The best time to begin feeding milk to premature babies receiving intravenous nutrition is not known.
Necrotizing enterocolitis (NEC) is a life-threatening bowel illness in newborn babies born prematurely. As there is concern that feedings in the gastrointestinal tract may increase the risk of NEC, some babies receive only intravenous nutrition for prolonged periods. However, there is also a concern that delaying feedings could lead to growth and feeding problems. This review examined comparisons between early (by 4 days of age) and late (after 4 days of age) initiation of milk feedings. There was not enough evidence to determine whether early or late feeding is better and further research is needed.
Enteral feedings in very low birth weight or sick preterm infants are often delayed for several days or weeks after birth even though delayed enteral feeding could diminish the functional adaptation of the gastrointestinal tract and result in feeding intolerance later. Early initiation of feedings could promote growth and shorten the duration of parenteral nutrition and hospital stay if early feedings did not increase the risk for necrotizing enterocolitis (NEC).
For parenterally fed low birth weight or preterm infants, to assess the effects of early enteral feedings initiated shortly after birth compared to delayed enteral feedings (with similar schedules for advancing feedings in each group).
Searches were performed of MEDLINE (1966-June 2004), CINAHL (1982-June 2004), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), abstracts and conference proceedings, references from relevant publications in the English language, and studies identified by personal communication.
Only randomized or quasi-randomized clinical trials were considered. Trials were included if 1) they enrolled low birth weight or preterm infants who were all given parenteral nutrition; 2) the infants were randomly assigned to either early enteral feedings (mean or median age <=4 days) or late enteral feedings (>4 days) of formula or breast milk; 3) except when feeding intolerance developed, the feedings were progressively advanced starting within 72 hours after initiating feedings; and 4) the goals for total nutrient intake were similar for both groups. (We did not require the duration or total intake of parenteral nutrients to be similar for both groups because these variables may be affected by the age at which feedings are initiated.)
The two reviewers reached consensus for inclusion of trials. Data regarding clinical outcomes were extracted and evaluated by two reviewers independently. Authors were contacted as needed and feasible to clarify or provide missing data. The specific data that were needed were requested in writing and by telephone.
Only two small studies were eligible for inclusion (Davey 1994 with 60 patients and Khayata 1987 with 12 patients). Early feedings had no significant effect on weight gain, necrotizing enterocolitis, mortality, or age at discharge, although important effects cannot be excluded with the small number of patients studied. Some benefits of early feedings were noted in the larger trial (Davey) -- fewer days on parenteral nutrition, fewer infants who were treated with gastric suction and interruption of feedings, fewer infants with sepsis evaluations, and fewer infants with percutaneous central venous catheters.
The benefits and hazards of early versus delayed initiation of enteral feedings in parenterally fed preterm/LBW infants have received very little study in clinical trials, and the effects on major clinical outcomes, including necrotizing enterocolitis and death, remain uncertain. With the availability of parenteral nutrition in contemporary neonatal units, it is unclear whether high-risk infants should receive early or delayed feedings.
Enteral feedings in very low birth weight or sick preterm infants are often delayed for several days or weeks after birth because of respiratory compromise and caregivers' concern that early feedings might increase the risk of necrotizing enterocolitis. Therefore, nutrition is provided as intravenous glucose with or without parenteral amino acids and lipids. Because gut hormone secretion and motility in preterm infants are stimulated by ingesting only small volumes of milk (Lucas 1986, Berseth 1990), delayed enteral feeding could diminish the functional adaptation of the gastrointestinal tract and result in feeding intolerance later. One approach to avoid this problem is the use of minimal enteral nutrition or trophic feedings, a strategy in which small volume feedings are provided without advancing feedings for at least 5 days (Tyson 2004). Another strategy reviewed here is early initiation of feedings without a delay in advancing feedings. This strategy could promote growth and shorten the duration of parenteral nutrition and hospital stay if early feedings did not increase the risk for necrotizing enterocolitis (NEC).
