Original Article

Journal of Perinatology (2007) 27, S71–S74. doi:10.1038/sj.jp.7211713

Human milk and the premature infant

J Bhatia1

1Department of Pediatrics, Section of Neonatology, Medical College of Georgia, Augusta, GA, USA

Correspondence: J Bhatia, Section of Neonatology, Medical College of Georgia, Augusta, GA 30912, USA. E-mail: Jatindeb@mail.mcg.edu

Human milk from the preterm's own mother is the enteral feeding of choice.1 Human milk is species specific and has adapted throughout evolution to meet the nutritional needs of the human infant. The beneficial effects are generally thought to relate to improvement in host defense, digestion and absorption of nutrients, gastrointestinal function, neurodevelopmental outcome as well as maternal-infant bonding. However, the special needs of the premature infant cannot always be met by human milk to satisfy the current recommendations. Once growth is established, the nutritional needs of the preterm infant exceed the content of human milk for protein, calcium, phosphorus, magnesium, sodium, copper, zinc and vitamins B12, B6, C, D, E and K and folic acid.2, 3 With the increase in preterm birthrate as well as low birth weight rate,4 the increasing survival of these preterm infants and discharges at earlier body weights make nutritional considerations of paramount importance.

The physiologic basis for differences in compositional differences between term and preterm human milk vary and include early interruption of pregnancy, variable hormonal profile,5 delay in initiation of pumping, maternal anxiety and decreased milk flow, to name a few. Nonetheless, the benefits of providing human milk for premature infants are numerous and listed in Table 1.

In addition to various reasons for not providing human milk for their premature infants, breastfeeding rates fluctuate widely in the United States. Further, in particular infants, fluid restriction may preclude the use of enough human milk to satisfy the requirements. For example, to satisfy protein requirements of 3–3.6 g/kg/day, on an average, the intake would have to be between 180 and 210 ml/kg/day. Further, many infants do not achieve full enteral intake for several weeks after birth. Thus the need for both supplemental parenteral nutrition as well as fortification of human milk to satisfy the requirements of macro- and micronutrients of the growing preterm infant.

The adequacy of nutrient intake is further affected by the availability of human milk, the wide variation in its composition and the methods of milk collection. For example, a large variation is observed in both protein and energy.6 Similar variations are being observed in present day donor milk banks, thus, milk is now provided with labeled content of energy and protein based on pooled samples of donor milk. Fat content varies with the adequacy of milk collection and content varies during lactation, and has intra- and interwoman variation as well.7, 8, 9, 10 An inverse relationship between volume of human milk expressed and protein content has been demonstrated (Figure 1).11

Figure 1.
Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

(a and b) an inverse relationship between volume of human milk expressed and protein content has been demonstrated.11 Archives of Disease in childhood, 1984, vol. 59, pp. 831–836, reproduced with permission for the BMJ Publishing Group.

Full figure and legend (30K)

Milk expression techniques also affect fat content as full expression of fat rich hind milk will result in a much higher energy milk than after partial expression. Similarly, 'drip' milk from the breast other than one being pumped also has lower content of fat and energy. Disease states such as mastitis will increase the sodium content of milk and exercise may increase lactic acid levels leading to alterations in milk taste.

Limiting nutrients in human milk: in general, there is a significant decline in the content of protein and energy as lactation proceeds making unfortified human milk inadequate to meet the protein requirement of most preterm infants.12 Calcium and phosphorus, although less variable are present in inadequate amounts to sustain bone health. Metabolic complications associated with the long-term use of unsupplemented human milk in preterm infants include hyponatremia,13 hypoproteinemia14 and osteopenia.15 Poorer rates of growth and nutritional deficits have been described during hospitalization and post-hospital discharge.16, 17



Processes used in storage of human milk and feeding techniques also affects its composition. Freezing disrupts milk fat globules with an increase in triglyceride hydrolysis and poorer fat delivery as compared to refrigerated milk.18, 19, 20 Pasteurization leads to denaturation of bile salt-stimulated lipase which reduces fat digestion which in turn leads to poorer weight gain with additional losses of calcium and phosphorus as insoluble soaps. Both drip milk and foremilk are low in energy as previously stated.



Although both mastitis and reduction in milk production result in raised breast milk sodium content,21 sodium content is generally low and may become growth limiting in certain infants given the variability in sodium requirements.


