Early versus delayed initiation of progressive enteral feedings for parenterally fed low birth weight or preterm infants.

BACKGROUND Enteral feedings in very-low-birth-weight or sick preterm infants are often delayed for several days or weeks after birth even though delayed enteral feeding could diminish the functional adaptation of the gastrointestinal tract and result in feeding intolerance later. Early initiation of feedings, if well-tolerated, may promote growth and shorten the duration of parenteral nutrition and hospital stay without increasing the risk for necrotizing enterocolitis (NEC). OBJECTIVES For parenterally fed low-birth-weight infants, to assess the effects of early enteral feedings initiated shortly after birth compared to delayed enteral feedings (with similar schedules for advancing feedings in each group). SEARCH STRATEGY Searches were performed of the Oxford Database of Perinatal Trials, the Cochrane Neonatal Review Group registry, MEDLINE, abstracts and conference proceedings, references from relevant publications in the English language, and studies identified by personal communication. SELECTION CRITERIA Only randomized or quasi-randomized clinical trials were considered. Trials were included if 1) they enrolled low birth weight or preterm infants who were all given parenteral nutrition; 2) the infants were randomly assigned to either early enteral feedings (mean or median age <=4 days) or late enteral feedings (>4 days) of formula or breast milk; 3) except when feeding intolerance developed, the feedings were progressively advanced starting within 72 hours after initiating feedings; and 4) the goals for total nutrient intake were similar for both groups. (We did not require the duration or total intake of parenteral nutrients to be similar for both groups because these variables may be affected by the age at which feedings are initiated.) DATA COLLECTION AND ANALYSIS The two reviewers reached consensus for inclusion of trials. Data regarding clinical outcomes were extracted and evaluated by two reviewers (JET and KAK) independently. Authors were contacted as needed and feasible to clarify or provide missing data. The specific data that were needed were requested in writing and by telephone. MAIN RESULTS Only two small studies were identified (one with 60 patients and one with 12 patients). Five randomized trials were excluded because parenteral nutrition was not provided or because the groups were assigned to receive different parenteral intakes as well as different enteral intakes. An additional unpublished small trial was excluded because both groups were fed "late" according to our categorization. Because there were no clinical outcomes which were reported in both of the included studies, no meta analysis of the results was performed. Based on the results of the individual studies, early feedings had no significant effect on weight gain, necrotizing enterocolitis, mortality, or age at discharge, although important effects cannot be excluded with the small number of patients studied. Some benefits of early feedings were noted in the larger trial (Davey) -- fewer days on parenteral nutrition, fewer infants who were treated with gastric suction and interruption of feedings, fewer infants with sepsis evaluations, and fewer infants with percutaneous central venous catheters. REVIEWER'S CONCLUSIONS The benefits and hazards of early and delayed feedings have received very little study in clinical trials, and the effects on major clinical outcomes, including necrotizing enterocolitis and death, remain uncertain. With the availability of parenteral nutrition in contemporary neonatal units, it is unclear whether high-risk infants should receive early or delayed feedings.