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Review |

Gastroesophageal Reflux in Infants:  More Than Just a pHenomenon FREE

Rachel Rosen, MD, MPH1
[+] Author Affiliations
1Aerodigestive Center, Boston Children’s Hospital, Boston, Massachusetts
JAMA Pediatr. 2014;168(1):83-89. doi:10.1001/jamapediatrics.2013.2911.
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Published online

Importance  Rarely have the best methods of diagnosis or the treatment of a disease engendered more controversy than gastroesophageal reflux (GER), a highly prevalent condition in infants.

Objective  To discuss the latest controversies in the diagnosis and treatment of GER in infants.

Evidence Review  All articles related to the diagnosis and treatment of GER were reviewed and, whenever possible, literature about infants was weighted with greater importance than literature about older children and adults.

Findings  Although as many as 60% of infants have signs of GER, the role of GER in causing disease is difficult to elucidate. Despite new diagnostic tools to detect acid and nonacid reflux, our understanding of the relationship between reflux events and symptoms is complex. Furthermore, acid suppression, the mainstay of therapy for GER, increases the burden of nonacid reflux, which is already much higher in infants than in older children and which may worsen symptoms. Therefore, more conservative therapies are recommended for symptomatic infants.

Conclusions and Relevance  Although GER is a common reason for visits to primary care providers and specialists, few data suggest that GER results in many of the symptoms to which it has been attributed. A strong shift away from acid-suppression therapy in infants has occurred because of the adverse effects, lack of efficacy, and increase of nonacid reflux burden relative to acid burden. Nonpharmacologic measures should be used whenever possible because most infant GER will resolve without intervention.

Figures in this Article

Despite the high prevalence of gastroesophageal reflux (GER) in infants and the high cost of reflux in global health care dollars, a great divide remains among clinical practice, parent perception, and research advances in the field of infant reflux. Gastroesophageal reflux is clearly seen as a problem by parents and physicians, particularly in infants with associated symptoms of fussiness and crying.1 Practitioners have responded by prescribing acid-suppression therapy in record levels for infants (ie, <1 year of age).2 However, research has clearly shown that acid suppression is not beneficial in ameliorating “reflux” symptoms, suggesting that these symptoms are not due to reflux or that our therapies for reflux are ineffective. The goal of this report is to review the latest diagnostic and therapeutic advances for infant GER.

According to the guidelines of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition, GER is the passage of gastric contents into the esophagus and is a physiologic process.3 Gastroesophageal reflux changes to GER disease (GERD) when the reflux of gastric contents causes troublesome symptoms or complications. In nonverbal infants, determination of what constitutes troublesome is difficult because their main mode of communicating needs and distress is crying. This issue is further complicated by the high rate of GER in healthy infants. Therefore, if episodes of physiologic GER occur at the same time, by chance, as a period of crying, a causal relationship could be construed erroneously. Because of the difficulty in determining a troublesome symptom and relying on a third party, a parent, to decide what is troublesome and because of the high frequency of physiologic reflux in this age group, the definitions of GER and GERD are blurred for this population.

Gastroesophageal reflux is a common physiologic process. At its peak incidence, more than 60% of infants spit up on a daily basis and as many as 25% of infants spit up 4 or more times per day.1 Although reflux can occur at any age, the peak age for classic reflux is 4 months of age with tapering by 6 months and a precipitous decline in the frequency of reflux until 12 to 15 months, after which the frequency remains stable until later in childhood.1,4,5 This change in frequency makes visible GER, one of the most common daily occurrences in infants, even more common than bowel movements in many cases! Because GER predictably improves over time with no intervention, one must always ask when evaluating therapies whether the reflux improved because of the intervention or because it would have improved over time regardless? Based on these natural history studies, educating parents that reflux will get worse before it gets better becomes critical in managing expectations for the infant’s first 6 months of life.

