Enhanced weight gain in preterm infants receiving lactase-treated feeds: a randomized, double-blind, controlled trial. Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants. Establishing enteral feeding in preterm infants with feeding intolerance: a randomized controlled study of low-dose erythromycin. Early minimal feedings promote growth in critically ill premature infants. Randomized controlled trial of slow vs rapid enteral feeding advancements on the clinical outcomes of preterm infants with birth weight 750-1250 g. Influence of erythromycin on establishment of feeding in preterm infants: observations from a randomised controlled trial. Erythromycin fails to improve feeding outcome in feeding-intolerant preterm infants. Erythromycin and feeding intolerance in premature infants: a randomized trial. Enteral feeding of premature infants with Lactobacillus GG. Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Slow versus fast enteral feed advancement in very low birth weight infants: a randomized control trial.
To evaluate whether lactase-treated preterm feeds enhance weight gain and feeding tolerance in premature infants.
                Prospective, double-blind, randomized, controlled trial involving 130 infants (26-34 weeks postconceptual age). The primary outcome variable was weight gain (g per day). Other outcome measures included gains in length and head circumference, biochemical indexes of nutritional status, feeding intolerance, and incidence of necrotizing enterocolitis.
                On study day 10, weight gain (mean +/- SEM) of the treatment group was significantly greater (P <.05) than that of the control group (20.4 +/- 1.8 g/day vs 15.5 +/- 1.6 g/day). By study end, no significant difference in weight gain between treatment and control groups was observed. The difference in serum albumin level was significant at study day 14, with a value of 29.3 +/- 0.6 g/L in the treatment group compared with 27.1 +/- 0.4 g/L in the control group (P <.01). There were no significant differences in caloric intakes, length gain, head circumference gain, feeding intolerance, and incidence of necrotizing enterocolitis.
                Weight gain may be enhanced during the period of low functional lactase activity of prematurity by addition of lactase to preterm feeds. No adverse effects on feeding tolerance resulted from this treatment. To evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants.
                A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 56 preterm infants (< 1500 g) consecutively admitted to the neonatal unit. The infants were randomly allocated by minimisation to receive oral erythromycin (12.5 mg/kg, every six hours for 14 days) or an equivalent volume of placebo solution (normal saline) if they received less than half the total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral route on day 14 of life. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were compared between the two groups. Potential adverse effects of oral erythromycin and complications associated with parenteral nutrition were assessed as secondary outcomes.
                Twenty seven and 29 infants received oral erythromycin and placebo solution respectively. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were significantly shorter in the group receiving oral erythromycin than in those receiving the placebo (p < 0.05, p < 0.05 and p < 0.0001 respectively). There was also a trend suggesting that more infants with prolonged feed intolerance developed cholestatic jaundice in the placebo than in the oral erythromycin group (10 v 5 infants). None of the infants receiving oral erythromycin developed cardiac dysrhythmia, pyloric stenosis, or septicaemia caused by multiresistant organisms.
                Oral erythromycin is effective in facilitating enteral feeding in preterm very low birthweight infants with moderately severe gastrointestinal dysmotility. Treated infants can achieve full enteral feeding 10 days earlier, and this may result in a substantial saving on hyperalimentation. However, until the safety of erythromycin has been confirmed in preterm infants, this treatment modality should remain experimental. Prophylactic or routine use of this medication for treatment of mild cases of gastrointestinal dysmotility is probably not warranted at this stage. A prospective, double-blind, randomized, controlled trial was conducted to evaluate the effect of low-dose erythromycin on the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance.
                Two groups of preterm infants (birth weight </= 1500 g) with feeding intolerance were randomized to either low-dose erythromycin (5 mg/kg every 8 hours) or 5% dextrose placebo, both of which were discontinued 1 week after full enteral feedings were tolerated. The primary outcome variable was the time taken to attain full enteral feedings of at least 130 mL/kg/d.
                The gestational age at birth was similar in the two groups (erythromycin, 27.1 +/- 1.9 weeks; placebo, 27.5 +/- 2.9 weeks). The mean birth weight of the erythromycin group was lower (806.3 +/- 215.6 g) than the placebo group (981.4 +/- 285.4 g; P = 0.18), and included more infants who were small for gestational age (4/13 = 31% versus 1/11 = 9%; P = 0.224). There was no difference between the two groups with regard to the volume of feedings they were receiving at the time of enrollment. Reduction in symptoms of gastroesophageal reflux was similar in the two groups. 3 of 13 in the erythromycin group and 4 of 11 in the placebo group improved during the study (P = 0.565). The mean time to attain full enteral feedings after enrollment was 24.9 + 2.9 days in the erythromycin group and 30.8 +/- 4.1 days in the placebo group, a difference that did not reach statistical significance (P = 0.17).