Studies in which parenteral nutrients (glucose and amino acids with or without lipids) were not provided were excluded because parenteral nutrients are now a part of routine care for very-low-birth-weight or sick preterm infants. The risk/benefit ratio of early vs. late enteral feeding may be different in the presence or absence of parenteral nutrition. To compare the effects of early and late enteral feedings, we required the age at starting parenteral nutrients, the initial intake of parenteral nutrients, and the goals for nutrient and caloric intake to be similar for the two groups. We did not require the duration or the total intake of parenteral nutrients to be similar in the two feeding groups because these variables may be affected by the age at which feedings are started.
For parenterally fed high-risk infants, to assess the effects of early enteral feedings (started at a mean or median age of <=4 days) compared to delayed enteral nutrition (started at >4 days) with a progressive increase in feedings for both groups in the absence of feeding intolerance.
Randomized or quasi-randomized controlled trials
Infants at high risk for necrotizing enterocolitis or complications of parenteral nutrition on the basis of low birth weight (<2500 g) or prematurity (<37 weeks)
Infants randomized to receive enteral feedings of human milk or formula (dilute or full strength) initiated either at a mean (or median) of <=4 days postnatal age or at a mean (or median) of >4 days. Except when feeding intolerance developed, feedings had to be progressively advanced starting within 72 hrs of initiation of feedings. Initial parenteral intake and nutritional goals had to be similar for both groups.
Days to reach full feeding (e.g.., receiving no IV fluid or receiving >100kcal/kg/day enterally)
Days feedings held
Days to regain birth weight
Hours of phototherapy
Days of parenteral nutrition
Days of hospital stay
Serum direct bilirubin >2.0 mg/dl
Necrotizing enterocolitis (greater than stage 1 by Bell's modified criteria)
Mortality
Electronic searches of the MEDLINE (1966 - June 2004) and CINAHL (1982
- June 2004) databases were performed using the following strategy:
1) enteral nutrition OR enteral feeding (as MeSH terms or text word)
2) AND (infant, premature OR infant, low birth weight) (as MeSH terms or text word)
3) limited to humans
Additional searches were performed of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), references in review articles and relevant chapters of textbooks on neonatal nutrition, trials identified in a previous systematic review (Steer PA, Lucas A, Sinclair JC. Feeding the low birthweight infant. In: Sinclair JC, Bracken MB, eds, Effective Care of the Newborn Infant. New York: Oxford University Press, 1992: 130-132), review of recent American Pediatric Society - Society for Pediatric Research abstracts (1990-2004), personal files, and personal communication.
Both authors participated in identifying trials for consideration and in describing the main results and conclusions. Both of the authors were masked to study outcomes in making decisions regarding inclusion of trials. Each author independently evaluated whether the trial met the eligibility criteria for inclusion in the meta-analysis, extracted data from the trials, and evaluated the methodologic quality.
Twenty studies were identified as possibly eligible. Eighteen were excluded for the reasons given in the Table, Characteristics of excluded studies. Details of the two included studies are included in the table, Characteristics of Included Studies. Davey 1994's study was performed in clinically stable preterm infants (n=60) who had a low umbilical artery catheter to assess whether their feedings should be initiated before the catheter was removed or deferred until 24 hours after the catheter was removed. The mean birth weight was more than 1100 g in both groups. The early feeding group had feedings initiated at a median age of 2 days at 2-5 ml every 2 hrs of 1/4 strength formula (based on birth weight). The concentration and volume were increased gradually by protocol according to birth weight. The late feeding group had feedings initiated at a median age of 5 days. The starting volumes and rates of advancement were the same as in the early feeding group. Reported outcomes included days to regain birth weight, days to full feedings, days of parenteral nutrition, duration of phototherapy, days in NICU, discharge weight, gastric residuals, abdominal distention, bloody stools, stage II or greater NEC, surgical NEC, episodes of feedings held with or without gastric suction, use of percutaneous central venous catheters, sepsis evaluations, and cholestatic jaundice. Median rather than mean values were reported for many of the continuous outcome variables because they were not normally distributed. For this reason, the data could not be synthesized with the results of other studies using the usual methods for analysis for Cochrane systematic reviews.
