Human Milk Fortification Strategies for Low Birth Weight and Preterm Infants

Human milk fortification

Breast milk is recognized as the best source of nutrition for newborns and its use is officially recommended to feed term and preterm babies. When breast milk is not available, donated human milk can be used.

Human milk is an incredible product of evolution that naturally contains all the nutrients needed by newborns and components, such as human milk oligosaccharides (HMOs), which only mothers can produce. You can discover more about the unique characteristics of human milk in this article.

In addition to its nutritional benefits, breast milk helps newborns to strengthen the immune system, improve long-term neuro-cognitive development and, in the case of preterm infants, offers protection against the main complications that can arise during the stay in the Neonatal Intensive Care Unit (NICU).

Preterm babies need more

Preterm infants and all low birth weight (LBW) infants, have special nutritional needs, and sometimes human milk, despite its extraordinary characteristics, may not be sufficient to meet those needs. Human milk is a very complex substance whose nutritional values as protein, fat and HMOs change over time, making it an ever-changing substance from the chemical composition point of view.

For example, the most critical period for brain growth and development in humans corresponds to the third trimester of gestation; preterm babies who are born within this period may miss the placental transfer of nutrients needed during the postnatal period. This could mean that these babies will have greater nutritional requirements, more than those offered by the mother’s milk.

To overcome these problems, NICUs enrich the mother’s milk with specific nutrients to ensure optimal development and growth of preterm babies.

Human milk fortification strategies

The use of human milk fortifiers for preterm infants is now considered a common practice in most NICUs; they rely on fortifiers that differ in the origin (bovine, human or donkey milk) and composition (multi-nutrient fortifiers or supplements for proteins, lipids and carbohydrates). In particular, for preterm infants, protein supply is extremely important: protein intake deficiency affects growth and carries the risk of neuro-cognitive impairment.

The standard approach to human milk fortification calls for the addition of a standard amount of fortifier to a specific amount of milk, regardless of the nutritional content of the human milk. It is a very rapid and inexpensive fortification strategy which, however, does not take into account the needs of the individual infant nor the intrinsic variability in mother’s (or donated) milk macronutrients. As a result, standard fortification makes it almost impossible to achieve the internationally recommended nutritional targets, leaving space for potential negative consequences in terms of growth and development of infants.

In general, standard fortification can provide right energy intakes but is not recommended to provide the correct protein intake for very low birth weight and preterm infants. Besides, standard fortification increases the risk of incurring in infants’ over-nutrition, which can have serious health consequences as well. In order to favor the optimal growth of preterm infants in NICUs, it is, therefore, necessary to adapt the fortification strategy to the specific needs of each child over time.

The scientific community and experts are now engaged in promoting the practice of individualised fortification, which is believed to be the solution to the problem of low birth weight and preterm infants’ undernourishment. Individualised fortification consists of two methods, adjustable fortification and target fortification.

Adjustable fortification was designed specifically to avoid protein under-nutrition and over-nutrition: the logic behind this approach is to regulate protein intake based on the child’s metabolic response. Even though Blood Urea Nitrogen (BUN) levels only roughly correlate with the protein intake in infants, BUN is used to guide the amount of additional protein needed. NICUs analyze BUN levels twice a week and intervene accordingly, fortifying milk with the right protein intake for each child.

Adjustable fortification has the clear advantage of taking into account the actual protein levels of preterm children, therefore reducing the possibility of incurring in under- or over-nourishment. The reliability of the approach can be undermined by the fact that, in premature babies, BUN values ​​may be subject to confounding values. Furthermore, the variability of milk is also not considered.

Target fortification is about human milk and its characteristics. Human milk composition is analyzed in order to identify its wide range of macronutrients so to perform a targeted fortification that does not just focuses on protein, but also on other macronutrients that play an important role in baby’s development. Another benefit of this approach is the ease of analysis, the repeatability of which allows to take into account the natural variability of human milk. Recent improvements in this approach made target fortification a promising fortification practice: in this context, the European Commission funded a project that has the potential to innovate low birth weight and preterm health.

With Preemie, the analysis of human milk is performed via a NIR (Near InfraRed) spectroscopic sensor and NICUs’ operators get results in real-time, and can fortify milk accordingly, using single components fortifiers (i.e. each fortifier addresses one or more class of macronutrients). Until recently, target fortification has been considered impractical due to the size and high cost of the analyzers, the time it takes to get a result, the time-consuming procedures to analyze human milk and the need of skilled personnel performing the analysis.

