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Breast Anatomy and Products
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Each mature mammary gland or breast is composed of 15 to 25 lobes. They are arranged radially and are separated from one another by varying amounts of fat. Each lobe consists of several lobules, which in turn are composed of numerous alveoli. Each alveolus is provided with a small duct that joins others to form a single larger duct for each lobe as shown in Figure 36-5. These lactiferous ducts open separately on the nipple, where they may be distinguished as minute but distinct orifices. The alveolar secretory epithelium synthesizes the various milk constituents, described next.
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After delivery, the breasts begin to secrete colostrum, which is a deep lemon-yellow liquid. It usually can be expressed from the nipples by the second postpartum day. Compared with mature milk, colostrum is rich in immunological components and contains more minerals and amino acids (Ballard, 2013). It also has more protein, much of which is globulin, but less sugar and fat. Secretion persists for 5 days to 2 weeks, with gradual conversion to mature milk by 4 to 6 weeks. The colostrum content of immunoglobulin A (IgA) offers the newborn protection against enteric pathogens. Other host resistance factors found in colostrum and milk include complement, macrophages, lymphocytes, lactoferrin, lactoperoxidase, and lysozymes.
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Mature milk is a complex and dynamic biological fluid that includes fat, proteins, carbohydrates, bioactive factors, minerals, vitamins, hormones, and many cellular products. The concentrations and contents of human milk change even during a single feed and are influenced by maternal diet, as well as infant age, health, and needs. A nursing mother easily produces 600 mL of milk daily, and maternal gestational weight gain has little impact on its quantity or quality (Institute of Medicine, 1990). Milk is isotonic with plasma, and lactose accounts for half of the osmotic pressure. Essential amino acids are derived from blood, and nonessential amino acids are derived in part from blood or synthesized in the mammary gland. Most milk proteins are unique and include α-lactalbumin, β-lactoglobulin, and casein. Fatty acids are synthesized in the alveoli from glucose and are secreted by an apocrine-like process. Most vitamins are found in human milk, but in variable amounts. Vitamin K is virtually absent, and thus, an intramuscular dose is given to the newborn (Chap. 33, Hyperbilirubinemia). Vitamin D content is low—22 IU/mL. Thus, newborn supplementation is also recommended by the American Academy of Pediatrics (Wagner, 2008).
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Whey is milk serum and has been shown to contain large amounts of interleukin-6 (Saito, 1991). Human milk has a whey-to-casein ratio of 60:40, considered ideal for absorption. Prolactin appears to be actively secreted into breast milk (Yuen, 1988). Epidermal growth factor (EGF) has been identified in human milk. And because it is not destroyed by gastric proteolytic enzymes, it may be absorbed to promote growth and maturation of newborn intestinal mucosa (McCleary, 1991). Other critical components in human milk include lactoferrin, melatonin, oligosaccharides, and essential fatty acids.
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Endocrinology of Lactation
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The precise humoral and neural mechanisms involved in lactation are complex. Progesterone, estrogen, and placental lactogen, as well as prolactin, cortisol, and insulin, appear to act in concert to stimulate the growth and development of the milk-secreting apparatus (Porter, 1974). With delivery, there is an abrupt and profound decrease in the levels of progesterone and estrogen. This decrease removes the inhibitory influence of progesterone on α-lactalbumin production and stimulates lactose synthase to increase milk lactose. Progesterone withdrawal also allows prolactin to act unopposed in its stimulation of α-lactalbumin production. Serotonin is produced in mammary epithelial cells and has a role in maintaining milk production. This may explain the decreased milk production in women taking selective serotonin-reuptake inhibitors—SSRIs (Collier, 2012).
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The intensity and duration of subsequent lactation are controlled, in large part, by the repetitive stimulus of nursing and emptying of milk from the breast. Prolactin is essential for lactation, and women with extensive pituitary necrosis—Sheehan syndrome—do not lactate (Chap. 58, Sheehan Syndrome). Although plasma prolactin levels fall after delivery to levels lower than during pregnancy, each act of suckling triggers a rise in levels (McNeilly, 1983). Presumably a stimulus from the breast curtails the release of dopamine, also known as prolactin-inhibiting factor, from the hypothalamus. This in turn transiently induces increased prolactin secretion.
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The posterior pituitary secretes oxytocin in pulsatile fashion. This stimulates milk expression from a lactating breast by causing contraction of myoepithelial cells in the alveoli and small milk ducts (see Fig. 36-4). Milk ejection, or letting down, is a reflex initiated especially by suckling, which stimulates the posterior pituitary to liberate oxytocin. The reflex may even be provoked by an infant cry and can be inhibited by maternal fright or stress.