                Low-dose erythromycin did not reduce the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance. Gastroesophageal reflux decreased as a consequence of maturation of the gastrointestinal tract and not because of erythromycin. These preliminary results justify verification in larger multicenter trials. 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. To evaluate the effect of slow vs rapid rates of advancement of enteral feed volumes on the clinical outcomes in preterm infants with 750-1250 g birth weight.
                A total of 92 stable neonates 750-1250 g and gestational age <32 weeks were randomly allocated to enteral feeding advancement of 20 mL/kg/d (n = 46) or 30 mL/kg/d (n = 46). The primary outcome was days to reach full enteral feeding, defined as 180 mL/kg/d. Secondary outcomes included rates of necrotizing enterocolitis (NEC) and culture-proven sepsis, days of parenteral nutrition (PN), length of hospital stay, and growth end points.
                Neonates in the rapid-feeding advancement group achieved full enteral volume of feedings earlier than the slower advancement group. They received significantly fewer days of PN, exhibited a shorter time to regain birth weight, and had a shorter duration of hospital stay. The incidence of NEC and the number of episodes of feeding intolerance were not significantly different between the groups, whereas the incidence of culture-proven late-onset sepsis was significantly less in infants receiving a rapid feeding advancement. Excluding infants who were small for gestational age at birth, the incidence of extrauterine growth restriction was significantly reduced in the rapid-advancement group at 28 days and at hospital discharge.
                Rapid enteral feeding advancements in 750-1250 g birth weight infants reduce the time to reach full enteral feeding and the use of PN administration. Rapid-advancement enteral feed also decreases extrauterine growth restriction with improved short-term outcomes for these high-risk infants. To determine the effect of erythromycin on the establishment of enteral feeding in ventilated infants < 31 weeks gestation.
                Erythromycin was randomly allocated as an antimicrobial treatment for the first 7 days of life in 76 infants: 35 received erythromycin and 41 acted as controls. Feed toleration, time taken to establish full enteral feeding, vomiting, prescription of glycerine suppositories and occurrence of necrotising enterocolitis were recorded.
                There were no significant differences between the groups for any of the outcomes. The infants treated with erythromycin reached full feeding at a median (quartile) age of 8 (5-12) days compared with 9 (6-14) days for controls.
                Intravenous erythromycin in antimicrobial doses is unlikely to benefit the introduction of feeding in preterm infants. Approximately half of extremely low birth weight infants have feeding intolerance, which delays their achievement of full enteral feedings. Erythromycin, a motilin receptor agonist, triggers migrating motor complexes and accelerates gastric emptying in adults with feeding intolerance. Few studies have assessed the efficacy of this drug in preterm infants with established feeding intolerance. This study was designed to assess the efficacy of erythromycin in feeding-intolerant infants, as measured by gastric emptying, maturation of gastrointestinal motor patterns, and time to achieve full enteral feedings.
                Subjects were 27 preterm infants who were admitted to the neonatal intensive care unit and who did not achieve full enteral feeding volumes (150 mL/kg/day) within 8 days of the initiation of feedings. In a controlled, randomized, double-blinded clinical trial, infants received intragastric erythromycin or placebo for 8 days without crossover. At study entry, the authors recorded motor activity in the antrum and the duodenum during fasting, in response to intragastric erythromycin (1.5 mg/kg) or placebo, and in response to feeding. Gastric emptying at 20 minutes and transit time from duodenum to anus were determined. Each infant then received erythromycin or placebo for 8 days, and feeding characteristics were prospectively tracked.
                Gastric emptying and characteristics of antroduodenal motor contractions were similar in the two groups, as were the transit times from duodenum to anus. Feeding outcomes were comparable in the two groups.
                Intragastric erythromycin does not improve feeding tolerance in preterm infants with established feeding intolerance because it fails to improve gastrointestinal function in the short or long term. To evaluate the effectiveness of low-dose oral erythromycin to treat feeding intolerance in preterm infants.
                This study was a prospective, double-blind, randomized, placebo-controlled trial on 60 premature infants suffering from feeding intolerance. Thirty infants were given oral erythromycin 1 mg/kg every 8 h and 30 infants were given placebo (normal saline). Randomization was stratified on enrollment according to gestational age whether >32 weeks or <or=32 weeks. The primary end point was the length of time taken to establish full enteral feeding since enrollment. Potential adverse effects associated with erythromycin were also monitored. Groups of each corresponding stratum were compared using two-tail t-test and Mann-Whitney for continuous variables, and chi (2) and Fisher's exact for categorical variables.
                For infants with gestational age >32 weeks, the erythromycin group achieved full enteral feeding earlier than placebo group (10.5+/-4.1 vs 16.3+/-5.7 days, respectively; P=0.01) had fewer episodes of gastric residuals (P<0.05) and shorter duration of parenteral nutrition (PN) (P<0.05). On the other hand, in infants with gestational age <or=32 weeks, there were no significant differences between erythromycin and placebo groups regarding any of these variables.