Preemie system improves then the concept of target fortification introducing a portable and affordable NIR sensor specifically calibrated for human milk that will allow NICUs’ operators to easily perform human milk analyses. The system features an AI-engine running in the cloud able to provide precise recommendations on the fortification, correlating optimal growth for each infant over time. Preemie also helps milk banks by allowing donor’s milk traceability through a blockchain protocol and testing for spoilage before milk is pooled.



The Unique Value of Human Milk

Human Milk

According to statistics from the World Health Organization (WHO), today only 40% of newborns are breastfed during the first six months of life; so, the majority of newborns are fed with artificial human milk alternatives, contradicting some important guidelines suggested, by the WHO, to ensure the optimal development of newborns and maximum protection against many illnesses.

Breast milk is truly the perfect food. The long list of features and benefits of this incredible product of the human body increases steadily – a recent study found that human milk contributes to preventing the onset of heart disease in preterm babies. Understanding how this first food works is the first step towards a new awareness of the close relationship between the way we eat and our health.

The WHO guidelines recognize breastfeeding as essential for the first two years of the infant’s life. During this period, other foods can be introduced, but the recommendation, at least for the first six months, is to use exclusively breast milk: the reason is that the so-called baby formulas, which are commercial alternatives for breast milk, do not possess the nutritional and immunological characteristics that are unique to human milk because they do not contain antibodies and human milk oligosaccharides.

Human milk oligosaccharides (HMO) are complex chains of sugar molecules unique to human milk, whose role has been fully understood only in recent years: they are not digested by infants but used to feed the good bacteria that will seed the baby gut, thus strengthening his or her immune systems. This relationship between milk and the establishment and maintenance of the baby’s microbiome is a most wonderful example of the complexity of evolutionary mechanisms.

Breast milk also contains all the nutrients that babies need in the first six months of life and possesses many substances, like HMOs and vitamins, that protect them from diseases. In addition to being more resilient, babies fed with breast milk develop better cognitive skills and are less prone to develop obesity during childhood.

These are the components present in human milk and their role in infants’ growth:

Protein: Protein is the nutrient that contributes the most to the infant’s growth.

Lipids: Fat is crucial for the development of the infant’s neurological system.

Carbs: Carbohydrates are all the lactose and HMOs in the milk.

Immunoglobulins: Immunoglobulins are antibodies that fight off the germs that cause disease. Breast milk contains antibodies that fight off bacteria, viruses, fungus, and parasites.

Hormones: Hormones have many jobs in the human body. They control growth and development, metabolism, stress, pain, and blood pressure.

Vitamins: Vitamins contribute to healthy bones, eyes, and skin. Breast milk contains the vitamins that are necessary for the baby’s health as he/she grows.

Enzymes: There are important enzymes in human breast milk. Some enzymes help with digestion by breaking down fats or proteins, and others protect your baby from germs and illness.

Minerals: Breast milk is full of minerals. Some of the minerals in breast milk are iron, zinc, calcium, sodium, magnesium, and selenium.

Lactose: Lactose is the main sugar in milk, and provides most of the energy needed by the growing infant. It is a part of the total carbohydrates and is the nutritionally relevant sugar.

HMOs: These oligosaccharides are unique to human milk. They are not digestible by the infant, but rather serve to feed the gut microbiome, which has many nutritional and health benefits.

Energy: Calorie intake is key for the development of the baby and is calculated from the content of various components.

Water: An excess of water means a possible dilution of the milk that can reduce its nutritive value.

Sometimes human milk is not enough

Sometimes, even human milk needs to be fortified in order to fulfill the metabolic and growth demands of specific categories of infants: low birth weight (LBW) and preterm ones.

According to recent statistics, 20 million LBW children are born every year (15% of the total) and 15 million of them are born prematurely. In order to avoid undernourishment and to grow optimally, some of these babies have unique nutritional needs. The mother’s milk does not provide sufficient nutrition for some of these infants, leading to slow growth with the risk of neurocognitive impairment and other poor health outcomes. Also, current baby formulas, as mentioned, do not contain HMOs to boost their immune system. So, pediatricians and neonatologists turn to the fortification of the mother’s milk.

The objective of fortification is to increase the concentration of nutrients to the levels recommended for the individual preterm infant. The Preemie sensor is able to accurately analyze human milk composition and can suggest the best fortification according to the actual developmental needs of the child. This contributes to LBW and preterm infants’ health and development and provides them with the very same opportunities as all other babies.


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