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Deborah L. O’Connor
Mary Frances Picciano†
†Deceased. With the passing of Dr. Picciano, she unfortunately was unable to review the revision of this chapter.
Human milk, a complex food, provides both nutrition and bioactive components that confer benefits for the growth, development, and health of infants. In recognition of this, the World Health Organization (WHO), the American Academy of Pediatrics (AAP), and Health Canada all recommend exclusive breast-feeding for the first 6 months of life. At 6 months, it is advised that infants be introduced to nutrient-rich, solid foods and breast-feeding be continued for the first 12 to 24 months of life and beyond (1
). Exclusive breast-feeding is defined as not receiving any solids or liquids other than breast milk (4
). Despite these recommendations, only 33% and 13% of infants in the United States are exclusively breast-fed through 3 or 6 months, respectively (5
). In fact, only 43% of infants are fed any human milk at all at 6 months. Initiation rates are somewhat more encouraging, with 75% of US women initiating breastfeeding. The US Healthy People 2020 objectives are to increase the proportion of US mothers who breast-feed (any breast-feeding) their babies to 82% in the early postpartum period and to 61% at 6 months, as well as to increase exclusivity of breast-feeding at 3 and 6 months to 46% and 26%, respectively (6
). Few contraindications to breast-feeding exist. Generally, women who test positive for human immunodeficiency virus (HIV), have active and untreated tuberculosis, have human T-cell lymphotropic virus type 1 or type 2, or use either illegal drugs or certain prescribed drugs, such as chemotherapeutic drugs for cancer treatment, should not breast-feed (4
). Infants with galactosemia should not be breast-fed. In developing countries, however, a safe alternative to breast-feeding may not be available, and evaluation of the relative risks of infant feeding choices may be necessary.
Human milk is a unique food that provides much more than nutrition for the infant. In addition to macronutrients and micronutrients, an impressive body of evidence indicates that human milk contains a host of other components—including anti-inflammatory agents, immunoglobulins, antimicrobials, antioxidants, oligosaccharides, cytokines, hormones, and growth factors—that have biologic activities related to development, metabolic regulation, inflammation, and pathogenesis (7
). The combined effects of these bioactive components may result in the observed protection that human milk provides breast-feeding infants against infectious diseases, allergic disorders, and chronic diseases with an immunologic basis (8
This chapter summarizes information on the prevalence of lactation, its physiologic aspects, and the composition of human milk. In addition, it highlights the possible beneficial impact of lactation on both the breast-fed, fullterm infant and the breast-feeding mother and suggests directions for future lactation research.
Trends globally, from 1995 to 2008, in the percentage of infants less than 6 months who were exclusively breast-fed. Asterisks,
excluding China; CEE/CIS, Central and Eastern Europe/Commonwealth of Independent States region. (Data from UNICEF. UNICEF Global Databases 2010, from Multiple Indicator Cluster Surveys, Demographic Health Surveys, and Other National Surveys. Available at: www.childinfo.org/
breastfeeding_progress.html. Accessed June 28, 2011, with permission.)
PREVALENCE OF BREAST-FEEDING
Throughout the World
The WHO Global Data Bank on Breastfeeding provides surveillance data, primary from national and regional surveys, from 94 countries or 65% of the world’s infant population (<12 months) (9
). These data suggest that initiation rates for breast-feeding in the United States are similar to those of the United Kingdom (76%) and Germany (77%) but lower than those of Canada (93%) and Austria (93%). The percentage of mothers who exclusively breast-feed to 4 months in the United States (33%) is lower than in Canada (51%), but the exclusivity to 6 months is low in the United States (14%), Canada (14%), Germany (22%), and Austria (22.4%). The United Nations Children’s Fund (UNICEF) provides exclusivity of breast-feeding data globally by geographic region (10
). Rates for exclusive breast-feeding of infants from 0 to 5 months of life have been estimated to be highest in East Asia and the Pacific region (43%) and in Eastern and Southern Africa (41%), and lowest in West and Central Africa (20%) and in Central and Eastern Europe and the Commonwealth of Independent States (22%) (Fig. 53.1
). The global average of exclusive breast-feeding from 0 to 5 months reported by UNICEF was 37%.
