Lactation
October 21, 1998
Karl Goldstein
karlgold@socrates.berkeley.edu
 
  1. Background
    1. Breastfeeding was once a universal requirement for infant survival, and still is for many families in many areas of the world.
    2. In the late 1700's in England, infants were preferentially fed with breast milk from the mother.  Substitutes included  breast milk from a wet nurse, animal milks and pap or panada (mixtures of cereal and water or milk).
    3. Beginning in the 1920's and 1930's and continuing after World War II, rates of breast feeding declined precipitously in industrialized countries.  By 1970, as little as 25% of all infants were breast fed at birth, and only about 5% at 6 months.  Intense marketing and the 'medicalization' of childbirth by male obsetricians were important contributing factors to this trend.  (Transparency 1).
    4. Since 1970 there has been a  reversal in this downward trend.  Rates peaked in 1982 with 62% of mothers initiating breast feeding, and 30% continuing at 6 months.  Since then, rates have declined again somewhat.
    5. Currently, breast feeding rates vary widely with educational attainment and ethnicity of the mother.  (Transparency 2).  In the 1980's:
      1. about 60% of Caucasian women breast fed their infants, as opposed to 30% of African-American women.
      2. over 70% of women with over 13 years of education breast fed their infants, as opposed to 30% of those who did not complete high school.
  2. Development
    1. Embryology
      1. Mammary glands begin to develop during the sixth week of gestation as solid growths of epidermis into the underlying tissue.  This growth occurs along thickened strips of ectoderm called the mammary ridges, which extend from the armpit to the groin.  In humans, unlike in dogs and other mammals, the mammary glands only persist in the pectoral region.  (Slide 1).
      2. The original solid growths canalize to form ducts under the influence of estrogen produced in the placenta.  At birth the mammary glands of males and females are identical, composed of about 15 to 20 rudimentary lactiferous ducts.  (Slide 2)
    2. Puberty
      1. In females, the breasts develop further after puberty under the influence of estrogen secreted by the developing follicle and corpus luteum each month.  Enlargement occurs due to deposition of fat and connective tissue.  The nipple becomes enlarged and pigmented.  Further growth and branching of the lactiferous ducts also occurs.
    3. Pregnancy
      1. Even more intense growth and branching of the lactiferous ducts occurs during pregnancy, under the influence of high serum estrogen levels from the corpus luteum and later the placenta.  Growth hormone, glucocorticoids, prolactin, and insulin also play a role in growth.  (Slide 3).
      2. Final development of the mammary glands occurs under the influence of progesterone, which in concert with the hormones mentioned above causes alveoli to bud from the ends of the lactiferous ducts.  Each alveolus is lined by milk-secreting cells.  These cells are unique among exocrine glands in that they are capable of both merocrine and apocrine secretion (see Nutrition below).  (Slide 4).
    4. Extra
      1. Infection of a lactiferous duct can lead to obstruction and painful accumulation of milk and pus within the breast.  (Slide 5).
      2. Gynecomastia is the development of breasts in men!  (Usually results from accidental or intentional exposure to estrogen).  (Slide 6).
  3. Initiation and Maintenance of Lactation
    1. Milk Production
      1. The hormone prolactin, secreted by the pituitary gland, is primarily responsible for stimulating actual milk production.  Serum prolactin levels increase 10-20 times over baseline over the course of pregnancy.  However, the action of prolactin  is inhibited by high estrogen and progesterone levels during pregnancy.  Human chorionic sommatomammotropin also has a role in lactogenesis.
      2. Towards the end of pregnancy, the breasts are fully developed but milk production is suppressed except for a small amount of watery secretion called colostrum.  Colostrum contains the same concentration of proteins and lactose (sugar) as regular milk, but hardly any fat, which is harder to digest.
      3. After the infant is born and the placenta expelled, serum estrogen and progesterone levels rapidly drop, allowing for transition to copious milk production over a period of 1 to 7 days.
      4. Milk production requires adequate background secretion of hormones involved in protein, glucose, and calcium regulation, including growth hormone, cortisol, insulin, and parathyroid hormone.
      5. Basal serum prolactin levels return to normal within a few weeks after birth.  However, each time the infant feeds, another neurohumoral reflex arc is activated via the hypothalamus, which leads to a burst of prolactin secretion by the anterior pituitary.  This allows the mother to continue breast feeding for several years after birth, provided she does so without significant interruption.  (Transparency).
    2. Milk Ejection
      1. Milk produced in the alveoli tends to accumulate in the lactiferous sinuses, which are enlargements in the lactiferous ducts near the opening of the nipple.  Actual milk ejection is  mediated by way of a neurohumoral reflex arc.  Suckling of the infant sends nerve signals to the hypothalamus, which produces the hormone oxytocin released by the posterior pituitary.  Oxytocin stimulates contraction of the myoepithelial (smooth muscle) cells surrounding the ducts, thereby squirting out the milk.  (Remember that oxytocin also causes uterine contraction, so nipple stimulation can  accelerate expulsion of both the fetus and placenta during labor).  Negative emotions in the mother, such as frustration, anger or anxiety, can inhibit oxytocin secretion and thus suppress the milk ejection reflex.  (Transparency).
  4. Cessation of Lactation
    1. After the mother stops breast feeding and prolactin levels decline, the alveoli degenerate and are reabsorbed.  However, much of the duct structure is maintained until menopause.
