Breastfeeding: Unraveling the Mysteries of Mother’s Milk
Reproduced from Medscape Women’s Health eJournal 1(5), 1996.
© 1996 Medscape Portals, Inc
Margit Hamosh, PhD
Georgetown University Medical Center
Abstract and Introduction
Most of the major progress in understanding the unique and complex features of human breast milk has emerged in just the past 2 decades. Since the late 1970s, key research has examined such aspects as the composition of breast milk, effects of maternal and environmental factors on human milk, and the effect of human milk on the infant, including the protection against disease that breast milk can confer on the newborn. The composition of human breast milk includes growth factors, hormones, enzymes, and other substances that are immune-protective and foster proper growth and nutrition in the newborn. Research suggests that lactation is robust and that a mother’s breast milk is adequate in essential nutrients, even when her own nutrition is inadequate. Mature breast milk usually has constant levels of about 7g/dL carbohydrate and about 0.9g/dL proteins. But the composition of fats essential for neonatal growth, brain development, and retinal function varies according to a woman’s intake, the length of gestation, and the period of lactation. Vitamins and minerals also vary according to maternal intake. But even when these nutrients are lower in breast milk than in formulas, their higher bioactivity and bioavailability more nearly meet the complete needs of neonates than do even the best infant formulas. Also, in many instances human milk components compensate for immature function, such as a neonate’s inability to produce certain digestive enzymes, immunoglobulin A (IgA), taurine, nucleotides, and long-chain polyunsaturated fatty acids.
Introduction
Even when a mother’s own supply of nutrients and energy is limited, she still is able to produce breast milk of sufficient quantity and quality to support the growth and health of her infant. This finding that "lactation is robust" is one of several discoveries to emerge in recent years.[1] The quest to better understand the complex features of human breast milk has been building in the past 2 decades, as evidenced by the growing number of international meetings, expert work groups, and publications focusing on human breast milk. Since the late 1970s, key research has addressed such topics as analyzing human milk,[2-4] identifying how maternal and environmental factors affect breast milk,[5] and determining the effect of human milk on the infant,[6,7] including the protection against disease that breast milk can confer on the newborn.[8]
Human milk, like the milk of many other mammals, is specifically adapted to the needs of the newborn. Before birth, the mother transfers nutrients and bioactive components through the placenta[9]; after birth, these substances are transferred through colostrum and milk. In contrast to infant formula, human milk offers the infant nutrients with high bioavailability as well as a large number of bioactive components that confer immune and nonimmune protection against pathogens in the infant’s environment. Also, in many instances human milk components compensate for immature function, such as a neonate’s inability to produce certain digestive enzymes, immunoglobulin A (IgA), taurine, nucleotides, and long-chain polyunsaturated fatty acids (LC-PUFA), among other substances. Because many of these components remain intact during pasteurization, it is more advisable to feed pasteurized human donor milk to infants whose mothers are unable to nurse than it is to substitute formula.[1] Its bioactive components make human milk superior to even the best infant formulas.
Milk Volume and Composition
Figure 1. In general, healthy infants consume 450 to 1200mL/day first 4-5 months after birth. Milk volume is relatively constant irrespective of maternal nutritional status. Photo courtesy of Susanrachel Condon.
Major nutrients. Lactose, 5.5-6.0g/dL, is the most constant nutrient in human milk (Table I). Its concentration in breast milk is not affected by maternal nutrition.
