Breast milk, a living source of nutrition for babies, complements a baby’s immune system, supplementing undeveloped defenses with immune factors while creating the foundation for the innate and adaptive immune systems. Such immune development includes tolerance of the environment and, in the case of food allergy, a lack of tolerance. Recent research questions the previous opinion that breast milk is protective against food allergy. This article reviews the immature immune system, the immunology and nutrition of breast milk, the literature exploring breast milk and food allergy, and the current recommendations regarding breast milk and the prevention of food allergy.
Key points
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Breast milk has important effects on the developing newborn and infant immune and gastrointestinal systems.
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The role of breast milk in the development of an infant’s immunoglobulin E response is uncertain.
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Whether maternal dietary antigens appear in breast milk is the subject of ongoing research.
Introduction
Breast milk, the most natural source of nutrition for babies, is recommended by the American Academy of Pediatrics (AAP), who in 2012 reaffirmed its recommendation of “exclusive breastfeeding for about 6 months, followed by continued breastfeeding as complementary foods are introduced, with continuation of breastfeeding for 1 year or longer as mutually desired by mother and infant.” Breastfeeding rates are on the increase in the United States. In 2011, 79% of newborn infants started to breastfeed, 49% were breastfeeding at 6 months, and 27% at 12 months. The incidence of food allergies is also on the increase: between 1997 and 2007, the incidence of food allergy increased by 18% in children younger than 18 years. In 2011, 8% of children had food allergies. Moreover, 29% of patients with food allergies also reported other atopic conditions such as asthma and eczema, compared with only 12% of children without food allergies. The driving force, or forces, behind the increase in allergies is unknown, and the subject of wide discussions and research.
The objective of this article is to review the composition of human breast milk and its role in food allergy by exploring the nutrition and immunology of breast milk, including the effects of a mother’s diet and contemporary means of storage of breast milk. The current literature on breast milk and food allergy is also reviewed.
Introduction
Breast milk, the most natural source of nutrition for babies, is recommended by the American Academy of Pediatrics (AAP), who in 2012 reaffirmed its recommendation of “exclusive breastfeeding for about 6 months, followed by continued breastfeeding as complementary foods are introduced, with continuation of breastfeeding for 1 year or longer as mutually desired by mother and infant.” Breastfeeding rates are on the increase in the United States. In 2011, 79% of newborn infants started to breastfeed, 49% were breastfeeding at 6 months, and 27% at 12 months. The incidence of food allergies is also on the increase: between 1997 and 2007, the incidence of food allergy increased by 18% in children younger than 18 years. In 2011, 8% of children had food allergies. Moreover, 29% of patients with food allergies also reported other atopic conditions such as asthma and eczema, compared with only 12% of children without food allergies. The driving force, or forces, behind the increase in allergies is unknown, and the subject of wide discussions and research.
The objective of this article is to review the composition of human breast milk and its role in food allergy by exploring the nutrition and immunology of breast milk, including the effects of a mother’s diet and contemporary means of storage of breast milk. The current literature on breast milk and food allergy is also reviewed.
The physiology of breast milk
Human breast milk is synthesized to match the developmentally appropriate nutritional needs of the baby. The processes and structures needed to create human milk begin when the woman herself is in her mother’s womb. As reviewed by Creasy, the milk streak is present at the fourth week of gestation, and the mammary gland is formed at the sixth week of gestation. Proliferation of milk ducts continues throughout embryogenesis, and breast buds are present at birth but, as maternal hormones diminish in the baby’s circulation, the buds regress, growing proportionally to body growth until puberty.
Prepubertal changes in hormonal circulation induce the first phase of mammogenesis. Ductal growth is stimulated by estrogen production, which is generally unopposed in the first 1 to 2 years of menstrual cycles, creating type I lobules, which are alveolar buds clustered around a duct; upon cyclical changes in hormones, the types of lobules differentiate into type II lobules, which are more complex lobules that contain more alveoli. This process continues throughout puberty, completing mature breast development.