The primary mechanism driving reflux events in infants and children is the transient lower esophageal sphincter relaxation (TLESR), a normal phenomenon that occurs multiple times throughout the day. When the lower esophageal sphincter relaxes, gastric contents can be released up into the esophagus. Manometric studies in infants show that more than 80% of reflux episodes occur when the sphincter relaxes spontaneously.6,7 Infants with pathologic amounts of reflux have the same number of TLESRs as control infants, but their TLESRs allow reflux into the esophagus with a greater frequency compared with controls. The remaining reflux episodes occur during lower esophageal sphincter relaxations while swallowing or during actual vomiting episodes, when the abdominal pressure exceeds the lower esophageal sphincter pressure.6,7 In the latter case, anything that increases abdominal pressure, including sitting, crawling, or coughing, may worsen reflux. To prevent unnecessary worry, educating parents that a worsening of reflux may occur around specific developmental milestones is critical.

Other factors have been proposed to contribute to GER in infants, including delays in gastric emptying, dietary influences, medication use, and differences in acid production. Several studies have addressed whether gastric emptying affects the number of TLESRs or the likelihood of reflux occurring during the TLESRs. In each study, the impact of TLESRs had a much greater effect on reflux burden than gastric emptying.7,8 Also, TLESRs did not change with the type of food (formula vs breast milk) or with the presence of methylxanthine therapy.7 However, the rate of TLESRs could be altered with body position because left-sided positioning has been shown to reduce the number of TLESRs.7,8

One of the myths about GER, which is largely a product of the marketing of acid-suppression medications, is that these children produce too much acid. To address the hypothesis that abnormal acid production occurs in infants, several studies have shown that acid production is equivalent to that of adults on a weight-adjusted, per-kilogram basis or is significantly less than that of adults if not weight adjusted, reinforcing the position that reflux in infants is not a problem of excessive acid production.911

Last, as a word of caution, although the main mechanism of reflux is the TLESR, masqueraders of reflux have completely different mechanisms so that, for the child whose symptoms are severe; who may have warning signs that include bilious emesis, bloody emesis, late development of reflux, or neurologic signs; or who may have a food allergy, other differential diagnoses and mechanisms may need to be considered.3

Most infants who present to the general pediatric or gastroenterology clinic with symptoms of reflux do not undergo testing to “prove” that GER or GERD exists. Symptoms of reflux in infants can include spitting, vomiting, feeding difficulties, arching, hoarseness, and cough. Unfortunately, these symptoms are also associated with other conditions or could be present in healthy infants.12 Trying to determine whether these common symptoms are related to reflux is often difficult.

The most noninvasive method used to assess for reflux burden is the upper gastrointestinal tract series or barium swallow test. Unfortunately, the sensitivity of this test is poor when compared with that of pH monitoring; in a study of infants, barium testing had a sensitivity of 29% and a specificity of 50%, showing the inadequacy of the test to diagnose reflux.13 However, barium testing is helpful in detecting the masqueraders of reflux. In children with projectile vomiting, bilious vomiting, vomiting of undigested food, failure to thrive, or recurrent respiratory symptoms, barium testing will evaluate for anatomic abnormalities, such as pyloric stenosis, malrotation, tracheoesophageal fistulae, and other congenital anomalies of the upper gastrointestinal tract. If aspiration is suspected or if the infant has recurrent wheezing, bronchiolitis, or wet cough, a modified barium swallow test to focus on the mechanism of swallowing and the upper esophagus can also be performed to determine whether barium is aspirated. At present, the only utility of barium testing in the evaluation of GERD in infants is to exclude anatomic abnormalities.

