Cesarean section and antibiotic use found to be associated with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an emergent disease with unclear environmental causes. In the few studies of the epidemiology of EoE, male sex and white race have been identified as risk factors. A recent report suggested that cesarean section and early life antibiotic use may increase the risk of EoE, but other studies have not specifically looked at these factors, nor have they examined associations between early life gastrointestinal symptoms and EoE. The aim of this study was to investigate associations between EoE and dietary, environmental, and medical exposures during infancy. Subjects and controls ages 1-5 years old were recruited from the pediatric clinics at the Massachusetts General Hospital. EoE cases were identified by a systematic review of pediatric gastroenterology and allergy clinic visits (by International Classification of Diseases, Ninth Revision codes) between March 2011 and May 2012, and a review of all age-eligible endoscopy procedure visits between January 2008 and May 2012. A diagnosis of EoE was based on endoscopy findings of 15 eosinophils in any high-powered field on esophageal biopsy specimens while the subject was on adequate proton-pump inhibitor therapy ( 1 mg/kg/d for 6 weeks). Subjects were excluded if they had known eosinophilic gastroenteritis, inflammatory bowel disease, or any systemic hypereosinophilic syndromes. Control subjects were recruited from the Pediatric Ambulatory Care Clinic well-child and followup visits. This clinic has a comparable demographic profile to the specialty clinics, with a similar percentage of patients covered by state-assisted health insurance. Control subjects were excluded if they had symptoms suggestive of undiagnosed EoE, including feeding difficulty, frequent vomiting, frequent chest and/or abdominal pain, or dysphagia. Frequency matching of controls was performed for a family history of atopy and for sex. Approval for this study was given by the Massachusetts General Hospital Institutional Review Board. The parent of each subject completed a questionnaire at the time of a clinic visit or via electronic mail. The screening and study questionnaire included questions extracted from the International Study of Asthma and Allergies in Childhood study questionnaires. Study data were collected and managed by using REDCap electronic data capture tools hosted at Massachusetts General Hospital. Characteristics of subjects and controls were compared by the Fisher exact test for dichotomous variables and by the Mann-Whitney 2-sample statistic for continuous variables. Odds ratios (OR) were calculated by logistic regression. The only significant demographic difference between the groups was age; therefore, analyses were adjusted for age, and for the frequency matching variables (atopic family history and sex). To explore mediators of associations found, additional analyses of timing of dietary introduction were adjusted for history of formula intolerance, and analyses of mode of delivery and early life antibiotic use were adjusted for personal history of atopy. Calculations were done with STATA SE 11.2 (College Station, Texas). Twenty-five subjects with EoE and 74 controls were enrolled; 14 subjects were excluded because of symptoms that could be suggestive of undiagnosed EoE. Questionnaires were completed by 89% and 85% of approached subjects and controls, respectively. As seen in Table I, demographic characteristics of subjects and controls were similar, except that the subjects were younger (median 41 vs 51 months). The subjects with EoE were more frequently born by cesarean section than were the controls (60% vs 34%; P 1⁄4 .03) and had a significantly higher rate of antibiotic use in the first year of life (67% vs 33%; P 1⁄4 .004), differences that were significant when adjusting for age, family history of atopy, and sex. (Tables I and II). After also adjusting for a personal history of atopy, the subjects still had increased odds of antibiotic use in the first year of life (OR 3.61 [95% CI, 1.11e11.74]; P 1⁄4 .03), although the relationship with mode of delivery was no longer statistically significant (OR 2.69 [95% CI, 0.93e7.83]; P 1⁄4 .07). Patients with EoE reported a significantly higher frequency of signs and symptoms of gastrointestinal allergy early in life. Unexpectedly, lower gastrointestinal tract disease manifestations also were significantly associated with EoE. Specifically, the subjects with EoE had substantially higher rates of hematochezia (22% vs 4%; P 1⁄4 .02) and mucous in the stool (35% vs 7%; P 1⁄4 .002) during the first year of life, although the difference in hematochezia was no longer significant when adjusting for age, a family history of atopy, and sex (P 1⁄4 .07) (Table I). No significant differences were seen between groups on measures of breastfeeding; timing of first solid food introduction; or timing of introduction of dairy, concentrated egg, wheat, meats, corn, or peanuts. Small significant differences in timing of foods typically introduced later in infancy, including baked egg products, tree nuts, shellfish, and fish generally did not persist after adjusting for the use of hypoallergenic formula, although age of introduction of baked egg products and fish remained higher in the subjects than with the controls (see Tables E1 and E2 in this article’s Online Repository at www.jaci-inpractice.org). The aim of this study was to investigate the association between early life exposures with the later development of EoE. We found that cesarean delivery and antibiotic exposure in the first year of life were significantly associated with the development of EoE. The findings with regard to cesarean section and antibiotic use are of similar magnitude to another case-control study of EoE in children up to age 17 years old, despite the differences in ages. The mode of delivery has not otherwise been linked to EoE,