ABSTRACT: BACKGROUND:Multiple lines of evidence point to the potential importance of early-life environmental factors in the rapid increase in the incidence of eosinophilic esophagitis (EoE), but potential exposures have not been extensively studied. OBJECTIVE:We sought to assess the association between prenatal, intrapartum, and postnatal factors and the development of pediatric EoE using a case-control study. METHODS:Patients with EoE were recruited from an existing registry at Cincinnati Children's Hospital Medical Center (CCHMC). Population-based community control subjects were identified from a separate CCHMC registry. Mothers of study subjects were contacted and completed a Web-based questionnaire. Crude and adjusted models were used to estimate associations. RESULTS:Mothers of 127 cases and 121 control subjects were included. We observed a positive association between several early-life factors and EoE, including prenatal (maternal fever: adjusted odds ratio [aOR], 3.18; 95% CI, 1.27-7.98; preterm labor: aOR, 2.18; 95% CI, 1.06-4.48), intrapartum (cesarean delivery: aOR, 1.77; 95% CI, 1.01, 3.09), and infancy (antibiotic use: aOR, 2.30; 95% CI, 1.21-4.38; use of an acid suppressant: aOR, 6.05; 95% CI, 2.55-14.40) factors. We observed an inverse association between having a furry pet in infancy and EoE (aOR, 0.58; 95% CI, 0.34-0.97). No associations were observed for breast-feeding or maternal multivitamin or folic acid supplement use. CONCLUSION:Early-life factors, including maternal fever, preterm labor, cesarean delivery, and antibiotic or acid suppressant use in infancy, were associated with risk of pediatric EoE; having a pet in the home was protective. These results add to growing evidence that implicate early-life exposures in EoE pathogenesis.