COVER ARTICLE Gastroesophageal Reflux in Infants and Children ANDREW D. JUNG, M.D., University of Kansas School of Medicine–Wichita, Wichita, Kansas Gastroesophageal reflux is a common, self-limited process in infants that usually resolves by six to 12 months of age. Effective, conservative management involves thickened feed- O A patient informa- ings, positional treatment, and parental reassurance. Gastroesophageal reflux disease tion handout on gas- (GERD) is a less common, more serious pathologic process that usually warrants medical troesophageal reflux in infants and chil- management and diagnostic evaluation. Differential diagnosis includes upper gastroin- dren, written by the testinal tract disorders; cow’s milk allergy; and metabolic, infectious, renal, and central author of this article, nervous system diseases. Pharmacologic management of GERD includes a prokinetic agent is provided on the AFP such as metoclopramide or cisapride and a histamine-receptor type 2 antagonist such as Web site. cimetidine or ranitidine when esophagitis is suspected. Although recent studies have sup- ported the cautious use of cisapride in childhood GERD, the drug is currently not routinely available in the United States. (Am Fam Physician 2001;64:1853-60. Copyright© 2001 American Academy of Family Physicians.) common symptom com- with no underlying systemic abnormali- plex in infants is gastro- ties. GER is a common condition involv- esophageal reflux (GER), ing regurgitation, or “spitting up,” which which causes parental anx- is the passive return of gastric contents iety resulting in numerous retrograde into the esophagus. The preva- Avisits to the physician. The etiology of lence of GER peaks between one to four GER has not been well defined.1 In addi- months of age,2 and usually resolves by six tion to simple parental reassurance and to 12 months of age.3 No gender predilec- thickened feedings, multiple diagnostic tion or definite peak age of onset beyond and treatment options are available. infancy has been established.4 Regurgita- The term GER implies a functional or tion has been reported in 40 to 65 percent physiologic process in a healthy infant of healthy infants,5 but decreases to 1 per- cent by one year of age. Gastroesophageal reflux disease (GERD) TABLE 1 is a pathologic process in infants mani- Clinical Features Differentiating GER and GERD in Infants and Children fested by poor weight gain, signs of esoph- agitis, persistent respiratory symptoms, and changes in neurobehavior (Table 1). GER GERD Abnormal signs and symptoms that war- Regurgitation with normal weight gain Regurgitation with poor weight gain rant a diagnosis of GERD occur in No signs or symptoms of esophagitis Persistent irritability; pain in infants approximately one in 300 infants.6 After Lower chest pain, dysphagia, pyrosis in children the first year of life, GERD is more resis- Hematemesis and iron deficiency anemia tant to complete resolution. A higher No significant respiratory symptoms Apnea and cyanosis in infants Wheezing prevalence of GERD is present in children Aspiration or recurrent pneumonia who have the following: a history of Chronic cough esophageal atresia with repair7;neurologic Stridor impairment and delay8; hiatal hernia9; No neurobehavioral symptoms Neck tilting in infants (Sandifer’s syndrome) bronchopulmonary dysplasia10; asthma11; and chronic cough (Table 2). GERD is also GER = gastroesophageal reflux; GERD = gastroesophageal reflux disease. associated with pulmonary aspiration, chronic bronchitis, and bronchiectasis.12 DECEMBER 1, 2001 / VOLUME 64, NUMBER 11 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1853 or distal esophageal afferent signals stimulat- Gastric regurgitation occurs in up to two thirds of infants, ing mucous secretion, edema, and bronchial 15 but pathologic gastroesophageal reflux disease affects only smooth muscle contraction. Third, aspira- one in 300 infants. tion stimulates the chemical release of inflammatory mediators that cause further respiratory luminal obstruction. These responses can result in signs of upper airway Pathophysiology (apnea, stridor, laryngomalacia) and lower GASTROINTESTINAL TRACT airway (chronic cough, wheezing) obstruc- In the gastrointestinal (GI) tract, the lower tion. In infants, activation of laryngeal esophageal sphincter is located at the distal chemoreflexes associated with regurgitation end of the esophagus and is under tonic of gastric contents into the pharynx may be smooth muscle control. Transient lower associated with episodic prolonged apnea.16 esophageal sphincter relaxations unassociated with swallowing may be the major mecha- Clinical Manifestations nism allowing the gastric refluxate to return INFANTS into the esophagus.1,9,10 Delayed gastric emp- Infants with