Effects of Esophageal Acidification on Troublesome Symptoms: An Approach to Characterize True Acid GERD in Dysphagic Neonates

Abstract

Objective To quantify and compare maximal extent (height) of acid reflux events (AREs) on symptom generation in dysphagic neonates. Methods Dysphagic neonates (N=53), born at 30 ± 5.3 wks gestation, underwent 24-hour pH-impedance study for the evaluation of troublesome symptoms purported to be due to gastroesophageal reflux disease (GERD). AREs (pH < 4 for > 4 seconds) detected by impedance (Z) were categorized by maximal extent as refluxate reaching distal (Z6, Z5), middle (Z4, Z3), or proximal (Z2, Z1) impedance channels. AREs reaching the pH sensor only were categorized as distal. Symptom correlation (%, symptom index (SI), symptom sensitivity index (SSI), and symptom associated probability (SAP)) and temporal characteristics (clearance times) of AREs were analyzed using linear mixed and GEE models comparing height categories presented as mean ± SEM, median (IQR), and OR (95% CI). Results Of the 2003 AREs: 1) distal extent AREs (n=1642) had increased frequency (p < 0.05), decreased ACT (p<0.05), and decreased acidity (p<0.05), 2) in middle and proximal AREs, acid clearance was longer than bolus clearance, p < 0.01, and 3) the odds of having cardiorespiratory (cough or sneeze) symptoms are increased with proximal and middle AREs (p<0.05). Conclusion Most proximal ascent of AREs into middle or proximal esophagus likely activates protective aerodigestive reflexes (peristalsis) or vigilant states to facilitate bolus and chemical clearance. Heightened esophageal sensitivity, acid neutralization delays, or clearance mechanism delays may accentuate multi-systemic troublesome symptoms.

Cardiorespiratory events in infants with gastroesophageal reflux symptoms: Is there any association?

“…This finding confirms our initial hypothesis that, in some subjects with particular characteristics of reflux, there is a significant association between CR and GER events. This agrees with an earlier study by Sivalingam et al, which showed that CR events were associated with proximal GER events in subjects with pathological reflux index …”

“…It is noteworthy that in our study, we observed an almost double reflux index in the positive SAP group confirming the hypothesis that a pathological reflux index could be associated with an increased esophageal sensitization responsible for a greater likelihood to develop CR symptoms as a consequence of reflux …”

“…This agrees with an earlier study by Sivalingam et al, which showed that CR events were associated with proximal GER events in subjects with pathological reflux index. 35 Focusing the analysis on the association between CR and GER events in the positive SAP group, we noticed that about 83% of CR events associated with GER were GER-CR associations, and in these cases, the median bolus reflux extent and the percentage of proximal refluxes were higher than in CR-GER associations; no differences in bolus clearance time or pH value were observed. These data confirm that proximal reflux could represent a trigger for CR events independently from the acidity of the reflux, 13,36 as previously observed in animal models.…”

“…Thus, 66 infants fulfilled all the inclusion criteria and were enrolled into the study. They had a gestational age of 38 (32)(33)(34)(35)(36)(37)(38)(39)(40) weeks, 25 of them were preterm (37.9%) and the median APGAR score was 8 (5-9) at first minute and 8 (6-9) at fifth minute.…”

“…Gestational age (weeks) 29 (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) 38 (34)(35)(36)(37)(38)(39)(40) .073…”