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Carbohydrate supplementation of human milk to promote growth in preterm infants

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Authors

Kuschel CA, Harding JE

Background - Methods - Results - References


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 noted.

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: / /

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.

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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
    1. Growth to discharge
      1. Weight
      2. Length
      3. Head circumference
    2. Growth at 12-18 months
      1. Weight
      2. Length
      3. Head circumference
    3. Neurodevelopmental outcomes
      1. Neurodevelopmental outcome at 12 to 18 months.
  2. Secondary Outcomes
    1. Adverse effects
      1. Gastrointestinal disturbance
      2. Feeding intolerance
      3. Diarrhea
      4. Necrotizing enterocolitis (NEC)
      5. Hyperglycemi

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".

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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.

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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

  • None noted.

Potential conflict of interest

  • None noted.

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Characteristics of studies

Characteristics of included Studies

None noted.

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.

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References to studies

Included studies

  • None noted.

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.

Additional tables

  • None noted.

Amended sections

  • None noted.

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