Visible breaks in the esophageal mucosa are the endoscopic sign of greatest inter-observer reliability based on adult studies.(11) However, no studies in adults or in children support that microscopic esophagitis without evidence of erosive esophagitis is adequate to diagnose GERD defined as the presence of troublesome symptoms though microscopic esophagitis may, in some contexts, signify the presence of pathologic acid reflux defined by pH-metry.(43) The primary role for esophageal histology is to rule out other conditions in the differential diagnosis, such as eosinophilic esophagitis, Crohn’s disease, Barrett esophagus, infection and others. Compared with the results of 24-hour esophageal pH testing as a diagnostic test for GERD, the sensitivity of color Doppler ultrasound performed for 15 minutes post-prandially is about 95% with a specificity of only 11%, and reflux frequency detected by ultrasound does not correlate with reflux index (RI) detected by pH monitoring.(40, 41) At present, ultrasound has no role as a routine diagnostic tool for GERD in children, but this test may be of use to evaluate for other conditions that might mimic GERD including, most importantly in the infant population, pyloric stenosis. Abdominal ultrasound may also pick up other diagnoses which may trigger symptoms of discomfort and vomiting including diagnoses such as hydronephrosis, uretero-pelvic obstruction, gallstones and ovarian torsion.
Our findings also showed that pH-MII parameters correlated significantly with the endoscopically confirmed erosive esophagitis. Even though, endoscopy is still the diagnostic mode of choice for the confirmation of mucosal lesions, pH-MII parameters could be considered as potential markers for estimation of integrity of esophageal mucosa, which should be further investigated. Although, standardization is mandatory, pH-MII monitoring shows promising performances for the diagnosis of GERD, and tendency to become the gold standard for detection of this disorder in pediatric population. The prevalence of erosive esophagitis in children varies, from 12.4% reported in multicenter study from 2008  to 34.6% found in a single center study from 2001 . The problem is that patients who had endoscopy were not patients with GERD symptoms only, therefore the prevalence of esophagitis in children might be underestimated .
It is uncertain whether the use of lansoprazole leads to more side-effects in infants with GERD compared with hydrolyzed formula. Clarify the role of acid and non-acid reflux in the etiology of esophagitis and other signs and symptoms suggestive for GERD. In conclusion, there is insufficient evidence to support the use of pH-MII as a single technique for the diagnosis of GERD in infants and children. Clarify the role of acid reflux in the etiology of esophagitis and other signs and symptoms suggestive for GERD. In conclusion, there is insufficient evidence to support the routine use of pH-metry for the diagnosis of GERD in infants and children.
These findings are in concordance with previous reports [8,9]. Higher sensitivity of pH-metry in children above 8 years, which was found in our study, could be partially explained by possible presence of selection bias due to inclusion of children with more troublesome symptoms and frequent use of proton pump inhibitor test in this age group.
GERD management in children includes lifestyle changes, pharmacologic therapy, and surgery. Lifestyle changes which may contribute to prevent and improve reflux symptoms in infants have already been discussed in the previous sections. In children and adolescents, lifestyle changes include modification of diet and sleeping position, weight reduction, and smoking cessation [2, 71]. Although usually sufficient to manage physiologic GER, lifestyle changes alone are not effective in the treatment of GERD, which must include pharmacologic therapies and possible surgical intervention for severe, unresponsive cases.
Since the withdrawal of cisapride from commercial availability in most countries, prokinetic agents have been less frequently used, although domperidone is commercially available in Canada and Europe. Pediatric studies comparing pharmacologic agents for GERD have been impaired by small sample size, absence of controls, and use of unreliable endpoints. Therefore, most studies investigating effectiveness and safety of GERD drugs have been performed in adults, and their applicability to children of all ages is uncertain.
Histamine-2 receptor antagonists (H 2 RAs) inhibit histamine-2 receptors on gastric parietal cells, thus decreasing acid secretion. H 2 RAs currently available in most countries are cimetidine, ranitidine, famotidine, and nizatidine. These four drugs have similar spectra of activity, side effects, and clinical indications and are extremely well tolerated by patients [72, 73, 74, 75, 76, 77, 78, 79].
The term â€œhappy spitterâ€ has been used to identify these patients, in order to highlight the benignity of such condition. Infants regurgitate more frequently than adults due to the large liquid volume intake, the prolonged horizontal position of infants, and the limited capacity of both the stomach and esophagus . Irritability and excessive crying are also very frequent in infants and may present along with regurgitation and vomiting. Therefore, neither regurgitation and vomiting nor irritability and excessive crying, regardless of their severity extent and their extent, are sufficient to diagnose GERD.
Moreover, likewise infants and younger children, even older children and adolescents, may experience respiratory symptoms as the only manifestation of GERD . Although reflux does occur physiologically in most infants, clinicians should be aware that there is a continuum between physiologic GER and GERD leading to significant symptoms, signs, and complications. Therefore, a small proportion of symptomatic infants may deserve an instrumental diagnostic assessment for GERD or other GERD-mimicking diseases. To help identify this subgroup of infants, the latest international GER guidelines drafted a list of warning signals requiring investigations in infants with regurgitation or vomiting (Table 1).
In our study, symptom association between apneas and reflux episodes was not found. From the published studies, it is evident that in the majority of infants with apnea or apparent life-threatening event, GER is not the cause.
5.9 Based on expert opinion, the working group recommends the regular assessment of the ongoing need of long-term acid suppression therapy in infants and children with GERD (Algorithm 2). Determination of the value pH-metry as a diagnostic tool for GERD and to differentiate it from GER is difficult because of lack of a gold standard for comparison. Early pH-metry studies used esophageal manometry, endoscopy, scintigraphy, symptom presence and barium imaging as the gold standard methods to diagnose reflux events.(28, 29, 31) All of these â€œgold standardsâ€ have significant limitations, with high rates of false positivity. The diagnosis of GERD is based primarily on clinical suspicion, which can be strengthened by additional diagnostic investigations that are aimed to quantify and qualify GERD).
Proton pump inhibitors are reasonable treatment options for GERD in older children and adolescents, but their use in infants is questionable because of a lack of proven effectiveness. receptor antagonists are an option for acid suppression therapy in infants and children with GERD. Conservative treatments are the first-line strategies for most infants, older children, and adolescents with reflux and GERD.
In conclusion, it is uncertain whether the use of cimetidine improves histology/macroscopy in infants and children with GERD when compared to sucralfate. It is uncertain whether the use of cimetidine leads to more side-effects in infants and children with GERD compared with sucralfate. In conclusion, it is uncertain whether the use of lansoprazole improves signs and symptoms based on the I-GERQ-R questionnaire in infants with GERD compared with hydrolyzed formula.