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Early Infant Risk Factors for Pediatric Eosinophilic Esophagitis

Witmer, Claire P.*,†; Susi, Apryl; Min, Steve B.*,†; Nylund, Cade M.*,†

Journal of Pediatric Gastroenterology and Nutrition: November 2018 - Volume 67 - Issue 5 - p 610–615
doi: 10.1097/MPG.0000000000002123
Original Article: Gastroenterology: Eosinophilic GI Disease

Objectives: Eosinophilic esophagitis (EoE) is an inflammatory, atopic disease of the esophagus without a clear etiology. Our objective was to identify exposures and conditions in early infancy associated with the development of EoE.

Methods: A case-control study was performed using the Military Health System Database. Subjects diagnosed with EoE from October 2008 to September 2015 were matched 1:2 on age and sex. Early infant risk factors from the first 6 months of life were investigated.

Results: A total of 1410 cases with EoE were matched to 2820 controls. The median (interquartile range) age at diagnosis of EoE was 4.2 years (2.1–7.2) and 68.7% were boys. Proton pump inhibitors (adjusted odds ratio [aOR], 2.73; 95% confidence interval [CI] 1.93–3.88), histamine-2 receptor antagonists (aOR, 1.64; 95% CI 1.27–2.13), and antibiotics (aOR, 1.31; 95% CI 1.10–1.56) were associated with EoE. Prematurity (aOR, 1.46; 95% CI 1.12–1.89) and early manifestations of atopic disease such as milk protein allergy (aOR, 2.37; 95% CI 1.26–4.44) and eczema (aOR, 1.97; 95% CI 1.64–2.36) were related to increased odds for EoE. Erythema toxicum in infancy was strongly associated with a diagnosis of EoE (aOR 3.52; 95% CI 1.03–12.04). Infants with feeding difficulty (aOR, 1.45; 95% CI 1.18–1.77) and gastroesophageal reflux disease (aOR, 1.79; 96% CI 1.43–2.26) were also at increased risk for EoE.

Conclusions: Acid-blocking medications and antibiotics during infancy were associated with later diagnosis of EoE. Erythema toxicum neonatorum, an eosinophilic immune phenomenon, was strongly associated with EoE. Identifying early infant risk factors for EoE may help to risk stratify the need for endoscopy.

*Department of Pediatrics, Walter Reed National Military Medical Center

Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD.

Address correspondence and reprint requests to Claire P. Witmer, MD, Walter Reed National Military Medical Center Bethesda, 4954 North Palmer Road, Bethesda, MD 20889-5630 (e-mail:

Received 21 May, 2017

Accepted 5 May, 2018

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The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the United States Air Force, the United States Army, the Department of Defense, or the U.S. Government. Title 17 U.S.C. 101 defines a United States Government work as “a work prepared by a military service member or employee of the United States Government as part of that person's official duties.” This work was prepared as part of the official duties of the authors. Title 17 U.S.C. 105 provides that “Copyright protection under this title is not available for any work of the United States Government.”

Salary funding was provided by the United States Department of Defense.

The authors report no conflicts of interest relevant to this article to disclose.

© 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,