The trial by Khayata 1987 involved nonasphyxiated infants less than 1500 g birth weight. In the early feeding group, feedings were started at <=96 hours of age at 12 ml/kg/day of Enfamil (20kcal/oz). Feedings were increased to 24 ml/kg/day on the second day, 36 ml/kg/day on the third to fifth day, and as tolerated thereafter. In the late feeding group, feedings were started at 10 days of age or later using the same schedule as the early feeding group. Reported outcomes included caloric intake, fluid intake, weight, length, head circumference, and serum bilirubin levels during the first six weeks of postnatal life. Unfortunately, the trial has been described only in an abstract; this trial involved a small number of infants (n= 12) and information is not available for many of the planned outcome variables.
Quality assessments are included in the table, Characteristics of Included Studies. Blinding of caregivers would probably not be feasible in any trials of early feeding. In the trial by Davey 1994, there was blinding of randomization to prevent anticipation of the treatment group to which infants would be randomized, and it is likely that the radiologists who diagnosed necrotizing enterocolitis were blinded to treatment group. Two of 31 early-fed infants were excluded from the analysis because the umbilical artery catheter was removed shortly before feeding. These were probably relatively healthy infants and the direction of any bias resulting from their exclusion is likely to reduce the likelihood of finding a benefit from early feedings for many of the outcome variables (e.g., weight gain, age at full feeding, duration of parenteral nutrition, sepsis evaluations, and age at discharge).
The abstract that provides the only information available about the trial by Khayata 1987 does not indicate the method of randomization, whether the assessors were blinded, or whether all patients randomized were analyzed. The sample size was very small (n=12); it is unclear whether the groups were comparable at enrollment. Data were reported only for growth and serum bilirubin.
Feeding Outcomes:
In the Davey 1994 trial, early- and late-fed
infants did not differ significantly in median days to full feedings (19
vs. 22.5 days) or in the proportion of infants who had feedings held without
gastric suction (55 vs. 61%). However, fewer infants in the early-fed group
had feedings held with gastric suction initiated (21 vs. 45%). And there
was a significant reduction in duration of parenteral nutrition noted in
this study (median =13 days in the early-fed group and 30 days in the late-fed
group).
Weight Gain:
Neither study provides evidence that early enteral feedings result in
a clinically important increase in weight gain for infants given parenteral
nutrition. In the Khayata 1987 study, mean weight gain was 70 g/kg/wk in the early-fed group and 71 g/kg/wk in the late-fed group. In the Davey 1994 study, median time to regain birth weight was the same in both groups (13 days).
Morbidity:
The early- and late-fed groups in the Davey 1994
study did not differ significantly in age at discharge (36.6 vs. 37.5 corrected
weeks), necrotizing enterocolitis (7 vs. 13%), or mortality (3% vs. 0%),
although these findings do not exclude the possibility of clinically important
effects of early feedings. There was no significant effect on peak serum
bilirubin in the study by Khayata 1987 or in duration of phototherapy in the study by Davey 1994,
although potentially important clinical differences were not excluded. Median
duration of phototherapy tended to be shorter in the early-fed group than
the late-fed group (38 vs. 51.5 hours) in the Davey 1994 study. Cholestatic jaundice did not differ significantly between groups (10% vs. 17%). Additional findings in the Davey 1994
study included a lower proportion of infants in the early-fed group than
in the late-fed group who had sepsis evaluations (17% vs. 52%) and percutaneous
venous catheters (31% vs. 58%).
The definition of early feedings may vary among different practitioners
and neonatal units. Although we defined early feedings as the initiation
of enteral nutrition at a mean or median of 4 days or less after birth, many
clinicians might consider early feedings to include enteral nutrition begun
as late as 7, 10, or even 14 days after birth. While these definitions may
have merit, we found no data from clinical trials to compare early and delayed
feedings if feedings beyond 7 days were considered to be early feedings.
In the only trial of early vs. delayed feeding that has been published as
a full manuscript (Davey 1994), the median age
at starting enteral feedings in the late fed group was 5 days. The only trial
that was excluded by our categorization of early and delayed feedings (Mileur 1993) was a small trial (n=13) which has only been published as an abstract.
