Feeding strategies for premature infants: randomized trial of gastrointestinal priming and tube-feeding method. Early minimal feedings promote growth in critically ill premature infants. Effect of minimal enteral feeding on splanchnic uptake of leucine in the postabsorptive state in preterm infants. The early use of minimal enteral nutrition in extremely low birth weight newborns. Beneficial effects of early hypocaloric enteral feeding on neonatal gastrointestinal function: preliminary report of a randomized trial. Randomised controlled study of clinical outcome following trophic feeding. Minimal enteral feeding, fetal blood flow pulsatility, and postnatal intestinal permeability in preterm infants with intrauterine growth retardation. Gastrointestinal priming prior to full enteral nutrition in very low birth weight infants.
Data on enteral feeding management of premature infants are limited and often not the subject of randomized clinical trials. Several small studies suggest benefits from the early initiation of feeding, but do not assess the combined effects of time of initiation of feeding, tube-feeding method, and type of milk used. Either singly or in combination, these treatments may affect growth, bone mineralization, biochemical measures of nutritional status, and feeding tolerance, and, ultimately, the duration of hospitalization.
                A total of 171 premature infants, stratified by gestational age (26 to 30 weeks) and diet (human milk or preterm formula) were assigned randomly among four treatment combinations in a balanced two-way design comparing the presence or absence of gastrointestinal (GI) priming for 10 days and continuous infusion versus intermittent bolus tube-feeding.
                The major outcome, time required for infants to attain full oral feeding, was similar among treatments. GI priming was not associated with any measured adverse effect and was associated with better calcium and phosphorus retention, higher serum calcium and alkaline phosphatase activity, and shorter intestinal transit times. The bolus tube-feeding method was associated with significantly less feeding intolerance and greater rate of weight gain than the continuous method. In addition, the greater the quantity of human milk fed, the lower the morbidity.
                Early GI priming with human milk, using the bolus tube-feeding method, may provide the best advantage for the premature infant. Critically ill premature infants requiring mechanical ventilation and an umbilical artery catheter usually do not receive enteral feedings during the acute phase of their illness. We studied the safety and benefit of early minimal enteral feedings during this time in a prospective, controlled, and randomized study. Twenty-nine infants were randomly assigned to receive only standard intravenous fluid and nutrition (nothing per OS, NPO group; n = 13), or in addition to receive small-volume hypocaloric continuous feedings (1 ml/kg/h), beginning at 24 h of age (early-feeding group; n = 16). Standard enteral feedings were begun in both groups at the resolution of the acute phase of the illness and advanced by protocol. The two groups were of comparable birth weight, gestational age, and Apgar scores. There were no significant differences in the episodes of feeding intolerance. Two infants in the NPO group developed clinical signs of necrotizing enterocolitis. Serum diamine oxidase and somatomedin C were measured weekly until 30-60 days of age and were not different between the two groups. The early-feeding group required fewer days to reach 120 ml/kg/day enteral intake (early-feeding group 10 +/- 3 days, NPO group 13 +/- 4 days; p < 0.05). On day 30 of life the early-feeding group was 223 +/- 125 g above birth weight, while the NPO group was 95 +/- 161 g above birth weight (p < 0.05). The average intake (kcal/kg/day) from day 6 to day 30 was not different between the two groups. We conclude that early minimal feedings in critically ill very-low-birth-weight infants requiring mechanical ventilation are well tolerated and result in reduced time to reach 120 ml/kg/day of enteral feeding and in a greater weight gain by day 30 of life. We conducted a controlled, randomized trial to study the effect of minimal enteral feeding on leucine uptake by splanchnic tissues, as an indicator of maturation of these tissues, in preterm infants in the first week of life. Within a few hours after birth, while receiving only glucose, a primed constant infusion of [1-(13)C]-leucine was started and continued for 5 h via the nasogastric tube, whereas 5,5,5 D3-leucine was infused intravenously (for both tracers, priming dose 2 