Although there are huge advantages of human milk for the preterm infant, inadequate intake of some nutrients may occur with its prolonged use in a significant number of very low birth weight (VLBW) infants^1,2,3,4. This is not to say that human breastmilk is not the best form of nutrition for most preterm infants, it very definitely is, but that nutrient supplementation is sometimes necessary for optimal growth.

Commercially produced multi-component Breastmilk Fortifiers (BMF) provide additional energy, protein, sodium, calcium, phosphate, as well as vitamins and trace elements. A recent systematic review⁵ has concluded that there are short term growth advantages of the use of multi-component BMF. Because of small numbers, and difficulty in abstracting study data, the review cannot unfortunately be definitive on the safety of BMF but it states that there does not appear to be any increase in clinically significant adverse effects including no evidence of a significantly increased incidence of Necrotizing Enterocolitis (NEC) in supplemented babies. Further studies comparing fortification of human milk versus no supplementation are unlikely because to withhold supplementation, particularly of phosphate, must be questioned on an ethical basis.

Despite the knowledge of need for supplementation and proof of effectiveness of multi-component BMF, albeit in the short term, there is no universally accepted protocol for use of BMF and practice varies greatly with some units not using it at all.

This article attempts to provide a clear understanding of the role of BMF, when it may be needed, and how to use it safely.

Nutritional requirements of the preterm infant

Theoretical nutrient requirements have been set down in a number of reports including Klein et al, 2002⁶ and Tsang et al, 2005⁷. See Table 1.The evidence shows an increased need, above levels required for term infants, for nutrients including energy, protein, calcium and phosphorus (the 3^rd trimester is the time for peak bone mineralisation), sodium, iron , vitamin A and vitamin D. Most recent Tsang guidelines suggest slightly higher energy and protein intakes are needed than previously thought and that a higher protein:energy ratio is important. They also recognise that extremely low birthweight (ELBW) infants have even higher needs for energy and protein.

Table 1. Summary of selected enteral nutrient recommendations

*max of 400 IU
** for Chronic lung disease 2000-3000IU may be needed

Click here to download printable version of this table

Unfortunately many preterm infants are sick and the definition of their nutrition requirements cannot simply be extrapolated from the needs of the norm. These recommendations can only therefore be used as a guide and individual requirements need to be assessed in the light of clinical variables. The guidelines are however a useful yardstick for adequacy of intake generally.

Composition of human breastmilk – can it meet these requirements?

Studies looking at protein and fat levels in preterm milk have found much variation⁸. There may also be much variation in a range of other nutrients. It is virtually impossible to have accurate knowledge of an infants overall intake from their mothers own milk because of the variable nutrient content. Even though figures of average content have been produced, see Table 2, it is too simplistic an approach to look at individual volumes taken, make calculations of intake and compare to theoretical requirements.

Table 2

Component / litre	Ref	Preterm transitional 6-10 days	Preterm mature 22-30 days	Term mature >30 days
Protein g	9	19 +/- 0.5	15 +/- 1	12+/- 1.5
Fat g	10	34+/- 6	36+/- 7	34+/- 4
Energy kcals	10	660+/-60	690+/-50	640+/- 80
Phosphorus mg	9	4.9+/-1.4	3.0+/- 0.8	4.8+/- 0.8
Calcium mg	9	8.0+/- 1.8	7.2+/- 1.3	6.5+/-1.5

In theory, however, and in general, the figures on composition of milk would suggest that an infant having 180ml/kg of preterm transitional breastmilk would receive around 120 with 3.4g protein/day. Levels of protein and energy would seem therefore to be sufficient to meet the theoretical needs in the first 2-3 weeks. This is also borne out in studies, and preterm infants have been shown to grow satisfactorily on their own mother’s preterm milk over the first few weeks^{11, 12 ,13} .

After the first few weeks, analysis of pooled preterm breastmilk has shown that protein levels decline as shown. Again a theoretical calculation on an intake of 180ml/kg of preterm mature milk would suggest an intake of 124kcal/kg and 2.7g protein/kg. Looking at theoretical needs, the protein intake is likely to be a limiting factor and again this has been borne out in studies showing poor growth on unsupplemented human breastmilk after the first few weeks.¹⁴ Further evidence that a limiting factor is likely to be protein, is a commonly seen drop in urea level below 2mmol/l. This does need to be interpreted with care since low serum urea may occur independently due to immaturity of the urea synthetic pathway. Change in serum urea level dependant on protein intake has been shown in one study for infants >31 weeks¹⁵, and any serial decline in urea in the absence of any other influencing factors such as impaired renal function, dexamethasone treatment or dehydration has been suggested as a marker for supplementation of protein intake¹⁶.

