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This retrospective study was conducted to determine the incidence of cholestasis and liver failure in patients with intestinal resection in the neonatal period who subsequently become dependent on parenteral nutrition support and to assess the significance of associated clinical factors-gestational age, birth weight and length; length of bowel resected; presence of ileocecal valve; enteral feeding history; and infection to the incidence and severity of cholestasis.Retrospective chart review of all patients in a single institution from May 1984 to February 1997 with neonatal small intestinal resection dependent on parenteral nutrition for at least 3 months.Forty-two patients fitting the inclusion criteria were the subjects of this review. Cholestasis developed in 28 (67%) while they were receiving parenteral nutrition (direct serum bilirubin more than 2mg/dl). In 21, the elevated direct bilirubin normalized while patients continued to receive parenteral nutrition. Seven patients progressed to liver failure. In 14 patients, serum direct bilirubin never rose above 2 mg/dl. The cholestatic patients did not differ from the noncholestatic in gestational age, birth weight, and length; primary diagnosis; length of bowel resected; or presence of ileocecal valve. The duration of dependence on parenteral nutrition was longer in noncholestatic (33.2 ± 9 months) than in cholestatic patients progressing to liver failure (19.4 ± 3 months) or in cholestatic patients who recovered (16.1 ± 1.9 months) (p < 0.05). Invasive fungal or bacterial infections occurred in all but one noncholestatic patient. The number of infections per patient was similar in all groups. The mean age (days) at first infection was significantly younger in cholestatic patients progressing to liver failure (28.5 ± 5) and cholestatic patients who recovered (48.2 ± 14.2) than in noncholestatic patients(167 ± 43.2) (p 0.01). Infection preceded the onset of cholestasis in all but 3 patients by an average of 13.5 days. Infecting organisms and site of first infection were similar in all patients.Cholestasis is common in infants with neonatal intestinal resection. Liver failure develops in 16.6%. Bacterial infection early in life characterized the cholestatic patients, and cholestasis developed shortly after the first infection in 90% of patients.