Gastroesophageal reflux disease in children: What’s new right now?

Table 1 Summary of the pathogenesis of gastroesophageal reflux disease

Main underlying mechanism	Associated conditions	Mechanism of GERD
Anatomical defect	Hiatus hernia, immature esophageal anti-relux barrier, e.g., infants, surgical pull up for esophageal atresia	Increased risk of GER
Esophageal or gastric hypomotility/dysmotility	Esophageal disorders associated with dysmotility, e.g., esophageal atresia, achalasia, gastroparesis, cow’s milk protein allergy, sleeping, decreased saliva secretion, supine position	Impaired esophageal clearance of refluxate by peristalsis and/or production of neutralizing secretions
Esophageal mucosal defect	Eosinophilic esophagitis, esophageal infection	Impaired esophageal sensation
UES dysfunction	Extraesophageal or respiratory manifestations	Allows refluxate to access airways

GERD: Gastroesophageal reflux disease; UES: Upper esophageal sphincter.

Table 2 The signs and symptoms of gastroesophageal reflux disease and alarm features of its most significant mimics

Symptoms	Signs	Red flags from other serious conditions that may underlie or mimic GERD
General	General	General
Irritability	Dental erosion, not dental caries (Figure 2)	Excessive irritability
Failure to thrive	Anemia	Weight loss
Feeding refusal		Fever
Sandifer syndrome		Lethargy
Gastrointestinal	Gastrointestinal	Gastrointestinal
Recurrent regurgitation	Esophagitis	Onset of regurgitation at > 6 mo of age
Recurrent vomiting	Esophageal stricture	Persistent or progressive regurgitation at > 1 yr of age
Heartburn	Barrett esophagus	Vomiting: Persistent forceful, nocturnal or bilious vomiting
Dysphagia/odynophagia		Hematemesis
Epigastric pain		Marked abdominal distension
Airway	Airway	Neurological
Difficult to treat wheezing	Apnea	Bulging fontanelle
Unexplained stridor	Recurrent pneumonia	Seizure
Chronic cough	Recurrent otitis media	Macro/microcephaly
Hoarseness of voice		Neurological abnormalities
		Papilledema

GERD: Gastroesophageal reflux disease.

Table 3 Updated version of the Cow's Milk-related Symptom Score (CoMiSS) used to evaluate children suspected of cow’s milk protein allergy

Symptom	Characteristics and frequency	Score
Crying assessed by parents and without any obvious cause ≥ 1 wk, and not related to infection	≤ 1 h/d	0
	1.0-1.5 h/d	1
	1.5-2.0 h/d	2
	2-3 h/d	3
	3-4 h/d	4
	4-5 h/d	5
	≥ 5 h/d	6
Regurgitation ≥ 1 wk	0-2 episodes/d	0
	3-5 episodes (volume < 5 mL)/d	1
	> 5 episodes of volume > 5 mL	2
	> 5 episodes (volume < 50% of feeds)/d	3
	Small volume and happens > 30 min after each feed	4
	Regurgitation of ≥ 50% volume of a feed in ≥ 50% of total feeds	5
	Regurgitation of the complete feed after each feeding	6
Stool: Brussels Infant and Toddlers Stool Scale (BITSS); no change ≥ 1 wk	Hard stools	4
	Formed stools	0
	Loose stools not related to infection	4
	Watery stools not related to infection	6
Skin symptoms not related to infection	Atopic eczema ≥ 1/wk
	Absent	0
	Mild	1
	Moderate	2
	Severe	3
	Acute urticaria/angioedema that directly related to cow’s milk
	No	0
	Yes	1
Respiratory symptoms not related to infection ≥ 1 wk	No respiratory symptoms	0
	Slight symptoms	1
	Mild symptoms	2
	Severe symptoms	3

Table 4 Summarizes the drugs used in infants and children with gastroesophageal reflux disease[1-5] (for guidance only, prior to use please refer to local formulary and guidelines for accuracy and appropriate doses)

Medication	Dose	Adverse effect	Approved age (FDA indicated)
PPI1
Omeprazole	1-4 mg/kg/d od	Diarrhea, abdominal pain, flatulence, headache, enteric infection, respiratory infection, rebound hypersecretion	> 1 yr old
Lansoprazole	0.7-2 mg/kg/d od	1Esomeprazole: Tarry stool, darkened urine	> 1 yr old
Esomeprazole	3-5 kg: 2.5 mg od	1Rabeprazole: Light-colored stool	> 1 mo old
	> 5-7 kg: 5 mg od
	> 7.5 kg, < 20 kg: 10 mg od
	20 kg: 20 mg od
Pantoprazole	1-2 mg/kg/d od		> 5 yr old
Rabeprazole	0.5-1.0 mg/kg/d od		> 1 yr old
Pro-motility
Metoclopramide	0.4-0.9 mg/kg/d tid	Extrapyramidal side effect (1%), diarrhea, drowsiness	> 1 yr old
Domperidone	0.8-0.9 mg/kg/d tid	Dry mouth, QT prolongation (rare) Abdominal pain, diarrhea, (rare) HPS in infants, QT prolongation (rare)	> 12 yr old
Erythromycin	5 mg/kg/dose qid	Dizziness, diarrhea, dry mouth	All ages
Baclofen	0.5 mg/kg/d tid		All ages
Esophageal mucosal protection
Alginate antacid		Flatulence, diarrhea, nausea and vomiting	Younger than 12 yr of age is not generally recommended
Magnesium alginate plus simethicone	Infant: 1-2 mL/kg/dose after feeding
Sodium alginate (225.00 mg sodium alginate, 87.25 mg magnesium alginate per sachet)	Child: 2.5-5.0 mL oral tid after meal
Sucralfate (sucrose, polyaluminium hydroxide)	40-80 mg/kg/d qid	Constipation, aluminum toxicity in long-term use	In adult
Esoxx (sodium hyaluronate, sodium chondroitin sulfate, poloxamer 407, povidone K30, xylitol, potassium sorbate, sodium benzoate, red grape aroma, purified water) (10 mL/sachet)	1-2 sachet/d after main meal and bedtime	No serious adverse effect because of the poor absorption, however, no data of long-term adverse effect	In Italy, it is approval for adolescents age > 12 yr old
Probiotics
Lactobacillus reuteri DSM 17938	> 1 × 108 colony-forming units/d od	None	All ages

¹Dose depend on metabolizer via cytochrome P2C19. FDA; od; bid; tid; qid.

PPI: Proton pump inhibitor.

Table 5 Summarizes the updated diagnostic investigations and treatments for children with suspected GERD

Novel diagnosis tools	Treatment
Combined Video-MII-pH monitoring test to increase the detection of symptom associated reflux	Non-pharmacological treatment
	Supine 40-degree anti-Trendelenburg position
	Using the updated Cow Milk Symptom Score (CoMiSS) before and after therapeutic trial for CMPA
Esophageal manometry with pH-MII monitoring	Pharmacological treatment
	Novel prokinetics ex. mosapride, itopride, prucalopride and renzapride
Electrogastrography	Alginate antacid
	Esophageal mucosal protection: sucralfate, EsoxxTM
	Probiotics
Therapeutic trial with transpyloric feeding	Endoscopic treatment
	Transoral incisionless fundoplication

CMPA: Cow’s milk protein allergy; CoMiSS: Cow Milk Symptom Score.