Association between gastroesophageal reflux and pathologic apneas in infants: a systematic review.

BACKGROUND: In infants, apneas can be centrally mediated, obstructive or both and have been proposed to be gastroesophageal reflux (GER) induced. Evidence for this possible association has never been systematically reviewed. PURPOSE: To perform a systematic review using PubMed, EMBASE and Cochrane databases to determine whether an association between GER and apnea in infants exists. Studies with n ≥ 10 infants, aged <12 months, were included. GER had to be studied by pH-metry or pH-impedancemetry. GER episodes were defined as pH <4 for ≥ 5 s and/or a drop of >50% of baseline in impedance signal in distal channels. An apneic event was defined as a cessation of breathing for >20 s, or ≥ 10 s with hypoxemia or bradycardia. An epoch of ≤ 2 min was used to define temporal relation between GER and apnea. Methodological quality of studies was assessed with Newcastle Ottawa Scale (NOS). Of 1959 abstracts found, 6 articles met the inclusion criteria. All studies had poor methodological quality. A total of 289 infants were included. The temporal association of GER followed by apnea was assessed in all studies, with epochs varying from 10 s to 2 min. One study found an increase of apneic events after GER, the remaining 5 studies did not find an association. Two studies assessed apnea followed by GER as well, but did not find sufficient evidence for association. This systematic review showed insufficient evidence for an association between GER and apneas in infants. High quality studies using uniform inclusion criteria, definitions according to accepted guidelines, and patient relevant outcome measures are needed.

Diagnostic accuracy of tests in pediatric gastroesophageal reflux disease.

OBJECTIVE: To systematically review the literature evaluating the diagnostic accuracy of commonly used diagnostic tests over conventional history taking and physical examination in children ≤ 18 months and >18 months suspected of gastroesophageal reflux disease (GERD). STUDY DESIGN: We searched Medline, Embase, and the Cochrane database for studies assessing the diagnostic accuracy of pH-metry, pH-impedance, esophagogastroscopy, barium contrast study, scintigraphy, and empirical treatment as diagnostic tools. Quality was assessed according to Quality Assessment of Studies of Diagnostic Accuracy Included in Systematic Reviews criteria. RESULTS: Of the 2178 studies found, 6 studies were included, containing 408 participants (age 1 month-13.6 years) and 145 controls (age 1 month-16.9 years). Studies included children with GERD symptoms; 1 included an atypical presentation. In all the studies, the diagnostic accuracy of pH-metry was investigated, and in 2 studies esophagogastroscopy was investigated as well. Sensitivity and specificity were calculated in 3 studies. The range of reported sensitivity and specificity was broad and unreliable because of poor methodological quality according to Quality Assessment of Studies of Diagnostic Accuracy Included in Systematic Reviews criteria and inadequate study design. CONCLUSION: Diagnostic accuracy of tests in children suspected of GERD remains unclear and implications for practice are hard to give. There is an urgent need of well-designed randomized controlled trials where the effect of treatment according to specific signs and symptoms will be compared with the effect of treatment based on the results of additional diagnostic tests, for patient relevant outcomes.

Measurement of mucosal conductivity by MII is a potential marker of mucosal integrity restored in infants on acid-suppression therapy.

Esophageal multichannel intraluminal impedance (MII) allows measurement of the conductivity of adjacent contents. During esophageal rest, raw impedance levels may represent mucosal integrity. We assessed the influence of proton pump inhibitors (PPIs) on presumed mucosal integrity by reanalyzing raw MII levels of 21 pH-MII tracings from infants with gastroesophageal reflux (GER) disease before and after esomeprazole treatment. Median (interquartile range) esophageal MII increased during treatment, 938 (652-1304) versus 1885 (1360-2183) Ohm, P < 0.0001. Patients with lower MII levels demonstrated a larger increase on therapy: Spearman r2 = 0.28, P = 0.014. No correlation with standard GER parameters was observed. In conclusion, PPI therapy increases MII levels in infants with symptomatic GER disease.

Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review.

INTRODUCTION: Use of proton-pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD) in children has increased enormously. However, effectiveness and safety of PPIs for pediatric GERD are under debate. OBJECTIVES: We performed a systematic review to determine effectiveness and safety of PPIs in children with GERD. METHODS: We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for randomized controlled trials and crossover studies investigating efficacy and safety of PPIs in children aged 0 to 18 years with GERD for reduction in GERD symptoms, gastric pH, histologic aberrations, and reported adverse events. RESULTS: Twelve studies were included with data from children aged 0-17 years. For infants, PPIs were more effective in 1 study (compared with hydrolyzed formula), not effective in 2 studies, and equally effective in 2 studies (compared with placebo) for the reduction of GERD symptoms. For children and adolescents, PPIs were equally effective (compared with alginates, ranitidine, or a different PPI dosage). For gastric acidity, in infants and children PPIs were more effective (compared with placebo, alginates, or ranitidine) in 4 studies. For reducing histologic aberrations, PPIs showed no difference (compared with ranitidine or alginates) in 3 studies. Six studies reported no differences in treatment-related adverse events (compared with placebo or a different PPI dosage). CONCLUSIONS: PPIs are not effective in reducing GERD symptoms in infants. Placebo-controlled trials in older children are lacking. Although PPIs seem to be well tolerated during short-term use, evidence supporting the safety of PPIs is lacking.