Prior to the last 10 years, the focus of reflux testing was to associate the evidence of pathologic acid reflux with symptoms. Upper gastrointestinal tract endoscopy is used to evaluate for inflammation, and pH probe testing is used to determine total acid burden and to correlate symptoms with esophageal acid exposure. Often, these tests were performed together based on the recognition that patients with esophageal inflammation have an esophageal pH of less than 4 for a larger percentage of time than patients without esophageal inflammation. Furthermore, subsequent treatment studies showed that when the acid burden is reduced, the inflammation heals in most patients.1416 Although the diagnosis and treatment of esophageal inflammation is relatively straightforward, the key question remains: Does this esophageal inflammation explain the patient’s symptoms? Results of studies in infants have shown that the correlation between reflux symptoms and the presence of esophagitis diagnosed during endoscopy is poor, so diagnosing GERD in an infant based on esophageal histologic findings alone is not adequate.1719

Theoretically, the pH probe is more suited to assessing for the relationship between symptoms and reflux events; during the 24-hour testing, temporal correlation of acid reflux events, defined as drops in pH levels to less than 4, with symptoms occurring during the test is possible. Unfortunately, the infant pH data suggest that, although occasional patients may clearly have reflux-related symptoms, most of the studies show no significant difference in acid reflux burden between controls and infants undergoing evaluation for excessive crying, apnea, bradycardia, respiratory symptoms, and regurgitation.1923 Therefore, one must conclude that our diagnostic tests are flawed (and some adult data suggest that the pH probe has a reproducibility of only 70%) or that reflux is not to blame for these symptoms.24

The idea that our testing was flawed gained appeal when in the late 1990s, multichannel intraluminal impedance with pH (pH-MII) was developed. Like the pH probe, pH-MII uses a catheter that is passed through the nose into the esophagus, where it remains for 24 hours. Multichannel intraluminal impedance with pH offers advantages compared with a pH probe because pH-MII is a pH-independent method of measuring esophageal flow and bolus presence. The catheter measures, at 6 different esophageal levels, the type of reflux (acid or nonacid [Figure] and liquid or gas), the length of time that reflux is present in the esophagus, and the height of the refluxate. Using pH-MII, investigators have found that nonacid reflux (defined in this report and the pediatric literature as a pH >4) is common in infants and that the sensitivity of the pH probe, compared with pH-MII, is as low as 40%.25,26 Studies using pH-MII in infants have shown that as much as 89% of reflux in infants has a pH greater than 4 and is missed using standard pH probes.7,2628 The reason for this low sensitivity is that pH probes, which cannot detect bolus flow, could not differentiate refluxate with a pH greater than 4 from the ambient pH of the esophagus, which is typically 5 or greater. The main factor driving this high nonacid reflux burden in infants is the high frequency of feedings. Most postprandial reflux in infants is nonacidic7,29 and, in infants who feed every 2 to 3 hours, the refluxate consists of nonacidic milk or formula. Once we were able to measure acid and nonacid reflux, our ability to finally correlate reflux events with symptoms and prove a causal relationship seemed possible.

Place holder to copy figure label and caption
Figure.
Examples of Multichannel Intraluminal Impedance With pH

Reflux episodes (shaded areas) are shown as drops in impedance channels (IMPs, given in ohms) moving from the distal IMPs up the esophagus in a retrograde fashion (arrows). A, In an acid reflux episode, the lowest channel, pH, drops to levels less than 4 (dashed line). B, In a nonacid reflux episode, no drop in pH level is seen.

Graphic Jump Location

Unfortunately, as is often the case with medicine, the more we know, the less we understand, and the relationship between nonacid reflux and symptoms is complicated. Several infant studies have tried to correlate reflux events with symptoms using pH-MII. The best-studied symptom model in infants is the association among apnea, acute life-threatening events (ALTEs), and reflux. A number of pH-MII studies27,2931 have failed to show a consistent relationship among these 3 events. The relationships between reflux and other respiratory and gastrointestinal tract symptoms are less well studied; the patient numbers are small and the populations are heterogenous, so determining causality based on these studies is difficult.28,32 The pH-MII studies raise the following issues: How close in time does a reflux episode need to occur next to a symptom to be considered causal? How many symptoms need to be associated with reflux episodes in a 24-hour period to be considered clinically important? Is the degree of association different between reflux events and gastrointestinal tract symptoms compared with reflux events and respiratory symptoms? Does a positive temporal association necessarily correlate with a therapeutic response to medications or surgery? Clearly, additional studies using pH-MII are needed to answer these questions.

