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The objective of this case-control study nested within a surveillance study conducted at 3 hospitals (Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's Hospital of New Orleans, New Orleans, LA; and Hasbro Children's Hospital, Providence, RI) was to identify risk factors for rotavirus gastroenteritis requiring hospitalization.Cases were children ≤59 months of age who were admitted with acute gastroenteritis (AGE) and found to have rotavirus infection. Controls were selected from a birth certificate registry (Cincinnati and Providence) or a registry of patients from a large practice consortium in 11 locations (New Orleans).Three hundred forty-nine rotavirus-infected cases and 1242 control subjects were enrolled. Breast feeding was protective against hospitalization for rotavirus AGE for infants <6 months of age. (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.2–13.2). Low-birth-weight (<2500 g) infants had increased risk for hospitalization even beyond the first few months of life (OR, 2.8; 95% CI, 1.6–5.0). Children in child care were more likely to be hospitalized for rotavirus AGE than those cared for at home, particularly those ≥24 months of age (OR, 3.0; 95% CI, 1.8–5.3). Other characteristics associated with rotavirus AGE hospitalization were children <24 months of age covered by Medicaid or without insurance (OR, 2.1; 95% CI, 1.4–3.2) and having another child in the house <24 months of age (OR, 1.6; 95% CI, 1.1–2.3). The data suggest that maternal age <25 years (OR, 1.4; 95% CI, 1.0–2.0) and a mother with less than a high school education (OR, 1.5; 95% CI, 1.0–2.3) may also increase risk of rotavirus hospitalization.There are socioeconomic and environmental factors and aspects of the child's medical and dietary history that identify children at risk for hospitalization with rotavirus AGE.