For such a fundamental issue in the care of sick preterm infants, we
have embarrassingly little data on which to base decisions about when to
begin enteral feedings. This lack of data is compounded by the problems inherent
in evaluating the effects of feeding practices on important neonatal outcomes,
particularly necrotizing enterocolitis. These problems include the inability
to blind caregivers and the possibility of inadvertent bias affecting the
evaluation of infants or other aspects of their care, difficulty in objectively
defining feeding intolerance (caregiver bias might influence decisions about
feeding and weight gain), and diagnostic surveillance bias in the diagnosis
of NEC (more x-rays might be ordered in one feeding group than in the other
because of caregiver bias). Even if delayed feedings resulted in a truly
lower incidence of necrotizing enterocolitis, the benefit from delayed feedings
might be offset by increased mortality or long-term morbidity as a result
of greater malnutrition or the hazards of prolonged use of vascular lines
and parenteral nutrients. The number of infants needed to identify an effect
on mortality or major long-term morbidity would of course be very large.
Despite plausible rationale and some evidence of benefit from early feedings, it is unclear whether low birth weight or preterm infants who receive parenteral nutrition should be given early or delayed feedings.
A large multicenter trial comparing different ages of initiation of feedings among parenterally fed low birth weight infants is needed. A definitive assessment of the benefits and risks of early feedings is likely to require a large multicenter trial with sufficient high-risk infants to identify an important effect on one of the following variables:1) death before discharge home 2) death or necrotizing enterocolitis requiring surgical resection before discharge home 3) death or very prolonged hospital stay (an outcome that is associated with major long-term morbidity and that would address not only necrotizing enterocolitis but sepsis or other major complications of prolonged parenteral nutrition) or 4) death or major morbidity (including severe developmental delay and short bowel syndrome) at follow-up. To be feasible and valid, such a large trial would require a simple protocol, investigators/clinicians without strong preferences for age at which feedings are initiated, and a well organized group of participating centers.
None
Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
Davey 1994 | Method of randomization - sealed envelopes. Blinding of caregivers - no. Blinding of assessors - no. All or almost all subjects analyzed - yes. | 60 preterm infants with BW<2000g who were in stable condition by clearly defined criteria and who had a low umbilical artery catheter in place. Infants who had a lethal condition or who had received a double-volume exchange transfusion were excluded. | Early feeding group (median age = 2 days, n=29): Milk
feedings were initiated at 2-5 ml every 2 hrs of 1/4 strength formula (based
on birth weight). The concentration and volume were increased gradually
by protocol according to birth weight. Late feeding group (median age = 5 days, n=31): Milk feedings were not initiated until the umbilical artery catheter had been removed for 24 hours and the infant was clinically stable. Starting volumes and rates of advancement were the same as in the early feeding group. | Reported outcomes included days to regain birth weight, days to full feedings, days of parenteral nutrition, duration of phototherapy, days in NICU, discharge weight, gastric residuals, abdominal distention, bloody stools, stage II or greater NEC, surgical NEC, episodes of feedings held with or without gastric suction, use of percutaneous central venous catheters, sepsis evaluations, and cholestatic jaundice. | The differences between groups were not significant with respect to days to regain birth weight, days to achieve full feedings, duration of phototherapy, age at discharge, the proportion of infants who had gastric residuals, feedings withheld without gastric suctioning, abdominal distention, or grossly bloody stools. However, fewer infants in the early feeding group had sepsis evaluations and percutaneous central venous catheters. The early feeding group also received fewer days of parenteral nutrition. | A |
Khayata 1987 | Method of randomization - unstated. Blinding of caregivers - no. Blinding of assessors - presumably no. All or almost all patients assessed - can't tell. | 12 non-asphyxiated infants with BW <1500g. | Early
feeding group (n=5): Feedings were started at <=96 hours of age at 12
ml/kg/day of Enfamil (20kcal/oz). Feedings were increased to 24 ml/kg/day
on the second day, 36 ml/kg/day on the third to fifth day, and as tolerated
thereafter. Late feeding group (n=7): Feedings were started at 10 days of age or later using the same schedule as the early feeding group. | Reported outcomes included caloric intake, fluid intake, weight, length, head circumference, and serum bilirubin levels during the first six weeks of postnatal life. | During the first six weeks after birth, there were no significant differences in fluid intake, caloric intake, growth, or peak serum bilirubin levels between groups. This study included only 12 infants and has been reported only in a brief abstract. Baseline variables and many outcomes of interest were not reported. We were unable to obtain any additional information. | B |