Proteins amount to about 0.9g/dL in mature milk.[12]Recent studies comparing the impact of nutrition on lactation in industrialized and developing countries suggest that neither maternal diet nor body composition affects milk protein level.[1] However, limited data from earlier studies seem to indicate that short-term, high-protein diets can increase the protein and nonprotein nitrogen content of human milk,[13] while limiting maternal food intake can lead to lower milk protein levels.[13-15]
The majority of milk proteins provide the newborn with immune and nonimmune protection from infection. These proteins--immunoglobulins A, G, and M; lactoferrin; and lysozyme--have various functions in the newborn.[16] Early studies suggested that the level of these protective proteins in milk is affected by maternal diet, but more recent research suggests that immunoglobulins might be stable for a wide range of diets.[17-20]
Fat. While the amount and composition of carbohydrate and protein remain relatively constant in mature human milk, the composition of fat is highly variable and is affected within hours and to a large extent by maternal nutrition intake.[21] Gestation, lactation, parity, milk volume, caloric and carbohydrate intake, and weight changes are among the maternal factors that can alter the fat content and composition of breast milk. Specifically, phospholipid and cholesterol content are higher in colostrum preterm than term breast milk. Also, long chain polyunsaturated fatty acids (LC-PUFA) are higher in preterm and transitional milk and remain high for the first 6 months in women who deliver preterm. In term milk, on the other hand, LC-PUFA declines throughout the first 6 to 12 months of lactation. The endogenous synthesis of fatty acids (FA) declines with parity, most notably after 10 births, but FAs (C6-C16) rise with a high-carbohydrate diet. Palmitic acid (C16) content of breast milk increases in a low-calorie diet. Weight gain during pregnancy is positively associated with higher milk fat content. During infant feedings, fore milk has less fat content than hind milk. Also, the higher the volume of breast milk, the lower the milk fat concentration.[92] The lengths of both gestation and lactation affect phospholipid and cholesterol, the lipids that constitute the milk fat globule membrane.[22]In the early stage of lactation, because the milk fat globules are much smaller than in mature milk,[23,24] the total "membrane" lipid level is higher in colostrum and transitional milk than in mature milk. The period of colostrum lasts less than 10 days, but during this short time the higher lipid levels are beneficial in such processes as neonatal cell membrane production needed for growth, brain development, and bile salt synthesis. LC-PUFAs--C20:4n6 and C22:6n3, arachidonic, and docosahexaenoic acids, respectively--are milk fats essential for neonatal growth, brain development, and retinal function.[25,26] These fatty acids are stored in the fetus only in the last trimester of pregnancy; therefore, preterm infants are born with low reserves of LC-PUFA, and their best source for these essential fatty acids is human milk. LC-PUFA levels normally decrease in breast milk during lactation, but in women who have delivered infants before term, the levels remain constant in preterm milk for at least 6 months[27]. Holman and colleagues[28] have reported that levels of LC-PUFA often decline in pregnant and lactating women, suggesting that there is a preferential transfer of these essential fatty acids from mother to fetus or to the newborn through milk, even at the cost of possible depletion of maternal reserves. Depletion of maternal reserves might suggest the need for supplementation of pregnant and lactating women with LC-PUFA.
Milk fat content changes dramatically during each feeding[29,30] and fat composition is markedly affected by the maternal diet.[31] Some studies have shown that the mechanism for endogenous synthesis of fatty acids (ie, mainly medium chain fatty acids) seems to become exhausted in women of very high parity[32]; that infants who receive milk with low fat content (ie, less than 3.0 g/dl when the norm is 3.5 to 4.5 g/dl) tend to nurse more frequently and for longer time periods, thereby causing an increase in milk volume[33]; and that there is a strong positive relationship between weight gain during pregnancy and milk fat content.[34]
Vitamins and minerals. The vitamin content of human milk depends on the mother’s vitamin status; when maternal intake of specific vitamins is chronically low, these vitamins in turn are found in low levels in the milk. Vitamin supplementation raises vitamin concentrations in milk. Water-soluble vitamins in milk are generally more responsive to maternal dietary intake than fat-soluble ones.[1]
The relationship between maternal intake of vitamins and their concentration in milk varies according to the specific vitamin. For example, excess vitamin C intake does not further increase the level in milk (above that associated with adequate intake), whereas vitamin B6 concentrations in milk continue to rise with higher intakes. Folate levels in milk remain normal even at the expense of maternal folate stores and do not decrease until the latter are depleted.[1] Based on infant needs and the concentrations of fat-soluble vitamins in human milk, the Institute of Medicine (IOM) advises that in the US all newborns receive 0.5-1.0mg vitamin K by injection or 1.0-2.0mg orally immediately after birth.[1,10]Infants should receive 5.0-7.5ug vitamin D per day if exposure to sunlight seems inadequate.
