Pediatric Gastroesophageal Reflux Michael Peyton, MD UCI/CHOC Pediatric Residency Program Objectives

● Learn pathophysiology of reflux in pediatric patients ● Understand factors that improve or worsen reflux ● Expand on differential diagnosis and mimickers ● Determine which diagnostic modalities help with diagnosis ● Current treatment recommendations GER in Pediatrics

● Spitting up - effortless passage of gastric contents into or mouth ● Vomiting - forceful expulsion ● Rumination - voluntary, habitual, and effortless regurgitation of recently ingested food then either expulsed or re-swallowed Gastroesophageal Reflux Disease (GERD) ● GER complications present Gastroesophageal Reflux (GER) ○ Significant irritability ○ Feeding difficulties ● “Spitting up”, ○ Poor weight gain “Regurgitation” ● Risk factors ● Passage of stomach ○ Hiatal contents up into ○ Neuromuscular disease ○ Prematurity ○ Hx , achalasia, or esophageal dysmotility GER in Infants

● Normal physiologic process (at least 1/d) ● < 3 months ~50% ● Worst at 4 months old ~67% ● At 7 mo 20%, at 12 mo ~5% or less

Confounding factors: ● Starting infant foods ● More time upright and sitting ● Decreased number of lower esophageal (LES) relaxations GER in Infants

Pathophysiology

● Transient lower esophageal sphincter relaxations (TLESR) ○ Postprandial period → gastric distension → inc intragastric pressure ● Large volume feeds and delayed gastric emptying worsen distension GER in Infants

Anti-Reflux Barrier:

● Diaphragmatic crural support ● Intra-abdominal segment of esophagus ● Angle of His

Sliding compromises barrier GERD in Infants

● Effortless regurgitation and spitting up most common presentation ● “Happy spitters” ● GERD less common ● Rare extraintestinal signs GERD in Infants

Sandifer Syndrome

● Dystonic spasmodic movement with head, neck, and back posturing ● ?? Shared innervation of diaphragm and head/neck muscles causing reflex contraction ● ?? Symptomatic relief due to improved esophageal motility ● Uncommon GERD in Infants

Brief Resolved Unexplained Events (BRUEs)

● Data to support association with BRUEs are limited ● ~15% of 527 apneic episodes were temporally linked with reflux ○ Prospective study - pneumogram + impedance pH study ● There can be temporal relation from history and observation ○ Close proximity to feed, infant was awake, obstructive apnea ● ?? Exaggeration of normal protective reflexes GERD in Children

● Reflux/heartburn in ~2% of 3- 9 yo, 5-8% in 10-17 yo ● Association between GER and asthma ● PNA not often from aspiration of refluxed content, but possible abn swallow ● → cologastric brake causing delayed gastric emptying GERD in Children: Warning Signs

● Concerning signs warrant evaluation ● Reassurance for uncomplicated reflux ● Referral to peds GI if symptoms persist beyond 12 - 18 mo Non-reflux causes of vomiting

Infections Neurologic GI ● Sepsis ● Increased ICP ● ● Meningitis ● Migraine ○ EOE ● ○ Pill ● UTI Respiratory ○ Infectious ● Otitis Media ● Posttussive emesis ● Achalasia ● Pneumonia ● Anatomic/Obstructive ○ PUD ● Foreign body Renal ○ H. pylori ● ● Obstructive ● ● Malrotation ● Renal insufficiency ● Cholelithiasis ● Intussusception ● ● SMA syndrome Onc ● ● Lymphoma ● Celiac Psych/Behavioral ● Crohn disease Drugs and alcohol ● Eosinophilic GI Cardiac disease ● CHF Pregnancy Diagnosis and Evaluation

History

● Inquire about the nature of vomiting ○ Bile or Blood? ○ Forceful or projectile? ○ Systemic symptoms - irritable fever, lethargy?

