title: Twenty-four-hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acidic, and weakly alkaline gastroesophageal reflux.
abstract: OBJECTIVE
  Gastroesophageal reflux is a physiologic process and is considered pathologic (gastroesophageal reflux disease) when it causes symptoms or results in complications. It is common in preterm infants and occurs in healthy neonates. Twenty-four-hour pH monitoring commonly is used in children for diagnosis of gastroesophageal reflux disease, and abnormal reflux is considered with detection of increased esophageal acid exposure. However, in neonates, relatively few gastroesophageal reflux episodes cause esophageal acidification to pH < 4. Premature infants receive frequent feeds, which can induce a weaker acid secretory response than that observed in older infants and adults. As a consequence, gastric pH may be > 4 for prolonged periods, and reflux of gastric contents might be less acidic or even alkaline. Esophageal impedance monitoring can detect weakly acidic and even alkaline gastroesophageal reflux. The role of weakly acidic reflux in the pathophysiology of gastroesophageal reflux disease in preterm infants is not clear. To date, studies that have used impedance-pH in neonates assessed the association between nonacid reflux and cardiorespiratory symptoms, but no impedance data from healthy preterm neonates have been available to determine whether those symptomatic neonates had an increased number of weakly acidic reflux episodes or increased reactivity to a physiologic number of reflux events. Our aim with this study was to provide impedance-pH values for acid, weakly acidic, and weakly alkaline reflux from healthy preterm neonates.
  
  
  METHODS
  Esophageal impedance was recorded for 24 hours in 21 asymptomatic preterm neonates by replacing the conventional feeding tube with a specially designed feeding tube that included 9 impedance electrodes (8 French). All neonates were asymptomatic, with spontaneous breathing. Reflux monitoring was performed after comprehensive explanation and on receipt of written parental consent. Esophageal and gastric pH were monitored using a separate parallel pediatric catheter (6 French). According to the corresponding pH change, impedance-detected reflux was classified as acid, weakly acidic, and weakly alkaline. For each infant, the total number of reflux events, the acid exposure and bolus exposure times at 2 cm above the respiratory inversion point, and average proximal extent of reflux were calculated.
  
  
  RESULTS
  Twenty-six preterm neonates were recruited into this study. A preliminary analysis was performed, and tracings were classified according to their quality and the presence of technical artifacts (spontaneous pH and impedance drifts, esophageal probe migration, and dysfunction of 1 or more impedance channels). Five studies were excluded because of 1 or more technical artifacts; a total of 21 neonates represent the final cohort included. At birth, the infants had a median postmenstrual age of 32 weeks, and the measurements were performed at a median age of 12 days. The total recording time was 23.7 +/- 2 hours. Gastric pH was higher than 4 during 69.3 +/- 20.4% of the recording time. The median number of reflux events in 24 hours was 71, 25.4% (range: 0%-53.1%) of which were acid, 72.9% (range: 45.3%-98.0%) were weakly acidic, and 0% (range: 0%-8.1%) were weakly alkaline. Compared with fasting periods, feeding periods tended to be associated with a higher number of total reflux events per hour. The acidity of reflux, however, was significantly different: during fasting, the number of acid reflux episodes per hour was higher, whereas during feeding, the number of weakly acidic reflux episodes was increased. Most reflux events were only liquid, whereas gas was present either mixed with liquid or pure only in 7.7% of all reflux episodes detected. The proximal esophageal segments were reached in 90% of reflux episodes. Reflux-related acid exposure (pH drops associated with impedance-detected reflux) was 1.66% (range: 0%-6.43%), whereas total acid exposure (associated and not associated with reflux detected by impedance) was 5.59% (range: 0.04%-20.69%). There was no relationship between the number or acidity of reflux events and anthropometric parameters such as weight and gestational age.
  
  
  CONCLUSIONS
  We present the first study using 24-hour impedance-pH recordings in asymptomatic premature neonates. Previous studies that used pH-metry suggested that neonatal cardiorespiratory symptoms could be related to acid gastroesophageal reflux. However, pH-metry could not detect accurately weakly acidic or nonacid reflux. Our healthy premature neonates had approximately 70 reflux events in 24 hours, 25% of which were acid, 73% were weakly acidic, and 2% were weakly alkaline. The number of reflux events per hour (2-3 per hour) was slightly lower than that described in premature neonates with cardiorespiratory events (4 per hour). We confirmed that weakly acidic reflux is more prevalent than acid reflux, particularly so during the feeding periods. In contrast, similar to healthy adults, weakly alkaline reflux was very rare. We confirmed findings from previous studies in which most reflux events were pure liquid during both fasting and during postprandial periods and gas reflux was very rare. As in neonates with cardiorespiratory symptoms, the majority of reflux events in asymptomatic preterms reached the proximal esophagus or pharynx, and there were no differences between acid and weakly acidic reflux. The lack of differences between asymptomatic and diseased infants contravenes the hypothesis for macro- or microaspiration but does not exclude hypersensitivity to reflux as a cause for respiratory symptoms. The acid exposure that was related to reflux events and detected by impedance was significantly lower than the total acid exposure during 24 hours. Increased acid exposure could be attributable to pH-only reflux events or, less frequently, to slow drifts of pH from baselines at approximately 5 to values < 4. These changes were not accompanied by a typical impedance pattern of reflux but by slow drifts in impedance in 1 or 2 channels. Our findings confirm the need for the use of impedance together with pH-metry for diagnosis of all gastroesophageal reflux events. The relationship between gastroesophageal reflux and cardiorespiratory events in neonates and older infants has been studied extensively. The current evidence for such a relationship is controversial. This study provides values of impedance-pH monitoring for acid, weakly acidic, and weakly alkaline reflux from healthy preterm neonates that can be used for comparison when evaluating gastroesophageal reflux in preterm infants with a cardiorespiratory disease.
authors.affiliation: Department of Pediatric Surgery, Children's Hospital Virgen del Rocío, Seville, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: López-Alonso
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Moya
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Cabo
authors.forename: Juan
authors.initials: J
authors.lastname: Ribas
authors.forename: Maria
authors.initials: M
authors.lastname: del Carmen Macías
authors.forename: Jiry
authors.initials: J
authors.lastname: Silny
authors.forename: Daniel
authors.initials: D
authors.lastname: Sifrim
mesh_terms: D002021:Buffers; D017097:Electric Impedance; D004750:Enteral Nutrition; D004947:Esophagus; D005260:Female; D005745:Gastric Acidity Determination; D005764:Gastroesophageal Reflux / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007225:Infant Food; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D007441:Intubation, Gastrointestinal; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods*; D012016:Reference Values
chemical_list: D002021:Buffers