Childhood gastroesophageal reflux disease: A comprehensive review of disease, diagnosis, and therapeutic management

Table 1 Symptoms, risk factors, and complications associated with pediatric gastroesophageal reflux disease

Category	Details	Ref.
Symptoms	Vomiting, regurgitation, feeding refusal, failure to thrive, Sandifer syndrome	Gonzalez Ayerbe et al[5], Czinn and Blanchard[6]
Extraesophageal symptoms	Chronic cough, wheezing, dental erosions, halitosis	Baird et al[7]
Risk factors	Prematurity, obesity, neurologic impairments, congenital anomalies (e.g., esophageal atresia, hernia)	Marseglia et al[8], Pashankar et al[9], Dziekiewicz et al[10]
Complications	Esophagitis, anemia, aspiration pneumonia, chronic lung disease, Barrett’s esophagus	Leung and Chan[11], Gaude[12], Khoshoo et al[13]

Table 2 Diagnostic tools for pediatric gastroesophageal reflux disease

Diagnostic tool	Use	Advantages	Ref.
Clinical history and exam	Identifies symptoms and risk factors	Accessible, non-invasive	Gonzalez Ayerbe et al[5], Friedman et al[16]
PH monitoring	Detects acid reflux (pH < 4); assesses reflux index	Gold standard for acid reflux	Leung and Hon[17], Mousa et al[18]
Multichannel intraluminal impedance	Measures acid and non-acid reflux events	Evaluates atypical symptoms, non-acid reflux	Mousa et al[18]
Upper endoscopy	Detects complications (e.g., esophagitis, strictures)	Direct visualization, biopsy possible	Arasu et al[19], Mousa and Hassan[20], Rosen et al[21]
Barium swallow	Rules out structural abnormalities (e.g., atresia, malrotation)	Useful for anatomical evaluation	Winter[22], Michail[23]
Esophageal manometry	Rules out motility disorders	Identifies achalasia or rumination syndrome	Mousa and Hassan[20], Michail[23]

Table 3 Lifestyle and dietary modifications for pediatric gastroesophageal reflux disease

Intervention	Details	Ref.
Thickened feeds	Adding cereal to formula or breast milk	Duncan et al[29], Forbes[30]
Positional therapy	Upright positioning after feeding	Vandenplas et al[27]
Dietary modifications	Hypoallergenic formula, avoiding overfeeding	Vandenplas et al[28], Lightdale et al[31]
Lifestyle modifications	Breastfeeding, avoiding secondhand smoke, weight management	Forbes[30], Lightdale et al[31]

Table 4 Summary of pharmacologic treatments for pediatric gastroesophageal reflux disease, including their uses, advantages, side effects, and relevant references

Drug category	Examples	Uses	Advantages	Side effects	Ref.
H2RAs	Cimetidine, nizatidine	Treats erosive esophagitis, reduces acid secretion	Effective short-term relief, better than placebo	Tachyphylaxis after approximately 6 weeks, risk of liver disease, gynecomastia with cimetidine	Canani et al[36], Orenstein et al[37]
Proton pump inhibitors	Omeprazole, lansoprazole	Treats GERD, maintains gastric pH > 4, effective for esophagitis resistant to H2RAs	Long-term effectiveness, better symptom control	Headaches, diarrhea, nausea, increased risk of infections (e.g., pneumonia)	Canani et al[36], Illueca et al[38]
Prokinetic agents	Erythromycin	Improves esophageal peristalsis, accelerates gastric emptying	Helpful in cases where acid suppressants are insufficient	Potential gastrointestinal discomfort, antibiotic-related side effects	Chicella et al[40]
Gamma-aminobutyric acid(B) receptor agonists	Baclofen, AZD3355, AZD9343	Reduces TLESRs	Promising for refractory cases, fewer CNS effects with newer agents	Baclofen: CNS side effects; AZD3355 and AZD9343: Not yet validated in pediatrics	Lehmann[42], Kuo and Holloway[44]
Metabotropic glutamate receptor 5 modulators	ADX10059	Reduces acid reflux, targets TLESRs	Potential for symptom improvement in GERD	Dizziness, limited data, needs further research	Lehmann[42], Keywood et al[43]

CNS: Central nervous system; GERD: Gastroesophageal reflux disease; H2RAs: Histamine-2 receptor antagonists; TLESRs: Transient lower esophageal sphincter relaxations.