● Feeding history ○ Volume and frequency ○ Type of formula and how prepared ○ Positioning during and after feeds

● symptoms ○ Eating slowly ○ Cutting food into small pieces, avoiding particular foods Diagnosis and Evaluation

History Physical Exam

● PMH ● General appearance ○ Prematurity ● Weight and length ○ Neurologic problems ● Pulmonary and cardiac ○ Growth or developmental concerns ● Abd -- distention, tenderness, ○ Past surgeries or hospitalizations bowel sounds, HSM ○ Allergies ● Neurologic assessment

● ROS ○ Respiratory or ENT symptoms

● Fam Hx ○ GI diseases including GERD ○ Atopic disease Diagnosis and Evaluation

Upper GI Study

● Poor sensitivity, specificity, and PPV

● Evaluate anatomy ○ Hiatal hernia ○ Malrotation ○ Stenosis ○ Esophageal web or stricture ○ ○ Tracheoesophageal fistula ○ Vascular rings ○ Achalasia ○ Gastric outlet obstruction Diagnosis and Evaluation

Esophageal Manometry

● Assessing esophageal peristalsis and upper esophageal sphincter and LES pressures ● Useful for esophageal motility disorder ● Not used to dx GERD Diagnosis and Evaluation

Scintigraphy

● “Gastric emptying scan” ● Uses formula/food labeled with 99technetium ● May ID esophageal reflux and aspiration, but poor sensitivity and specificity for GERD compared to pH monitoring Diagnosis and Evaluation

24-hr impedance pH study

● Frequency of reflux episodes ● Acid vs non-acid reflux ● Extent (to proximal esophagus) ● Correlation with symptoms

GER - drop in impedance progression distally to proximally as liquid advances from stomach to esophagus

pH probe to determine pH < 4.0, number of episodes, duration, symptom index Diagnosis and Evaluation

Endoscopy with Biopsy

● Direct visual inspection and histologic examination ● Evaluate for diseases that mimic reflux and may be recommended for refractory or recurring GERD Treatment and Management

Lifestyle Modifications (Infants)

● Smaller more frequent feeds ● Inc caloric density with dec vol ● Frequent burping ● Keeping upright after feeds ● Avoiding vigorous handling ● Elevating HOB when sleeping ● Avoid tobacco smoke exposure

** Inc SIDs while prone ** Car seat inc intraabdominal pressure Treatment and Management

Thickeners

● Decreased number of regurgitation and vomiting episodes ● pH monitoring showed no change in reflux index (episodes of acid reflux per hour → 0.6/d) ● Rice cereal inc caloric density ○ Requires faster flow nipple ● Avoid xanthum gum-based thickeners in < 1 yo due to association with NEC Treatment and Management

Formula Change

● Higher whey? Whey empties faster from stomach than casein ● If suspect cow-milk protein allergy, can trial casein hydrosylate or AA formula for 2 wk Treatment and Management

Lifestyle Modification (Older Children)

● Elevated HOB ● Avoid caffeine, chocolate, peppermint, and spicy foods ● Fat can slow gastric emptying ● Eat smaller portions ● Avoid tobacco and alcohol (dec LES pressure) Treatment and Management

Histamine-2 Receptor Antagonists (H2RAs) ● Dec acid secretion by inhibiting H2 receptor on gastric parietal cell ● Onset in 30 mins, peak 2.5 hrs ● First-line therapy → famotidine (Pepcid) ● Tachyphylaxis with chronic use

Proton Pump Inhibitors (PPI) ● Suppress acid production by inhibiting the H+/K+ ATPase on gastric parietal cell ● Onset 1-2 hr, peak in several days ● High rates of healing erosive/ulcerative esophagitis ● AE: HA, n/d, abd pain

If symptoms improve, wean after 4-8 weeks Treatment and Management

Prokinetic Agents ● Improve GER by stimulating more rapid emptying of the stomach ● AE (Metoclopramide): dystonic reactions, lethargy, irritability, gynecomastia, permanent tardive dyskinesia ● AE (Erythromycin): prolonged QT interval

