Carbohydrate supplementation of human milk to promote growth in preterm
infants
Kuschel CA, Harding JE
Background - Methods
- Results - References
Cover sheet
Title
Carbohydrate supplementation of human milk to promote growth in preterm
infants
Reviewers
Kuschel CA, Harding JE
Dates
Date edited: 27/05/2002
Date of last substantive update: 29/11/1998
Date of last minor update: 10/05/2002
Date next stage expected / /
Protocol first published: Issue 3, 1997
Review first published: Issue 2, 1999
Contact reviewer
Dr Carl A Kuschel
Staff Neonatologist
Newborn Services
National Women's Hospital
Private Bag 92 189
Auckland
NEW ZEALAND
Telephone 1: +64 9 638 9919 extension: 3200
Facsimile: +64 9 630 9753
E-mail: CarlK@ahsl.co.nz
Contribution of reviewers
Intramural sources of support
National Women's Hospital, Auckland, NEW ZEALAND
University of Auckland, Auckland, NEW ZEALAND
Extramural sources of support
None
What's new
This is an update of the existing review of "Carbohydrate supplementation
of human milk to promote growth in preterm infants", The Cochrane Library,
Issue 2, 1999.
No new trials were located in the search done in April 2002, and as
a result, no substantive changes were made in the review. There was no
change to the conclusion that the addition of carbohydrate supplements
to human milk in preterm infants has not been studied sufficiently to make
recommendations for practice.
Dates
Date review re-formatted: 07/09/1999
Date new studies sought but none found: 10/04/2002
Date new studies found but not yet included/excluded: / /
Date new studies found and included/excluded: / /
Date reviewers' conclusions section amended: / /
Date comment/criticism added: / /
Date response to comment/criticisms added: / /
Text of review
Synopsis
No evidence to show the effect of adding carbohydrate to breast milk to
promote growth in babies born preterm
Breast milk is the best source of nutrition for full-term babies for
at least the first six months of life. Babies born preterm (before 37 weeks)
have different nutritional needs and it is possible that premature breast
milk may not meet all these needs. Adding carbohydrate to breast milk may
help. It may help gain weight, without the problems that can come from
protein supplements (see Cochrane review on protein supplements). However
carbohydrate supplements may cause diarrhea and feeding problems. There
have been no published trials evaluating the effect of adding carbohydrate
to breast milk to promote growth in preterm babies. More research is needed.
Abstract
Background
This section is under preparation and will be included in the next issue.
Objectives
The main objective was to determine if addition of carbohydrate supplements
to human milk leads to improved growth and neurodevelopmental outcomes
without significant adverse effects in preterm infants.
Search strategy
The standard search strategy of the Neonatal Review Group was used. This
includes searches of the Oxford Database of Perinatal Trials, MEDLINE (1966-Apr
2002), Cochrane Controlled Trials Register (The Cochrane Library, Issue
2, 2002), previous reviews including cross references, abstracts, conferences
and symposia proceedings, expert informants, journal handsearching mainly
in the English language.
Selection criteria
All trials utilising random or quasi-random allocation evaluating the supplementation
of human milk with carbohydrate in preterm infants within a nursery setting
were eligible.
Data collection & analysis
Not applicable.
Main results
No eligible trials were found.
Reviewers' conclusions
There are no studies which have specifically evaluated the addition of
carbohydrate alone for the purpose of improving growth and neurodevelopmental
outcomes. No recommendations for practice can be made. Research should
be directed towards comparison of different quantities and types of carbohydrate
in multicomponent fortifiers containing protein and minerals, specifically
evaluating short-term growth and long-term growth and neurodevelopmental
outcomes.
Background
Human milk is the recommended nutritional source for full-term infants
in at least the first six months of postnatal life. It is known that in
this group of infants, breast milk supplies adequate substrate to meet
the infant's nutritional demands, as well as supplying the infant with
other substances that may afford some physiological advantage (for example,
immunoglobulins and gastrointestinal hormones). Breast feeding may also
contribute to maternal-infant bonding.
However, the role of human milk in feeding premature infants is less
well defined. The nutrient content of premature human milk provides insufficient
quantities of protein, sodium, phosphate and calcium to meet the estimated
needs of the infant. In addition, large fluid volumes may be required to
provide sufficient calories to maintain adequate growth. Observational
studies have shown that premature infants fed human milk have lower growth
rates than infants fed term or preterm infant formula. For a detailed discussion
of the suitability of human milk for low-birthweight infants, see Schanler
1995.
