Differentiating Esophageal Sensitivity Phenotypes using pH-Impedance in Intensive Care Unit Infants referred for Gastroesophageal Reflux Symptoms

OBJECTIVE: To identify esophageal sensitivity phenotypes relative to acid (S(Acid)), bolus (SBolus), acid and bolus (S(Acid+Bolus)), and none (S(None)) exposures in infants suspected with gastroesophageal reflux disease (GERD). METHODS: Symptomatic infants (N=279) were evaluated for GERD at 42(40–45) weeks postmenstrual age using 24-hour pH-impedance. Symptom associated probability (SAP) for acid and bolus components defined esophageal sensitivity: 1) S(Acid) as SAP≥95% for acid (pH<4), 2) S(Bolus) as SAP≥95% for bolus, 3) S(Acid+Bolus) as SAP≥95% for acid and bolus, or 4) S(None) as SAP<95% for acid and bolus. RESULTS: Esophageal sensitivity prevalence (S(Acid), SBolus, SAcid+Bolus, S(None)) was 28(10%), 94(34%), 65(23%), and 92(33%) respectively. Emesis occured more in SBolus and S(Acid+Bolus) vs S(None) (p<0.05). Magnitude (#/day) of cough and emesis events increased with S(Bolus) and S(Acid+Bolu)s vs S(None) (p<0.05). S(Acid+Bolus) had increased acid exposure vs S(None) (p<0.05). Distributions of feeding and breathing methods were distinct in infants with S(Bolus) vs S(None) (both, p<0.05). Multivariate analysis revealed that arching and irritability events/day were lesser at higher PMAs (p<0.001), greater for infants on NCPAP (p<0.01), with S(Bolus) and S(Acid+Bolu)s (p<0.05). Coughs/day was greater at higher PMAs (p<0.001), for infants with gavage and transitional feeding methods (p<0.02), with S(Bolu)s and S(Acid+Bolus) (p<0.05) but lesser with Trach (p<0.001). Number of emesis events/day were greater with SBolus and SAcid+Bolus (p<0.001). Sneezes/day decreased for infants on Trach (p=0.02). CONCLUSIONS: Feeding and breathing methods can influence the frequency and type of aerodigestive symptoms. We differentiated esophageal sensitivity phenotypes in NICU infants referred for GERD symptoms using pH-Impedance. Acid sensitivity alone was rare, which may explain poor response to acid suppressives; aerodigestive symptoms were predominantly linked with bolus spread. Magnitude of esophageal acid exposure and esophageal sensitivity to bolus spread may explain the pathophysiological basis for symptoms.