Feeding strategies for premature infants: randomized trial of gastrointestinal priming and tube-feeding method. Establishing enteral feeding in preterm infants with feeding intolerance: a randomized controlled study of low-dose erythromycin. A prospective randomized trial of feeding methods in very low birth weight infants. Feeding tolerance in preterm infants: randomized trial of bolus and continuous feeding. Controlled study of transpyloric and intermittent gavage feeding in the small preterm infant. Randomized controlled trial of slow vs rapid enteral feeding advancements on the clinical outcomes of preterm infants with birth weight 750-1250 g. Individualized developmental care for the very low-birth-weight preterm infant. Medical and neurofunctional effects. Continuous feeding promotes gastrointestinal tolerance and growth in very low birth weight infants. Effects of sweet taste stimulation on growth and sucking in preterm infants. Influence of erythromycin on establishment of feeding in preterm infants: observations from a randomised controlled trial. Erythromycin and feeding intolerance in premature infants: a randomized trial.
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. 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. To test the hypothesis that very low birth weight infants fed by continuous nasogastric gavage (CNG) would achieve full enteral feedings (100 kcal/kg/d) at an earlier postnatal age and have less feeding intolerance (FI) than infants fed by intermittent bolus gavage (IBG).
                Eighty infants were stratified by birth weight (700 to 1000 g and 1001 to 1250 g) and randomized into CNG or IBG feeding groups. CNG infants were comparable with IBG in birth weight, gestational age, sex, race, and day of onset of feeding (5.7 +/- 2.1 days vs 5.6 +/- 2.2 days, respectively). Feedings were given as undiluted Similac Special Care formula (Ross Laboratories, Columbus, OH) via a specific protocol designed for each 50 to 100 g birth weight category. Feedings were advanced isoenergetically by a maximum of 25 mL/kg/d until an endpoint of 100/kcal/kg/d for at least 48 hours was reached. An infant whose feedings were withheld for >12 hours based on predetermined criteria was considered to have an episode of FI.
                Infants in the CNG group reached full enteral feeding at 17.1 +/- 8.9 days compared with 15.5 +/- 5.5 days in the IBG group; these were not statistically different. Secondary outcome variables such as days to regain birth weight (CNG, 12.6 +/- 5 days vs IBG, 12.5 +/- 3.7 days), days to reach discharge weight of 2040 g (CNG, 60 +/- 13.4 days vs IBG, 62 +/- 13.6 days), and number of episodes of FI were not significantly different between feeding methods. FI was primarily associated with birth weight </=1000 g (71%) vs 1001 to 1250 g (38%).
                Feeding methods are associated with similar outcomes when feeding regimens are comparable. To test the hypothesis that continuous gastric infusion (CGI) is better tolerated than intermittent gastric bolus (IGB) in small very low birth weight (VLBW) infants.
                Two-center, prospective, randomized, unmasked clinical trial.
                28 VLBW infants (birth weight <1250 g). A strict feeding protocol was followed.
                Patients were randomized to IGB or CGI.
                Time to reach full feeds (160 cc/kg/d)(by design and real), daily weight, caloric intake, residual gastric volume and type of feeding (formula vs. human milk vs. both).
                Five infants failed to complete the study because of death (n = 4) or protocol violation (n = 1). The two groups did not differ by birth weight or gestational age; infants fed via IGB reached full feeds earlier (p = 0.03) and had less delay in reaching full feeds than infants fed via CGI.
                Contrary to our hypothesis, gravity IGB is more effective than CGI in improving feeding tolerance in small VLBW infants. There were 53 appropriate for gestational age infants with a birth weight of less than 1,700 gm admitted to the Children's Hospital in Denver who were randomly assigned to two groups for gavage or transpyloric (nasojejunal) feedings. The two groups were not significantly different in terms of gestational age, birth weight, and morbidity. No significant differences were observed for caloric intake after 4 days of age, growth parameters (weight, length, and head circumference), serum total protein levels, feeding-related complications, duration of intravenous fluid supplementation, and length of hospitalization. The results indicate that intermittent gastric gavage feedings are as efficacious as transpyloric feedings in supplying nutrition to the low birth-weight infant. Because of inherently greater risks, costs, radiation, and requisite personnel expertise, transpyloric feedings cannot be recommended as a routine method of feeding for the low birth-weight infant. 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 investigate the effectiveness of individualized developmental care in reducing medical and neurodevelopmental sequelae for very low-birth-weight infants.
                Randomized controlled trial.
                Newborn intensive care unit.
                Thirty-eight singleton preterm infants, free of known congenital abnormalities, weighing less than 1250 g, born before 30 weeks' gestation, mechanically ventilated within 3 hours of delivery and for more than 24 hours in the first 48 hours, randomly assigned to a control or an experimental group.