The second phase of mammogenesis occurs when a woman becomes pregnant so that breast milk may be produced by lactocytes, which use 5 transport mechanisms to create breast milk ( Table 1 ). During the first half of pregnancy, lobules further differentiate into types III and IV, which have increased numbers of alveoli per lobule, thus establishing the milk-producing and milk-secreting framework. During the second half of pregnancy, protein synthetic structures, such as the rough endoplasmic reticulum, mitochondria, and Golgi apparatus, begin to increase within the alveoli, and complex protein, milk fat, and lactose synthetic pathways are activated. Regarding hormonal regulation, the initiation of human lactation involves (1) secretory differentiation, whereby mammary epithelial cells differentiate into lactocytes in the presence of progesterone, estrogen, and prolactin, and (2) secretory activation, whereby lactocytes secrete copious amounts of milk in the presence of prolactin, insulin, and cortisol when progesterone levels drop. This ability to synthesize and secrete milk is termed lactogenesis. Lactogenesis I occurs about 12 weeks before parturition as acini produce colostrum while progesterone inhibits the production of milk. Lactogenesis II occurs around 2 to 3 days after delivery, when the sudden drop in progesterone causes changes in the mammary epithelium, resulting in the beginning of mature milk production. Lactogenesis III is the establishment of mature milk production, occurring about 10 days after delivery, and was formerly called galactopoiesis.
| Method of Transport | Transported Components |
|---|---|
| Exocytosis | Milk proteins Lactose Calcium Other components of the aqueous phase of milk |
| Lipid synthesis | Fat secretion with formation of cytoplasmic lipid droplets Secreted as a membrane-bound milk fat globule |
| Apical membrane transport | Monovalent ions Water Glucose |
| Transcytosis | Proteins such as immunoglobulins |
| Paracellular transport | Components of the interstitial space |
Nutrition of expressed breast milk
Regarded by the World Health Organization (WHO) and AAP as the optimum first food for infants, human milk is sufficient to meet the nutrition needs of the developing infant exclusively through the first 6 months of life and is the standard to which infant formulas are designed. The AAP recommends breastfeeding duration of 1 year minimum or as long as preferred by mother and child, and the WHO recommends breastfeeding continue through age 2 years so that breast milk may continue to provide a substantial proportion of toddlers’ nutrition needs.
Although human milk is the standard for infant nutrition, its exact profile of nutritive substances is fairly dynamic. On average, a deciliter of mature human milk provides 65 to 70 kilocalories, 0.9 to 1.2 g of protein, 3.2 to 3.6 g of lipid, and 6.7 to 7.8 g of lactose. In reality, the composition of human milk varies diurnally, within feedings, and individually from mother to mother; furthermore, compared with mature milk, the nutrient profiles of breast milk differ greatly among colostrum, transitional milk, and preterm milk.
Macronutrients
Protein
The total protein concentration of human milk is relatively low in comparison with other mammalian milks, but the makeup is uniquely suited to provide both nutritive and nonnutritive benefits related to tolerance, development, and immune function. The relatively high proportion of whey compared with casein, the 2 main protein fractions, allows for greater solubility in gastric acid and faster gastric emptying in comparison with bovine proteins. Whey proteins of human milk include serum proteins (eg, α-lactalbumin, lactoferrin), enzymes (eg, lysozyme), and immunoglobulins (eg, secretory immunoglobulin A [IgA]). Lactoferrin, lysozyme, and secretory IgA are resistant to proteolysis and impart initial immune defense in the gastrointestinal tract. Casein phosphopeptides, intermediates of casein digestion, maintain the solubility of calcium, thereby aiding in absorption. In addition, free amino acids taurine and glutamine may stimulate intestinal growth, and nonprotein nitrogen from urea and nucleotides is used for the synthesis of nonessential amino acids, hormones, growth factors, and nucleic acids.
Lipid
Human milk is lipid rich. Half of the total energy in human milk is provided by its lipid fraction, and its globule structure, which contains bile salt-stimulating lipase, promotes efficient digestion. Lipid concentrations are lower at the start of feed (foremilk) and rich toward the end of a feed (hindmilk). Breast milk is also high in cholesterol, which contributes to cell membrane construction of the rapidly growing infant.
Unlike its protein and carbohydrate constituents, the fatty acid profile of human milk is affected directly by maternal diet, making it the most variable macronutrient. Despite this element of variability, breast milk remains higher in the polyunsaturated fatty acids arachidonic acid and docohexaenoic acid (DHA) in comparison with bovine milk. DHA is integral to visual and neurologic function.
Carbohydrate
Lactose is the major carbohydrate source in breast milk, followed by oligosaccharides. Lactose facilitates calcium absorption and may contribute to the soft stools generally observed in breastfed infants. Oligosaccharides serve as prebiotics, aiding in the proliferation of beneficial bifidobacteria and lactobacilli in the gut. Because they structurally resemble bacterial antigen receptors, they also impede bacteria from attaching to the gut mucosa.
