juices 1–17 y Administer capsule contents in juice through nasogastric tube Strawberry-flavored disintegrating tablet Orally disintegrating tablet via oral syringe or nasogastric tube (≥8 French) Esomeprazole 0.7–3.3 mg/kg/d Sprinkle contents of capsule onto soft foods 1–17 y Administer capsule contents in juice through nasogastric tube Rabeprazole 20 mg daily Oral tablet 12–17 y Dexlansoprazole 30–60 mg daily Oral tablet No pediatric indication Pantoprazole 40 mg daily (adult dose) Oral tablet No pediatric indication

GERD, it is important to recognize that difference between the various for- PPIs they are not entirely without risk. In- mulations of H2RAs. Randomized placebo- Most recently, PPIs have emerged as deed, several studies link aluminum- controlled pediatric clinical trials have the most potent class of acid sup- containing preparations with alumi- shown that cimetidine and nizatidine pressants by repeatedly demonstrat- num toxicity and its complications in are superior to placebo for the treating superior efficacy compared with 49–51 children. Similarly, milk-alkali syn- ment of erosive esophagitis in chil- H2RAs. PPIs decrease acid secretion by drome, a triad of hypercalcemia, al- dren.52,53 Pharmacokinetic studies in inhibition of H+,K+-ATPase in the gas- kalosis, and renal failure, has been school-aged children suggest that tric parietal cell canaliculus. PPIs are described in children receiving calcium- gastric pH begins to increase within 30 uniquely able to inhibit meal-induced containing preparations and adds to minutes of administration of an H2RA acid secretion and have a capacity to a note of caution. According to the and reaches peak plasma concen- maintain gastric pH >4 for a longer new guidelines, chronic antacid ther- trations 2.5 hours after dosing. The period of time than H2RAs. These apy is generally not recommended in acid-inhibiting effects of H2RAs last properties contribute to higher and 4 pediatrics for the treatment of GERD. for approximately 6 hours, so H2RAs faster healing rates for erosive fi In addition, the safety and ef cacy of are quite effective if administered 2 esophagitis with PPI therapy com- surface protective agents, such as or 3 times a day. pared with H2RA therapy. Finally, alginates or sucralfate, an aluminum- However, H2RAs inherently have some unlike H2RAs, the acid suppression containing preparation, have not been limitations. In particular, a fairly rapid ability of PPIs has not been observed adequately studied in the pediatric tachyphylaxis can develop within 6 to diminish with chronic use. population. As such, no surface agent weeks of initiation of treatment, lim- The timing of dosing most PPIs is is currently recommended as indepen- iting its potential for long-term use. In important for maximum efficacy. dent treatment of severe symptoms addition, H2RAs have been shown to be Both pediatricians and pediatric of GERD or erosive esophagitis in less effective than PPIs in symptom medical subspecialists must be dili- children.4 relief and healing rates of erosive gent at educating their patients to esophagitis. Although most of these administer PPIs, ideally, approxi- H2RAs downsides have been demonstrated mately 30 minutes before meals.7 H2RAs represent a major class of most clearly in adults, they are also All clinicians should also recognize medications that has completely rev- believed to affect children. It is also that the metabolism of PPIs is olutionized the treatment of GERD in important to recognize that cimetidine knowntodifferinchildrencom- children. H2RAs decrease the secretion has specifically been linked to an in- pared with adults, with a trend of acid by inhibiting the histamine-2 creased risk of liver disease and gy- toward a shorter half-life, necessi- receptor on the gastric parietal cell. necomastia, and that these associations tating a higher per-kilogram dose to Expert opinion suggests little clinical may be generalizable to other H2RAs. achieve a peak serum concentration