In the United States
The prevalence of breast-feeding in the United States has been estimated by several large national surveys, including the Ross Laboratories Mothers Survey, the National Health and Nutrition Examination Survey (NHANES, 1996 to 2006), and the Centers for Disease Control and Prevention National Immunization Survey (5
). The Ross Laboratories Mothers Survey was initiated in 1954 and has expanded considerably since then. It was designed to determine patterns of milk feeding during infancy. The reported percentage of mothers who ever breast-fed increased from low levels in the 1950s and 1960s to a high point in 1982, declined throughout the 1980s, but then increased through the 1990s (Table 53.1
According to NHANES, the percentage of infants who were ever breast-fed increased from 60% among infants born in 1993 to 1994 to 77% among infants born in 2005 to 2006 (11
). In contrast, no significant change in the rate of breast-feeding at 6 months of age occurred for infants born between 1993 and 2004. Both in-hospital
breast-feeding and 6-month breast-feeding were more common among white and Hispanic women than among black women (11
). In the 2005 to 2006 birth cohort group, 65% of non-Hispanic black infants were breast-fed compared with 80% of Mexican-American and 79% of non-Hispanic white infants.
TABLE 53.1 IN-HOSPITAL AND 6-MONTH BREASTFEEDING RATES ACCORDING TO PARTICIPATION IN THE SPECIAL SUPPLEMENTAL NUTRITION PROGRAM FOR WOMEN, INFANTS, AND CHILDREN
IN-HOSPITAL BREAST-FEEDING (%)
BREAST-FEEDING AT 6 MO (%)
WIC, Special Supplemental Nutrition Program for Women, Infants, and Children.
Data from Ryan AS, Zhou W. Lower breastfeeding rates persist among the Special Supplemental Nutrition Program for Women, Infants, and Children participants, 1978-2003. Pediatrics 2006;117:1136-46, with permission. Some data extrapolated from figures.
Breast-feeding rates have increased significantly with increasing maternal age overall and for all race and ethnicity groups, and they remain lowest among lowincome women (11
). Data from the Ross Laboratories Mothers Survey indicate that the breast-feeding initiation rates among women who participated in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) between 1978 and 2003 lagged considerably behind those of non-WIC mothers, by an average of 24% (13
). From 1999 to 2003, the gap in breast-feeding rates at 6 months between WIC and non-WIC mothers exceeded 20%. To be eligible for WIC, a woman must fall at or below 185% of the US poverty income guidelines, or she or a family member must receive some form of financial assistance from the government. WIC revised their food packages to enhance the monetary value of the breast-feeding packages, which were thought to be a disincentive to breast-feeding. Before these changes, the market value of the food package for an exclusive formula-feeding mother and infant was approximately $1380 compared with $670 for a mother who decided to breast-feed exclusively for the first year.
