Human Milk Fortifiers

Breast milk is the perfect, complete diet for newborn babies. But is it still perfect for the tiniest premature babies with their very specific needs?  This article looks at the nutritional needs of premature babies and the pros and cons of human milk fortifiers.

Mothers’ own milk

Breast milk is the superior nutrition for all babies and a mother’s own milk is recommended for premature or low-birth-weight babies including very preterm (<32 weeks gestation) or very low-birth-weight (<1.5kg) babies.¹ The colostrum produced by the mother of a premature baby has many components to protect the baby against infection. Preterm milk also has more protein and certain micronutrients than term milk in the early weeks of life—to nourish the premature baby.²

Micronutrient supplementation

Growth restriction or “under-nutrition” in tiny babies could be from placental insufficiency or inadequate nutrition after the birth and could permanently affect a baby’s long-term health.³ Concerns that the very lowest birth weight babies may need more of certain nutrients than breast milk will provide means common practice in some baby units is to supplement with additional minerals, vitamins or nutrients. These may be supplied as fortifiers which are often cows’ milk based. However not all babies need additional supplements.

Not all preemies need fortifiers

Mathur et al ⁴ found breast milk alone was enough for very low birthweight babies, particularly in the weight group 1251-1500g. Sullivan et al ⁵ found extremely premature babies fed with an exclusively human milk-based diet had significantly lower rates of NEC (necrotising enterocolitis, see below) than a diet that included cows’ milk products.

Jack Newman, Canadian paediatrician and breastfeeding expert, explains vitamin and mineral supplements can be supplied as single preparations without using fortifiers:

There may be a need for additions to the breastmilk, depending on the baby’s levels in the blood. It is possible to add vitamin D, phosphorus, calcium, even human protein (albumin) and human milk fat (from a breastmilk bank) to the baby’s milk without using fortifiers. If the baby doesn’t need fortifiers, then fortifiers actually should be considered diluters since they decrease the concentration of all those elements that make breastmilk special and unique.

World Health Organization vitamin and micronutrient recommendations

In a 2022 report, the World Health Organization (WHO) lists their recommendations for supplementing iron, zinc, vitamin A, vitamin D, calcium, phosphorus, and multiple micronutrient (MMN) supplementation.⁶ MMN supplements generally include A, D, E, and B group vitamins, with some containing iron, zinc, folate and magnesium (WHO, 2022).

WHO recommendations summary 2022:

• Iron. Supplementation is recommended for breastfed preterm or low-birth-weight infants
  who are not having iron from another source
• Zinc and vitamin D. Supplementation may be considered for breastfed preterm or low-birth-weight infants who are not receiving these from another source
• Vitamin A. Supplementation may be considered for breasted very preterm (< 32 weeks’
  gestation) or very-low-birth-weight (< 1.5 kg) infants who are not receiving vitamin A from another
  source.
• Calcium and phosphorous. No recommendation on supplementation as there is little evidence of benefits or harms.
• Multiple micronutrient (MMN). No recommendation on MMN supplementation as there is no evidence of benefits or harms.

Human milk fortifiers

Many neonatal intensive care units (NICU) traditionally supplement the smallest premature babies by adding extra nutrients and minerals to mothers’ breast milk; usually in the form of commercially produced cows’ milk based fortifiers called human milk fortifiers (HMF). Human milk fortifiers have varying amounts of protein, calcium, phosphate and carbohydrate, as well as vitamins and trace minerals. Eats on Feets explain:

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.

First Steps Nutrition Trust is a charity which provides evidence-based and independent information and support for good nutrition from pre-conception to five years of age. They say:

Human milk fortifiers (HMF) are commonly used as a dietary supplement when babies are born prematurely, particularly among those born at under 33 weeks. For babies over 33 weeks gestation, breastmilk in sufficient volume (220ml/kg/day) is considered nutritionally adequate, although some vitamin and mineral supplements may be needed (Shaw, 2015).

Human-milk derived milk fortifiers are gradually becoming available.⁷⁸ In the above document First Steps Nutrition Trust describe more about a breast milk derived fortifier available in the UK from Prolacta Bioscience and summarise studies comparing human milk based fortifier with cows’ milk based fortifiers.⁹

WHO guidance on use of fortifiers

Current guidance from the World Health Organisation (WHO) states:

Multicomponent Fortification of Human Milk
RECOMMENDATION A.4 (UPDATED)
Multicomponent fortification of human milk is not routinely recommended for all preterm or low-birth-weight (LBW) infants but may be considered for very preterm (< 32 weeks’ gestation) or very LBW (< 1.5 kg) infants who are fed mother’s own milk or donor human milk.

Preterm Formula
RECOMMENDATION A.5 (UPDATED)
When mother’s own milk and donor human milk are not available, nutrient-enriched preterm formula may be considered for very preterm (< 32 weeks’ gestation) or very low-birth-weight infants.

*Babies are termed Low Birth Weight (LBW) if they weigh less than 2,500g; Very Low Birth Weight (VLBW) if they weigh less than 1,500g and Extremely Low Birth Weight (ELBW) if they weigh less than 1000g.

The doctors in a baby’s Neonatal Infant Care Unit (NICU) will individually assess each baby taking account of availability of breast milk, your baby’s gestational age, and their medical needs.

Not enough breast milk?

Jack Newman, queries whether “under-nutrition” could be caused in part by false expectations of how a premature baby grows outside the womb and how often premature babies are fed:

There is often great emphasis on making sure the baby gains weight at the rate he would if still in his mother’s womb. But there is no proof that this rate of gain is necessary or even desirable. In fact, there are studies in the medical literature that suggest that too rapid a weight gain is harmful.