Study | Reason for exclusion |
Becerra 1996 | Infants in the intervention group were fed a constant amount (20-25 ml/kg/day) for 4-7 days, at which time the feedings were progressively advanced in both groups. This study is included in the Cochrane review of trophic feedings for promoting tolerance and preventing morbidity in parenterally fed infants. |
Berseth 1992 | Infants in the intervention group were fed a constant amount (24 ml/kg/day) for 5-11 days, at which time the feedings were progressively advanced in both groups. This study is included in the Cochrane review of trophic feedings for promoting tolerance and preventing morbidity in parenterally fed infants. |
Berseth 1993 | Infants in the intervention group were fed a constant amount (24 ml/kg/day) for 10 days, at which time the feedings were progressively advanced in both groups. This study is included in the Cochrane review of trophic feedings for promoting tolerance and preventing morbidity in parenterally fed infants. |
Dunn 1988 | Infants in the intervention group were fed a constant amount (15-20 ml/kg/day) for 9 days, at which time the feedings were progressively advanced in both groups. This study is included in the Cochrane review of trophic feedings for promoting tolerance and preventing morbidity in parenterally fed infants. |
Glass 1984 | Infants were quasi-randomized (by alternating assignment) into a transpyloric feeding group and a parenteral nutrition group. The feeding group had feedings initiated at an average age of 9.9 hrs and advanced to full feedings by an average age of 4.9 days (over 4 days). The parenteral nutrition group had feedings initiated at an average age of 6.7 days and advanced to full feedings by an average age of 20.7 days (over 14 days). |
Higgs 1974 | The early feeding group did not receive the same parenteral nutrients (glucose only) as the late feeding group (glucose, casein hydrolysate, lipid). |
Keitel 1965 | Parenteral nutrients were not provided. In the late feeding group, enteral feedings were started at 48 hours of life, an age that we categorized as early feeding in this review. |
LaGamma 1985 | Seven infants were assigned (not randomized) to the total parenteral nutrition (late feeding) group because they were deemed either "too well" or "too sick" to be fed enterally. |
McClure 2000 | Infants in the intervention group were fed a constant amount (0.5-1 ml/hr) until mechanical ventilation was discontinued, at which time the feedings were progressively advanced in both groups. This study is included in the Cochrane review of trophic feedings for promoting tolerance and preventing morbidity in parenterally fed infants. |
Meetze 1992 | Infants in the intervention group were fed a minimal amount (2-18 kcal/kg/day) of enteral feedings for 11 days, at which time the feedings were progressively advanced in both groups. This study is included in the Cochrane review of trophic feedings for promoting tolerance and preventing morbidity in parenterally fed infants. |
Mileur 1993 | Early feeding included feedings up to 7 days postnatal age and the mean age of onset of feedings in the early feeding group was 5.4 days, an age that we categorized as late feeding in this review. This study included only 13 infants and has been reported only in a brief abstract. |
Ostertag 1986 | Infants in the intervention group were fed a constant amount (1 ml/hr) for 7 days, at which time the feedings were progressively advanced in both groups. This study is included in the Cochrane review of trophic feedings for promoting tolerance and preventing morbidity in parenterally fed infants. |
Schanler 1999 | Infants in the intervention group were fed a constant amount (20 ml/kg/day) for 10 days, at which time the feedings were progressively advanced in both groups. This study is included in the Cochrane review of trophic feedings for promoting tolerance and preventing morbidity in parenterally fed infants. |
Slagle 1988 | Infants in the intervention group were fed a constant amount (12 ml/kg/day) for 10 days, at which time the feedings were progressively advanced in both groups. This study is included in the Cochrane review of trophic feedings for promoting tolerance and preventing morbidity in parenterally fed infants. |
Troche 1995 | Infants in the intervention group were fed a constant amount (0.5-1 ml/hr) until the umbilical catheter was removed, at which time the feedings were progressively advanced in both groups. This study is included in the Cochrane review of trophic feedings for promoting tolerance and preventing morbidity in parenterally fed infants. |
Wharton 1965 | Parenteral nutrients were not provided and the timing of late feeding was between 12 and 16 hours of age (categorized as early feeding in this review). |
Wilson 1997 | The intervention group received not only early enteral feedings but also earlier parenteral lipids and amino acids. In addition, the maximum parenteral lipid and amino acid intake were greater and a different lipid preparation was used in the early feeding group. |
Wu 1967 | Parenteral nutrients were not provided and the timing of late feeding was between 24 and 36 hours of age (categorized as early feedings in this review). |
Davey AM, Wagner CL, Cox C et al. Feeding premature infants while low umbilical artery catheters are in place: a prospective, randomized trial. Journal of Pediatrics 1994;124:795-9.
