Mechanisms of Aerodigestive Symptoms in Infants with Varying Acid Reflux Index Determined by Esophageal Manometry

Abstract

To test whether symptom generation in infants is related to the severity of gastroesophageal reflux disease (GERD) symptoms as determined by the Acid Reflux Index (ARI), stimulus media, and stimulus volume during provocative esophageal manometry. Symptomatic neonates (n = 74) born at a median of 28.9 weeks gestation (range, 23.4-39.4 weeks) were studied at a median of 41.0 weeks (range, 34.6-48.0 weeks) postmenstrual age using 24-hour pH-impedance methods to determine ARI severity, followed by provocative esophageal manometry with graded mid-esophageal infusions (0.1-5.0 mL) of air, water, and apple juice. Peristaltic reflexes and symptom characteristics were compared among ARI severity categories using linear mixed models and generalized estimating equations. The effects of 2635 separate esophageal stimuli on reflexes and symptoms were analyzed. Peristaltic reflexes occurred in 1880 infusions (71%), and physical, cardiorespiratory, sensory symptoms were seen in 439 infusions (17%). Symptom prevalence did not differ across the ARI severity categories (ARI <3, 18%; ARI 3-7, 17%; ARI >7, 16%; P = 1.0). Symptom and peristaltic responses increased with incremental stimulus volumes (all media, P < .001). Symptoms and peristaltic reflexes are manifestations of the recruitment of several neurosensory and neuromotor pathways evoked by mid-esophageal infusions. ARI severity grade plays no role in symptom generation, indicating that GERD should not be diagnosed and severity should not be assigned based on symptoms alone. An increase in symptom occurrence was noted with increasing stimulus volumes, which provided increased activation of receptors, afferents, and efferents in evoking peristaltic clearance reflexes.