GER regurgitate without any tying13,14 is another mechanism in infants and secondary signs or symptoms of inadequate older children that predisposes them to gastric growth, esophagitis, or respiratory disease. distension, increased acid secretion, and Infants with GER are thriving and represent esophagitis. Gravitational and positional fac- the majority of infants who present to the tors may exacerbate GER and increase the risk physician with this condition. of GERD by allowing reflux to occur in a Patients with GERD may manifest persis- supine position. tent regurgitation with secondary poor weight gain and failure to thrive.17 Failure to thrive RESPIRATORY TRACT occurs when caloric intake is less than ongo- In the respiratory tract, complex reflex ing losses. Other infants may manifest signs of responses to the gastric refluxate occur in esophagitis, including persistent irritability, children by three mechanisms. First, the aspi- pain, feeding problems, and iron deficiency rated material may cause luminal mechanical anemia. A subset of infants may demonstrate obstruction. Second, neurally mediated im- significant reflux by esophageal pH monitor- pulses from the refluxate result in local airway ing but will not have symptoms of regurgita- tion, known as “silent” GERD.14 All infants with GERD, therefore, do not visibly regurgi- TABLE 2 tate, and the majority of infants who regurgi- Childhood Diagnoses Associated tate do not have GERD. with Increased Risk of GERD A variety of respiratory symptoms occur in infants. Apnea with cyanotic episodes may Esophageal atresia with repair occur secondary to upper airway stimulation Neurologic impairment and delay by pharyngeal regurgitation, as previously Hiatal hernia described. Instead of a pure obstructive apnea Bronchopulmonary dysplasia (preterm infants with lung disease) pattern, a mixed pattern of both obstructive Asthma and central types generally predominates. A Cystic fibrosis well-defined relationship between apnea sec- ondary to GERD and an apparent life-threat- GERD = gastroesophageal reflux disease. ening event has not been established.10 Another sign of upper airway disease is recurrent stri- 1854 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 64, NUMBER 11 / DECEMBER 1, 2001 TABLE 3 Differential Diagnosis of GERD in Infants and Children Affected system Signs or symptoms Diagnostic studies Gastrointestinal Pyloric stenosis Nonbilious projectile vomiting Abdominal US or UGI Malrotation Bilious vomiting, abdominal distension UGI and/or contrast enema Cow’s milk allergy Vomiting, diarrhea, eczema, urticaria Milk-free diet and milk challenge Peptic ulcer disease Epigastric pain and/or nausea Endoscopy and Helicobacter pylori testing Hepatitis Jaundice and right upper quadrant pain Hepatitis serology and liver function tests Viral gastroenteritis Vomiting, diarrhea, fever None usually required Urinary tract Infection Vomiting, fever in infants Urine culture, urinalysis Obstruction Abdominal mass, failure to thrive Renal US and VCUG Central nervous system Hydrocephalus Vomiting, increased head size Head computed tomography Meningitis Fever, lethargy, vomiting CSF studies/culture Metabolic disorders Renal tubular acidosis Vomiting, failure to thrive Electrolyte panel Hyperchloremic, normal gap acidosis Urinalysis for urine pH Urea cycle defects Poor feeding, lethargy, hypotonia Serum ammonia (NH4+) Hypocalcemia Apnea, poor feeding, tetany, seizures Calcium, phosphate, parathyroid hormone Drugs/toxins Vomiting, lethargy, ingestion history Urine and serum drug screen Respiratory Wheezing, cough, stridor Dependent on history and examination Functional Rumination, anorexia Psychiatric evaluation GERD = gastroesophageal reflux disease; US = ultrasound; UGI = upper gastrointestinal series; VCUG = void- ing cystourethrogram; CSF = cerebrospinal fluid. dor. Lower airway symptoms secondary to Barrett’s esophagus may increase the risk of bronchoconstriction and airway inflammation esophageal adenocarcinoma in adulthood, include wheezing and chronic cough. Aspira- but the risk is much lower in children.10 tion of refluxate may lead to pneumonia, espe- cially in infants with neurologic impairment. Differential Diagnosis of GERD Finally, abnormal hyperextension of the Other GI and systemic disorders must first neck with torticollis (Sandifer’s syndrome) be excluded before considering GERD as the may be seen solely in infants with more severe main cause of an infant’s or child’s symptoms GERD. This movement is perhaps a protec- of silent or visible regurgitation or vomiting tive mechanism of an infant with acidic reflux (Table 3). Additional upper GI disorders that causing esophagitis. require diagnostic consideration include pyloric stenosis, hiatal hernia, pyloric and CHILDREN