The concentration of trace minerals (iron, copper, zinc, selenium) varies as a function of length of lactation. Concentrations of iron[35,36] and fluoride[37] in milk seem to be independent of maternal nutrition. Concentrations of manganese,[38] iodine,[39] and selenium[40] depend on maternal nutrition. Iodine is unique among trace elements in that it is avidly accumulated by the mammary gland[1].
Because of the high bioavailability of iron in human milk, exclusively breast-fed infants do not need iron supplements during the first 6 months of life. When supplementary foods are introduced (as recommended after 4-6 months of exclusive breast-feeding), iron supplements should be added to the infant’s nutrition[35, 36]. It is recommended that breast-fed infants receive supplemental fluoride if the water supply in the area has only low levels (<0.3ppm).
It is important to assess not only the concentration of milk components but also the amount delivered to the infant. Thus, while some milk components are present at a higher concentration in colostrum than in milk, one has to consider the marked differences in volume: colostrum amounts to about 100mL/day, whereas average milk volumes are 750-850mL/day.
Bioactivity of Human Milk
Immune and Nonimmune Protecting Agents
Most proteins in human milk are heavily glycosylated[44] and are therefore resistant to proteolysis both after ingestion by the infant[42,45] and after short-term storage (4-24 hours) at low to moderate ambient temperatures (15deg.-25deg.C).[46,47]
Early in studies of human milk, researchers became aware that certain substances--most notably, IgA, lysozyme, and lactoferrin--that are abundant in human milk (compared with bovine milk)[41] might protect the infant from infection.[47] This observation has progressed within the last 2 decades to a fuller appreciation of several characteristics of breast milk’s protective features:
- Immunoprotective substances act at mucosal sites.
- Because of their resistance to digestive enzymes, protective factors are well adapted to persist in the hostile environment of the gastrointestinal tract.
- They kill certain bacterial pathogens synergistically.
- Protection is achieved without triggering inflammatory reactions.
- The daily production of many immunoprotective factors changes as lactation proceeds.
- The secretion of many soluble defense agents by the mammary gland is inversely related to the capacity of the recipient infant to produce them at mucosal sites.[41, 49-51]
Table III summarizes the enteric and respiratory pathogens against which the infant is protected by specific IgA antibodies in human milk. IgA is resistant to proteolysis, acts at mucosal surfaces, and protects by noninflammatory mechanisms; all of these properties enable efficient action in the infant.
Human milk lacks inflammatory mediators, and contains anti-inflammatory agents such as antiproteases, antioxidants, and enzymes that degrade inflammatory mediators and modulators of leukocyte activation (Table IV).[49] Furthermore, IgE (the principal immunoglobulin responsible for immediate hypersensitivity reactions), basophils, mast cells, eosinophils (the principal effector cells in these reactions), and the mediators from these cells are absent in human milk. Immune and nonimmune protecting agents are present in milk throughout lactation and some, such as lysozyme, are present at higher concentrations during prolonged lactation than during the early stages. Therefore, although it is strongly advocated that breast-fed infants receive food supplements after 4 to 6 months of exclusive breast-feeding, it is advisable to breast-feed for longer periods in geographic areas where the environment may be contaminated with pathogenic microorganisms, in order to provide the infant and toddler the benefits of milk-borne protective agents.