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Immunological Consequences of Breast Feeding
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Human milk contains several protective immunological substances, including secretory IgA and growth factors. The antibodies in human milk are specifically directed against maternal environmental antigens such as against Escherichia coli (Iyengar, 2012). As a result, breast-fed infants are less prone to enteric infections than bottle-fed ones (Cravioto, 1991). Human milk also provides protection against rotavirus infections, a major cause of infant gastroenteritis (Newburg, 1998). Moreover, the risks of atopic dermatitis and respiratory infections are reduced (Ip, 2009). Bartick and Reinhold (2010) calculated that significant economic burdens from pediatric disease could be lessened by improved breast-feeding rates.
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Much attention has been directed to the role of maternal breast-milk lymphocytes in neonatal immunological processes. Milk contains both T and B lymphocytes, but the T lymphocytes appear to differ from those found in blood. Specifically, milk T lymphocytes are almost exclusively composed of cells that exhibit specific membrane antigens. These memory T cells appear to be an avenue for the neonate to benefit from the maternal immunological experience (Bertotto, 1990).
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Human milk is ideal food for neonates. It provides age-specific nutrients as well as immunological factors and antibacterial substances (American College of Obstetricians and Gynecologists, 2013a). Milk also contains factors that act as biological signals for promoting cellular growth and differentiation. The American Academy of Pediatrics (2012) has provided a list of dose-response benefits of nursing (Table 36-2). For both mother and infant, the benefits of breast feeding are long-term. For example, women who breast feed have a lower risk of breast and reproductive cancer, and their children have increased adult intelligence independent of a wide range of possible confounding factors (Jong, 2012; Kramer, 2008). Breast feeding is associated with decreased postpartum weight retention (Baker, 2008). In addition, rates of sudden-infant-death syndrome are significantly lower among breast-fed infants. Last, in the Nurses’ Health Study, women who reported breast feeding for at least 2 cumulative years had a 23-percent lower risk of coronary heart disease (Stuebe, 2009). For all these reasons, the American Academy of Pediatrics (2012) supports the World Health Organization (2011) recommendations of exclusive breast feeding for up to 6 months, with avoidance of exposure to cow milk proteins.
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The Surgeon General of the U.S. Department of Health and Human Services (2011) lists some barriers for breast feeding and suggests practical means of overcoming them. Educational initiatives that include father and peer counseling may improve these rates (Pisacane, 2005; Wolfberg, 2004). The Baby Friendly Hospital Initiative is an international program to increase rates of exclusive breast feeding and to extend its duration. It is based on the World Health Organization (1989) Ten Steps to Successful Breastfeeding (Table 36-3). Worldwide, almost 20,000 hospitals are designated as “baby-friendly.” Forrester-Knauss and coworkers (2013) described successful trends toward exclusive breast feeding in Switzerland during 9 years in which a Baby-Friendly Hospital Initiative was implemented. However, in 2011 in the United States, fewer than 10 percent of births in 43 states and the District of Columbia occurred in “baby friendly” hospitals (Centers for Disease Control and Prevention, 2012a). In a large population-based study, fewer than two thirds of term neonates were exclusively breast fed at the time of discharge (McDonald, 2012).
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There are a variety of individual resources available for breast-feeding mothers that include online information from the American Academy of Pediatrics (http://www.aap.org) and La Leche League International (http://www.lalecheleague.org).
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The nipples require little attention other than cleanliness and attention to skin fissures. Fissured nipples render nursing painful, and they may have a deleterious influence on milk production. These cracks also provide a portal of entry for pyogenic bacteria. Because dried milk is likely to accumulate and irritate the nipples, washing the areola with water and mild soap is helpful before and after nursing. When the nipples are irritated or fissured, it may be necessary to use topical lanolin and a nipple shield for 24 hours or longer. If fissuring is severe, the infant should not be permitted to nurse on the affected side. Instead, the breast should be emptied regularly with a pump until the lesions are healed. Poor latching of the neonate to the breast can create such fissures. Proper technique for positioning the mother and infant during latch-on and nursing has been reviewed by the American College of Obstetricians and Gynecologists (2013a).
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Contraindications to Breast Feeding
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Nursing is contraindicated in women who take street drugs or do not control their alcohol use; have an infant with galactosemia; have human immunodeficiency virus (HIV) infection; have active, untreated tuberculosis; take certain medications; or are undergoing breast cancer treatment (American Academy of Pediatrics and American College of Obstetricians and Gynecologists, 2012; Faupel-Badger, 2013). Breast feeding has been recognized for some time as a mode of HIV transmission and is proscribed in developed countries in which adequate nutrition is otherwise available (Chap. 65, Breast Feeding). Other viral infections do not contraindicate breast feeding. For example, with maternal cytomegalovirus infection, both virus and antibodies are present in breast milk. And although hepatitis B virus is excreted in milk, breast feeding is not contraindicated if hepatitis B immune globulin is given to the newborns of affected mothers. Maternal hepatitis C infection is not a contraindication because breast feeding has not been shown to transmit infection. Women with active herpes simplex virus may suckle their infants if there are no breast lesions and if particular care is directed to hand washing before nursing.