mg/kg, continuous infusion 2 mg/kg/h). Patients were thereafter randomized to receive solely parenteral nutrition (C), parenteral nutrition and 20 mL breast milk/kg/d (BM), or parenteral nutrition and 20 mL formula/kg/d (F). On d 7, the measurements were repeated, after discontinuing the oral intake for 5 h. Fourteen infants were included in group C, 12 in group BM, and 12 in group F. There was no difference in energy intake or nitrogen balance at any time. On d 1, plasma enrichment for the nasogastric tracer was lower than for the intravenous tracer for all three groups, both for leucine and for alpha-keto-isocaproic acid. On d 7, the enrichment for leucine and alpha-keto-isocaproic acid for the nasogastric tracer was lower than for the intravenous tracer for the groups BM and F (BM: 3.65 +/- 1.20 nasogastric versus 4.64 +/- 0.64 i.v.; F: 4.37 +/- 1.14 nasogastric versus 5.21 +/- 0.9 i.v.). In the control group, there was no difference between tracers. The lower plasma enrichment for the nasogastric tracer compared with the intravenous tracer suggests uptake of leucine by the splanchnic tissues. We conclude that minimal enteral feeding--even in low volumes of 20 mL/kg/d--increases the leucine uptake by the splanchnic tissue. We speculate that this reflects a higher protein synthesis of splanchnic tissues in the groups receiving enteral nutrition. To gather information regarding the efficacy of early minimal enteral nutrition on overall feeding tolerance in extremely low birth weight infants.
                Prospective randomized controlled trial comparing the early use of minimal enteral nutrition in extremely low birth weight infants from day 2 to day 7 vs control infants. On day 8, feeding volume in both groups were advanced by 10 ml kg(-1) day(-1) until full enteral feedings were reached. Time to full feeds, number of intolerance episodes, anthropometric measurements, peak total bilirubin levels, incidence of necrotizing enterocolitis and incidence of sepsis were compared between the two groups with t-test and chi (2) test.
                Eighty-four infants were enrolled in the study but only 61 infants completed the feeding protocol. No statistically significant differences were found between the groups with regards to growth patterns, feeding tolerance, mortality, length of hospital stay and incidence of sepsis and necrotizing enterocolitis.
                Early minimal enteral nutrition use in extremely low birth weight infants did not improve feeding tolerance. In a prospective randomized trial, we studied the effects of early hypocaloric enteral feedings (PO) begun at 48 hours of age in 19 infants compared with 20 infants who received no enteral feedings (NPO) for at least the first 9 days of life. Both groups initially received the majority of their calories by parenteral alimentation. The groups were similar with respect to birth weight, gestational age, sex, Apgar score, and major neonatal diagnoses. The early enteral feeds proved to be significantly beneficial without an increased incidence of complications. The PO group reached full enteral feedings faster than the NPO group (31.2 vs 47.3 days). The PO group had a greater decline in serum bilirubin concentration over the first 2 weeks of life and spent less time under phototherapy (6.8 vs 9.5 days). Less cholestasis was observed among the PO infants (6.7% vs 33%), and peak direct bilirubin levels were also lower (0.7 vs 2.5 mg/dL). Osteopenia of prematurity, manifested by significantly lower alkaline phosphatase activity, was also decreased in the PO group, perhaps because of greater calcium intake during the first month among PO infants (1.3 vs 0.8 g). Compared with complete bowel rest, early onset of hypocaloric enteral feedings has beneficial effects on indirect hyperbilirubinemia, cholestatic jaundice, and metabolic bone disease of very low birth weight infants. To determine the effect of trophic feeding on clinical outcome in ill preterm infants.
                A randomised, controlled, prospective study of 100 preterm infants, weighing less than 1750 g at birth and requiring ventilatory support and parenteral nutrition, was performed. Group TF (48 infants) received trophic feeding from day 3 (0.5-1 ml/h) along with parenteral nutrition until ventilatory support finished. Group C (52 infants) received parenteral nutrition alone. "Nutritive" milk feeding was then introduced to both groups. Clinical outcomes measured included total energy intake and growth over the first six postnatal weeks, sepsis incidence, liver function, milk tolerance, duration of respiratory support, duration of hospital stay and complication incidence.