[Fortifiers] are intended to fix the “deficiencies” of breastmilk, but these “deficiencies” are, in large part, a function of how we feed premature babies. For example, the amounts we give them are very restricted much of the time. Prematures are often fed by the clock, typically every two or three hours. This is not normal for the baby born at term and I don’t see why it would be appropriate for the baby born prematurely.

The “need” for fortifiers and preterm formulas disappears for some babies if we simply give them more breastmilk.

Do bovine milk fortifiers help growth?

Adding multi-nutrient fortifiers to breast milk is associated with short-term increases in weight, length and head growth. However by 12 months of age no differences were found between infants receiving fortified breast milk and those receiving unfortified breast milk.¹⁰¹¹ Lucas et al also report on a study that showed breast milk fortifiers can help short-term growth when breast milk intake is high, but long term benefits were not proven.¹²

Risks of adding bovine based fortifiers to human milk

When premature babies are fed cows’ milk products they have poorer health outcomes including increased necrotizing enterocolitis and increased infections (WHO, 2022). Linda Palmer summarises:

it is well shown that feeding of cow products is also consistently associated with greatly increased chances of necrotizing enterocolitis, respiratory infections, other infections (sepsis), and other health risks including reduced survival. Re-hospitalizations are also more frequent in preterm infants who had been receiving formulas. The studies that have taken diet into account show greater developmental and intellectual benefits to fully human milk-fed preemies, as well as overall survival benefits, even though their weight gain is slower.

Health issues associated with cows’ milk based fortifiers include:

#1 Higher risk of gastrointestinal disease

• More episodes of necrotizing enterocolitis (NEC)— the most serious life-threatening gastrointestinal disorder that occurs for premature babies.^{13 14}
• More episodes of diarrhea and urinary tract infections with more antibiotic therapy.¹⁵
• Increased osmolarity (concentration) of the feed can increase morbidity, risk of gastrointestinal disease including NEC, or bowel obstruction.^16171819
• More episodes of gastroesophageal reflux.²⁰

#2 Higher risk of infection

• Bovine fortifiers cancel some anti-infective properties of human milk, eg lactoferrin, lysozyme, IgA specific to E coli.^2122 23 One study showed a bovine fortifier reduced white blood cells by 76% and lipase activity (enzyme digesting fats) by 56% and a decrease in total protein.²⁴
• Bovine fortifier does not protect against infection by bacteria compared with human-milk derived fortifiers (Chan, 2007)
• Bovine fortifiers increase the risk of contamination of breast milk because powdered fortifiers are not sterile, and liquid fortifiers dilute breast milk’s anti-infective properties.²⁵²⁶

#3 Risk of allergy and diabetes

• Introducing cows’ milk protein to premature babies can increase their risk of allergy ²⁷ and diabetes mellitus ²⁸.
• Artificial feeding is associated with increased gut permeability and decreased lactase activity (a marker of intestinal maturity).²⁹

Soy-based formulas

Particular issues identified with soy based formulas include low bioavailability of soy protein for low birth weight infants, poor growth, low plasma levels of methionine, chloride and iodine, and high levels of aluminium and phytoestrogen (WHO, 2006).

Mixing cows’ milk products with human milk

Studies referenced above by Chan et al and Quan et al found that the cows’ milk protein in human milk fortifier and cows’ milk formula can prevent some of the important anti-infective properties in breast milk from working. Rates of necrotizing enterocolitis were also significantly higher in infants fed mixed human and bovine-milk products compared to those fed breast milk exclusively.

To minimise this effect breast milk could be given first rather than mixing breast milk with formula. If practical, waiting (20 minutes to one hour) before giving cows’ milk based products would allow time for breast milk to start to leave the stomach. When breast milk fortifiers are added to breast milk, First Steps Nutrition state:

It is currently advised that HMF be added to the minimum amount of breastmilk possible, and that this is used before fortifying any more milk to avoid prolonged storage, since the HMF may impact on the breastmilk’s immunological components (although this has yet to be quantified) (Shaw, 2015).

Helping preemie growth rates

• Skin-to-skin contact and kangaroo care can significantly help a premature baby’s rate of growth.
• The calories in breast milk can be increased by using ‘breast milk cream’, the fattier proportion of breast milk, see Breastfeeding a Premature Baby.
• Human milk derived milk fortifiers are gradually becoming available (Czank C et al, 2010)
• Milk banks usually give priority to premature or sick babies should a mother be struggling with her milk supply. See organisations such as the Human Milk Banking Association of North America (HMBANA) or the European Milk Banking Association (EMBA) to locate a milk bank in your area. Human milk is far superior for these vulnerable babies.

Discussion documents and further reading

Various useful discussion documents for parents to find further information about human milk fortifiers include:

#1 What about fortifiers and premature babies?  Eats on Feets, 2011

A good review of research findings and who says what with the conclusion:

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.

#2 Fortify human milk for premature infants? Linda F Palmer, 2015

Author Linda Palmer comes to the conclusion that research on bovine fortifiers is poor:

Although current thinking is strongly in favor of fortifying human milk with additions of cow milk products, I am unable to find one study that shows human milk fortifiers provide survival benefits; reduced disability, such as blindness or cerebral palsy; or other neurological or health benefits. I find only studies showing increases in early growth along with increases in illnesses, with formula additions to breastmilk.

#3 Human milk fortifiers. Information for health professionals. First Steps Nutrition Trust. Westland. 2020

Summary

There is a general consensus that breast milk is the best form of nutrition for premature babies. Babies over a certain size do not need human milk fortifiers since there are a number of documented risks associated with these supplements. Each baby will need special nutritional evaluation on a case by case basis by their Neonatal Intensive Care Unit (NICU). More research is needed.