283. Does Proton Pump Inhibitor Exposure Increase the Risk of Developing Eosinophilic Esophagitis in Children With Esophageal Atresia?

Abstract

Children with esophageal atresia (EA) receive proton pump inhibitors (PPIs) long-term due to gastroesophageal reflux disease susceptibility. They have also demonstrated greater susceptibility to eosinophilic esophagitis (EoE) compared to the general pediatric population. No studies have investigated EoE risk factors in EA. This study aimed to determine whether PPI exposure and early-life factors are associated with an increased risk for subsequent EoE development in children with EA. A retrospective chart review was undertaken at a paediatric hospital in Sydney, Australia. The study cohort consisted of children with EA who had their repair and/or follow-up at this hospital between 1 January 2005 and 31 December 2020. Children with EA and EoE (cases) were matched (1:2) with those with only EA (controls), for sex, prematurity and presence of long-gap, to compare PPI exposure. Other early-life factors were analysed without matching, using simple and multivariable logistic regression. Of the 184 children with EA, 46 (25%) developed EoE during this period. Thirty-eight EoE participants were matched to 76 controls. Children with EA and EoE received PPI for significantly higher durations (p = 0.018) and at significantly higher cumulative doses (p = 0.017) than children with EA but no EoE. Food allergy (adjusted odds ratio [aOR], 10.515; 95% confidence interval [CI], 2.659–41.581), family history of atopy (aOR, 5.312; 95% CI, 1.575–17.911) and infantile antibiotic exposure (aOR, 1.048; 95% CI, 1.011–1.086) were also significantly associated with an increased risk of developing EoE in the EA cohort. Longer durations of PPI exposure and exposure to higher cumulative doses of PPI were both associated with the subsequent development of EoE in children with EA. Other early life factors such as atopic family history, food allergy and infantile antibiotic exposure were also significantly associated with an increased risk of developing EoE in children with EA.

Proton pump inhibitors in esophageal atresia: A systematic review and meta‐analysis

“…When analyzing the three studies including a comparison group, 21,26,51 we neither could find any effects of PPI on AS (OR: 0.90; 95% CI: 0.60–1.37, p = 0.64 (Figure S4b).…”

“… Prevalence of BE 43% 51 : 42% 50 GM, 1% 1 IM pPPIs and PPIs have no significant effect on BE by multivariate analysis…”

“…We selected a total of 38 reports on the topic that met the criteria selection (Table S1), representing a cumulative 6044 patients with EA 16–53 . Fourteen studies were prospective and 24 were retrospective.…”

“…Only one study 51 has addressed the relations between neonatal pPPI use and later EoE occurrence, demonstrating a positive association between PPI duration (p = 0.018) and cumulative dose (p = 0.017) with EoE development in EA. When EoE was associated with EA, PPIs alone induced remission in 50%-66% 25,43,50,53 of patients.…”

“…Reported long-term suspected side effects have included an increased prevalence of EoE, depending on duration and cumulative dose 29,51 and increased Clostridium difficile infection was shown in one retrospective study of 92 participants 52 (3% vs. 0.036% in the general pediatric population). Bone mineral density decrease was not found in only one prospective study of 17 participants.…”