Nutrients other than protein are limiting in unsupplemented breastmilk. Analysis shows average content of calcium and phosphorus are present at levels that may not support optimal preterm growth rate. Clinical studies have proven that preterm infants on unfortified mothers milk develop hypophosphataemia with and without hypocalcaemia¹⁷. The fat soluble vitamin content of human preterm milk is low and will not meet the recommendation for vitamin D or vitamin A. The water soluble content of mother’s milk varies with diet and because all mothers may not eat well these nutrients may be limiting. Without an additional source of iron the premature infant will become depleted by around 8 weeks¹⁸. Reports on whether the zinc content of human breastmilk is adequate are conflicting with one group finding normal status¹⁹, but a number of reports have found zinc deficiency in human milk fed preterm infants²⁰.

These are the main limiting nutrients but it should also be remembered that further nutrients will be lost on handling and processing.

The many advantages of continuing to breastfeed

In the light of these inadequacies specialised preterm infant formulae were developed. There will always be a place for preterm formulas where mums cannot or choose not to breastfeed and these products will support the growth of the preterm infant very adequately. However, it is worth bearing in mind the numerous other factors present in breastmilk and the immunological, nutritional, gastrointestinal, neuro-developmental and long term advantages that they confer. These are too extensive to discuss fully here but for an excellent review see reference 16. It is suffice to say that probably one of the most important approaches to feeding that can be employed on a Neonatal unit is one that aims to maintain maternal lactation. To allow this, and at the same time to meet nutritional requirements, it is likely that BMF will need to be used.

But what are the perceived risks and is there any foundation for these?

Delay in starting BMF in practice has often been because of concerns of potential feed intolerance, but often more specifically because of concerns of Necrotizing Enterocolitis (NEC) even though there is no evidence of a specific link with BMF, and recognition that the causes are likely to be multifactorial. There are conflicting reports on the effect of fortification on gastric emptying but these are probably due to differences in the composition of BMF studied. The perceived risk of NEC is most likely related to some studies which have shown an increase in osmolality of fortified milks²¹ and that increased osmolality is one of the putative causes of NEC. The link between use of BMF and incidence of NEC has however been largely unfounded. In one randomised controlled trial (RCT)²² infants on BMF were found to have significantly more infection, but incidence of NEC was not significantly increased. The recently updated systematic review on multi-component BMF, although it could not be definitive on deleterious effects, found no evidence of increase in NEC. However, in view of the increased osmolality with prolonged storage of fortified milk, likely to be due to the hydrolysis of BMF carbohydrate polymers by active amylase in the milk, measures should be taken to minimise osmolality change in line with the recommendation to keep osmolality below 460mosm/l to limit risk of NEC²³. For this reason product information includes recommendation to fortify EBM just before feeding.

Using BMF in practice

If the benefit of continued human breastmilk is recognised, then use of a BMF must be considered as an alternative to introducing some preterm formula. The following are suggested practices relating to the use of BMF. They cannot be said to be evidence based guidelines but do reflect the authors practice and would seem to represent a commonsense approach, with the aim of ensuring safety and effectiveness.

• Use BMF after first 2 weeks- before this preterm breastmilk is more likely to meet nutritional requirements and this will also avoid risk of high protein intake >4g/kg where preterm transitional milk is higher in protein content.
• Aim to push volumes up to maximum tolerated before supplementing. If an infant can tolerate up to 220ml/kg and grow this would be the preferable option. However, consider BMF for all babies under 1.5kg.
• Always fortify the minimum amount of milk as close as possible to the feed time. Smaller scoops or syringes can be calibrated to measure the small amounts needed for feeds < 50mls.
• Assess closely for feed intolerance. If feed intolerance means that feed volumes are reduced then the measure is counterproductive.
• Change only one thing at a time. If increasing volume do not on the same day add in BMF.
• Do not use where there is a strong family history of atopy.
• Continue to monitor bone profile.
• Additional iron will still be necessary by 8 weeks at the latest. Tsang 2005 recommends a supplement to provide 2-4mg/kg/day from 2 weeks. Adding iron to EBM can further increase osmolality. The volume of milk to which the dose of iron is added is important²⁴.
• Do not use in infants with short bowel.
• Use with caution in infants on dexamethasone.
• Don’t add BMF to formula since with preterm formula it will lead to very high protein intakes and also gastrointestinal bolus obstruction has been reported²⁵.

Conclusion

In summary, BMF have been shown to promote growth in the short term. In theory, and from observational studies, we know that breastmilk is likely to provide inadequate nutrition for some preterm babies. However the benefits of human breastmilk are numerous and strategies aimed at maintaining lactation are of great importance in Neonatal Units. Preterm formulas will of course support good growth of preterm infants where there is no breastmilk or where the mother chooses not to breastfeed. It is however suggested that BMF can be used safely and effectively to meet nutritional requirements where there is a supply of EBM and that their use can help to maintain lactation.

Click here for more information on the Cow & Gate Nutriprem range or to download a copy of our Specialist Infant Milks leaflet If parents would like information on feeding thier preterm baby why not tell them to visit the Cow & Gate website hereClick here to view the latest research on preterm infant milk formulas


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