BACKGROUND: Although many therapeutic interventions are necessary for the survival of the preterm infant, understanding the potential effects of these treatments is important to decrease the rate of necrotizing enterocolitis (NEC) in preterm infants. OBJECTIVE: The aim of this study was to examine the relationship between preterm infant treatments administered prior to the development of NEC, specifically the number of packed red blood cell (PRBC) transfusions, weeks of antibiotic therapy for nosocomial infection, and number of mechanical ventilation days, and the development of NEC in preterm infants. METHODS: A retrospective cohort controlled study design examining 4 years of raw data of preterm infants between the gestational ages of 23 and 30 6/7 weeks was used. Of the 549 infants, there were 65 cases of NEC. Using logistic regression, the relationship between NEC and PRBC transfusions administered prior to NEC, number of mechanical ventilation days prior to NEC, and number of weeks of antibiotic therapy for nosocomial infections experienced prior to NEC (proxy for nosocomial infection) were examined. RESULTS: Preterm infants from 23 to 30 6/7 weeks who developed NEC experienced significantly more PRBC transfusions and more weeks of antibiotic therapy for nosocomial infection prior to the development of NEC than did infants who did not develop NEC. There was no relationship between mechanical ventilation days and the development of NEC. DISCUSSION: Future research should focus on causal relationships between NEC and PRBC administration and the reduction of nosocomial infections in preterm infants to minimize risk for NEC in this population.