Studies also indicate that a glycoconjugate present in human milk, but absent in either human serum or bovine milk, inhibits the binding of HIV envelope glycoprotein (gp120) to the CD4 receptor of T lymphocytes.[53,54]
In addition to soluble antigens and anti-infective agents, human milk contains leukocytes; the majority (90%) are neutrophils and macrophages. Lymphocytes account for approximately 10%. The number and type of leukocytes change with duration of lactation. Most of the lymphocytes in milk are T cells. The proportions of CD4 (helper) to CD8 (suppressor/cytotoxic) cells in human milk are similar to those in blood. Cytokines in human milk (eg, TNF-alpha and IL-1-beta) have been shown to enhance the anti-infective function of milk leukocytes. Milk macrophages might participate in the process of immunogenesis in the infant.
The immune and nonimmune protection provided by milk results in a lower incidence of necrotizing enterocolitis[55] and other gastrointestinal and respiratory infections in breast-fed infants than in formula-fed infants[56]. The incidence of otitis media is also lower than in formula-fed infants. In addition to protection against some infectious diseases, breast-fed infants might also be protected at later ages from diseases that are sequelae of infectious insults (eg, insulin-dependent diabetes mellitus, lymphoma, and Crohn’s disease). Immune factors provided by human milk that compensate for their delayed production by the infant are summarized in Table V.
Oligosaccharides (which amount to 1.0-1.5g/100mL of human milk),[53]glycoconjugates, mucins, and glycolipids act as receptor analogs and thereby inhibit the binding of enteric and respiratory microorganisms and their toxins.[57] In addition, the hydrolysis of milk triglycerides (the major component of milk fat) during digestion in the stomach and intestine[59]produces free fatty acids and monoglycerides that have been shown to have antiviral, antiprotozoan, and possibly also antibacterial activity.[60]
Growth Factors and Hormones
It appears that variants of prolactin are present in the circulation of the newborn and that the prolactin acquired from breast milk, and not endogenous prolactin secreted by the newborn’s pituitary gland, is essential for the normal development of the neuroendocrine regulation of prolactin in the newborn.[62,65]
Many hormones act in the newborn. While the exact mechanisms of uptake from milk and their mode and site of action in the newborn are known for some, further study is needed to identify these mechanisms for most hormones. Agents in milk seem to stabilize hormones in the gastrointestinal tract of the newborn.
In addition to prolactin, other hormones such as progesterone are present in different form in breast milk than in maternal serum. Transfer of these hormones from milk to infant was documented in some studies directly; in other studies, this transfer is inferred from the documentation of higher serum level of the hormone--for example, thyrotropin releasing hormone (TRH) and somatostatin--in breast-fed than in formula-fed newborns[61]. The milk hormones may also be modified as they pass through the gastrointestinal tract and prior to release into the newborn’s blood.
Enzymes
The digestive enzymes in milk (amylase and digestive lipase) act in the newborn to compensate for immature pancreatic function. These enzymes are remarkably stable for years in milk stored at low temperature (-20deg.C or -70deg.C). Moreover, activity is unchanged after storage for 24 hours at 38deg.C. The stability of enzymes and of other proteins in milk might be due to the antiprotease activity of milk. Furthermore, many enzymes are stable in the gastrointestinal tract of the newborn.
Amylase,[68] an enzyme identified in milk more than a century ago,[69]may be more important to the infant after initiation of starch supplements[70] or when formula that contains oligosaccharides hydrolyzed by amylase is fed to partially breast-fed infants. Amylase activity in the duodenum of the newborn is only 0.2% to 0.5% of the adult level. At the time of supplementation (after 4 to 6 months of exclusive breast-feeding), the infant is still deficient in endogenously produced amylase.[71] The latter secreted from salivary glands and pancreas does not reach adequate levels until 2 years after birth. Other infants and toddlers who might benefit from milk amylase are those with pancreatic insufficiency caused by diseases such as cystic fibrosis[72] or malnutrition.[73-75] Because of the potential of bile salt-dependent lipase in milk[76] to compensate for the low pancreatic lipase in the newborn,[77,78] this enzyme has received great attention in the past decade.[44,66] The characteristics of the digestive enzymes of human milk are summarized in Table IX.