e1690 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from www.aappublications.org/news by guest on September 24, 2021 FROM THE AMERICAN ACADEMY OF PEDIATRICS and area under the curve similar to those in adults.45 A fairly wide range of effective doses is evident in children. For example, an open-label study of omeprazole in children re- vealed an effective dosage range of 0.7 to 3.3 mg/kg daily, on the basis of improvement in clinical symptoms and the results of esophageal pH monitoring.47 Lansoprazole, 0.7 to 3.0 mg/kg daily, improved GERD symptoms and healed all cases of erosive esophagitis in the treatment of 1- to 12-year-old children with GERD.48 Other trials of PPI therapy support the efficacy of treatment of severe esophagitis and esophagitis refractory to H2RAs in children.4,45 As in adults, PPIs are considered safe and generally well tolerated with relatively few adverse effects. In terms of their long-term use, published studies have reported PPI use for up to 11 years in small numbers of children.16 The Food and Drug Administration has approved a number of PPIs for use in pediatric patients in recent years, including omeprazole, lansoprazole, and esomeprazole for people 1 year and older and rabeprazole for people 12 years and older. Nonetheless, the new guidelines strike a note of caution when discussing the dramatic increase in past years in the number of PPI prescriptions written for pediatric patients, particularly infants, who may be at increased risk of lower respiratory tract infections.54–56 Overuse or misuse of PPIs in infants with reflux is a matter for great concern. Placebo-controlled trials in infants have not demonstrated supe- riority of PPIs over placebo for reduction in irritability.57 Headaches, diarrhea, constipation, and nausea have been described as occurring in up to 14% of older children and FIGURE 1 adults prescribed PPIs.25,58 Although Approach to the infant with recurrent regurgitation and vomiting. considered a benign histologic change, enterochromaffin cell hyperplasia has

PEDIATRICS Volume 131, Number 5, May 2013 e1691 Downloaded from www.aappublications.org/news by guest on September 24, 2021 recentlybeendemonstratedinupto children. Fundoplication, whereby the morbidity and do not reduce the risk 50% of children receiving PPIs for more gastric fundus is wrapped around the of direct aspiration of oral contents. than 2.5 years.25 Finally, a growing body distal esophagus, is most common Careful patient selection is one of the of evidence suggests that acid sup- and can be performed to prevent reflux keys to successful outcome.17 Children pression, in general, with either H2RAs by increasing baseline pressure of the who have failed pharmacologic treat- or PPIs, may be a risk factor for pedi- lower esophageal sphincter, decreasing ment may be candidates for surgical atric community-acquired pneumonia, the number of transient lower esoph- therapy, as are children at severe risk gastroenteritis, candidemia, and necro- ageal sphincter relaxations, and in- of aspiration of their gastric contents. tizing enterocolitis in preterm infants.59,60 creasing the length of the esophagus In most patients, if acid suppression that is intra-abdominal to accentuate with PPIs is ineffective, the accuracy of Prokinetic Agents the angle of His and reduce a hiatal the diagnosis of GERD should be reas- hernia, if indicated.17,56,57 Total esoph- sessed, because fundoplication may Desired pharmacologic effects of agogastric dissociation is another op- not produce optimum clinical results. prokinetic agents include improving erative procedure that is rarely used Clinical conditions, such as cyclic contractility of the body of the after failed fundoplication. Both pro- vomiting, rumination, gastroparesis, esophagus, increasing lower esoph- cedures are associated with significant and eosinophilic esophagitis, should ageal sphincter pressure, and increasing the rate of gastric emptying. To date, efforts to design a prokinetic agent with benefits that outweigh adverse effects has proven difficult. Even metoclopramide, the most common prokinetic agent still available, recently received a black box warning regarding its adverse effects. Indeed, adverse effects have been reported in 11% to 34% of patients treated with metoclopramide, including drowsiness, restlessness, and extrapyramidal reac- tions. Although a meta-analysis of 7 randomized controlled trials of metoclopramide in patients younger than 2 years with GERD confirmed a decrease in GERD symptoms, it was clearly at the cost of such significant adverse effects.61 Other drugs in this category include bethanechol, cisapride (no longer available commercially in the United States), baclofen, and eryth- romycin. Each works as a prokinetic by using a different mechanism. Nev- ertheless, after careful review, guidelines unequivocally state that there is insufficient evidence to support the routine use of any prokinetic agent for the treatment of GERD in infants or older children.4

Surgery for Pediatric GERD

Several surgical procedures can be FIGURE 2 used to decrease GER disorders in Approach to the infant with recurrent regurgitation and weight loss.

e1692 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from www.aappublications.org/news by guest on September 24, 2021 FROM THE AMERICAN ACADEMY OF PEDIATRICS be carefully ruled out before surgery, because they are likely to still cause symptoms after surgery. If antireﬂux surgery is pursued, the new guidelines also stress the importance of providing families with adequate counseling and education before the procedure so that they have a “re- alistic understanding of the potential complications…including symptom recurrence.”4