Energy which remains following excretion and utilisation is available
for energy storage (growth). In premature infants, the total energy cost
of growth (including both the energy content of tissue formed and energy
expended in its synthesis) is estimated to be approximately 5-6 kcal per
gram of weight gain (Brooke 1979). Energy may
be provided as protein, fat, or carbohydrate. Carbohydrate is relatively
easy to administer enterally as there are several preparations available
commercially. Carbohydrate is also without the concerns of possible metabolic
and neurological adverse effects associated with protein supplementation
(Goldman 1974). However, the increased osmotic
load may lead to diarrhea, feeding intolerance, and possibly necrotizing
enterocolitis.
Thus, there is a need to systematically review randomised trials which
have assessed the benefits and risks of supplementing human milk with carbohydrate
in the feeding of preterm infants. Protein, fat, and non-protein energy
supplementation of human milk are to assessed in other reviews.
Objectives
To determine if addition of carbohydrate to human milk leads to improved
growth and neurodevelopmental outcomes without significant adverse effects
in preterm infants.
Criteria for considering studies for this review
Types of studies
Randomised controlled trials utilising either random or quasi-random patient
allocation.
Types of participants
Premature infants receiving care within a nursery setting.
Types of interventions
All randomised controlled trials evaluating the supplementation of human
milk with carbohydrate in which treatment was compared with unsupplemented
human milk, are included.
Types of outcome measures
1. Primary outcomes
a. Growth to discharge
Weight
Length
Head circumference
b. Growth at 12-18 months
Weight
Length
Head circumference
c. Neurodevelopmental outcomes
Neurodevelopmental outcome at 12 to 18 months.
2. Secondary Outcomes
a. Adverse effects
Gastrointestinal disturbance
Feeding intolerance
Diarrhea
Necrotizing enterocolitis (NEC)
Hyperglycemia
Search strategy for identification of studies
Searches of the Oxford Database of Perinatal Trials, MEDLINE (1966 - April
2002), Cochrane Controlled Trials Register (The Cochrane Library, Issue
2, 2002), previous reviews including cross references, abstracts, conferences
and symposia proceedings, expert informants, journal handsearching mainly
in the English language.
Search keywords included "Infant,-Newborn", "Carbohydrate,-dietary",
"Glucans", and "Milk,-Human".
Methods of the review
The criteria and standard methods of the Cochrane Collaboration and its
Neonatal Review Group were to be used to assess the methodological quality
of the included trials.
Additional information was to be requested from the authors of each
trial to clarify methodology as necessary.
Methods used to collect data from the included trials: each author was
to extract the data separately, data were to be compared, and differences
resolved.
Standard methods of the Neonatal Review Group were to be used to synthesize
the data.
Description of studies
No studies fitting the eligibility criteria were identified.
Excluded studies are listed in the Table 'Characteristics of Excluded
Studies'. Singhal (1992) randomised term small-for-gestational-age infants
to a sugar fortified formula. Other studies (Gross
1987, Modanlou 1987, Pettifor
1989, Lucas 1996, Wauben
1998) used carbohydrate as only one component of a multicomponent fortifier.
These studies are included in the systemic review on multicomponent fortification
of human milk (Kuschel 1998).
Methodological quality of included studies
Not applicable.
Results
No eligible trials were found.
Discussion
There are no randomised controlled trials in preterm infants evaluating
supplementation of human milk with carbohydrate for the purpose of improving
growth and neurodevelopmental outcomes. One short term study using sugar-fortified
milk formula for the prevention of hypoglycemia in at-risk infants was
identified (Singhal 1992). Randomised studies
using carbohydrate as one component of a multicomponent fortifier are included
in another systematic review (Kuschel 1998).
Reviewers' conclusions
Implications for practice
The addition of carbohydrate supplements to human milk in preterm infants
has not been studied sufficiently to make recommendations for practice.
Implications for research
Research should be directed towards evaluating short term and long term
growth outcomes in preterm infants supplemented with dietary carbohydrates.
It may be most appropriate to do so in the context of evaluation of the
effects of different formulations of multicomponent (carbohydrate, protein,
minerals) fortifiers. Research should take into account adverse effects
such as feed intolerance, necrotizing enterocolitis, hyperglycemia, and
diarrhea. Studies should evaluate any potential effect on neurodevelopmental
outcomes. The sample sizes required to evaluate differences between multicomponent
fortifiers - particularly evaluating long-term neurodevelopmental outcomes
- would be large.
