Gastroesophageal reflux disease (GERD) is more common in infants and children, with a prevalence of approximately 3.3% in children. With a growing body of literature suggesting the lack of efficacy of acid-suppressive therapy and the need to be aware of side effects, a growing body of evidence also suggests that the use of acid-suppressive agents in children should be limited. Unlike gastroesophageal reflux disease, gastroesophageal reflux (GER) is a normal physiologic process for the passage of gastric contents into the esophagus and may be associated with involuntary reflux, particularly common in infants. In contrast, when reflux causes additional symptoms and/or comorbidities (irritability, crying, slow weight gain), we call it GERD. In 2009, the North American and European Societies of Pediatric Gastroenterology, Hematology, and Nutrition jointly published clinical guidelines for the management of GER in children, which help distinguish GER from GERD and provide an evidence-based basis for diagnosis and treatment. However, in 2014, an evaluation of guideline use surveyed 567 pediatricians and only 1.8% followed the guidelines. A significant proportion of pediatricians (39%) prescribed proton pump inhibitors (PPIs) for unexplained crying infants, and 36% prescribed PPIs for infants with simple reflux symptoms, although the evidence and recommended medications argue against such use. For simple GER in infants, interventions such as education, anticipatory guidance, and feeding modification are recommended. For endoscopically diagnosed reflux esophagitis or non-erosive reflux disease, taper and discontinue after 3 months of treatment with PPIs is recommended. Chronic recurrent esophagitis requires long-term treatment. Children with nerve damage, obesity, post-repair of esophageal atresia, cystic fibrosis, esophageal hiatal hernia, post-repair of achalasia, and lung transplantation may develop severe chronic GERD. In the October issue of JAMA Pediatrics, van der Pol et al. conducted a systematic review of randomized clinical trials of histamine 2 receptor antagonists (H2RAs). This review included eight studies with 276 children (0-15 years of age). They found very little evidence of the effectiveness of treatment with H2RAs, and all were low-quality studies. However, what was more consistent in the findings was that H2RAs were more effective for symptom reduction, histological recovery, and elevated gastric pH when compared to placebo. In infants, however, H2RAs did not improve overall symptoms. Two randomized double-blind controlled trials have studied the efficacy and safety of PPIs in infants with GERD. 162 infants given PPIs or placebo were included in the study by Orenstein et al. and found no significant difference in symptomatic improvement in GERD between the two groups. similar results. The signs and symptoms of GERD due to acid reflux did not change with the administration of PPIs. Even in the presence of effective acid suppression therapy, the infant’s symptoms did not change significantly. In a recent prospective randomized clinical trial, investigators looked at the effects of body posture and medication on GER in 51 infants with GERD symptoms. In this study, PPI therapy combined with left lateral body position was most effective in reducing GER attacks and esophageal acid exposure, however, there was no improvement in symptoms other than a reduction in vomiting. It is important to strike a balance between the efficacy and side effects of the medications used. van der Pol et al. did not provide clear data on the safety analysis, making it difficult to draw convincing conclusions from this study and leaving medical professionals confused as to what treatment is best for children. H2RAs are known to reduce acid secretion by inhibiting histamine-2 receptors in gastric lining cells; H2RAs have also been associated with side effects such as irritability, headache, and drowsiness. van der Pol et al. also noted that although generally safe, necrotizing small bowel colitis, community-acquired pneumonia, and gastrointestinal infections have been reported. Proton pump inhibitors irreversibly block sodium-potassium adenosine triphosphate, which is the ultimate common pathway for acid secretion by gastric lining cells. Unlike H2RAs, PPIs can maintain intragastric pH above 4 for longer periods of time and also inhibit postprandial acid secretion. Similar to adults, PPIs are also very effective in children for treating symptoms of GERD and erosive esophagitis. But at what cost? In addition to increased respiratory infections, PPIs have been associated with gastrointestinal infections. One study found that acid-suppressive treatment with PPIs in hospitalized children increased the risk of C. difficile infection. In addition, the FDA in its 2012 life published that PPIs may increase the risk of C. difficile infection, which can lead to diarrhea. Similar to H2RA treatment, hypogastric acidity due to PPIs may be associated with community-acquired pneumonia, gastroenteritis, and necrotizing small bowel colitis. In adult patients, it has been documented that PPIs may reduce bone strength, which is associated with decreased vitamin B12 and calcium absorption due to long-term acid suppression. Similar studies have not been replicated in children, and the results remain controversial. Hypomagnesemia, hypokalemia, and hypocalcemia have been reported in adults during long-term treatment with PPIs, but have not been reported in children to date. There is a growing interest in microbiology, but only a few studies have been reported on gut microbes in children with GERD and acid suppression conditions. In this study, acid suppression therapy was associated with positive gastric bacterial cultures (P=.003) and increased median gastric bacterial concentrations (P<.001). Nonacid reflux may be associated with high concentrations of bacteria in the lungs, and there was no statistical difference in the number of positive cultures of bacteria in the lungs between patients who received and those who did not receive acid suppression therapy. < p=""> The effectiveness of H2RAs and PPIs in increasing gastric pH is unquestionable, but the evidence regarding their improvement in symptoms is insufficient. A growing body of data suggests that acid suppression may increase the risk of gastrointestinal and respiratory tract infections in children, potentially with microbial associations. There is growing evidence that in many moderate cases, prescribing acid-suppressing drugs to infants has no significant effect but rather increases risk.