Khayata 1987 {unpublished data sought but not used}
Khayata S, Gutcher G, Bamberger J et al. Early versus late feeding of low birth weight (LBW) infants: Effect on growth and hyperbilirubinemia. Pediatric Research 1987;21:431A.
Becerra M, Ambiado S, Kuntsman G, Figueroa A, Balboa P, Fernandez P, Uauy R. Feeding VLBW infants: Effect of early enteral stimulation (EES) [abstract]. Pediatric Research 1996;39:304A.
Berseth 1992 {published data only}
Berseth CL. Effect of early feeding on maturation of the preterm infant's small intestine. Journal of Pediatrics 1992;120:947-53.
Berseth 1993 {published data only}
Berseth CL, Nordyke C. Enteral nutrients promote postnatal maturation of intestinal motor activity in preterm infants. American Journal of Physiology 1993;264:G1046-51.
Dunn 1988 {published data only}
Dunn L, Hulman S, Weiner J, Kleigman R. Beneficial effects of early hypocaloric enteral feeding on neonatal gastrointestinal function: Preliminary report of a randomized trial. Journal of Pediatrics 1988;112:622-9.
Glass 1984 {published data only}
Glass EJ, Hume R, Lang MA, Forfar JO. Parenteral nutrition compared with transpyloric feeding. Archives of Disease in Childhood 1984;59:131-5.
Higgs 1974 {published data only}
Higgs SC, Malan AF, DeV Heese H. A comparison of oral feeding and total parenteral nutrition in infants of very low birthweight. South African Medical Journal 1974;48:2169-73.
Keitel 1965 {published data only}
Keitel HG, Chu E. Premature infant feeding. I. The clinical usefulness of caloric concentration of formulas, of early versus late feedings and of low stearic acid content formulas. Pediatric Clinics of North America 1965;12:309-35.
LaGamma 1985 {published data only}
LaGamma EF, Ostertag S, Birenbaum H. Failure of delayed oral feedings to prevent necrotizing enterocolitis. American Journal of Diseases of Children 1985;139:385-9.
McClure 2000 {published data only}
McClure RJ, Newell SJ. Randomised controlled study of clinical outcome following trophic feeding. Archives of Disease in Childhood. Fetal and Neonatal Edition 2000;82:F29-33.
Meetze 1992 {published data only}
Meetze WH, Valentine C, McGuigan JE, Conlon M, Sacks N, Neu J. Gastrointestinal priming prior to full enteral nutrition in very low birth weight infants. Journal of Pediatric Gastroenterology and Nutrition 1992;15:163-70.
Mileur 1993 {published data only}
Mileur LM, Meyer JA, Chan GM. Effect of early, low volume enteral feedings on very low birthweight (VLBW) infants. Pediatric Research 1993;4:307A.
Ostertag 1986 {published data only}
Ostertag SG, LaGamma EF, Reisen CE, Ferrentino FL. Early enteral feeding does not affect the incidence of necrotizing enterocolitis. Pediatrics 1986;77:275-80.