SUMMARY The updated guidelines published in 2009 are particularly rich with de- scriptions of typical presentations of GERD across all pediatric age groups.4 With an emphasis on evidence-based, best practice, they present a number of algorithms that can be of great use to both general pediatricians and pediatric medical subspecialists. The guidelines discuss the evaluation and management of recurrent regurgitation and vomiting in both infants and older FIGURE 3 children and the importance of dis- Approach to the older child or adolescent with heartburn. tinguishing GERD from numerous other disorders. The ﬁgures shown demonstrate the recommended approaches Pediatricians must also be able to who are not at risk for complications for commonly encountered presenta- recognize infants with recurrent re- to avoid unnecessary diagnostic proce- tions of GERD in pediatric patients and gurgitation and troublesome symp- dures or pharmacologic therapy.62–64 are summarized here. toms of GERD (Fig 2). The new In the infant with uncomplicated re- guidelines emphasize weight loss as LEAD AUTHORS Jenifer R. Lightdale, MD, MPH current regurgitation, it may be im- a crucial warning sign that should David A. Gremse, MD portant to recognize physiologic GER alter clinical management. Older chil- that is effortless, painless, and not dren with heartburn may beneﬁtfrom SECTION ON GASTROENTEROLOGY, affecting growth (Fig 1). In this situa- empirical treatment with PPIs (Fig 3). HEPATOLOGY, AND NUTRITION – tion, pediatricians should focus on In general, there is a paucity of stud- EXECUTIVE COMMITTEE, 2011 2012 Leo A. Heitlinger, MD, Chairperson minimal testing and conservative ies in pediatrics that demonstrate the Michael Cabana, MD management. Overuse of medications effectiveness of this approach. In- Mark A. Gilger, MD in the so-called “happy spitter” should stead, it is essential to carefully follow Roberto Gugig, MD be avoided by all pediatric physicians. all patients empirically treated for Jenifer R. Lightdale, MD, MPH Ivor D. Hill, MB, ChB, MD Instead, pediatricians are well served GERD to ensure that they are improv- to diagnose GER and provide signif- ing, because there are many clinical FORMER EXECUTIVE COMMITTEE icant parental education, anticipa- conditions that may mimic its symp- MEMBERS tory guidance, and reassurance. In toms. It cannot be overemphasized Robert D. Baker, MD, PhD turn, they will provide high-value, that pediatric best practice involves David A. Gremse, MD Melvin B. Heyman, MD high-quality care without risk to both identifying children at risk for their patients or unnecessary direct complications of GERD and reassuring STAFF and indirect costs. parents of patients with physiologic GER Debra L. Burrowes, MHA

PEDIATRICS Volume 131, Number 5, May 2013 e1693 Downloaded from www.aappublications.org/news by guest on September 24, 2021 REFERENCES