Other Essential Components in Human Milk
The breakdown of milk casein produces beta-casomorphins; these short peptides have been shown to affect a variety of physiologic systems.[83]Because they are opioid agonists, these peptides also have behavioral effects, such as lowering response to pain and elevating mood, that can affect the nursing mother or the newborn. Most of the effects of the beta-casomorphins have been studied in such animals as rats, pigs, and chickens[83].
Human Milk After Preterm Delivery
Some of the nutritional needs of preterm infants, therefore, cannot be met by feeding the preemie breast milk only. While the mother’s own preterm milk is preferable to donor-banked full-term milk, either diet has to be supplemented with protein, calcium, and phosphorus in the preterm infant.[85] However, given the many benefits to the preterm infant that accrue from the mother’s own milk, efforts should be made to encourage mothers of preterm infants to breast-feed, even if during the early stages this might necessitate milk pumping while the infant is hospitalized or is too immature to nurse.
Long-Term Effects of Breast-feeding
Conclusion: Continuing the Progress in Understanding and Promoting Breast-feeding
We have just begun to assess the many components in human milk and their interaction with the infant. Much work lies ahead to understand in depth the immediate and long-term effects of feeding mother’s milk to newborns. As researchers continue to discover the unique features of breast milk, clinicians need to encourage the practice for the sake of the benefits breast-feeding can bring to both mothers and infants.
Tables
Table I. Concentrations of Nutrients in Mature Human Milk
Major nutrients g/liter Carbohydrate 72.0±2.5 Protein 10.5±2.0 Fat 39.0±4.0 Macronutrients Minerals mg/liter Calcium 280±26 Chloride 420±60 Magnesium 35±2 Phosphorus 140±22 Potassium 525±35 Trace Elements ug/liter Chromium 50±5 Copper 250±30 Fluoride 16±5 Iodine 110±40 Iron 300±100 Manganese 6±2 Molybdenum NR Selenium 20±5 Zinc 1200±200 Vitamins Fat-soluble mg/liter Vitamin A, RE* 670±200 (2230 IU) Vitamin D 0.55±0.10 Vitamin E 2300±1000 Vitamin K 2.1±0.1 Water-soluble mg/liter Vitamin B6 93,000±8,000 Vitamin B12 0.97 Biotin 4±1 Vitamin C 40,000±10,000 Folate 85±37 Niacin 1500±200 Pantothenic acid 1800±200 Riboflavin 350±25 Thiamin 210±35 Reprinted from Hamosh et al: Nutrition During Lactation, (1991, p 116), Copyright (c) 1991, National Academy Press.Data (means ± SD); IU = international units; NR = not reported; RE = retinol equivalents.
Table II. Cytokines in Human Milk: Mean Concentrations and Potential Functions*
Cytokines Possible Functions Concentrations IL-1b Activates T cells ~ 1130pg/mL IL-6 Enhances IgA production ~ 151pg/mL IL-8 Chemotaxin for neutrophils/T cells ~ 3500pg/mL IL-10 Decreased inflammatory cytokine synthesis ~ 3500pg/mL TNF-a Increased secretory component production ~ 620pg/mL TGF-b Enhances Ig isotype switching to IgA+ B cells ~ 130pg/mL M-CSF Induce proliferation and differentiation of macrophages ~ 2000-9000 U/mL *Milk collected during the first several days of lactation. Data are mean values.