Reflux therapies have diagnostic and therapeutic roles. Treatments are aimed at alleviating symptoms, but they are also used to make a diagnosis; if symptoms improve with reflux therapy, one presumes that the patient had symptoms related to GERD. Therapies fall into the following 3 categories: nonpharmacologic, pharmacologic, and surgical.

Nonpharmacologic Therapies

Nonpharmacologic therapies include positioning, thickening of feedings, changes in formula, and modifications in meal frequencies. Probably the most widespread intervention for the treatment of GERD is positioning. Beginning with early pH probe studies, positioning has had variable efficacy in reducing reflux. One of the earliest positioning studies by Orenstein et al33 showed that positioning children in car seats had no beneficial effect in reducing the acid reflux burden as measured by pH probe. Additional studies have shown that acid reflux, measured by pH probe, is reduced to the greatest degree in the prone position followed by the left lateral, right lateral, and supine positions in descending order of effectiveness.34,35 Studies using pH-MII have confirmed that the prone and left lateral positions reduce reflux to a greater degree3638 than the supine and right lateral positions. However, supine positioning is still recommended because of the risk of sudden infant death syndrome.39 Studies of pH-MII further show that, although gastric emptying is slower in the left lateral position, the benefits to reflux and TLESRs outweigh the negative effects on gastric emptying. Finally, although no data have determined the effect of head-of-the-bed elevations on infant reflux, studies35,40 have shown a marginal benefit in reducing acid reflux burden in adults. Because of the risk of suffocation, the Centers for Disease Control and Prevention has reported on deaths related to sleep positioners, which are therefore not recommended.35,4043

Formula thickening has also been proposed as a therapy for reflux. Early pH studies4446 suggest inconsistent benefits of thickening to reduce acid burden. Some very elegant studies using pH-MII testing have also been performed in which infants are fed standard and thickened formula in random order. Although thickening does not reduce the total number of esophageal reflux episodes or symptoms, such as apnea, some benefit to parents may result in reducing the number of visible vomiting episodes, and improvements in sleep and possibly failure to thrive may also result.40,45,47,48 Changing smaller and more frequent feedings has also been proposed as a treatment for infant reflux. Studies using pH-MII7 have suggested that the type of reflux may vary (acid vs nonacid reflux) depending on the feeding frequency, but the total number of reflux episodes may not differ greatly. In the only study in infants to look at different feeding methods and their effect on reflux, Jadcherla et al49 found that caloric density and feeding volume did not change reflux burden in preterm infants but that faster flow rates and shorter durations resulted in a higher reflux burden. That study49 was limited because the infants did not undergo identical changes in feeding methods and the patient numbers were small, but it constitutes a good starting point for additional studies.

Finally, some data suggest formula or dietary changes may be used to treat reflux. In the NASPGHAN guidelines, a 2-week trial of a hypoallergenic formula has been suggested to treat symptoms of GER. Symptoms of milk protein intolerance are similar to reflux symptoms, including fussiness, regurgitation, arching, and colic. Although very few data suggest that changing to a hydrolysate formula reduces the amount of reflux, clear evidence exists that a trial of a hypoallergenic formula improves colic, which is often mistaken for GER because of the symptom overlap.5052 In addition, new data suggest that children with a history of allergy to the protein in cow’s milk who are exposed to this protein in formula have a significantly higher reflux burden than the same infants when they were given an amino acid–based formula, suggesting that, in a subpopulation of patients, modification of diet may improve reflux burden.53