Micronutrients
Vitamins
The vitamin content of breast milk is partly reflective of maternal diet and, in the case of fat-soluble vitamins, the overall fat content of the milk. An appropriately growing, healthy infant of a mother with a nutritionally adequate diet generally will meet his or her micronutrient requirements with the exceptions of vitamins K and D. Because of the low production of vitamin K by infant intestinal flora, infants are provided a single dose of vitamin K at birth to prevent deficiency-associated hemorrhagic disease of the newborn. The vitamin D content of breast milk can be improved by maternal diet and sun exposure, but average levels are generally insufficient to meet the infant recommended dietary allowance, necessitating routine supplementation.
Minerals
Mineral content of breast milk decreases gradually over the first 4 months of infant life, but this decline does not affect infant growth and may be kidney protective. Human milk is notable for having lower amounts of calcium and phosphorus in comparison with bovine milk, but these are more bioavailable, as are magnesium, iron, and zinc. Nearly half of the iron content of breast milk is absorbed, compared with 10% in bovine milk and bovine milk–based infant formulas. Maternal diet does not greatly affect the mineral content of breast milk.
Immunology of breast milk
Neonatal Immune System
To better understand how immune development may go amiss (eg, the development of food allergy) and how breast milk is immunologically beneficial, a basic comprehension of a baby’s immune system is beneficial. The ultimate goal of a newborn baby’s immune system is to possess both innate and adaptive systems of protection with complement bridging these 2 arms of immunity. The innate immune system identifies and combats immediate defense concerns while also signaling the development and recruitment of the adaptive immune system. Because both the innate and the adaptive immune systems take time to develop, babies benefit from exogenous sources of immune protection, specifically in the form of breast milk.
Though immunologically immature, the innate immune system, composed primarily of complement, natural killer cells, polymorphonuclear cells, monocytes, and macrophages, provides more immune protection to the neonate than does the more immature adaptive immune system, which is composed of T lymphocytes, B lymphocytes, and immunoglobulins. The 4 major categories of immunity are impaired in babies: phagocytosis, cell-mediated immunity, humoral immunity, and complement activity ( Table 2 ). Collectively the diffuse immaturity in these individual areas of immunity results in great susceptibility to infection, and the immunologic foundation developed during infancy in the presence of breast milk may contribute to tolerance more than is currently recognized.
| Major Mechanism of Immune Activity | Status in the Neonate and Explanation |
|---|---|
| Phagocytosis: process of ingesting and killing microbes | Immature : neutrophil chemotaxis is limited as is the presence of signaling molecules that participate in phagocytosis, such as immunoglobulins and complement |
| Cell-mediated immunity: the protection against intracellular pathogens provided by T cells and macrophages | Immature : neutrophils, monocytes, and antigen-presenting cells all hold both quantitative and qualitative defects |
| Humoral immunity: the antibody-mediated protection against extracellular microbes and microbial toxins | Immature : neutrophils, monocytes, and antigen-presenting cells all hold both quantitative and qualitative defects |
| Immature : complement proteins are found in limited amounts in neonate and, thus, also convey less protection |
Breast Milk Immunology
Breast milk is composed not only of macronutrients and micronutrients but also of living cells, antibodies, and other immunologically active agents, some of which fill immunologic gaps of the immature immune system. Breast milk composition is dynamic, changing as the baby develops and even altering with clinical changes, such as in the face of infection. Although breast milk generally contains a repertoire of components, mothers produce milk with different defense functionality profiles.
Antimicrobial, anti-inflammatory, and immunomodulatory factors that are underdeveloped in the neonatal immune system are found in human breast milk, playing a substitute role for those immune agents until the baby has developed them. Secretory IgA, lactoferrin, complement C3, and lysozyme are just a few of the antimicrobial factors found in expressed breast milk. Secretory IgA provides antimicrobial protection not by activating complement but by immune exclusion, which is the prevention of bacteria traversing the gut epithelium, and possibly immune inclusion, which is the maintenance of protective gut biofilms.