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Drugs Secreted in Milk
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Most drugs given to the mother are secreted in breast milk, although the amount ingested by the infant typically is small. Many factors influence drug excretion and include plasma concentration, degree of protein binding, plasma and milk pH, degree of ionization, lipid solubility, and molecular weight (Rowe, 2013). The ratio of drug concentration in breast milk to that in maternal plasma is the milk-to-plasma drug-concentration ratio. Most drugs have a ratio of ≤ 1, approximately 25 percent have a ratio > 1, and about 15 percent have a ratio > 2 (Ito, 2000). Ideally, to minimize infant exposure, medication selection should favor drugs with a shorter half-life, poorer oral absorption, and lower lipid solubility. If multiple daily drug doses are required, then each is taken by the mother after the closest feed. Single daily-dosed drugs may be taken just before the longest infant sleep interval—usually at bedtime (Spencer, 2002).
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There are only a few drugs that are absolutely contraindicated while breast feeding (Berlin, 2013; Bertino, 2012). Cytotoxic drugs may interfere with cellular metabolism and potentially cause immune suppression or neutropenia, affect growth, and, at least theoretically, increase the risk of childhood cancer. Examples include cyclophosphamide, cyclosporine, doxorubicin, methotrexate, and mycophenolate. If a medication presents a concern, then the importance of therapy should be ascertained. It should be determined whether there is a safer alternative or whether neonatal exposure can be minimized if the medication dose is taken immediately after each breast feeding (American Academy of Pediatrics and the American College of Obstetricians and Gynecologists, 2012). Data on individual drugs are available through the National Institutes of Health website, LactMed, which can be found at: toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT.
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Radioactive isotopes of copper, gallium, indium, iodine, sodium, and technetium rapidly appear in breast milk. Consultation with a nuclear medicine specialist is recommended before performing a diagnostic study with these isotopes (Chap. 46, Sonography). The goal is to use a radionuclide with the shortest excretion time in breast milk. The mother should pump her breasts before the study and store enough milk in a freezer for feeding the infant. After the study, she should pump her breasts to maintain milk production but discard all milk produced during the time that radioactivity is present. This ranges from 15 hours up to 2 weeks, depending on the isotope used. Importantly, radioactive iodine concentrates and persists in the thyroid. Its special considerations are discussed in Chapter 63 (Thyroid Cancer).
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This is common in women who do not breast feed and is typified by milk leakage and breast pain. These peak 3 to 5 days after delivery (Spitz, 1998). Up to half of affected women require analgesia for breast-pain relief, and as many as 10 percent report severe pain for up to 14 days.
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Evidence is insufficient to firmly support any specific treatment (Mangesi, 2010). That said, breasts can be supported with a well-fitting brassiere, breast binder, or “sports bra.” Cool packs and oral analgesics for 12 to 24 hours aid discomfort. Pharmacological or hormonal agents are not recommended to suppress lactation.
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Fever caused by breast engorgement was common before the renaissance of breast feeding. In one study, Almeida and Kitay (1986) reported that 13 percent of postpartum women had fever from engorgement that ranged from 37.8 to 39°C. Fever seldom persists for longer than 4 to 16 hours. The incidence and severity of engorgement, and fever associated with it, are much lower if women breast feed. Other causes of fever, especially those due to infection, must be excluded. Of these, mastitis is infection of the mammary parenchyma. It is relatively common in lactating women and is discussed in Chapter 37 (Breast Infections).
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Other Issues with Lactation
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With inverted nipples, lactiferous ducts open directly into a depression at the center of the areola. With these depressed nipples, nursing is difficult. If the depression is not deep, milk sometimes can be made available by use of a breast pump. If instead the nipple is greatly inverted, daily attempts should be made during the last few months of pregnancy to draw or “tease” the nipple out with the fingers.
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Extra breasts—polymastia, or extra nipples—polythelia, may develop along the former embryonic mammary ridge. Also termed the milk line, this line extends from the axilla to the groin bilaterally. In some women, there may be vulvar breast tissue (Wagner, 2013). The incidence of accessory breast tissue ranges from 0.22 to 6 percent in the general population (Loukas, 2007). These breasts may be so small as to be mistaken for pigmented moles, or if without a nipple, for lymphadenopathy or lipoma. Polymastia has no obstetrical significance, although occasionally enlargement of these accessory breasts during pregnancy or engorgement postpartum may result in discomfort and anxiety.
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Galactocele is a milk duct that becomes obstructed by inspissated secretions. The amount is ordinarily limited, but an excess may form a fluctuant mass—a galactocele—that may cause pressure symptoms and have the appearance of an abscess. It may resolve spontaneously or require aspiration.
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There are marked individual variations in the amount of milk secreted. Many of these are dependent not on general maternal health but on breast glandular development. Rarely, there is complete lack of mammary secretion—agalactia. Occasionally, mammary secretion is excessive—polygalactia.