Calcium and phosphorus

Calcium and phosphorus are well absorbed from human milk with approx70% of calcium and 95% of phosphorus being absorbed. However, they are not present in adequate amounts to support appropriate accretion of these nutrients. Premature infants, by virtue of their timing of birth, are osteopenic when compared to their term counterparts. If fed parenterally or with unfortified human milk, the delivery of calcium and phosphorus, especially phosphorus, will lead to further deterioration of osteopenia leading to metabolic bone disease.22, 23 Absorption may also be reduced from donor milk.24 In the short term, appropriate supplementation of phosphorus should occur to avoid osteopenia, metabolic bone disease and ultimately, rickets. Paradoxically, better bone mineral density at 5 years of age in one study was associated with the feeding of unsupplemented human milk during the neonatal period.25



Preterm infants fed human milk will need additional sources of iron by approximately 6–8 weeks of age. If infants are on erythropoietin, iron supplementation will need to be increased. A concern about iron containing human milk fortifiers and infection has been raised.26



Although there is evidence that human milk provides zinc for most preterm infants,27 zinc status may become marginal requiring zinc supplementation.28


Human milk fortification

The fortification of human milk can be performed by the use of a liquid commercial preterm infant formula mixed with an equal volume of human milk. Alternatively, a powdered commercial product may be used and prepared according to manufacturer's instructions. Few randomized studies exist regarding the differences in different fortifiers. In general, the fortifiers are designed to increase the milk content in protein, energy, calcium, phosphorus, and various trace minerals as well as vitamins. At our institution, periodic determination of serum blood urea nitrogen (BUN) and attained weight gains are evaluated to determine if fortification needs to be increased. If so, it is increased in a balanced fashion. In certain patients, for example, infants of vegan mothers, a commercially available amino-acid formula is added as a fortifier. This formulation provides adequate amounts of minerals as well as protein and energy.

Although the preferred method of fortification would be to analyze the nutritional composition of mother's milk, this approach is only amenable at present to the use of purchased donor milk because the energy and protein contents can be obtained; other nutrients, with less variability, allow themselves to be added in a fixed fashion. For protein, in one study, fixed versus fortification adjusted according to serum urea nitrogen was studied.29 There was no significant difference in weight gain. In another study, Polberger et al.30 concluded that fortification based on analyses always left the infant 'behind' because of the time lag in analyses. Nonetheless, each unit appears to have evolved into a fortification scheme based on liquid or powdered fortifiers. The primary outcome of fortification should be to preserve the benefits of human milk while optimizing nutritional status and growth. This could be best obtained by using mothers' own milk with appropriate fortification; this approach not only makes the mother a part of the team, it also reaps the benefit of her own milk. In a recent study by Schanler et al.,31 donor milk was found to offer little short-term advantage over preterm formula for feeding low birth weight infants. There were no differences between infants fed donor milk and preterm formulas in length of stay, necrotizing enterocolitis, other infection-related events or mortality. Infants fed mothers own milk were observed to have fewer infection-related events and shorter hospital stays. Multicomponent fortification of human milk has been shown to be associated with short-term improvements in weight gain, linear and head growth. It was recommended that further research be directed toward evaluating the 'optimal' composition of fortifiers.32 In another review, it was concluded that simple fat supplementation of human milk for promoting growth could not be recommended based on current evidence.33 Further, in another review, it was concluded that protein supplementation of human milk in relatively well preterm infants increases short-term weight gain, linear and head growth. Urea levels were increased but may suggest protein adequacy rather than toxicity.34 In our institution, infants are provided human milk until they reach an intake of about two-thirds of required intake. At that time, we begin fortification with preterm infant formula in a 1:1 ratio, based on our concern regarding powdered formula products. Blood urea nitrogen is monitored weekly to assure protein adequacy and additional 'balanced' fortification provided if needed. With this approach, we have not observed frank metabolic bone disease or rickets and have attempted to achieve the maximal weight gain without adverse metabolic effects. The relationship between protein intake and serum urea nitrogen has been described. In very preterm infants serum urea may increase or decrease independent of protein intake;35, 36 however, in general, in the absence of renal dysfunction, urea can be useful to ascertain protein adequacy. Poorer fat absorption has been demonstrated with fortified compared to unfortified milk.37 In two large studies, infants fed fortified human milk grew more poorly than those fed preterm formula, but volumes fed are not clear.38, 39 O'Connor et al.39 assessed neurodevelopment at 12 months and found that development was similar in human milk and formula-fed infants despite poorer growth in the former. Although weight, length and head circumference were lower at discharge in human milk-fed infants, there was no difference at later ages.

There are several human milk fortifiers available commercially. The powder fortifiers may have variable tolerance, but that has not been proven in blinded studies. Amino-acid formula powders may need to be used to fortify human milk if a mother chooses a vegan diet for her infant. Commercially available premature infant formulas may be used safely to fortify human milk.

In summary, premature infants need fortification of human milk to achieve growth as recommended. The exact duration of fortification is not clear, nor is the issue of fortification for the larger infants. It is our practice to suggest fortification for a minimum of three months post discharge and reassess needs after that. In the larger premature infants, 33–34 weeks, careful assessment of growth and development is encouraged rather than mandated fortification.



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