1. Nelson SP, Chen EH, Syniar GM, Christoffel and gastroesophageal reflux. Pediatr Pul- 22. Chak A, Faulx A, Eng C, et al. Gastroesoph- KK; Pediatric Practice Research Group. monol. 1999;27(4):236–241 ageal reflux symptoms in patients with Prevalence of symptoms of gastroesopha- 11. Sheikh S, Stephen T, Howell L, Eid N. Gas- adenocarcinoma of the esophagus or car- geal reflux during childhood: a pediatric troesophageal reflux in infants with dia. Cancer. 2006;107(9):2160–2166 practice-based survey. Arch Pediatr Ado- wheezing. Pediatr Pulmonol. 1999;28(3): 23. Mohammed I, Cherkas LF, Riley SA, Spector lesc Med. 2000;154(2):150–154 181–186 TD, Trudgill NJ. Genetic influences in 2. Campanozzi A, Boccia G, Pensabene L, et al. 12. Mastronarde JG, Anthonisen NR, Castro M, gastro-oesophageal reflux disease: a twin Prevalence and natural history of gastro- et al; American Lung Association Asthma study. Gut. 2003;52(8):1085–1089 esophageal reflux: pediatric prospective Clinical Research Centers. Efficacy of eso- 24. Hassall E. Endoscopy in children with GERD: survey. Pediatrics. 2009;123(3):779–783 meprazole for treatment of poorly con- “the way we were” and the way we should 3. Shalaby TM, Orenstein SR. Efficacy of tele- trolled asthma. N Engl J Med. 2009;360(15): be. Am J Gastroenterol. 2002;97(7):1583– phone teaching of conservative therapy for 1487–1499 1586 infants with symptomatic gastroesophageal 13. Kiljander TO, Junghard O, Beckman O, Lind 25. Hassall E, Kerr W, El-Serag HB. Character- reflux referred by pediatricians to pediatric T. Effect of esomeprazole 40 mg once or istics of children receiving proton pump gastroenterologists. J Pediatr. 2003;142(1): twice daily on asthma: a randomized, inhibitors continuously for up to 11 years 57–61 placebo-controlled study. Am J Respir Crit duration. J Pediatr. 2007;150:262–267, 267. 4. Vandenplas Y, Rudolph CD, Di Lorenzo C, Care Med. 2010;181(10):1042–1048 e1 et al; North American Society for Pediatric 14. Littner MR, Leung FW, Ballard ED, II, Huang 26. Hassall E. Decisions in diagnosing and Gastroenterology Hepatology and Nutrition; B, Samra NK Lansoprazole Asthma Study managing chronic gastroesophageal reflux European Society for Pediatric Gastroen- Group. Effects of 24 weeks of lansoprazole disease in children. J Pediatr. 2005;146 terology Hepatology and Nutrition. Pediatric therapy on asthma symptoms, exacer- (suppl 3):S3–S12 gastroesophageal reflux clinical practice bations, quality of life, and pulmonary 27. Orenstein SR, McGowan JD. Efficacy of guidelines: joint recommendations of the function in adult asthmatic patients with conservative therapy as taught in the pri- North American Society for Pediatric Gas- acid reflux symptoms. Chest. 2005;128(3): mary care setting for symptoms suggest- troenterology, Hepatology, and Nutrition 1128–1135 ing infant gastroesophageal reflux. J (NASPGHAN) and the European Society for 15. Sopo SM, Radzik D, Calvani M. Does treat- Pediatr. 2008;152(3):310–314 Pediatric Gastroenterology, Hepatology, and ment with proton pump inhibitors for 28. Gupta SK, Hassall E, Chiu YL, Amer F, Heyman Nutrition (ESPGHAN). J Pediatr Gastroenterol gastroesophageal reflux disease (GERD) MB. Presenting symptoms of nonerosive and Nutr. 2009;49(4):498–547 improve asthma symptoms in children with erosive esophagitis in pediatric patients. Dig 5. Sherman PM, Hassall E, Fagundes-Neto U, asthma and GERD? A systematic review. J Dis Sci. 2006;51(5):858–863 et al. A global, evidence-based consensus on Investig Allergol Clin Immunol. 