Publications (2)2.25 Total impact
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ABSTRACT: Feeding intolerance is a common problem in the neonatal intensive care unit (NICU) and some cases might be 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. 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. 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). 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 as 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.Journal of Perinatology 02/2007; 27(1):28-31. · 2.25 Impact Factor
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ABSTRACT: Certain growth factors exist in relatively high concentrations in fluids swallowed by the fetus and neonate; namely amniotic fluid, colostrum, and human milk. We postulated that; 1) after these factors are swallowed they are not enterally digested into non-functional units, but remain biologically active, 2) the ingested factors bind to specific receptors on the luminal surface of villous enterocytes where they exert a topical antiapoptotic effect, 3) the ingested factors are not absorbed into the blood and have no systemic effect, 4) when a fetus is delivered prematurely and amniotic fluid swallowing abruptly ceases, if the patient is NPO (thus receiving no growth factors from colostrum or milk) disuse atro- phy of the small bowel mucosa can begin, leading to feeing intolerance once milk feed- ings are started. We developed a sterile, isotonic, growth factor-containing solution, sim- ulating second trimester amniotic fluid. We called the fluid SAFEstart® (an acronym for Simulated, Amniotic Fluid for Enteral administration); a patent was obtained by the Uni- versity of Florida. The growth factors contained in SAFEstart were concentrated 10 fold above natural amniotic fluid, so that 20 mL/k/d of SAFEstart would provide the amount of growth factors ingested by a fetus swallowing 200 mL/k/d of amniotic fluid. Preclini- cal studies on stability and digestion were followed by six clinical trials. Whether mixed with human milk, preterm infant formulas, or kept by itself, SAFEstart was stable for at least three weeks frozen, with only minimal and gradual degradation of activity in the weeks thereafter. No evidence of absorption of factors into the blood and no systemic effects were observed after usage. Four clinical trials have examined its use to prevent feeding intolerance and two additional trials have examined its treatment use among neonates with established feeding intolerance. CONCLUSIONS: One hundred-twenty neonates have now participated in six SAFEstart trials. It is feasible to administer 20 mL/k/d of SAFEstart (2.5 mL/k every 3 h) to ill preterm neonates, and it is well tolerated, with no safety issues uncovered to date. Early controlled studies suggest efficacy in pre- venting feeding intolerance and also in treating established feeding intolerance, presum- ably by topical actions of relevant growth factors on the small bowel mucosa. Multicen- tered randomized, placebo controlled trials are now needed to estimate the risks and benefits of administering SAFEstart to neonates who are otherwise NPO.