Pharmacologic Therapies

The mainstay of medical therapies for GERD in infants is acid suppression. The primary class of medications are histamine2 (H2) antagonists and proton pump inhibitors, both of which have been shown to reduce gastric acidity and heal esophagitis in children.14,5456 However, relatively few patients undergo endoscopic evaluation compared with the number of children presenting with GER symptoms in whom acid-suppression therapy is empirically started. The number of well-designed clinical trials including infants who receive acid-suppression therapy for symptom relief is small. The initial studies compared H2 antagonists with placebo. In a small double-blind phase of a study of famotidine vs placebo,57 no benefit of famotidine was seen compared with placebo in the treatment of crying or regurgitation frequency or in the global assessment of the infant by the parent. In a study of 103 infants58 who were randomized to receive cisapride plus ranitidine hydrochloride vs placebo vs behavioral intervention, no statistically significant difference was found in the improvement of crying among any of the 3 groups. One criticism of the studies of H2 antagonists is that the patients may receive inadequate acid suppression, which would explain the persistent symptoms. To address this issue, comparable studies were performed with the more potent proton pump inhibitors. Three well-designed, randomized, placebo-controlled clinical trials5961 of the proton pump inhibitors lansoprazole, pantoprazole sodium, and omeprazole magnesium have been conducted in infants, and all have failed to show any benefit in improving the classic reflux symptoms seen in infants, including crying, regurgitating, food refusal, arching, coughing, or wheezing. Furthermore, use of these therapies has been associated with an increased risk of gastrointestinal tract and pulmonary infections in infants and children.62,63 Therefore, in light of these randomized clinical trials in infants, NASPGHAN guidelines3 have recommended no acid-suppression therapy in the otherwise healthy infant who spits up. They further recommend a trial of a hypoallergenic formula and then, at most, a short trial of acid-suppression therapy for patients with intractable or severe symptoms.3

Recognizing that few data support the use of acid-suppression therapy in infants, that acid suppression increases the amount of nonacid reflux relative to acid reflux, and that acid suppression has been associated with an increased risk of infection, alternative reflux therapies, specifically motility agents that speed gastric emptying and thereby may reduce reflux, have been pursued. Unfortunately, all well-studied motility agents have been removed from the market because of adverse effects or carry black box warnings because the risk outweighs the benefit. Cisapride, a serotonin agonist that improved esophageal, gastric, and intestinal motility, has been removed from the market because of fatal cardiac arrhythmias. Metoclopramide hydrochloride, a receptor agonist for dopamine D2 and a serotonin 4 that improves gastric motility and may increase lower esophageal sphincter tone, has a black box warning for irreversible neurologic adverse effects, and all of the major adult and pediatric gastroenterology organizations state that the drug is not recommended because of the potential harm and lackluster efficacy.6466

At present, erythromycin ethylsuccinate, a motilin agonist that may improve antral contractility, has been proposed as an alternative motility therapy, but very few data on its efficacy, particularly in infants, are available. Although a single prospective randomized clinical trial of azithromycin67 has been performed in adults and has shown that azithromycin reduces acid reflux burden but does not reduce the nonacid burden, no comparable studies have been performed in infants or children. In studies of preterm infants receiving erythromycin at different doses,6870 no difference was found in the pH probe results before and after low-dose erythromycin. At higher doses, a benefit was found in the time to reach full feeds or higher weights. The effect on children older than 32 weeks’ gestation, the ideal dosage, and the effect on acid and nonacid reflux are not clear.6870 Although investigators have reported pyloric stenosis in neonates receiving macrolides, particularly in the first few weeks of life, the persistence of risk in older infants remains unknown and, as always, the risk to benefit ratio of the medication must be considered against the severity of the GERD symptoms.7072