Lactoferrin is an iron-binding glycoprotein secreted in breast milk. Its highest total amounts are found in colostrum. The amount decreases as milk matures; however, the percentage of total protein that is lactoferrin starts at 27% in colostrum, dips to 19% by day 28, then increases to 30% by day 84, the timing of which correlates with the iron-deficiency anemia found in some exclusively breastfed babies. High levels of lactoferrin, such as those found in colostrum, stimulate intestinal proliferation, whereas low levels stimulate intestinal differentiation, both of which elucidate the critical role of lactoferrin as a first line of defense against pathogens invading the gastrointestinal tract. Lactoferrin also takes up iron, preventing it from being used by bacteria and fungi, which thereby diminishes pathogen proliferation.
Components of the complement system, such as complement C3, are present in human milk. Although small concentrations are present, such opsonins supplement the neonate’s slowly developing complement system and aids in pathogen protection.
Secretory IgA, lactoferrin, and complement C3 (and secretory component, the chaperone of IgA from mammary gland into the gut) vary greatly among lactating mothers; however, the proteins decrease between weeks 2 and 5, seemingly decreasing as the baby’s immune system is expanding. Lysozyme is another important immunologic protein in breast milk. This enzyme disrupts glycosidic linkages of some bacteria, a process aided by lactoferrin damaging bacterial outer membranes, creating a synergistic bacterial killing process. From 6 weeks to 6 months, levels of secretory IgA, lactoferrin, lysozyme, and total protein vary greatly while playing important roles in neonatal immunity. Of note, lactoferrin and lysozyme play roles against inflammation, as do platelet-activating factor acetylhydrolase and interleukin (IL)-10.
Immunomodulatory factors are underdeveloped in the neonatal immune system, and the complete roster of factors present in breast milk continues to grow: humoral immunity is enhanced by IL-4 and IL-10; cellular immunity is enhanced by IL-12, tumor necrosis factor α, and interferon-γ; growth is enhanced by granulocyte-colony stimulating factor; and chemokine activity is enhanced by RANTES, which plays a role in macrophage recruitment.
Cells found in expressed breast milk include immune cells (leukocytes, such as granulocytes and mononuclear leukocytes including lymphocytes, monocytes, and macrophages), mammary epithelial cells, and stem cells. Whereas the roles of mammary epithelial cells and breast milk stem cells in the neonatal immune system are not fully understood, immune cells play a vital role in neonatal protection, increasing in maternal and infant infections.
Bacteria are also present in human breast milk. Although the sources of some of these microorganisms are thought to include maternal skin, infant mouth and skin, and the environment, maternal dendritic macrophages can transport bacteria from the maternal gut through the lymphatic system and into the mammary gland, where the bacteria are transferred into the breast milk. This process was further demonstrated in breastfeeding mothers who consumed the probiotic Lactobacillus , after which the same strain of Lactobacillus was found in the feces of both the mothers their babies. This mechanism is similar to the development of secretory IgA, which is produced by the mother when her enteric mucosa recognizes antigen and stimulates B-cell production of IgA; these B cells travel to the mammary glands, where the IgA is glycosylated and secreted into the breast milk. In addition, oligosaccharides are present in breast milk and serve an important role in the development of infant gut microbiota (see later discussion).
Effects of storage on breast milk
Cultural trends affecting infant feeding and the recognition of the importance of breast milk in the care of hospitalized infants have made feeding human milk apart from the breast increasingly a reality. The AAP and the Academy of Breastfeeding Medicine have published guidelines for the storage of breast milk to ensure not only safe infant feeding but also that the integrity of breast milk’s bactericidal and nutritional properties is preserved. Among these guidelines are parameters related to refrigeration, freezing and thawing, and storage containers.
Refrigeration
Fresh breast milk that is not used within 4 to 6 hours should be refrigerated for up to 5 days. During this time nutrients may degrade at variable rates, with vitamin C noted to degrade rapidly. The cream component of breast milk will separate during refrigeration but will blend easily with agitation on thawing; this does not affect the fat composition.
Freezing and Thawing
Breast milk that will not be used within 72 to 120 hours of expression should be frozen. Freezing preserves its nutritional and immunologic properties for up to 3 to 4 months in a refrigerator-freezer compartment or for up to 6 months in a deep freezer. It is recommended that thawed milk should be used within 24 hours and not be refrozen. Heating breast milk will reduce the content and bioactivity of heat-labile vitamins and proteins.
Containers
Glass and hard plastic containers with airtight seals are the ideal storage containers for breast milk. For short-term (<72 hours) storage, plastic bags designed for human milk storage are appropriate. Longer storage increases the adherence of milk components to the plastic, thus affecting the nutritional quality of the milk.
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