Human Milk Fortifiers (HMF) are added by NICUs to human milk that is intended for Low Birth Weight (LBW <2500 grams), Very Low Birth Weight (VLBW <1500 grams) babies, and Extremely Low Birth Weight (ELBW <1000 grams) babies.¹ These fortifiers can be bovine-, soy- or human-milk-based. Most HMF used in NICUs are bovine-based. However, due to concerns with powdered formula and HMF, many NICUs use a mixture of liquid preterm formula or various commercial protein powders and minerals compounded in the hospital pharmacy.

The current practice of adding fortifiers to milk for LBW, VLBW, and ELBW infants is based on studies that have shown that human milk does not provide sufficient nutrition for preterm infants, especially VLBW. At issue are the calcium and phosphorus requirements for the VLBW baby’s bone growth. Without enough of these minerals, VLBW babies are at risk for osteopenia of prematurity and decreased bone mineral content that occurs mainly because of a lack of adequate calcium and phosphorus intake. VLBW babies also require higher amounts of fat-soluble vitamins because they have not laid down adequate stores before birth. One solution is to supplement the baby with human milk fortifiers (HMF), which has improved short-term weight gain and linear and head growth in preterm babies over infants not fed HMF.²

Weight gain
While the addition of HMF has improved short-term weight gain and linear head growth in preterm babies over those who were not fed HMF, there is insufficient data to evaluate long-term neurodevelopmental and growth outcomes in preterm babies receiving fortified. Weight gain and growth may not be the only metrics needed to assess success.³ Some studies indicate possible issues with fast weight gain in preterm infants. For instance, fast weight gain can put premature babies small for gestational age at risk for central adiposity and insulin resistance later in life.⁴

It is important to remember that individual care plans are important when caring for a preterm infant. There are many factors to look at in regard to deciding on each infant’s care. Discussions with the NICU team are important, as well as finding lactation support from a qualified lactation consultant. The availability of one’s own milk, donor milk, gestational age, and medical needs will all play a part in planning the care of the infant.⁵

Developing countries
Regarding multicomponent fortification the WHO raises doubts about the routine use of multicomponent fortifiers, particularly in developing countries. The benefits appear to be only short-term increases in growth, the safety is uncertain and could be of more concern in developing countries with a greater risk of contamination. Further research in developing countries is needed to examine the role of multicomponent fortifiers. Meanwhile, their use should be restricted to infants <32 weeks gestation or <1500 g birth weight who fail to gain weight despite adequate breastmilk feeding.⁶

Liquid versus powdered fortifiers
One concern about added liquid (bovine or soy) fortifiers is that liquid fortifiers are for use in a 1:1 ratio with human milk and contribute a significant proportion of the infant’s fluid intake. Although they are designed to contain adequate quantities of all essential nutrients, mixing someone’s own milk with an equal volume of liquid fortifier dilutes the constituents of the human milk, including nutrients, growth factors, and anti-infective properties.

Powdered fortifiers may be insoluble in human milk, and unless the fortifier-milk mixture is well shaken, the nutrients may not be available for absorption.

These studies do not, however, address the use of liquid fortifiers made from human milk.⁷

Antibacterial factors
The antibacterial action of breastmilk against E. coli, Staphylococc⁸us, Enterobacter sakazakii, and Group B Streptococcus (GBS) is removed by the addition of iron and fortifiers that contain iron to the breastmilk.

An older but valuable study shows that all cow-milk formulas enhance E. coli growth. Soy formulas and other additives preserved the inhibition of bacterial growth but nutritional additives can impair the anti-infective properties of human milk and such interplay should be considered in the decision on the feeding regimen of premature infants.⁹

Human-milk based fortifiers
A solution to the above issues may lie in human-milk-based fortifiers, that is, fortifiers made out of human milk. Evidence shows that breastmilk from those who have delivered preterm has antibacterial activity that can be affected by the addition of bovine-based fortifier, but not by the addition of a human breastmilk-based fortifier.¹⁰

For extremely premature infants, an exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. However, this research did not set out to demonstrate that necrotizing enterocolitis (NEC) was reduced when premature babies were fed human milk and therefore the methods used in this study to show these results are in question. It is added here because these preliminary results are of interest as more is being done in the realm of human-milk-based fortifiers.¹¹