2009;19(1): 29. Salvatore S, Hauser B, Vandemaele K, the definition of gastroesophageal reflux dis- 1–5 Novario R, Vandenplas Y. Gastroesophageal ease in the pediatric population. Am J Gas- 16. Chan WW, Chiou E, Obstein KL, Tignor AS, reflux disease in infants: how much is troenterol. 2009;104(5):1278–1295, quiz 1296 Whitlock TL. The efficacy of proton pump predictable with questionnaires, pH-metry, 6. Shay S, Tutuian R, Sifrim D, et al. Twenty-four inhibitors for the treatment of asthma in endoscopy and histology? J Pediatr Gas- hour ambulatory simultaneous impedance adults: a meta-analysis. Arch Intern Med. troenterol Nutr. 2005;40(2):210–215 and pH monitoring: a multicenter report of 2011;171(7):620–629 30. Kleinman L, Revicki DA, Flood E. Validation normal values from 60 healthy volunteers. 17. DiMango E, Holbrook JT, Simpson E, et al; issues in questionnaires for diagnosis and Am J Gastroenterol. 2004;99(6):1037–1043 American Lung Association Asthma Clinical monitoring of gastroesophageal reflux 7. Rudolph CD, Mazur LJ, Liptak GS, et al; Research Centers. Effects of asymptomatic disease in children. Curr Gastroenterol North American Society for Pediatric Gas- proximal and distal gastroesophageal Rep. 2006;8(3):230–236 troenterology and Nutrition. Guidelines for reflux on asthma severity. Am J Respir Crit 31. Gold BD, Gunasekaran T, Tolia V, et al. Safety evaluation and treatment of gastroesoph- Care Med. 2009;180(9):809–816 and symptom improvement with esome- ageal reflux in infants and children: rec- 18. Gibson PG, Henry RL, Coughlan JL. Gastro- prazole in adolescents with gastroesopha- ommendations of the North American oesophageal reflux treatment for asthma geal reflux disease. J Pediatr Gastroenterol Society for Pediatric Gastroenterology and in adults and children. Cochrane Database Nutr. 2007;45(5):520–529 Nutrition. J Pediatr Gastroenterol Nutr. Syst Rev. 2003;(2):CD001496 32. Størdal K, Johannesdottir GB, Bentsen BS, 2001;32(suppl 2):S1–S31 19. Jung HK. Epidemiology of gastroesophageal Sandvik L. Gastroesophageal reflux disease 8. Martin AJ, Pratt N, Kennedy JD, et al. Nat- reflux disease in Asia: a systematic review. J in children: association between symptoms ural history and familial relationships of Neurogastroenterol Motil. 2011;17(1):14–27 and pH monitoring. Scand J Gastroenterol. infant spilling to 9 years of age. Pediatrics. 20. Dent J, El-Serag HB, Wallander MA, Johansson 2005;40(6):636–640 2002;109(6):1061–1067 S. Epidemiology of gastro-oesophageal reflux 33. Deal L, Gold BD, Gremse DA, et al. Age- 9. Fernandez S, Aspirot A, Kerzner B, Friedlander disease: a systematic review. Gut. 2005;54(5): specific questionnaires distinguish GERD J, Di Lorenzo C. Do some adolescents with 710–717 symptom frequency and severity in infants rumination syndrome have “supragastric 21. Cameron AJ, Lagergren J, Henriksson C, and young children: development and ini- vomiting”? J Pediatr Gastroenterol Nutr. Nyren O, Locke GR, III, Pedersen NL. Gastro- tial validation. J Pediatr Gastroenterol Nutr. 2010;50(1):103–105 esophageal reflux disease in monozygotic 2005;41(2):178–185 10. Sheikh S, Goldsmith LJ, Howell L, Hamlyn J, and dizygotic twins. Gastroenterology.2002; 34. Rosen R, Lord C, Nurko S. The sensitivity of Eid N. Lung function in infants with wheezing 122(1):55–59 multichannel intraluminal impedance and

