Treating feeding intolerance with an enteral solution patterned after human amniotic fluid: a randomized, controlled, masked trial

Objective: Feeding intolerance is a common problem in the neonatal intensive care unit (NICU) and some cases might he causally related to atrophic changes in the small bowel mucosa. We, speculated that for such patients, feeding tolerance might improve after oral administration of enterocyte growth factors in a sterile, isotonic solution patterned after amniotic fluid. Study Design: Twenty neonates meeting criteria for feeding intolerance were eligible for this trial. They were randomized to either Group 1 (test, solution) or Group 2 (control). Group 1 received 2.5 ml of test solution/kg every 3 h by oral-gastric or nasal-gastric (OG/NG) tube. This was begun when the patient was NPO because of feeding intolerance and continued until 80 ml/k/day of milk feedings were tolerated, or for a maximum of 7 days. Group 2 received a sham OG/NG administration every 3 h, until 80 ml/k/day of milk feedings were tolerated, or for a maximum of 7 days. Only the bedside nurse and the NICU pharmacist were aware which patients received the test solution and which received the sham administrations. The volumes of milk feedings were increased by order of the attending neonatologist and nurse practitioner. The study outcome was enteral calories/kg/day during and for 7 days after the cessation of the treatments. Results: Eleven patients were randomized to receive the test solution and nine to receive sham administrations. At study entry, the two groups were not different in gestational age, postnatal age, signs of feeding intolerance or cal/k/day taken enterally during the previous 3 days. The study doses were given for an average of just under 6 days (range, 2 to 7 days). During the week following the administrations, the test solution recipients trended toward more enteral calories. Specifically, they had an increase averaging 78+/-20.8 cal/k/day more than before the study, whereas the sham recipients had an increase averaging 55.9+/-33 cal/k/day more than before the study (P = 0.05 for a one-sided test and P = 0.10 for a two-sided test). The test solution recipients also had a trend toward fewer formula changes than did the sham recipients (P = 0.10). Conclusion: In this small, randomized, controlled, masked trial, the administration of a sterile, non-caloric, growth factor containing solution patterned after human amniotic fluid was associated with trends that we interpret,is reflecting better tolerance of milk feedings. On this basis, we suggest that a phase III efficacy trial should be accomplished, using the present data for sample size calculations.