From Goldman AS, et al.[42]
Table III. Enteric and Respiratory Pathogens Commonly Targeted By Secretory IgA Antibodies Found in Human Milk
Enteric Pathogens Respiratory Pathogens
- * Bacteria, Toxins, Virulence Factors
- Clostridium difficile
Escherichia coli
Salmonella spp
Shigella spp
Vibrio cholerae- * Parasites
- Giardia lamblia
- * Viruses
- Polioviruses
Rotaviruses
- * Bacteria
- Haemophilus influenzae
Streptococcus pneumoniae
Klebsiella pneumoniae- * Viruses
- Influenza viruses
Respiratory syncytial virus- * Fungi
- Candida albicans
- * Food Proteins
- Cow’s milk
SoyFrom Goldman AS, Goldblum RM. Immunologic systems in human milk: Characteristics and effects, in Lebenthal E (ed): Textbook of Gastroenterology and Nutrition in Infancy, ed 2. New York, Raven Press, 1989, pp 135-142.
Table IV. Anti-Inflammatory Components in Human Milk
Component Enzymes Function Catalase Degrades hydrogen peroxide Histaminase Degrades histamine Arysulfatase Degrades leucotrienes Antioxidants
a-Tocopherol
Cysteine
Ascorbic acidScavengers of oxygen radicals Antiproteases
a -1-antitrypsin
a -1-antichymotrypsinNeutralize enzymes that act in inflammation Prostaglandins
PG-E2
PG-F2Cytoprotective Reprinted from Acta Paediatr Scand (1986; 689), Copyright (c) 1986, Scandinavian University Press.
Table V. Immune Factors in Human Milk that Compensate for Delayed Production in Infants
Immune Factors in Human Milk When Immune Factors Mature in the Infant Secretory IgA (sIgA) ~ 4-12 months Full antibody repertoire ~ 24 months Lysozyme ~ 1-2 years Lactoferrin ? Interleukin-6 ? PAF-acetylhydrolase ? Memory T cells 2 years Reprinted from Pediatr Infect Dis J (1993; 12:664-672), Copyright (c) 1993, Williams and Wilkins.
Table VI. Growth Factors in Human Colostrum and Milk
Growth Factor Colostrum Milk EGF* 6-73 nM 3-19 nM NGF Not quantified Insulin* 21.5±5mg/L 2.6±0.3mg/L IGF-I 10.9±5.3mg/L 7.1-19.1mg/L IGF-II NR 2.7±0.7mg/L Relaxin 327±110mg/L 509±5.3ng/L TGF-a 2.2-7.2mg/L 0-8.4mg/L * EGF concentration higher in preterm colostrum and milk, insulin concentration lower in preterm colostrum and milk than in term milk. From Donovan et al. [64]
Table VII. Function of Milk-Growth Factors and Hormones in the Mammary Gland and Newborn
Growth Factor/Hormone Maternal Mammary Gland Newborn PRL Maintenance of lactation Neuroendocrine and immune system Corticosterone Synthetic capacity (enzymes, specific proteins, etc.) Response to stress in the adult Insulin Growth via IGF-II or IGF-I Neonatal glycemia IGFs Growth and (?) differentiation of gland GI growth, affect IGF receptors in intestine (?) systemic growth effects Relaxin Growth and differentiation EGF, TGF-a Growth GI growth, gut closure, eye opening TGF-b Inhibits growth Inhibits enterocyte growth in ovarian GnRH receptors GnRH (?) GH secretion GRH (?) GH secretion TRH (?) TSH secretion PTHrP (?) Ca/P/Mg in milk Salmon calcitonin-like peptide PRL inhibiting factor Erythropoietin Stimulates erythropoiesis Prostaglandins Cytoprotection for intestine EGF: epidermal growth factor; IGF: insulin like growth factor; PRL: prolactin.
