GERD in Infants and Children

• Gastroesophageal Reflux Disease (GERD) in Infants and Children was reviewed on March 15, 2023.

Objectives

• Distinguishing between gastroesophageal reflux (GER) and gastroesophageal reflux disease (GERD) in infants and children
• Reviewing the prevalence and age-based symptoms/signs of GER in children
• Describing the pathophysiology and potential complications of GERD
• Differentiating GERD from other masqueraders
• Reviewing the diagnosis and management of GER/GERD in children
• Briefly reviewing the management of erosive esophagitis in children

Case 1

• An appropriate action for a 4-week old infant with frequent spitting-up after feeds, who is feeding well, is not irritable, and has an unremarkable physical exam, is to educate and reassure the parents.

Case 2

• A 6-week old baby with a history of vomiting since birth, whose weight gain has been sub-optimal, but has no other worrisome symptoms, has a physical exam showing an irritable baby with decreased subcutaneous fat, but rest of the exam is unremarkable, should have their formula changed to partially hydrolyzed formula

Case 3

• A 14-year old male with a history of heartburn and intermittent vomiting, whose appetite is normal, has no other symptoms, and a physical exam showing an overweight male, whose exam is otherwise normal, should implement lifestyle modifications and PPI for 2-4 weeks

Case 4

• A 16-year old male with a one-year history of intermittent dysphagia with solids, who has a history of atopy and environmental allergies, but is otherwise well, and has been treated with a PPI for 6 weeks, without any improvement in symptoms, should be referred to a Pediatric Gastroenterologist

GER vs GERD

• It's important to differentiate between GER and GERD
• GER is the retrograde passage of gastric contents into the esophagus or oropharynx, with or without regurgitation +/- vomiting
• GER is often postprandial, and does not cause any harm
• GERD is the retrograde passage of gastric contents into the esophagus resulting in a constellation of troublesome symptoms +/- complications such as esophagitis or stricture

Refractory GERD

• GERD that is not responsive to optimal therapy (PPI for 4-8 weeks)

Regurgitation

• Effortless, non-bilious and non-projectile passage of gastric contents into the pharynx or mouth
• 70-85% of infants regurgitate within the first 2 months of life and is considered physiological
• Regurgitation resolves spontaneously in 95% of infants by 1 year of age

Non-Erosive Reflux Disease (NERD)

• Symptomatic patient with troublesome symptoms, who has a normal gastroscopy (endoscopy negative reflux disease)

Rumination

• Rumination is effortless regurgitation of recently ingested food into the mouth due to voluntary contraction of abdominal muscles, with subsequent mastication and re-swallowing of food
• Rumination is common in children with neurological impairment
• Rumination is increasingly recognized among older children and adolescents within the spectrum of eating disorders

Differentiating Conditions

• It is important to differentiate between regurgitation, rumination, and vomiting
• Food allergy is indistinguishable from GER in infants, and a protein hydrolysate formula or amino-acid based formula is sometimes considered
• Bilious vomiting is not GERD, but suggests obstruction such as pyloric stenosis or malrotation

Prevalence of GER in children

• The global prevalence of GER has been gradually increasing
• There has been a concomitant increase in medication use
• The prevalence varies in different parts of the world
• The prevalence of GER in children is around 5-7% (25% in adults)

Age-Based Symptoms of GER

• Symptoms of GER are non-specific and vary widely by age
• Symptoms in infants are regurgitation and food refusal
• Kids 1-6 years - regurgitation, abdominal pain (7.2%)
• Kids 6-17 years - regurgitation (8.2%), heartburn (5.2%), vomiting, epigastric pain (5%)
• Adults: heartburn, regurgitation (cardinal symptoms of GER)

Natural History of GER in Infancy

• Spitting-up or regurgitation in infancy is physiologic in up to 60-70% of infants
• GER resolves without intervention in 95% of infants by 12-14 months
• Peak prevalence is 41% by 3-4 months of age
• 21% have symptoms at 7-9 months of age
• Symptoms resolve spontaneously in 60% of infants by 6 months of age
• Symptoms resolve in 90% of infants by 8-10 months of age

