Background - Methods - Results - Characteristics of Included Studies - References - Data Tables & Graphs
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 there is insufficient evidence evaluating the supplementation of human milk with fat in preterm infants to make recommendations for practice.
However, the role of human milk in preterm infants is less well defined. The nutrient content of preterm 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. Studies have shown that preterm infants fed human milk have lower than expected growth rates than infants fed a modified, preterm infant formula (Cooper 1984, Lucas 1984, Calvert 1985, Roberts 1985).
Fat provides approximately 50% of the calories supplied in human milk, although the exact content can vary both between and within individuals, depending on the time of the day and the phase of lactation at which milk is collected (for example, hindmilk obtained at the end of nursing has a higher fat content). Fat separates from human milk when left standing and may adhere to collection containers and delivery devices, so the delivery method may impact on the eventual provision of calories. Preterm infants have relatively poor digestion and absorption of fat, due partly to immaturity of the various lipases in the gut (Zoppi 1972, Lebenthal 1980) and decreased bile salt secretion (Norman 1972, Signer 1974, Watkins 1975). The presence of bile-salt stimulated lipase in human milk may be important in improving the availability of the contained lipids to preterm infants (Hamosh 1987). An alternative approach is to provide fat supplements as medium-chain triglycerides (MCT), which are absorbed without the need for initial cleavage in the gut, and may therefore be more readily used by the preterm infant.
For a detailed discussion of the suitability of human milk for low-birthweight infants, see Schanler 1995.
It was intended to perform subgroup analyses of supplementation with MCT, and of supplementation with other forms of fat.
2. Secondary outcomes
a. Adverse effects
Gastrointestinal disturbance
Feeding intolerance
Diarrhea
Necrotizing enterocolitis (NEC)
The MEDLINE search included the search terms "Milk,-Human", "Infant,-Newborn", and "Lipids", including all subheadings for each term.
Additional information was requested from the authors of each trial to clarify methodology and results as necessary.
Each author extracted the data separately, compared data, and resolved differences.
The standard method of the Cochrane Neonatal Collaborative Review Group was used to synthesize the data. Results were expressed as relative risk and weighted mean difference.
Polberger 1989 assigned infants to receive either fat (1g human milk fat per 100ml of human milk) or no supplementation. Two other arms of the study evaluated supplementation with protein alone and protein and fat. The intervention was commenced once the infants were tolerating enteral feeds at 170ml/kg/day and was ceased when the infants were breast fed or weighed 2200g. Supplemental vitamins and minerals (calcium and phosphate) were given to all infants.
The study by Rönnholm 1982 was excluded. Infants were randomised by alternate allocation to no supplementation, supplementation with protein, supplementation with fat (medium-chain triglyceride, MCT), or supplementation with both protein and fat (MCT). The authors state that there was no apparent effect from the addition of fat alone and, therefore, combined the groups according to protein supplementation. Data were not able to be extracted for the group of infants receiving only MCT.
Growth was calculated using a regression of growth parameters against time. The slope of the regression was converted to units of g/kg/day and cm/week for the study period.
There were no significant differences in weight gain (WMD 0.60 g/kg/day, 95% CI -2.36 to 3.56 g/kg/day), linear (WMD 0.10 cm/week, 95% CI -0.08 to 0.28 cm/week) or head growth (WMD 0.15 cm/week, 95% CI -0.07 to 0.37 cm/week) over the short term study period.
There were no cases of necrotizing enterocolitis in those infants for whom results are reported. Feeding intolerance (undefined) occurred in one infant in the treatment group.
This study did not evaluate any of the other prespecified outcomes (long term growth, neurodevelopmental outcome, or other adverse gastrointestinal disturbance).
No subgroup analysis could be performed to separately assess the effects of MCT supplementation and other forms of fat supplementation.
Fat is a component in some commercial multicomponent human milk fortifiers - often in very low quantities. Fat has some theoretical advantages over other energy sources such as protein and carbohydrate in that it provides more calories per gram than protein and carbohydrate, does not appear to be associated with metabolic imbalance (unlike protein), and may result in a lower respiratory quotient and therefore less carbon dioxide production than carbohydrate supplementation (Pereira 1994). There are concerns, however, about the quality of growth in preterm infants - namely, that fat accretion or deposition in these infants may be greater than that of fetuses in utero even when not supplemented with excessive quantities of fat (Reichman 1981, Putet 1984, de Gamarra 1987). It is unknown whether this results in any long term advantage or disadvantage.
| Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
| Polberger 1989 | Randomised trial. Single center
Method of randomisation: Sealed envelopes Blinding of intervention: Double blind Complete follow-up: No Blinding of outcome measure: Adequate |
Number of treatment infants randomised: 8
Number of control infants randomised: 8 Preterm infants <1500g, appropriate for gestational age Enteral feeds tolerated at 170ml/kg/day Exclusions: major illness or abnormality, oxygen dependency |
1.0g human milk fat per 100ml human (unpasteurized maternal or unpasteurized
term banked donor) milk vs. unsupplemented human milk.