Surgical Therapies

The 2 primary surgical options for the treatment of intractable GER in infants are fundoplication and transpyloric feeding for patients who are fed enterally. Most of the fundoplication data come from case series conducted 20 to 30 years ago, when institutions reviewed their surgical results. In these early studies,73,74 70% to 87% of patients experienced resolution of symptoms, including failure to thrive, emesis, and aspiration events. However, GER was diagnosed by a variety of different methods, no controls were enrolled to determine the natural history of improvement in these conditions, the populations included in the studies were heterogeneous, and the outcome of “improvement” was subjectively defined.73,74 In the more recent literature, several important fundoplication studies have looked at reflux-related hospitalizations as a more objective outcome for surgical success. In a study of 1142 fundoplications in children of all ages, Goldin et al75 found a clear benefit to reducing reflux-related hospitalizations when the surgery was performed in younger compared with older children. In a study of 342 patients with a median age of 1 year, Lee et al76 found that reflux-related hospitalizations for pneumonias, respiratory distress, and failure to thrive did not significantly decrease after fundoplication.

Although not the focus of this review, a brief note should be made of the use of fundoplication in the treatment of ALTE, a phenomenon largely of infancy. In a case series of 81 infants who had reflux diagnosed by pH probe testing or an upper gastrointestinal tract series and who underwent fundoplication,77 only 3.7% of the infants had a recurrence of the ALTE after fundoplication. This study is limited because no data were presented on the patients with ALTE who did not undergo surgery, so determining how the fundoplication changed the natural history in these patients compared with untreated patients remains unclear.77 In another study of 469 infants with ALTE,78 40% were diagnosed with reflux at the time of the admission but only 1.5% underwent fundoplication, suggesting that fundoplication is not necessary in most patients with ALTE. Of the 469 patients, only 2 deaths occurred after the initial ALTE; in both cases, the cause of death was related to seizure, not GER.78 Therefore, with conflicting studies, fundoplication cannot be recommended for every infant with ALTE and GER-positive test results.

Finally, as an alternative to fundoplication, infants who need enteral tube feeding may experience reduced reflux with transpyloric feeding, which reduces the volume in the stomach and thereby reduces the likelihood of reflux into the esophagus. Transpyloric feeding in older children has been shown to reduce the rate of reflux compared with patients with GERD, and transpyloric feeding can be used as a trial to see if symptoms improve when reflux is reduced.79 In preterm infants, Malcolm et al80 found lower rates of apnea and bradycardia in infants who received postpyloric feeding. Similarly, Misra et al81 found improvement in apnea events in infants receiving postpyloric feeding. Because studies in older children show equivalent results with transpyloric feeding and fundoplication, a trial of transpyloric feeding may be warranted to determine whether symptoms improve and are thereby likely to be reflux related and to assess as a trial whether fundoplication is likely to benefit the patient.82

Gastroesophageal reflux is common in infants, and in most of the cases, GER is a self-limited physiologic process. In most patients, no diagnostic testing is needed, and management should involve conservative measures, including education, changes in positioning, changes in formula type, or thickening of feedings. Acid suppression has not been shown to reduce symptoms typically associated with reflux. Although a role for acid suppression exists in the infant with evidence of esophagitis or with gastrointestinal tract bleeding, use of acid suppression in infants with symptoms should be limited to, at most, a short trial of acid-suppression therapy. If no clear symptomatic improvement results, this therapy should be stopped owing to an imbalance in the risk to benefit ratio.

Accepted for Publication: May 8, 2013.

Corresponding Author: Rachel Rosen, MD, MPH, Aerodigestive Center, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115 (rachel.rosen@childrens.harvard.edu).

Published Online: November 25, 2013. doi:10.1001/jamapediatrics.2013.2911.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by grant R03DK089146 from the National Institutes of Health and by a Translational Research Program Award from the Boston Children’s Hospital (Dr Rosen).