Symptoms of GE Reflux

• Symptoms of GE reflux encompass esophageal and extra-esophageal symptoms
• Esophageal symptoms include heartburn, regurgitation, waterbrash, globus, vomiting, epigastric pain, and dysphagia
• Extra-esophageal symptoms include cough, sore throat, laryngitis, otitis media, dental erosions, Sandifer syndrome, asthma, apnea, ALTE, and chest pain
• Sandifer syndrome is spasmodic torsional dystonia with back arching and opisthotonic posturing, vagally mediated reflex to esophageal acid exposure, and is considered a specific presentation of GER in infancy

Pathophysiology of GER

• Primary Mechanisms of GERD are transient LES relaxation (TLESR) and impaired esophageal clearance
• Secondary mechanisms of GERD are increased intra-abdominal pressure, decreased gastric compliance, delayed gastric emptying, and reduced esophageal compliance

Complications of GERD

• Erosive esophagitis (mucosal breaks)
• Esophageal stricture - late presentation
• Barrett’s esophagus:
  • Endoscopically suspected esophageal metaplasia
  • Esophageal squamous epithelium is replaced by intestinal columnar cells
• Adenocarcinoma

Risk Factors for Severe GERD

• Neurologic impairment like cerebral palsy
• Some genetic syndromes like Cornelia de Lange syndrome
• Congenital esophageal abnormalities like esophageal atresia
• Hiatal hernia
• Obesity
• Family history of GERD or GERD related complications

Masqueraders of GER in Children (Vomiting)

• Gastroesophageal reflux (GER)
• Food allergy (CMP allergy)
• Infection like viral gastroenteritis, UTI, or meningitis
• Eosinophilic esophagitis (EE) – vomiting in young children and dysphagia in adolescents
• GI obstruction like pyloric stenosis, intestinal atresia, or malrotation
• GI disorders like Achalasia or scleroderma
• Metabolic/Endocrine disorders
• Neurologic disorders like tumors or increased ICP
• Toxic ingestion
• Other like Celiac disease or lactose intolerance

Warning Signs (Red Flags)

• Frequency and amount of emesis
• Failure to thrive, known genetic or metabolic syndromes
• Forceful/projectile vomiting
• Bilious emesis or hematemesis
• Associated fever, lethargy, diarrhea, constipation
• Bulging fontanelle, micro or macrocephaly
• Hepatosplenomegaly
• Sleep history, presence of nocturnal symptoms
• Onset of symptoms at < 1 week, and after 6 months of age

Diagnosis of GER in Infants and Children

• GER is generally diagnosed by clinical symptoms
• Most patients are and should be diagnosed at the primary care level
• History and physical examination is important to rule out red flags
• Reliable and valid symptom-based questionnaires for GERD in children of all ages has not been validated

GER in Infants and Children: Diet/ Feeding History

• Ensure preparation of formula is accurate
• Note amount and frequency of feeding to avoid overfeeding
• Consider positioning during feeding
• Ensure Burping
• Note Feeding behavior like choking, gagging, cough, arching, discomfort, and refusal
• Note Intolerance to types of formula or food
• Note Food impaction

GER in Infants and Children: Medical, Family, and Medication History

• Medical History: Prematurity, esophageal atresia, recurrent illnesses, cough, hoarseness, dental erosions, celiac disease, thyroid disease, and other chronic conditions
• Family History: Esophageal dilatations, esophageal cancer/Barrett’s, food allergies, esophageal surgeries, thyroid disease, Celiac disease, and functional dyspepsia
• Medications: Current and past medication use - use of antacids, H2 receptor antagonists, PPI, medications affecting motility (chemotherapy, vincristine, antibiotics, anticholinergics, and opioids)

GER in Infants (Neonates)