e1694 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from www.aappublications.org/news by guest on September 24, 2021 FROM THE AMERICAN ACADEMY OF PEDIATRICS

the pH probe in the evaluation of gastro- respiratory symptoms. Allergy Asthma assessing the efficacy and safety of proton esophageal reflux in children. Clin Gastro- Immunol Res. 2012;4(1):17–23 pump inhibitor lansoprazole in infants with enterol Hepatol. 2006;4(2):167–172 45. Avidan B, Sonnenberg A, Schnell TG, Sontag symptoms of gastroesophageal reflux dis- 35. Rosen R, Nurko S. The importance of mul- SJ. Walking and chewing reduce post- ease. JPediatr. 2009;154:514–520.e4 tichannel intraluminal impedance in the prandial acid reflux. Aliment Pharmacol 57. Moore DJ, Tao BS, Lines DR, Hirte C, Heddle evaluation of children with persistent re- Ther. 2001;15(2):151–155 ML, Davidson GP. Double-blind placebo- spiratory symptoms. Am J Gastroenterol. 46. Moazzez R, Bartlett D, Anggiansah A. The controlled trial of omeprazole in irritable 2004;99(12):2452–2458 effect of chewing sugar-free gum on infants with gastroesophageal reflux. J 36. Thakkar K, El-Serag HB, Mattek N, Gilger MA. gastro-esophageal reflux. J Dent Res. 2005; Pediatr. 2003;143(2):219–223 Complications of pediatric EGD: a 4-year 84(11):1062–1065 58. Tolia V, Fitzgerald J, Hassall E, Huang B, experience in PEDS-CORI. Gastrointest 47. Smoak BR, Koufman JA. Effects of gum Pilmer B, Kane R III. Safety of lansoprazole in – Endosc. 2007;65(2):213 221 chewing on pharyngeal and esophageal pH. the treatment of gastroesophageal reflux 37. Volonaki E, Sebire NJ, Borrelli O, et al. Ann Otol Rhinol Laryngol. 2001;110(12): disease in children. J Pediatr Gastroenterol – Gastrointestinal endoscopy and mucosal 1117–1119 Nutr. 2002;35(suppl 4):S300 S307 fi biopsy in the rst year of life: indications 48. Cucchiara S, Staiano A, Romaniello G, 59. Canani RB, Cirillo P, Roggero P, et al; and outcome. J Pediatr Gastroenterol Nutr. Capobianco S, Auricchio S. Antacids and Working Group on Intestinal Infections of – 2012;55(1):62 65 cimetidine treatment for gastro-oesophageal the Italian Society of Pediatric Gastroenter- 38. Isolauri E, Tahvanainen A, Peltola T, Arvola T. reflux and peptic oesophagitis. Arch Dis ology, Hepatology and Nutrition (SIGENP). Breast-feeding of allergic infants. J Pediatr. Child. 1984;59(9):842–847 Therapy with gastric acidity inhibitors in- 1999;134(1):27–32 creases the risk of acute gastroenteritis and 49. Sedman A. Aluminum toxicity in childhood. community-acquired pneumonia in children. 39. Vance GH, Lewis SA, Grimshaw KE, et al. Ex- Pediatr Nephrol. 1992;6(4):383–393 posure of the fetus and infant to hens’ egg Pediatrics. 2006;117(5). Available at: www. 50. Tsou VM, Young RM, Hart MH, Vanderhoof JA. ovalbumin via the placenta and breast milk pediatrics.org/cgi/content/full/117/5/e817 Elevated plasma aluminum levels in normal in relation to maternal intake of dietary egg. 60. Saiman L, Ludington E, Dawson JD, et al; Na- infants receiving antacids containing alumi- Clin Exp Allergy. 2005;35(10):1318–1326 tional Epidemiology of Mycoses Study Group. num. Pediatrics. 1991;87(2):148–151 40. Clarke P, Robinson MJ. Thickening milk feeds Risk factors for Candida species colonization 51. American Academy of Pediatrics, Committee may cause necrotising enterocolitis. Arch of neonatal intensive care unit patients. on Nutrition. Aluminum toxicity in infants Dis Child Fetal Neonatal Ed. 2004;89(3):F280 Pediatr Infect Dis J. 2001;20(12):1119–1124 and children. Pediatrics. 1996;97(3):413–416 41. Bhat RY, Rafferty GF, Hannam S, Greenough 61. Craig WR, Hanlon-Dearman A, Sinclair C, 52. Gremse DA. GERD in the pediatric patient: A. Acid gastroesophageal reflux in conva- Taback S, Moffatt M. Metoclopramide, lescent preterm infants: effect of posture management considerations. MedGenMed. thickened feedings, and positioning for and relationship to apnea. Pediatr Res. 2004;6(2):13 gastro-oesophageal reflux in children un- 2007;62(5):620–623 53. Simeone D, Caria MC, Miele E, Staiano A. der two years. Cochrane Database Syst 42. Corvaglia L, Rotatori R, Ferlini M, Aceti A, Treatment of childhood peptic esophagitis: Rev. 2004;(4):CD003502 Ancora G, Faldella G. The effect of body a double-blind placebo-controlled trial of 62. Marchant JM, Masters IB, Taylor SM, Cox positioning on gastroesophageal reflux in nizatidine. J Pediatr Gastroenterol Nutr. NC, Seymour GJ, Chang AB. Evaluation and – premature infants: evaluation by combined 1997;25(1):51 55 outcome of young children with chronic impedance and pH monitoring. J Pediatr. 54. Barron JJ, Tan H, Spalding J, Bakst AW, cough. Chest. 2006;129(5):1132–1141 2007;151:591–596, 596.e1 Singer J. Proton pump inhibitor utilization 63. Størdal K, Johannesdottir GB, Bentsen BS, 43. Orenstein SR, Whitington PF, Orenstein DM. patterns in infants. J Pediatr Gastroenterol et al. Acid suppression does not change The infant seat as treatment for gastro- Nutr. 2007;45(4):421–427 respiratory symptoms in children with esophageal reflux. N Engl J Med. 1983;309 55. Orenstein SR, Hassall E. Infants and proton asthma and gastro-oesophageal reflux (13):760–763 pump inhibitors: tribulations, no trials. J disease. Arch Dis Child. 2005;90(9):956–960 44. Jung WJ, Yang HJ, Min TK, et al. The efficacy Pediatr Gastroenterol Nutr. 2007;45(4):395–398 64. Chang AB, Connor FL, Petsky HL, et al. An ob- of the upright position on gastro- 56. Orenstein SR, Hassall E, Furmaga-Jablonska jective study of acid reflux and cough in chil- esophageal reflux and reflux-related re- W, Atkinson S, Raanan M. Multicenter, double- dren using an ambulatory pHmetry-cough spiratory symptoms in infants with chronic blind, randomized, placebo-controlled trial logger. Arch Dis Child. 2011;96(5):468–472

PEDIATRICS Volume 131, Number 5, May 2013 e1695 Downloaded from www.aappublications.org/news by guest on September 24, 2021 Gastroesophageal Reflux: Management Guidance for the Pediatrician Jenifer R. Lightdale, David A. Gremse and SECTION ON GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION Pediatrics 2013;131;e1684 DOI: 10.1542/peds.2013-0421 originally published online April 29, 2013;

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