MAMMARY GLAND AND REGULATION OF MILK SECRETION
The mature breast of nonpregnant, nonlactating women has a treelike pattern of branching ducts that extends from the nipple to the edges of the fat pad. Alveolar clusters exist in a dynamic state, with growth and complexity increasing and decreasing in response to the hormonal changes of the menstrual cycle. During pregnancy, lobular alveolar complexes expand dramatically in response to progesterone, prolactin, and placental lactogen. Secretory differentiation occurs around midpregnancy (stage 1 lactogenesis), but milk secretion is inhibited by high progesterone levels (14
Lactogenesis and lactation are regulated through complex endocrine system control mechanisms that coordinate the actions of various hormones, including the reproductive hormones prolactin, progesterone, placental lactogen, oxytocin, and estrogen (15
). Although it is known that progesterone suppresses active milk secretion during lactogenesis 1, hormonal regulation during this stage is not well understood (16
). After parturition, lactogenesis 2, also called secretory activation, is initiated through progesterone withdrawal, combined with high levels of prolactin; this process results in secretion of colostrum (“early milk”) and then milk. Initiation of lactogenesis 2 does not require infant suckling, but suckling must begin by 3 to 4 days postpartum to maintain milk secretion. Prolactin, required to maintain milk production after lactation is established, is released into the circulation from the anterior pituitary in response to suckling. During lactation, release of prolactin is mediated by a transient decline in the secretion of dopamine, an inhibiting factor, from the hypothalamus. Because plasma prolactin levels do not correlate with rate of milk secretion, investigators have suggested that prolactin may be a permissive factor for milk secretion rather than a regulatory factor (16
A diagram of an alveolar complex, the milk-secreting unit of the human breast, is shown in Figure 53.2
). It consists of a layer of epithelial cells surrounded by various supporting structures, including myoepithelial cells, vasculature, and a stroma that contains adipocytes, fibroblasts, and plasma cells. To produce milk, four integrated secretory processes take place in the alveolar complex. These are as follows: exocytosis of milk protein, lactose, and other components of the aqueous phase via Golgi-derived secretory vesicles; fat synthesis and secretion through milk fat globules; secretion of ions, water, and glucose; and transcytosis of immunoglobulins and other substances from the interstitial spaces. Milk is secreted into the alveolar lumina and stored there until ejection by contraction of the myoepithelial cells (14
). Although milk secretion is a continuous process, the amount produced is regulated primarily by infant demand.
Suckling causes neural impulses to be sent to the hypothalamus; this triggers oxytocin release from the posterior pituitary. Oxytocin brings about contraction of the myoepithelial cells and thus forces milk into the ducts of the nipple so it is available for the infant. This response (let-down) also can be triggered simply by seeing the infant or hearing the infant cry. When milk is removed from the breast after parturition, milk volume increases significantly within several days postpartum. During lactation, the typical daily volume of milk transferred to the infant increases from 0.50 mL on day 1, to 500 mL by day 5, to 650 mL by 1 month, and to 750 mL by 3 months. Most women are capable of secreting considerably more milk than needed by a single infant. When milk is not removed, either by infant suckling or other means, involution of the mammary epithelium occurs, and milk secretion stops within 1 to 2 days.
COMPOSITION OF HUMAN MILK
Human milk is a remarkably complex biologic fluid. It is composed of thousands of constituents that are dispersed throughout various phases, including an aqueous phase with true solutions (87%), colloidal dispersions of casein molecules (0.3%), emulsions of fat globules (4%), fat globule membranes, and live cells. Milk composition changes substantially as early milk develops the characteristics of mature milk that are evident by day 10 of lactation.
For example, lactose increases; sodium, potassium, and chloride decrease; total lipids increase; the immune factors lactoferrin and secretory immunoglobulin A decrease; and oligosaccharides decrease. Representative values for early and mature human milk constituents are listed in Table 53.2
). Both the composition and volume of human milk secreted are influenced to some degree by factors such as genetic individuality, maternal intake (particularly fatty acids, vitamin B12, thiamin, riboflavin, vitamin B6
, vitamin A, selenium, and iodine), and stage of lactation (19
Fig. 53.2. Diagram of the mammary alveolus and alveolar epithelial cell showing pathways for milk secretion. Milk is secreted by alveolar epithelial cells into the lumen and is then expressed through the ducts by contraction of myoepithelial cells (ME). The alveolus is surrounded by a well-developed vasculature and a stroma that includes extracellular matrix components, fibroblasts, and adipocytes. The region inside the box is expanded to show key structural and transport properties of alveolar cells. I, Exocytotic secretion of milk proteins, lactose, calcium, and other aqueous-phase milk components. II, Formation of cytoplasmic lipid droplets that move to the apical membrane to be secreted as a membrane-bound milk fat globule (MFG). III, Vesicular transcytosis of proteins such as immunoglobulins from the interstitial space. IV, Transporters for the movement of monovalent ions, water, and glucose across the apical and basal membranes of the cell. V, Transport of plasma components and leukocytes through the paracellular pathway (open only during pregnancy, involution, and in inflammatory states such as mastitis). BM, basement membrane; FDA, fat-depleted adipocyte; GJ, gap junction; JC, junctional complex; N, nucleus; PC, plasma cell; RER, rough endoplasmic reticulum; SV, secretory vesicle. (Redrawn from McManaman JL, Neville MC. Mammary physiology and milk secretion. Adv Drug Del Rev 2003;55:629-41, with permission.)