• Characterized by Regurgitation & Vomiting if no warning signs occur, and referred to as "happy spitter"
• Unexplained crying and distressed behavior
  • Non-specific, do not assume GER
• Failure to thrive
  • Get detailed feeding history -Look for non-GERD causes if intake is appropriate

Diagnosis of GER: Barium Study

• Useful in diagnosing anatomic abnormalities (stenosis, TEF, hiatal hernia, pyloric stenosis, malrotation)
• Useful in diagnosing motility disorders (achalasia, scleroderma)
• Useful in diagnosing post fundoplication by assessing obstruction and loose fundoplication
• NOT useful in diagnosing GER and is not recommended by 2018 GERD guidelines

Diagnosis of GER; Esophageal Manometry

• Useful in detecting motor disorders like achalasia
• Not useful in the diagnosis of GER(D) in children according to GERD guidelines 2018

Diagnosis of GER: 24-hour pH Monitoring Study

• Prolonged monitoring of acid reflux with symptom correlation
• Useful for evaluating the efficacy of anti-secretory therapy
• Disadvantages: discomfort wearing tube, can affect normal activities and can be falsely negative
• Not used in most pediatric cases per GERD guidelines 2018

Diagnosis of GER: Capsule Based pH Monitoring Study

• Placed endoscopically, allows for prolonged monitoring
• Limitations: accidental dislodgement/impaction of capsule and chest pain
• Not used in children

Diagnosis of GER: Multichannel Intraluminal Impedance Testing

• Detects acid and non-acid reflux
• Needs normative and outcome data in pediatric patients
• Not required for diagnosis of GERD in children per GERD guidelines 2018

Diagnosis of GER: Gastroscopy

• Insufficient data to recommend gastroscopy for diagnosis of GER in children
• Can rule out masqueraders of GERD like candida, EoE, hiatal hernia, Barrett's esophagus, and adenocarcinoma
• Advantage: Allows visualization of mucosa and can obtain biopsies
• Disadvantage: Requires sedation, invasive and expensive
• Not required for diagnosis of GERD in children per GERD guidelines 2018

Diagnosis of GER: Ultrasound

• Used in Dx of pyloric stenosis and other anatomic abnormalities
• No role for diagnosis of GER

Diagnosis of GER: Gastric Emptying Study

• May demonstrate aspiration of gastric contents
• Used to evaluate gastric emptying (if gastroparesis is suspected)
• Not used for diagnosis of GERD in children (GERD guidelines 2018)

Management of GER

• 20% of infant caregivers seek medical attention for spitting-up (normal behavior)

Primary Prevention Strategies for Infants

• Positioning in infancy
• Formula changes (allergy)
• Thickening the formula
• Avoid overfeeding

Management of GER (Infants) when with regurgitation and normal exam

• Educate, reassure and provide anticipatory guidance
• You may consider thickened formula, and other primary prevention strategies
• No other intervention is necessary
• Irritability with uncontrolled crying or distressed behavior, has no evidence to support acid suppression
• If symptoms persist beyond 12-18 months of age, or if warning signs develop, refer to pediatric GI specialist
• If failure to thrive, consider H2RA (for limited time), and reassess
• If PPI is necessary, use the smallest dose once daily for 4-8 weeks, then wean and discontinue therapy

Management of GER (Children): Conservative measures for GER in children & adolescents

• Dietary modifications like losing weight (if overweight/obese), eating small/more frequent meals, and avoiding eating for 1-2 hours before sleeping
• Avoid caffeine, alcohol, tomato, spicy/citrus foods, deep fried or fatty foods, and chocolates
• Positioning changes like elevating the head of the bed and using the left lateral decubitus position
• Avoid passive (second-hand) cigarette or tobacco smoke

Management of GER - Children: Pharmacologic Methods

• Pharmacologic methods are designed to control symptoms, promote healing, and prevent complications
• Antacids (gastric acid buffers) – be aware of aluminum toxicity & milk alkali syndrome
• Surface agents - available OTC (Sucralfate)
• Histamine-2 receptor antagonists (anti-secretory medication)
• Proton pump inhibitors (anti-secretory medication)
• Prokinetic agents (promotes gastric emptying)