Lactoengineering
As a viable alternative to fortifiers, many breastfeeding advocates propose ‘lacto-engineering’ for preterm infants as opposed to fortifiers. Milk fat rises as the breast is emptied. For the healthy breastfed infant who takes in a volume that represents most of what is produced via a parent’s own lactation, this fact is not relevant. However, for the parent of a VLBW infant, whose infant consumes only a small fraction of their daily output, special lactoengineering strategies may be warranted. Hind milk, the higher fat milk obtained several minutes following milk ejection, has been shown to enhance growth rates when fed to the VLBW infant. When it is known that the daily milk volume is more than double the infant’s daily volume needs, special instructions can be given for the collection and feeding of hind milk.¹² A creamatocrit, the length of the cream column separated from milk by centrifugation and expressed as a percentage of the length of the total milk column, can be performed when an accurate measure of the lipid content is required.¹³

Conclusions:
When it comes to adding fortifiers or other additives to breastmilk or not, there seem to be as many practices as there are NICUs. Controversy exists about many common and current practices. It is however unlikely that further long-term studies evaluating fortification of human milk versus no supplementation will be performed. It was found unethical to withhold phosphorus supplementation in control infants and other studies since then have also supplemented the control groups. Future research needs to be directed toward comparisons between different proprietary preparations of HMF and evaluating both short-term and long-term outcomes and adverse effects, in search of the ‘optimal’ composition of fortifiers. The number of study subjects required to adequately evaluate these outcomes would be extremely large.¹⁴

The value of human milk and human milk feeding for preterm infants is well established. The challenge for NICU staff is to provide parents with the necessary tools and support to provide this precious product and facilitate the establishment of this special relationship. As careful attention is given to other aspects of the NICU environment and standards of care, consideration of the lactation needs of the parent as an extension of their infant’s care is required. A critical review of current NICU policies and procedures should be performed to ensure the avoidance of hospital-induced obstacles to the successful provision of expressed human milk and human milk feeding for preterm infants.

Analysis of the available studies on the nutritional needs of preterm infants is hampered by the many variables involved, chief amongst them being the question of post-conceptional age (PCA). Most older studies do not indicate whether the PCA of the infants being studied is the same. While more recent studies typically provide more information on the infants’ PCA, it frequently remains difficult to evaluate the methodology used to gather all data, especially when comparing multiple studies. Therefore the extent of PCA’s statistical significance remains unclear. In addition, the outcome of these nutritional studies may be further influenced by factors such as gut maturation, NICU policies based on gestational age or weight, and the varying medical needs of individual infants. Clearly, this is an area that calls for further research in order to deepen our understanding.¹⁵

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1. ELBW babies also tend to be the earliest gestation, usually <27 weeks. ↩︎
2. Lauwers, J., and Swisher, A. Counseling the nursing mother: a lactation consultant’s guide. p. 467. 2005. Print. ↩︎
3. Kushel and Harding, 2004. Multicomponents fortified human mik for promoting growth in preterm infants ↩︎
4. M L Giannì, et al. 2012. Adiposity in small for gestational age preterm infants assessed at term equivalent age ↩︎
5. Paula M. Sisk, Ph.D., et al. 2006. Lactation Counseling for Mothers of Very Low Birth Weight Infants: Effect on Maternal Anxiety and Infant Intake of Human Milk ↩︎
6. World Health Organization. 2006. In Optimal feeding of low-birth-weight infants ↩︎
7. World Health Organization. 2006. (p.18) Optimal feeding of low-birth-weight infants ↩︎
8. Gary M. Chan, MD. 2003. Effects of Powdered Human Milk Fortifiers on the Antibacterial Actions of Human Milk ↩︎
9. Richard Quan, et al. 1994. The Effect of Nutritional Additives on Anti-Infective Factors in Human Milk ↩︎
10. Gary M. Chan. 2007. Effects of a Human Milk-Derived Human Milk Fortifier on the Antibacterial Actions of Human Milk ↩︎
11. Sandra Sullivan, MD, et al. 2009. An Exclusively Human Milk-Based Diet Is Associated with a Lower Rate of Necrotizing Enterocolitis than a Diet of Human Milk and Bovine Milk-Based Products ↩︎
12. Nancy Hurst. 2007. Three M’s Of Breast Feeding The Preterm Infant ↩︎
13. Hsiang-Yu Lin, et al. 2010. Efficacy of Creamatocrit Technique in Evaluation of Premature Infants Fed With Breast Milk ↩︎
14. Kushel and Harding, 2004. Multicomponents fortified human mik for promoting growth in preterm infants ↩︎
15. Nancy Hurst. 2007. Three M’s Of Breast Feeding The Preterm Infant ↩︎