Acknowledgements
Potential conflict of interest
Nil known.
Characteristics of excluded studies
| Study |
Reason for exclusion |
| Gross 1987 |
Carbohydrate included in multicomponent fortification. |
| Lucas 1996 |
Carbohydrate included in multicomponent fortification. |
| Modanlou 1987 |
Carbohydrate included in multicomponent fortification. |
| Pettifor 1989 |
Carbohydrate included in multicomponent fortification. |
| Singhal 1992 |
Carbohydrate added to formula in term small-for-gestational-age infants
for prevention of hypoglycemia. |
| Wauben 1998 |
Carbohydrate included in multicomponent fortification. |
References to studies
References to excluded studies
Gross 1987 {published data only}
Gross SJ. Bone mineralization in preterm infants fed human milk with
and without mineral supplementation. J Pediatr 1987;111:450-458.
Lucas 1996 {published data only}
Lucas A, Fewtrell MS, Morley R, Lucas PJ, Baker BA, Lister G, Bishop
NJ. Randomized outcome trial of human milk fortification and developmental
outcome in preterm infants. Am J Clin Nutr 1996;64:142-151.
Modanlou 1987 {published data only}
Modanlou HD, Lim MO, Hansen JW, Sickles V. Growth, biochemical status,
and mineral metabolism in very-low-birth-weight infants receiving fortified
preterm human milk. J Pediatr Gastroenterol Nutr 1986;5:762-767.
Pettifor 1989 {published data only}
Pettifor JM, Rajah R, Venter A, Moodley GP, Opperman L, Cavaleros M,
Ross FP. Bone mineralization and mineral homeostasis in very low-birth-weight
infants fed either human milk or fortified human milk. J Pediatr Gastroenterol
Nutr 1989;8:217-224.
Singhal 1992 {published data only}
Singhal PK, Singh M, Paul VK, Lamba IM, Malhotra AK, Deorari AK, Ghorpade
MD. Prevention of hypoglycemia: a controlled evaluation of sugar fortified
milk feeding in small-for-gestational age infants. Indian Pediatr 1992;29:165-9.
Wauben 1998 {published data only}
Wauben IP, Atkinson SA, Grad TL, Shah JK, Paes B. Moderate nutrient
supplementation of mother's milk for preterm infants supports adequate
bone mass and short-term growth: a randomized, controlled trial. Am J Clin
Nutr 1998;67:465-472.
* indicates the primary reference for the study
Other references
Additional references
Brooke 1979
Brooke OG, Alvear J, Arnold M. Energy retention, energy expenditure,
and growth in healthy immature infants. Pediatr Res 1979;13:215-220.
Goldman 1969
Goldman HI, Freudenthal R, Holland B, Karelitz S. Clinical effects of
two different levels of protein intake on low-birth-weight infants. J Pediatr
1969;74:881-889.
Goldman 1971
Goldman HI, Liebman OB, Freudenthal R, Reuben R. Effects of early dietary
protein intake on low-birth-weight infants: evaluation at 3 years of age.
J Pediatr 1971;78:126-129.
Goldman 1974
Goldman HI, Goldman JS, Kaufman I, Liebman OB. Late effects of early
dietary protein intake on low-birth-weight infants. J Pediatr 1974;85:764-769.
Kuschel 1998
Kuschel CA, Harding JE. Fortification of human milk: multicomponent
(Cochrane Review). In: The Cochrane Library, Issue 4, 1998. Oxford: Update
Software.
Schanler 1995
Schanler RJ. Suitability of human milk for the low-birthweight infant.
Clin Perinatol 1995;22:207-222.
Other published versions of this review
Kuschel 1999
Kuschel CA, Harding JE. Carbohydrate supplementation of human milk to
promote growth in preterm infants (Cochrane Review). In: The Cochrane Library,
Issue 2, 1999. Oxford: Update Software.
Notes
Published notes
Amended sections
None selected
Contact details for co-reviewers
Prof Jane JE Harding
Professor of Neonatology
Department of Paediatrics
University of Auckland
Private Bag 92 019
Auckland
NEW ZEALAND
1001
Telephone 1: +64 9 373 7599 extension: 6439
Telephone 2: +64 9 638 9909
Facsimile: +64 9 373 7497
E-mail: j.harding@auckland.ac.nz
Secondary address:
National Women's Hospital
Claude Road, Epsom
Auckland
NEW ZEALAND