Management of GER: H2 Receptor Antagonists

• Inhibit H2 receptors on gastric parietal cells
• Cimetidine (Tagamet)
• Famotidine (Pepcid AC)
• Nizatidine (Axid AR)
• Ranitidine (Zantac)

Management of GER: Proton Pump Inhibitors (PPI)

• Inhibit H+K+ ATPase (proton pump), the final common pathway of parietal cell acid secretion
• Omeprazole (Losec)
• Esomeprazole (Nexium)
• Lansoprazole (Prevacid)
• Rabeprazole (Aciphex)
• Pantoprozole (Pantaloc)

Management of GER - Children: Long Term PPI Use

• Long-term PPI use is well tolerated
• Be aware of adverse effects of long-term acid suppression:
  • Increased risk of C. difficile colitis with PPI use
  • Increased risk of community and hospital-acquired pneumonia with PPI and H2RA use
  • Risk of small bowel bacterial overgrowth in those on prolonged PPI Rx
  • Hypomagnesemia is a concern in those on prolonged PPI's, or those on other cardiac drugs, diuretics, etc.
  • There is other evidence of fractures seen in adults, however, there is no evidence in children

Management of GER - Prokinetic agents

• Metoclopramide
  • A 5HT4 agonist and dopamine antagonist -increases upper GI contractions, thus promotes gastric emptying
  • Side effects include dystonic reactions and tardive dyskinesia (FDA had a black box warning in 2009 on risks with high doses and long-term use)
• Domperidone
  • Peripheral dopamine D2 receptor antagonist that facilitates gastric emptying and esophageal motility
  • Dose is 0.3-0.6 mg/kg t.i.d, but it's efficacy is uncertain (available in Canada)

Manage of GER - Other Agents

• Cisapride: Blocks non-dopamine receptor, non-cholinergic Benzamide derivative, however it causes Cardiac arrhythmia and prolonged QT syndrome, so has been withdrawn from the market
• Erythromycin (low dose) acts as a Motilin receptor agonist and promotes antral contractions and gastric emptying
  • An RCT in neonates saw no benefit from use of 5 mg/kg/dose q 8 hours
  • An RCT using 12.5 mg/kg/dose q 6 hours improved time to full feeds, but reflux burden was not assessed
• Baclofen - Decreases TLESR's and therefore GER, and may be considered prior to surgery

Management of GER - Surgery

• Nissen Fundoplication (Open vs. Laparoscopic)
  • Considered in those with established diagnosis of GERD
  • Failed medical therapy or is dependent on prolonged medical therapy
  • If patient has persistent asthma or recurrent pneumonia due to GERD -Patient has life-threatening complications of GERD
• A treatment option for neurologically impaired children, although it yields high morbidity and high failure rates

Management of GERD - Neurologically Impaired Children

• Often resistant to standard medical treatment
• Consider thickened feeds
• Long term acid suppression therapy
• Use of G-tube or GJ tube feeds
• Fundoplication can be associated with a high risk of complications and re-operation
  • Dysphagia
  • Aspiration
  • Esophagogastric disconnection (significant morbidity and mortality)

Esophagitis in Children: Differential Diagnosis

• GE Reflux/Erosive esophagitis
• Eosinophilic esophagitis
• Infectious esophagitis (Candida, Herpes, CMV)
• Pill esophagitis
• Crohn's disease
• Vomiting, Bulimia
• GVHD
• Caustic ingestion
• Post sclerotherapy/Band ligation

Management of Erosive Esophagitis

• Treat with a PPI once daily for three months
• If symptom control is inadequate, increase the PPI dose at 4 weeks
• Efficacy can be monitored by extent of symptom relief without routine endoscopic follow-up
• Wean the dose after 3 months of treatment, or withdraw treatment
• Recurrence of symptoms after repeat trials of PPI withdrawal indicates chronic relapsing GERD, whichrequires long-term PPI therapy or anti-reflux surgery