Role of the Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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PubMed   |  Link to Article
Wenzl  TG, Schenke  S, Peschgens  T, Silny  J, Heimann  G, Skopnik  H.  Association of apnea and nonacid gastroesophageal reflux in infants: investigations with the intraluminal impedance technique. Pediatr Pulmonol. 2001;31(2):144-149.
PubMed   |  Link to Article
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Link to Article
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PubMed   |  Link to Article
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PubMed   |  Link to Article
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PubMed   |  Link to Article
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PubMed   |  Link to Article
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PubMed   |  Link to Article
Corvaglia  L, Rotatori  R, Ferlini  M, Aceti  A, Ancora  G, Faldella  G.  The effect of body positioning on gastroesophageal reflux in premature infants. J Pediatr. 2007;151(6):591-596.e1. doi:10.1016/j.jpeds.2007.06.014.
Link to Article
Loots  C, Smits  M, Omari  T, Bennink  R, Benninga  M, Van Wijk  M.  Effect of lateral positioning on gastroesophageal reflux (GER) and underlying mechanisms in GER disease (GERD) patients and healthy controls. Neurogastroenterol Motil. 2013;25(3):222-229, e161-e162. doi:10.1111/nmo.12042.
PubMed   |  Link to Article
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Link to Article
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PubMed   |  Link to Article
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PubMed
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Ng  SC, Gomez  JM, Rajadurai  VS, Saw  SM, Quak  SH.  Establishing enteral feeding in preterm infants with feeding intolerance: a randomized controlled study of low-dose erythromycin. J Pediatr Gastroenterol Nutr. 2003;37(5):554-558.
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PubMed
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Lee  SL, Shabatian  H, Hsu  JW, Applebaum  H, Haigh  PI.  Hospital admissions for respiratory symptoms and failure to thrive before and after Nissen fundoplication. J Pediatr Surg. 2008;43(1):59-65.
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Zimbric  G, Bonkowsky  JL, Jackson  WD, Maloney  CG, Srivastava  R.  Adverse outcomes associated with gastroesophageal reflux disease are rare following an apparent life-threatening event. J Hosp Med. 2012;7(6):476-481.
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Rosen  R, Hart  K, Warlaumont  M.  Incidence of gastroesophageal reflux during transpyloric feeds. J Pediatr Gastroenterol Nutr. 2011;52(5):532-535.
PubMed   |  Link to Article
Malcolm  WF, Smith  PB, Mears  S, Goldberg  RN, Cotten  CM.  Transpyloric tube feeding in very low birthweight infants with suspected gastroesophageal reflux: impact on apnea and bradycardia. J Perinatol. 2009;29(5):372-375.
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Misra  S, Macwan  K, Albert  V.  Transpyloric feeding in gastroesophageal-reflux-associated apnea in premature infants. Acta Paediatr. 2007;96(10):1426-1429.
PubMed   |  Link to Article
Srivastava  R, Downey  EC, O’Gorman  M,  et al.  Impact of fundoplication versus gastrojejunal feeding tubes on mortality and in preventing aspiration pneumonia in young children with neurologic impairment who have gastroesophageal reflux disease. Pediatrics. 2009;123(1):338-345.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure.
Examples of Multichannel Intraluminal Impedance With pH

Reflux episodes (shaded areas) are shown as drops in impedance channels (IMPs, given in ohms) moving from the distal IMPs up the esophagus in a retrograde fashion (arrows). A, In an acid reflux episode, the lowest channel, pH, drops to levels less than 4 (dashed line). B, In a nonacid reflux episode, no drop in pH level is seen.

Graphic Jump Location

Tables

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PubMed   |  Link to Article
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PubMed   |  Link to Article
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PubMed   |  Link to Article
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Link to Article
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PubMed   |  Link to Article
van Wijk  MP, Benninga  MA, Dent  J,  et al.  Effect of body position changes on postprandial gastroesophageal reflux and gastric emptying in the healthy premature neonate. J Pediatr. 2007;151(6):585-590.e1-e2. doi:10.1016/j.jpeds.2007.06.015.
Link to Article
American Academy of Pediatrics Task Force on Sudden Infant Death Syndrome.  The changing concept of sudden infant death syndrome. Pediatrics. 2005;116(5):1245-1255.
PubMed   |  Link to Article
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