Human milk is a unique, species-specific, complex nutritive fluid with immunologic and growth-promoting properties. This unique fluid actually evolves to meet the changing needs of the baby during growth and maturation. Milk synthesis and secretion by the mammary gland involve numerous cellular pathways and processes (summarized in Media file 4).
The pathways for milk secretion and synthesis by the mammary epithelial cell. I: Exocytosis of milk protein, lactose, and other components of the aqueous phase in Golgi-derived secretory vesicles. II: Milk fat secretion via the milk fat globule. III: Direct movement of monovalent ions, water, and glucose across the apical membrane of the cell. IV: Transcytosis of components of the interstitial space. V: The paracellular pathway for plasma components and leukocytes. Pathway V is open only during pregnancy, involution, and in inflammatory states such as mastitis. SV = Secretory vesicle; RER = Rough endoplasmic reticulum; BM = Basement membrane; MFG = Milk fat globule; CLD = Cytoplasmic lipid droplet; N = Nucleus; PC = Plasma cell; FDA = Fat-depleted adipocyte; TJ = Tight junction; GJ = Gap junction; D = Desmosome; ME = Myoepithelial cell.
The processing and packaging of nutrients within human milk changes over time as the recipient infant matures. For example, early milk or colostrum has lower concentrations of fat than mature milk but higher concentrations of protein and minerals (see Media file 5). This relationship reverses as the infant matures.
In addition to the changes from colostrum to mature milk that mirror the needs of the developing neonate, variation exists within a given breastfeeding session. The milk first ingested by the infant (fore milk) has a lower fat content. As the infant continues to breastfeed over the next several minutes, the fat content increases. This hind milk is thought to facilitate satiety in the infant. Finally, the diurnal variations in breast milk reflect maternal diet and daily hormonal fluctuations.
Specific enzymes to aid neonatal digestion
Human milk contains various enzymes; some are specific for the biosynthesis of milk in the mammary gland (eg, lactose synthetase, fatty acid synthetase, thioesterase), whereas others are specific for the digestion of proteins, fats, and carbohydrates that facilitate the infant’s ability to break down food and to absorb human milk. Certain enzymes also serve as transport moieties for other substances, such as zinc, selenium, and magnesium.
Three-dimensional structure of human milk
Under a microscope, the appearance of human milk is truly amazing. Although it is a fluid, human milk has substantial structure in the form of compartmentation. Nutrients and bioactive substances are sequestered within the various compartments of human milk. The most elegant example of this structure involves lipids. Lipids are enveloped at the time of secretion from the apical mammary epithelial cell within its plasma membrane, becoming the milk-fat globule. Certain proteins, growth factors, and vitamins also become sequestered within this milk-fat globule and are embedded within the membrane itself.
The membrane acts as a stabilizing interface between the aqueous milk components and compartmentalized fat. This interface allows controlled release of the lipolysis products and transfer of polar materials into milk serum (aqueous phase). The bipolar characteristics of the membrane are also necessary for the emulsion stability of the globules themselves; thus, the structure of human milk provides readily available fatty acids and cholesterol for micellar absorption in the small intestine.
Proteins, carbohydrates, and designer fats for optimal brain development
Human milk provides appropriate amounts of proteins (primarily alpha-lactalbumin and whey), carbohydrates (lactose), minerals, vitamins, and fats for the growing term infant. The fats are composed of cholesterol, triglycerides, short-chain fatty acids, and long-chain polyunsaturated (LCP) fatty acids. The LCP fatty acids (18- to 22-carbon length) are needed for brain and retinal development. Large amounts of omega-6 and omega-3 LCP fatty acids, predominately the 20-carbon arachidonic acid (AA) and the 22-carbon docosahexaenoic acids (DHAs), are deposited in the developing brain and retina during prenatal and early postnatal growth.
An infant, particularly a preterm infant, may have a limited ability to synthesize optimal levels of AA and DHA from linoleic and linolenic acid. Therefore, these 2 fatty acids may be considered essential fatty acids. Many infant formulas in the United States have added AA, DHA, or both. The amount of AA and DHA in breast milk varies with the maternal diet. The unique blend of fatty acids in the breast milk has been linked to the development of innate and adaptive immune regulation. Prior to routine fortification of formulas with DHA and AA, infants who received breast milk demonstrated better visual acuity at age 4 months and slightly enhanced cognitive development than formula-fed infants; however, this was not a universal finding, and the benefits of DHA and AA remain controversial.
A recent study compared growth and bone mineralization in very low birth weight infants fed preterm formula with those who received term formula; the conclusion was that preterm formula better aided in growth and development.
One study examined maternal dietary manipulation of fatty acid concentration and neurodevelopmental differences in human milk.Despite higher levels of AA and DHA in the heavily supplemented maternal groups, no differences were observed in the neurodevelopmental outcomes of the 3 groups. This finding supports a more global effect of human milk as opposed to a single agent that renders developmental differences.
Thus, whether healthy term infants benefit from the addition of DHA and AA to formula remains unclear because they are able to convert very LCP fatty acids to DHA and AA. Ill term infants and those born prematurely are most likely to benefit from formulas enriched with DHA, AA, or both.
Rather than producing better vision or greater intelligence, breast milk may somehow protect the developing neonatal brain from injury or less optimal development by providing necessary building materials and growth factors that act synergistically rather than in isolation
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