Differentiating esophageal sensitivity phenotypes using pH-impedance in intensive care unit infants referred for...

To identify esophageal sensitivity phenotypes relative to acid (S_Acid), bolus (S_Bolus), acid and bolus (S_Acid+Bolus), and none (S_None) exposures in infants suspected with gastroesophageal reflux disease (GERD).

Symptomatic infants (N = 279) were evaluated for GERD at 42 (40-45) weeks postmenstrual age using 24-h 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.

Esophageal sensitivity prevalence (S_Acid, S_Bolus, S_Acid+Bolus, S_None) was 28 (10%), 94 (34%), 65 (23%), and 92 (33%), respectively. Emesis occurred more in S_Bolus and S_Acid+Bolus vs S_None (p < 0.05). Magnitude (#/day) of cough and emesis events increased with S_Bolus and S_Acid+Bolus 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) and greater for infants on NCPAP (p < 0.01) with S_Bolus and S_Acid+Bolus (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_Bolus and S_Acid+Bolus (p < 0.05) but lesser with Trach (p < 0.001). Number of emesis events/day were greater with S_Bolus and S_Acid+Bolus (p < 0.001). Sneezes/day decreased for infants on Trach (p = 0.02).

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.

Objective GERD diagnosis and reasons for symptoms in NICU infants remains unclear. Differentiation of esophageal sensitivities by acid and bolus components of GER reveal distinct symptom profiles, specifically the bolus component of GER significantly contributes to symptom occurrence. Acid only sensitivity to GER is rare, and acid-suppressive therapy alone may not improve symptoms in a majority of NICU infants. Magnitude of esophageal acid exposure and esophageal sensitivity to any bolus spread may explain the pathophysiological basis for symptoms. Feeding and breathing methods can influence the frequency and type of aerodigestive symptoms. GERD treatments should be individualized to the patient's GERD phenotype and likely also target the bolus component of GER.