** Current guidelines do not recommend the use of prokinetic agents for GERD Treatment and Management

Surface Agents ● Sucralfate (sucrose, sulfate, aluminum) when exposed to acidic pH, forms a gel that binds to eroded mucosa ● AE: Al3+ toxicity or gastric bezoar

Antacids ● Acts within minutes to buffer gastric acid ● Should be used after meals ● AE: elevated Al3+ can cause osteopenia, rickets, microcytic anemia, neurotoxicity Treatment and Management

Fundoplication ● Inc the LES pressure and inc the intraabdominal length of the esophagus ● Post-op complications ○ Gas-bloat syndrome ○ Dysphagia/Retching ○ ● 10% complications, 10% need revision ● 75% restart anti-reflux medications ● Consider for severe refractory or life- threatening complications of GERD Questions

A 2-month-old boy is brought to the clinic by his parents because of persistent vomiting for the past 2 weeks. The mother thinks that the child might be vomiting green occasionally. The child has not had significant weight gain since the last time you saw him at 2 weeks of age. On physical examination, he is less than the 5th percentile for weight. You are concerned that the child may have some underlying anatomic condition. Which of the following is the most appropriate next step in diagnosis in this patient?

A. 24-hour impedance pH study test. B. Surgery consultation. C. Ultrasonography of the abdomen. D. Upper gastrointestinal series. E. Radiography of the abdomen. Questions

A 2-month-old boy is brought to the clinic by his parents because of persistent vomiting for the past 2 weeks. The mother thinks that the child might be vomiting green occasionally. The child has not had significant weight gain since the last time you saw him at 2 weeks of age. On physical examination, he is less than the 5th percentile for weight. You are concerned that the child may have some underlying anatomic condition. Which of the following is the most appropriate next step in diagnosis in this patient?

A. 24-hour impedance pH study test. B. Surgery consultation. C. Ultrasonography of the abdomen. D. Upper gastrointestinal series. E. Radiography of the abdomen. Questions

You are seeing a 3-month-old boy in your clinic. The mother reports that he has been “vomiting with every feed” and she is concerned that he is “not keeping down anything.” He is taking a regular cow milk–based formula. On physical examination, he is an alert, active infant with stable and normal vital signs. The infant is growing well and has been at the 75th percentile for height and weight on the growth curve. The remainder of the physical examination findings is unremarkable. Which of the following is the most appropriate next step in management for this patient?

A. Follow-up in 1 week for weight check. B. Prescribe acid suppressants. C. Pyloric ultrasonography. D. Reflux precautions. E. Switch to an elemental formula. Questions

You are seeing a 3-month-old boy in your clinic. The mother reports that he has been “vomiting with every feed” and she is concerned that he is “not keeping down anything.” He is taking a regular cow milk–based formula. On physical examination, he is an alert, active infant with stable and normal vital signs. The infant is growing well and has been at the 75th percentile for height and weight on the growth curve. The remainder of the physical examination findings is unremarkable. Which of the following is the most appropriate next step in management for this patient?

A. Follow-up in 1 week for weight check. B. Prescribe acid suppressants. C. Pyloric ultrasonography. D. Reflux precautions. E. Switch to an elemental formula. Summary

● Physiologic reflux should resolve by 12 mo ● Red flags or persistence beyond 12 mo old warrants workup ● UGI should not be ordered as dx test for reflux ● Impedance + pH probe can dx acid vs non-acid reflux ● H2RA or PPI are generally effective medications ● Fundoplication reserved for refractory symptoms, but risk of complications References

Adamiak, T. and Plati, K. Pediatric Esophageal Disorders: Diagnosis and Treatment of Reflux and . Pediatrics in Review. 2018; 39; 392. http://pedsinreview.aappublications.org/content/39/8/392

Sullivan, J. and Sundaram, S. Gastroesophageal Reflux. Pediatrics in Review. 2012; 33; 243. http://pedsinreview.aappublications.org/content/33/6/243