Trophic feedings for parenterally fed infants.
BACKGROUND
Because of concern that feedings may increase the risk of necrotizing enterocolitis, some high-risk infants have received prolonged periods of parenteral nutrition without enteral feedings. Providing trophic feedings (small volume feedings given at the same rate for at least 5 days) during this period of parenteral nutrition was developed as a strategy to enhance feeding tolerance and decrease time to reach full feedings. Whether trophic feedings result in better outcomes than initially withholding feedings or providing progressively increasing feedings can be established only in proper clinical trials.


OBJECTIVE
1. For high-risk neonates receiving parenteral feedings, to assess the effect of trophic feeding compared to no enteral nutrient intake on measures of feeding tolerance and neonatal outcome.2. For high-risk neonates receiving parenteral feedings to assess the effect of trophic feedings compared to a specific initial feeding regimen involving a greater enteral nutrient intake on measures of feeding tolerance and neonatal outcome.


METHODS
Searches were performed of MEDLINE (1966 - June 2004), CINAHL (1982 - June 2004), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), abstracts and conference proceedings, references from relevant publications in the English language, and studies identified by personal communication.


METHODS
Only randomized or quasi-randomized clinical trials were considered. Trials were included if they enrolled high-risk infants randomly assigned to receive trophic feedings (defined as dilute or full strength feedings providing < = 25 kcal/kg/d for > = 5d) compared to either 1) no enteral nutrient intake (no feedings or water only) or 2) a specific feeding regimen involving a greater enteral intake of formula or human milk than with trophic feedings.


METHODS
The two reviewers reached consensus for inclusion of trials. Data regarding clinical outcomes were extracted and evaluated by the two reviewers independently of each other. Authors were contacted as needed and feasible to clarify or provide missing data. The specific data that were needed were requested in writing.


RESULTS
1. Trophic feedings vs. no feedings (10 trials): Among infants given trophic feedings, there was an overall reduction in days to full feeding (weighted mean difference [WMD] = -2.6 [95% confidence limits = -4.1, -1.0]), total days that feedings were held (WMD = -3.1 [-4.6, -1.6]), and total hospital stay (WMD = -11.4 [-17.2, -5.7] compared to infants given no enteral nutrient intake. Tests for heterogeneity were significant in analyses of days to full enteral feedings, days to regain birth weight, days of phototherapy, and hospital stay. There was no significant difference in necrotizing enterocolitis, although the findings do not exclude an important effect (relative risk = 1.16 [0.75, 1.79]; risk difference = 0.02 [-0.03, 0.06].2. Trophic feedings vs. advancing feedings (one trial): Infants given trophic feedings required more days to reach full enteral feeding (13.4 [8.2, 18.6]) and tended to have a longer hospital stay (11.0 [-1.4, 23.4]) than did infants given advancing feedings. With only eight total cases of necrotizing enterocolitis, trophic feedings were associated with a marginally significant reduction in necrotizing enterocolitis (relative risk =0.14 [0.02, 1.07]; risk difference = -0.09 [-0.16, -0.01].


CONCLUSIONS
In both comparisons, the group with the greater enteral intake (trophic feedings in the first comparison and advancing feedings in the second comparison) required significantly less time to reach full feedings and had a significant or near significant reduction in hospital stay. In both comparisons, the group with the greater intake also had a higher incidence of necrotizing enterocolitis although the difference was not statistically significant. The concern is greatest for the advancing feeding regimen. Even when trophic feedings were compared to no feedings, the relative risk for necrotizing enterocolitis was 1.16 (0.75 - 1.79), a finding consistent with a 16% increase in necrotizing enterocolitis and a number needed to harm of 50. A true increase of this magnitude might outweigh any short- or long-term benefits of trophic feedings. Moreover, the 95% confidence interval does not exclude the possibility that trophic feedings increase necrotizing enterocolitis by as much as 79% with a number needed to harm of 17. Whether no feedings, trophic feedings, or advancing feedings should initially be used is difficult to discern for a variety of reasons--the inherent difficulty of assessing enteral feedings in high-risk infants, the limited sample size and methodologic limitations of most studies to date, unexplained heterogeneity with respect to a number of outcomes, the potential for bias to affect the findings in unblinded studies, and the large number of infants who must be studied to assess the effect on necrotizing enterocolitis. One or more large, well designed, multi-center trials are needed to compare these approaches to early feeding with respect to important clinical outcomes. A conclusive evaluation would assess effects on not only the survival rate without necrotizing enterocolitis prior to discharge from the neonatal unit but also on the survival rate without severe gastrointestinal or neurodevelopmental disability at >= 18 months age.
Tyson
J E
JE
Pediatrics, University of Texas at Houston Medical School, 6431 Fannin, Suite 2.106, Houston, TX 77030, USA. Jon.E.Tyson@uth.tmc.edu
Kennedy
K A
KA
D004750:Enteral Nutrition / Q000379:methods*; D020345:Enterocolitis, Necrotizing / Q000517:prevention & control; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D010288:Parenteral Nutrition; D016032:Randomized Controlled Trials as Topic