The mammary gland is able to extract most nutrients actively from the circulation, independently of maternal regulatory systems, so milk may contain adequate levels of nutrients even during inadequate maternal intake. However, persistent maternal deficiencies may result in inadequate micronutrient concentrations in the milk. Although most constituents of human milk, including nutrients, are in fact bioactive, nutritional factors are grouped separately in the following discussion.
The protein constituents of human milk provide essential amino acids for growth, protective factors (e.g., immunoglobulins, lysozymes, lactoferrin), carriers for vitamins (e.g., folate-, vitamin D-, and vitamin B12
-binding proteins) and for hormones (e.g., thyroxine- and corticosteroid-binding proteins), enzymatic activity (e.g., amylase, bilesalt-stimulated lipase), and other biologic activities (e.g., insulin, epidermal growth factor). Although the total protein content of human milk is the lowest among species, it is easily digestible; and evidence indicates that nitrogen use from human milk for deposition of lean body mass is exceptionally high (24
). The nonprotein nitrogen
fraction of human milk comprises more than 200 compounds, including free amino acids, carnitine, taurine, amino sugars, nucleic acids, nucleotides, and polyamines. Maternal nutrition may alter both the total protein and nonprotein nitrogen constituents of human milk; however, healthy full-term exclusively breast-fed infants do not, as a rule, show signs of protein deficiency, regardless of maternal intake (22
TABLE 53.2 REPRESENTATIVE VALUES FOR CONSTITUENTS OF HUMAN MILK
CONSTITUENT (PER LITER)a
Total nitrogen (g)
Nonprotein nitrogen (g)
Protein nitrogen (g)
Total protein (g)
Serum albumin (g)
Serum immunoglobulin A (g)
Immunoglobulin M (g)
Immunoglobulin G (g)
Total lipids (%)
Triglyceride (% total lipids)
Cholesterolb (% total lipids)
Phospholipids (% total lipids)
Fatty acids (weight %)
Vitamin C (mg)
Vitamin B6 (mg)
Vitamin B12 (µg)
Pantothenic acid (mg)
Vitamin A (mg)
Vitamin K (µg)
Vitamin D (µg)
Vitamin E (mg)
a All values are expressed as per liter of milk with the exception of lipids, which are expressed as a percentage on the basis of either milk volume or weight of total lipids.
b The cholesterol content of human milk ranges from 100 to 200 mg/L in most samples of human milk after day 21 of lactation.
Reprinted with permission from Picciano MF. Representative values for constituents of human milk. Pediatr Clin North Am 2001;48:263-4.
Human milk lipids, the major energy-yielding fraction (45% to 55% of total kcal), are the most variable constituents in human milk. Circulating lipids, a reflection of maternal diet and adipose stores, are the main substrates for human milk fat. The characteristic features of human milk lipids are reviewed elsewhere (25
). Human milk is a rich source of linoleic acid (LA) and α-linolenic acid (ALA), both essential fatty acids, as well as their longchain polyunsaturated fatty acid (LC-PUFA) derivatives, arachidonic acid (ARA) and docosahexaenoic acid (DHA). Because fat digestion is not yet fully developed in the newborn, several enzymes join forces to aid in digestion of milk lipids. These include the following: lingual lipase, which initiates hydrolysis in the stomach; gastric lipase; pancreatic lipase; and bile salt-dependent lipase, which is a constituent of human milk.
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