Intervention ceased at 2200g or when breast fed. All infants were supplemented with additional vitamins, calcium lactate (30mg/kg/day) and sodium phosphate (20mg/kg/day). From 4 weeks, 2mg/kg/day elemental iron was given to all infants. |
Short term growth | This study had four arms - unsupplemented vs. supplemented with protein,
vs. supplemented with fat, vs. supplemented with fat and protein. Supplementation
with protein alone and protein in combination with fat are discussed in
other reviews on protein and multicomponent fortification respectively.
34 infants were enrolled in all four study arms - 6 infants were withdrawn
following randomization (reasons discussed in separate reviews). 7 infants
were left in each arm.
There were large fluctuations in the energy intake for all four groups across the study. |
A |
| Study | Reason for exclusion |
| Rönnholm 1982 | Unable to extract data for infants supplemented with fat alone. |
* Polberger SKT, Axelsson IA, Räihä NCE. Growth of very low birth weight infants on varying amounts of human milk protein. Pediatr Res 1989;25:414-419.
Polberger SKT, Axelsson IE, Räihä NCR. Amino acid concentrations in plasma and urine in very low birth weight infants fed protein-unenriched or human milk protein-enriched human milk. Pediatrics 1990;86:909-915.
Polberger SKT, Fex GA, Axelsson IE, Räihä NCR. Eleven plasma proteins as indicators of protein nutritional status in very low birth weight infants. Pediatrics 1990;86:916-921.
Rönnholm KAR, Sipila O, Siimes MA. Human milk protein supplementation for the prevention of hypoproteinemia without metabolic imbalance in breast milk-fed, very low-birth-weight infants. J Pediatr 1982;101:243-247.
Rönnholm KAR, Siimes MA. Haemoglobin concentration depends on protein intake in small preterm infants fed human milk. Arch Dis Child 1985;60:99-104.
Rönnholm KAR, Simell O, Siimes MA. Human milk protein and medium-chain triglyceride oil supplementation of human milk: plasma amino acids in very low-birth-weight infants. Pediatrics 1984;74:792-799.
Rönnholm KAR, Perheentupa J, Siimes MA. Supplementation with human milk protein improves growth of small premature infants fed human milk. Pediatrics 1986;77:649-653.
* indicates the primary reference for the study
Calvert SA, Soltesz G, Jenkins PA, Harris D, Newman C, Adrian TE, Bloom SR, Aynsley-Green A. Feeding premature infants with human milk or preterm milk formula. Effects on postnatal growth and on circulating concentrations of intermediary metabolites, amino acids, and regulatory peptides. Biol Neonate 1985;47:189-198.
Cooper PA, Rothberg AD, Pettifor JM, Bolton KD, Devenhuis S. Growth and biochemical response of premature infants fed pooled preterm milk or special formula. J Pediatr Gastroenterol Nutr 1984;3:749-54.
de Gamarra ME, Schutz Y, Catzeflis C, et al. Composition of weight gain during the neonatal period and longitudinal growth follow-up in premature babies. Biol Neonate 1987;52:181-187.
Hamosh M. Lipid metabolism in premature infants. Biol Neonate 1987;52(Suppl 1):50-64.
Lebenthal E, Lee PC. Development of functional response in human exocrine pancreas. Pediatrics 1980;66:556-560.
Lucas A, Gore SM, Cole TJ, et al. Multicentre trial on feeding low birthweight infants: effects of diet on early growth. Arch Dis Child 1984;59:722-730.
Norman A, Strandvik B, Ojamae O. Bile acids and pancreatic enzymes during absorption in the newborn. Acta Paediatr Scand 1972;61:571-576.
Pereira GR, Baumgart S, Bennett MJ, et al. Use of high-fat formula for premature infants with bronchopulmonary dysplasia: metabolic, pulmonary, and nutritional studies. J Pediatr 1994;124:605-611.
Putet G, Senterre J, Rigo J, Salle B. Nutrient balance, energy utilization and composition of weight gain in very low birth weight infants fed pooled human milk or preterm formula. J Pediatr 1984;105:79-85.
Reichman B, Chessex P, Putet G, Verellen G, Smith JM, Heim T, Swyer PR. Diet, fat accretion, and growth in premature infants. New Engl J Med 1981;305:1495-1500.
Roberts SB, Lucas A. The effects of two extremes of dietary intake on protein accretion in preterm infants. Early Hum Dev 1985;12:301-7.
Schanler RJ. Suitability of human milk for the low-birthweight infant. Clin Perinatol 1995;22:207-222.
Signer E, Murphy GM, Edkins S. Role of bile salts in fat malabsorption of premature infants. Arch Dis Child 1974;49:174-180.
Watkins JB, Szczepanik P, Gould JB, Klein P, Lester R. Bile salt metabolism in the human premature infant. Preliminary observations of pool size and synthesis rate following prenatal administration of dexamethasone and phenobarbital. Gastroenterology 1975;69:706-713.
Zoppi G, Andreotti G, Pajo-Ferrara F, Njai DM, Gaburro D. Exocrine pancreatic function in premature and full-term neonates. Pediatr Res 1972;6:880-886.
Kuschel CA, Harding JE. Fat supplementation of human milk for promoting growth in preterm infants (Cochrane Review). In: The Cochrane Library, Issue 3, 1999. Oxford: Update Software.
Kuschel CA, Harding JE. Fat supplementation of human milk for promoting growth in preterm infants (Cochrane Review). In: The Cochrane Library, Issue 1, 2000. Oxford: Update Software.