From Grosvenor et al.[62]
Table VIII. Functions of Enzymes in Human Milk
Function Enzyme(s) Process(s) Biosynthesis of milk components in the mammary gland Phosphoglucomutase Synthesis of lactose Lactose synthetase Synthesis of lactose Fatty acid synthetase Synthesis of medium-chain fatty acids Lipoprotein lipase Uptake of circulating triglyceride fatty acids Digestive function in the infant Amylase Hydrolysis of polysaccharides Lipase (bile salt-dependent) Hydrolysis of triglycerides Proteases* Proteolysis (not verified) Transport in the infant Xanthine oxidase Carrier of iron, molybdenum Glutathione peroxidase Carrier of selenium Alkaline phosphatase Carrier of zinc, magnesium Preservation of milk components Antiproteases Protection of bioactive proteins (ie, enzymes and immunoglobulins) Sulfhydryl oxidase Maintenance of structure and function of proteins containingS-S bonds Anti-infective agents Lysozyme Bactericidal Peroxidase Bactericidal Lipases (lipoprotein lipase, bile salt-dependent lipase) Release of free fatty acids that have antibacterial, antiviral,and antiprotozoan actions Protection against enterocolitis PAF-AH Hydrolysis of platelet necrotizing activity factor *It is not known whether the proteolytic enzymes of milk are active because of possible interaction with milk antiproteases. PAF-AH = Platelet activity factor acetyl hydrolase.
From Hamosh.[66]
Table IX. Characteristics of Milk Enzymes Active in Infant Digestion Enzyme
Characteristic Maternal factors Amylase Bile salt-dependent lipase High parity (>10) Low activity ? Malnutrition ? Decrease in activity Diurnal and within feed activity Constant Constant Pattern of secretion Prepartum ? Present Colostrum Colostrum greater than milk Colostrum lower than milk Milk after preterm (PT) and term (T) delivery Equal activity PT and T Equal activity PT and T Weaning ? Activity constant independent of milk volume Distribution in milk Aqueous phase Aqueous phase Effect of milk storage Temperature Cold: -20deg.C to -70deg.C Stable Stable Warm: +15deg.C to +38deg.C Stable (at least 24 hrs) Stable (at least 24 hrs) Effect of pH Low pH (pH>3.0) (passage through stomach) Stable Stable pH optimum 6.5-7.5 7.4-8.5 Enzyme character Identical to salivary amylase isozyme Identical to pancreatic carboxyl ester lipase Evidence of activity in infant’s intestine Yes Yes Presence in milk of other species ? Yes, in primates and carnivores From Hamosh.[66]
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- Mehta NR, Jones JB, Hamosh M: Lipases in human milk: Ontogeny and physiologic significance. J Pediatr Gastroenterol Nutr 1:317-326, 1982.
- Alemi B, Hamosh M, Scanlon JW, et al: Fat digestion in very low birth weight infants: Effect of addition of human milk to low birth weight formula. Pediatrics 68(4):484-489, 1981.
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- Hamosh M: Should infant formulas be supplemented with bioactive components and conditionally essential nutrients present in milk? J Nutr 1997. In press.
- Hamosh M, Hong MH, Hamosh P: beta-Casomorphins: milk-beta-casein derived opioid peptides, in Lebenthal E (ed): Textbook of Gastroentorology and Nutrition in Infancy, ed 2. New York, Raven Press, 1989, pp 143-150.
- Hamosh M, Hamosh P: Differences in composition of preterm, term and weaning milk, in Xanthou M (ed): New Aspects of Nutrition in Infancy and Prematurity. Amsterdam, Elsevier, 1987, pp 129-141.
- Schanler RJ, Hurst NM: Human milk for the hospitalized preterm infant. Seminar Perinatol 18:476, 1994.
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- Mayer EJ, Hamman RF, Gay EC, et al: Reduced risk of IDDM among breast fed children. The Colorado IDDM Registry. Diabetes 37(12):1625-1632, 1988.
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- Rogan WJ, Gladen BC: Breast-feeding and cognitive development. Early Hum Devel 31(3):181-193, 1993.
- Hamosh M: Lipid metabolism in pediatric nutrition. Pediatr Clin North Am 42:839-959, 1995.
Dr. Hamosh is a professor of pediatrics and chief, Division of Developmental Biology and Nutrition, Department of Pediatrics, at Georgetown University Medical Center in Washington, D.C.