                Groups were well matched for birthweight, gestation and CRIB scores. Infants in group TF had significantly greater energy intake, mean difference 41.4 (95% confidence interval 9, 73.7) kcal/kg p=0.02; weight gain, 130 (CI 1, 250) g p = 0.02; head circumference gain, mean difference 0.7 (CI 0.1, 1.3) cm, p = 0.04; fewer episodes of culture confirmed sepsis, mean difference -0.7 (-1.3, -0.2) episodes, p = 0.04; less parenteral nutrition, mean difference -11.5 (CI -20, -3) days, p = 0. 03; tolerated full milk feeds (165 ml/kg/day) earlier, mean difference -11.2 (CI -19, -3) days, p = 0.03; reduced requirement for supplemental oxygen, mean difference -22.4 (CI-41.5, -3.3) days, p = 0.02; and were discharged home earlier, mean difference -22.1 (CI -42.1, -2.2) days, p = 0.04. There was no significant difference in the relative risk of any complication.
                Trophic feeding improves clinical outcome in ill preterm infants requiring parenteral nutrition. To study the effect of minimal enteral feeding (MEF) on intestinal permeability and feeding tolerance in preterm infants with intrauterine growth retardation (gestational age < 37 weeks, birth weight for gestational age p < 10). Furthermore, to determine whether fetal blood flow pulsatility or intestinal permeability predict feeding tolerance in these infants.
                Randomised controlled trial.
                Within 48 hours of birth, infants were randomised to MEF or no enteral feeding (NEF) for five days in addition to parenteral feeding. Intestinal permeability was measured by the sugar absorption test before (SAT1) and after (SAT2) the study. The sugar absorption test measured the urinary lactulose/mannitol (LM) ratio after oral ingestion of a solution (375 mosm) containing mannitol and lactulose. Charts of all infants were assessed for measures of feeding tolerance. Fetal blood flow pulsatility index (U/C ratio) was measured within the seven days before birth.
                Of the 56 infants enrolled, 42 completed the study: 20 received MEF and 22 NEF. The decrease in LM ratio (LM ratio 1 - LM ratio 2) was not significantly different between the two groups (0.25 v 0.11; p = 0.14). Feeding tolerance, growth, and incidence of necrotising enterocolitis were not significantly different between the two groups. Neither the U/C nor the LM ratio 1 predicted feeding tolerance.
                The results suggest that MEF of preterm infants with intrauterine growth retardation has no effect on the decrease in intestinal permeability after birth. Neither fetal blood flow pulsatility nor intestinal permeability predicts feeding tolerance. Priming of the gastrointestinal (GI) tract with low-volume feedings before giving full enteral feedings to very premature, high-risk infants is a controversial practice. We designed a study of infants weighing less than 1,250 g and receiving total parenteral nutrition to determine whether GI priming would hasten weight gain, improve tolerance of subsequent feedings, enhance nutritional status, and increase serum concentration of gastrin, a hormone trophic for intestinal growth. Infants were randomly assigned to receive total parenteral nutrition (TPN) alone (N = 21) or GI priming plus TPN (N = 19) for 12 days beginning on day 3 of life. Full-strength premature infant formula was used for priming. Both groups received the same total nutrition. Beginning on day 15, feedings in both groups were increased daily to a maximum of 120 kcal/kg/day on day 20, where they were maintained until day 30. After day 30, the feedings were modified according to the infants' condition. The groups did not differ in birth weight, gestational age, or 5-min Apgar scores. GI-primed infants had improved feeding tolerance after day 20 and a faster rise in serum gastrin during the initial phase of the study. There was no significant difference in weight gain. GI priming improves tolerance of feedings, accelerates rate of rise of serum gastrin during the first weeks of life, and does not increase the risk of feeding complications when compared to TPN alone. This may lead to more rapid maturation of the GI tract in primed infants.
The available trial data do not provide evidence of important beneficial or harmful effects of early trophic feeding for very preterm or very low birth weight infants. The applicability of these findings to extremely preterm, extremely low birth weight or growth restricted infants is limited. Further randomised controlled trials would be needed to determine how trophic feeding compared with enteral fasting affects important outcomes in this population.