    2. Prolactin either directly or indirectly (or both) inhibits the pulsatile secretion of GnRH by the hypothalamus, and thus may cause amenorrhea for the duration of lactation.  This is an important, albeit unreliable, form of contraception in many families.  It is unreliable because in most women  menstruation eventually resumes after a period of  months to years after delivery, despite continued lactation.
  5. Nutrition
    1. A general principle is that the composition of breast milk varies with the time of day, from the beginning to the end of a feeding session, and  from one breast to the other.   It also changes with the age of the child.
    2. Proteins
      1. Proteins are synthesized in the alveolar cells and are secreted by exocytosis, whereby intracellular vacuoles filled with proteins fuse with the cell membrane, dumping the contents of the vacuoles directly  into the lumen of the alveolus.  (Transparency).
      2. A general principle is that the proteins in animal milk have antigenic properties, meaning they can cause an allergic or hyperimmune response in the infant.
      3. Casein is the predominant protein in both human and cow milk, but is present in lower concentrations in human milk.  Lactalbumin is the other important protein.
    3. Fats
      1. Lipids are packaged as membrane-surrounded droplets that pinch off of the cell membrane into the alveolus, and remain in suspension in the milk (colloid).
      2. Lipid concentrations vary the most among the nutritional components of milk, being higher early in the day and more generally, early in the life of the child.
      3. Breast milk is high in essential fatty acids (omega-3 and omega-6 polyunsaturated fatty acids, docosahexaenoic acid, arachidonic acid) that are necessary for proper brain and retina development, especially in premature infants.  Low levels of EFA's in soy-based formulas has been implicated in development delay.
    4. Carbohydrates
      1. Lactose is the predominant sugar in milk.  It is a disaccharide of glucose and galactose.  Glucose is a primary direct source of energy, while galactose can be used for both energy and in many biosynthetic pathways.  Lactose favors the growth of beneficial bacteria in the gut (Lactobacillus).
    5. Vitamins
      1. Are completely adequate to cover the needs of the infant.  No supplements are required.
    6. Minerals
      1. Iron in breast milk has very high bioavailability (% absorbed).
      2. Milk production can deplete the mother's calcium stores (decrease bone density) unless she has adequate dietary intake or takes a supplement.
  6. Immunology
    1. A general principle is that the infant's immune system is immature at birth and is much less able to ward off infection than adults are.  Newborns receive some protection in utero through transfer of antibodies across the placenta, but this protection tapers off quickly after birth.
    2. Breast milk contains a number of components to help protect the infant from pathogens.
      1. Secretory IgA
        1. IgA is one of five classes of antibodies produced by the immune system.  It is secreted into the lumen of the respiratory and gastrointestinal tracts, where it binds to pathogens and prevents them from penetrating the epithelium and entering surrounding tissues and the bloodstream.
        2. The alveoli in the mammary glands are surrounded by high concentrations of plasma cells (antibody-producing B cells), which produce IgA specific for pathogens to which the mother has been exposed.  This IgA crosses the alveolar cells and  is secreted into the milk, where it helps protect against  pathogenic invasion through the infant's gastrointestinal tract.
      2. There are a wide variety of other antimicrobial molecules in breast milk, some of which can inhibit the growth of infectious agents and others which promote the growth of beneficial bacteria.
      3. White blood cells (neutrophils and macrophages) are relatively abundant in breast milk and can directly attack pathogens in the infant's gut, as well as activate the infant's own immune system.
      4. Growth factors and other stimulatory factors, including epidermal growth factor, nerve growth factor, somatomedin C, and  insulin-like growth factor, help accelerate maturation of  the intestinal mucosa so it becomes less susceptible to attack.
  7. Benefits of Breastfeeding
    1. Benefits to the Infant
      1. Breastfed infants have well-documented reductions in the  incidence and severity of almost all common infectious diseases compared to formula fed infants.  This includes diarrhea, upper respiratory infections, ear infections, septicemia, and urinary tract infections.
      2. Breastfed infants grow faster initially than formula fed infants, and then taper off around one year.  Formula fed infants have a higher incidence of obesity in adulthood.
      3. An increasing number of studies suggest that breastfeeding has positive effects on mental development, although the generally better socioeconomic and educational status of breastfeeding mothers confuses the issue substantially.
    2. Benefits to the Mother
      1. Because of the extra metabolic demands of breastfeeding, women who do it may experience more rapid and sustained weight loss after delivery.
      2. Extended periods of lactational amenorrhea are associated with decreased risk of contracting breast cancer over the lifetime of a woman.
    3. More generally, incredible psychosocial benefits to the mother, child, and father as well!
  8. Complications to Breastfeeding
    1. In the past, health professionals generally considered breastfeeding to be beneficial under ideal circumstances, but were quick to recommend formula feeding in the presence of maternal illness, stress, or inadequate milk production.
    2. Today, mothers receive much greater encouragement to start and continue breastfeeding at least through the first six months, even in the face of complications.
      1. Mothers with HIV may breastfeed provided they are not recently infected.  The risk of transmission is much greater at birth than from breastfeeding (Mexican Health Ministry).
      2. Mothers with Hepatitis B may breastfeed provided the infant receives gamma globulin (American Academy of Pediatrics).
      3. Some drugs are absolutely contraindicated in a breastfeeding mother because they are excreted in breast milk and have negative effects on growth and development.  However, substitutes are often available provided the mother's doctor is willing to do the required research.
      4. Supplementation is generally required for premature infants because their nutritional needs are different from those of full-term infants.
      5. Most hospitals now employ lactation consultants to help new mothers with problems of insufficient (perceived or otherwise) production, pumping, and generally providing support to breastfeeding mothers.