Schanler 1999 {published data only}
Schanler RJ, Schulman RJ, Lau C, Smith O, Heitkemper MM. Feeding strategies for premature infants: randomized trial of gastrointestinal priming and tube-feeding method. Pediatrics 1999;103:343-439.
Slagle 1988 {published data only}
Slagle TA, Gross SJ. Effect of early low-volume enteral substrate on subsequent feeding tolerance in very low birth weight infants. Journal of Pediatrics 1988;113:526-31.
Troche 1995 {published data only}
Troche B, Harvey-Wilkes K, Engle WD, Nielsen HC, Frantz ID, Mitchell ML, Hermos RJ. Early minimal feedings promote growth in critically ill premature infants. Biology of the Neonate 1995;67:172-81.
Wharton 1965 {published data only}
Wharton BA, Bower BD. Immediate or later feeding for premature babies? A controlled trial. Lancet 1965;2:969-72.
Wilson 1997 {published data only}
Wilson DC, Cairns P, Halliday HL et al. Randomised controlled trial of an aggressive nutritional regimen in sick very low birthweight infants. Archives of Disease in Childhood 1997;77:F4-11.
Wu PYK, Teilman P, Gabler M, Vaughan M, Metcoff J. Early versus late feeding of low birth weight neonates: Effect on serum bilirubin, blood sugar, and responses to glucagon and epinephrine tolerance tests. Pediatrics 1967;39:733-9.
* indicates the primary reference for the study
Berseth CL. Neonatal small intestinal motility; Motor responses to feeding in term and preterm infants. Journal of Pediatrics 1990;117:777-82.
Kennedy KA, Tyson JE. Rapid versus slow rate of advancement of feedings for parenterally fed low birth weight or preterm infants (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.
Lucas A, Bloom SR, Aynsley-Green A. Gut hormones and minimal enteral feeding. Acta Paediatrica Scandinavica 1986;75:719-23.
Tyson JE, Kennedy KA. Minimal enteral nutrition for promoting feeding tolerance and preventing morbidity in parenterally fed infants (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.
Kennedy KA, Tyson JE. Early versus delayed initiation of progressive enteral feedings for parenterally fed low birth weight or preterm infants (Cochrane Review). In: The Cochrane Library, Issue 4, 1998. Oxford: Update Software.
Kennedy KA, Tyson JE, Chamnanvanikij S. Early versus delayed initiation of progressive enteral feedings for parenterally fed low birth weight or preterm infants (Cochrane Review). In: The Cochrane Library, Issue 1, 2000. Oxford: Update Software.
01.01 Infants whose feedings were interrupted and gastric suctioning used
01.02 Weight gain (g/kg/week)
01.03 Infants with direct bilirubin >2mg/dl
01.04 Necrotizing enterocolitis (>Bell's stage 1)
01.05 Mortality prior to discharge
Comparison or outcome | Studies | Participants | Statistical method | Effect size |
---|---|---|---|---|
01 Effects of early vs. delayed enteral feedings | ||||
01 Infants whose feedings were interrupted and gastric suctioning used | 1 | 60 | RR (fixed), 95% CI | 0.46 [0.20, 1.03] |
02 Weight gain (g/kg/week) | 1 | 12 | WMD (fixed), 95% CI | 1.00 [-125.37, 127.37] |
03 Infants with direct bilirubin >2mg/dl | 1 | 60 | RR (fixed), 95% CI | 0.64 [0.17, 2.45] |
04 Necrotizing enterocolitis (>Bell's stage 1) | 1 | 60 | RR (fixed), 95% CI | 0.53 [0.11, 2.70] |
05 Mortality prior to discharge | 1 | 60 | RR (fixed), 95% CI | 3.20 [0.14, 75.55] |
This review is published as a Cochrane review in The
Cochrane Library, Issue 4, 2004 (see http://www.thecochranelibrary.com/ for information).
Cochrane reviews are regularly updated as new evidence emerges and in response
to comments and criticisms, and The Cochrane Library should be consulted
for the most recent version of the Review. |