                Low-dose enteral erythromycin is associated with better tolerance of feeding and shorter duration of PN in infants >32 weeks gestation. A similar effect on younger preterm infants was not demonstrable. The objectives of this study were to determine whether or not the probiotic Lactobacillus GG can colonise the immature bowel of premature infants and if so, does colonisation result in a reduction of the size of the bowel reservoir of nosocomial pathogens such as enterobacteriaceae, enterococci, yeasts or staphylococci, and does colonisation with Lactobacillus GG have any effect on the clinical progress and outcome. Twenty preterm infants with a gestational age of 33 weeks or less who were resident on a neonatal unit were studied from the initiation of milk feeds until discharge. The infants were randomised to receive either milk feeds or milk feeds supplemented with Lactobacillus GG 10(8) colony forming units twice a day for two weeks. The clinical features of the two groups of infants were similar. Orally administered Lactobacillus GG was well tolerated and did colonise the bowel of premature infants. However, colonisation with Lactobacillus GG did not reduce the faecal reservoir of potential pathogens and there was no evidence that colonisation had any positive clinical benefit for this particular group of infants. Although recent reports suggest that supplementation with probiotics may enhance intestinal function in premature infants, the mechanisms are unclear, and questions remain regarding the safety and efficacy of probiotics in extremely low-birth-weight infants.
                The objective was to evaluate the efficacy of probiotics on the digestive tolerance to enteral feeding in preterm infants born with a very low or extremely low birth weight.
                In a bicentric, double-blind, randomized controlled clinical trial that was stratified for center and birth weight, 45 infants received enteral probiotics (Bifidobacterium longum BB536 and Lactobacillus rhamnosus GG; BB536-LGG) and 49 received placebo. The primary endpoint was the percentage of infants receiving >50% of their nutritional needs via enteral feeding on the 14th day of life. A triangular test was used to perform sequential analysis.
                The trial was discontinued after the fourth sequential analysis concluded a lack of effect. The primary endpoint was not significantly different between the probiotic (57.8%) and placebo (57.1%) groups (P = 0.95). However, in infants who weighed >1000 g, probiotic supplementation was associated with a shortening in the time to reach full enteral feeding (P = 0.04). Other than colonization by the probiotic strains, no alteration in the composition of intestinal microbiota or changes in the fecal excretion of calprotectin was observed. No colonization by probiotic strains was detected in infants who weighed < or =1000 g, presumably because of more frequent suspensions of enteral feeding, more courses of antibiotic treatment, or both.
                Supplementation with BB536-LGG may not improve the gastrointestinal tolerance to enteral feeding in very-low-birth-weight infants but may improve gastrointestinal tolerance in infants weighing >1000 g. This trial was registered at clinicaltrials.gov as NCT 00290576. To evaluate the tolerance of rapid advancement of enteral feeds in VLBW babies.
                Tertiary teaching hospital.
                Randomized controlled trial.
                All stable neonates with birth weight less than 1250 grams were included in the study. The primary outcome variable was the time taken to achieve full enteral feeds (defined as 180 ml/kg/day). The secondary outcome variables were incidence of Necrotizing enterocolitis (NNEC) and incidence of apnea. At 48 hours, the infants were randomized into the slow advancement group (enteral feeds advanced by increments of 15 ml/kg/day) or fast advancement group (enteral feeds advanced by increments of 30 ml/kg/day). The monitoring during feeding included daily weight record, two hourly abdominal girth charting, gastric aspirates, apnea, time taken to reach full enteral feedings and for NNEC.
                There were 53 infants who were enrolled for the study (27 in the fast advancement group and 26 in the slow advancement group). In the fast advancement group, 20 percent completed the trial; whereas 14 (53.8 percent;) in the slow advancement group completed the study. The two groups were comparable for birth weights, gestational age, sex, intrauterine growth status, Apgar and CRIB scores. The infants in the fast group reached full enteral intake of 180 ml/kg/day significantly earlier (10 +/- 1.8 days) than in the slow group (14.8 +/- 1.5 days). The two groups were comparable for episodes of feed intolerance, apnea, NNEC. Infants in the fast group regained birth weight significantly earlier (median 18 days) than in the slow advancement group (median 23 days).
                Stable VLBW neonates can tolerate rapid advancements of enteral feeding without increased risk of adverse effects.
The only randomized trial to date provides no evidence of significant benefit to preterm infants from adding lactase to their feeds. Further research regarding effectiveness and safety are required before practice recommendations can be made. Randomized controlled trials comparing lactase versus placebo treated feeds and enrolling infants when enteral feeds are introduced are required. The primary and secondary outcomes for effectiveness and safety should include those identified in this review.