                Caregiving by nurses specifically trained in individualized developmental care; observation and documentation of the infants' behavior within 12 hours of admission, and subsequently every 10th day; developmental care recommendations and ongoing clinical support for the nurses and parents based on regular observation of the infant by developmental specialists; and the availability of special caregiving accessories.
                Medical outcome, including average daily weight gain; number of days the infant required mechanical ventilation, oxygen, gavage tube feeding, and hospitalization; severity of retinopathy of prematurity, bronchopulmonary dysplasia, pneumothorax, and intraventricular hemorrhage; pediatric complications; age at discharge; and hospital charges. Neurodevelopmental outcome, including Assessment of Preterm Infants' Behavior scale and quantified electroencephalography (2 weeks after due date); and Bayley Scales of Infant Development and Kangaroo Box Paradigm (9 months after due date).
                The infants in the experimental group had a significantly shorter duration of mechanical ventilation and supplemental oxygen support; earlier oral feeding; reduced incidence of intraventricular hemorrhage, pneumothorax, and severe bronchopulmonary dysplasia; improved daily weight gain; shorter hospital stays; younger ages at hospital discharge; and reduced hospital charges compared with the infants in the control group. At 2 weeks after their due dates, these infants also showed improved autonomic regulation, motor system functioning, self-regulatory abilities, and visual evoked potential measures; and at 9 months, they had improved Bayley Mental and Psychomotor Developmental Index scores, as well as Kangaroo Box Paradigm scores.
                Very low-birth-weight preterm infants may benefit from individualized developmental care in the neonatal intensive care unit in terms of medical and neurodevelopmental outcome. To compare the effects of continuous versus intermittent feeding on gastrointestinal tolerance and growth in very low birth weight (VLBW) infants.
                In a randomized, controlled trial conducted at 3 neonatal units, 70 premature infants with a gestational age 24 to 29 weeks and birth weight < 1200 g were assigned to 1 of 3 feeding methods: continuous nasogastric feeding, intermittent nasogastric feeding, or intermittent orogastric feeding. Feeding was initiated within 30 hours of birth. Daily enteral and parenteral volumes, caloric and protein intakes, growth, enteral intolerance, and clinical complications were recorded. Cox regression analysis was used to determine primary outcome, the time to achieve full enteral feeding.
                The continuously fed infants achieved full enteral feeding significantly faster than the intermittently fed infants (hazard ratio [HR] = 1.86; 95% confidence interval [CI] = 1.07 to 3.22). In stratified analysis according to birth weight, the improvement was even more pronounced in the smallest infants, those with birth weight < or = 850 g (adjusted HR = 4.13; 95% CI = 1.48 to 11.53). Growth rate was significantly faster in the continuously fed infants ( P = .002).
                In VLBW infants, continuous feeding seems to be better than intermittent feeding with regard to gastrointestinal tolerance and growth. To evaluate the effect of sweet taste stimulation in augmenting the reported growth-enhancing effects of nonnutritive sucking in preterm infants who are gavage-fed.
                Random assignment of preterm infants to receive stimulation by one of three methods during each feeding until totally orally fed.
                Hospital intensive-care and infant transitional units.
                Eligibility criteria included body weight greater than or equal to 1,250 g, gestational age younger than 34 weeks, growth parameters appropriate for gestational age, tolerating at least 100 kcals/kg/day by gavage feeding with evidence of weight gain, and no clinical evidence of health complications. Data are presented for 42 infants who completed 14 days of treatment.
                Exposure to a sweet pacifier, a latex pacifier, or maternal heartbeat sounds during gavage feedings.
                Growth, time to total oral feeding, and sucking responses.
                No significant differences in sucking measures were noted among treatment groups. Differences in progression time to total oral feedings and weight gain favored the sweet-pacifier group but were not statistically significant.
                Oral stimulation of gavage-fed, preterm infants during a 2-week hospitalization was not sufficient to elicit a significant improvement in growth efficiency, progression to total oral feedings, or sucking maturation. Additional studies may show a beneficial effect of chemosensory stimulation in preterm 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. 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.
There was one small cross-over study that was included in this review. There is insufficient evidence to recommend either method of gavage feeding. A randomised trial is needed to evaluate the benefits and harms of push versus gravity bolus tube feeding in preterm infants. Infants should be stratified by gestational age at birth (above and below 32 weeks) or birth weight (above and below 1500 grams) and respiratory support (ventilated versus non-ventilated) and the sample size should be of sufficient size to evaluate the primary outcomes outlined in this review (time to establish full tube feeds and feeding intolerance).