Why is milk produced by a woman only after delivery not before

Lactation Support for Mothers of Preterm Infants

Lactogenesis I begins in pregnancy and is composed of cellular and glandular development, whereas lactogenesis II is the stage of milk production and secretion69 and occurs by 48 to 72 hours in most women.70 The mammary gland is a complex system of myoepithelial cells and alveolar epithelium that requires the closure of tight junctions,29 lactation secretion, and maintenance71 that are influenced by local and endocrine factors11 (Fig. 13-1).

Mothers of preterm infants often demonstrate delayed lactogenesis.72 The etiology of delayed lactogenesis in mothers who deliver prematurely may be multifactorial12 and may include hormonal imbalances, stress-related cortisol inhibition of the pituitary release of oxytocin, or inflammatory-mediated changes in the gland. Maternal characteristics attributed to living in the United States and obese population have been documented to be associated to delayed lactogenesis.70,73,74

Lactation support with anticipatory guidance,75 breast-friendly hospital designation,76,77 skin-to-skin holding,78 and training the mother regarding the use of electric pumps and hand expression regimens are strategies that can improve milk volume. It is essential that lactation consultants are involved early and often for maternal support.11

2.2 Milk Producers

Milk production in the United States in 2003 totaled 170 billion pounds, resulting from the tireless efforts of 9 million cows in more than 70,000 dairy herds (USDA, 2004b). Production is concentrated in 20 states, which house 7.8 million cows producing 147 billion pounds of milk. California is the largest milk producer, accounting for 20% of the U.S. milk supply (USDA National Agricultural Statistics Service, 2004).

Milk production and processing routines may vary slightly from state to state. In California, a farm will milk its cows and ship the raw milk by tanker truck to a silo, which can hold from 50,000 to 200,000 gallons. The milk then proceeds from the silo into a processing plant where pasteurization (heating to 170°F for 15 minutes), homogenization, and vitamin fortification occurs. The processor packages the milk and places it into the distribution chain, where it heads (via wholesale distributors) to retail stores and institutional purchasers, including restaurants and catering services. The processor cleans each milk silo every 72 hours.

The U.S. Department of Agriculture (USDA) inspects milk processing plants under a voluntary program, set up under the Agricultural Marketing Act of 1946. Because compliance with USDA standards helps sell milk, participation is high. Inspections are designed to show the extent of a plant's raw milk, equipment, and procedure compliance with standards set forth in 7 CFR 58, subpart B, “General Specifications for Dairy Plants approved by USDA Inspection and Grading Service” (USDA, 2004a). The USDA will inspect processing plants under this arrangement at frequencies that depend on the plant's status. Usually, inspections are conducted every 5 to 9 months, although plants on probation will be inspected 10 days after the probationary citation.

USDA grades milk by sanitary manufacturing standards. The highest grade of milk is “A,” which denotes milk that the processor has collected and cooled promptly; that has passed inspection for appearance, odor, and sediment; and that has bacterial cell counts of no more than 500,000 per milliliter. The producer retains milk production data but would send it to USDA as well.

3 Milk Secretion

In lactogenesis, the mammary gland develops the capacity to secrete milk. Lactogenesis includes all changes that transform the mammary gland from its undifferentiated state in early pregnancy to its fully differentiated stage just after delivery. Initial stage on lactogenesis (Stage I) occurs during pregnancy. It is defined by the differentiation of mammary alveolar epithelial cells into lactocytes, the specialized secretory cells, in response to progesterone, prolactin, and placental lactogen. The mammary gland is able to produce small amounts of immunoglobulin-rich secretion, called colostrum, although milk secretion is inhibited by the high progesterone levels. After delivery of the placenta, the withdrawal of progesterone as well as the high levels of prolactin triggers the secretory activation (Stage II lactogenesis). There is a sudden increase in intracellular lactose that draws water into the lactocyte and the mother notice an increase in milk volume (“milk coming in”).14 The phenomenon happens within the first 72 h postpartum. A delayed onset of lactogenesis is related with short BF duration. Initiation of lactogenesis II does not require infant suckling, but suckling must begin by 3–4 days postpartum to maintain milk secretion (galactopoiesis).

Although milk secretion is a continuous process, the amount of milk is regulated by infant demand. Suckling causes neural impulses that are sent to the hypothalamus, and then oxytocin is released from the posterior pituitary. Oxytocin causes contraction of the myoepithelial cells present in the alveolar complex and then allows milk to be poured out to the ducts in the nipple making it available for the infant (Fig. 2).

Most women are capable of secreting considerably more milk than needed by a single infant. The regulation of milk synthesis is quite efficient (around 800 mL/day). The rate of milk synthesis is related to the degree of breast emptiness or fullness. Nevertheless it is difficult to assess BM intake. With stable isotopes methods it was calculated that the mean HM intake in the first year of life was 0.78 kg/d. There is a steady increase over the first 3–4 months and remains above 0.80 kg/d until 6–7 months.15

Milk production is related to maternal states of well-being. If stress or fatigue is present they affect milk supply. This downregulation is mediated by increased levels of dopamine, norepinephrine or both, which inhibit prolactin synthesis. Relaxation is a key factor for successful lactation.

If milk is not removed by infant suckling, milk secretion stops within 1–2 days, and involution of the mammary epithelium occurs by an average of 40 days after last BF.

Stage I

Stage I lactogenesis starts approximately 12 weeks before parturition and is heralded by significant increases in lactose, total proteins, and immunoglobulin; decreases in sodium and chloride; and the gathering of substrate for milk production. The composition of prepartum secretion is fairly constant until delivery, as monitored by the milk protein α-lactalbumin.

Lactogenesis is initiated in the postpartum period by a fall in plasma progesterone, but prolactin levels remain high (Fig. 3.6). The initiation of the process does not depend on suckling by the infant until the third or fourth day, when the secretion declines if milk is not removed from the breast.27

14.7.3 Glucose Metabolism

Milk production is associated with a large increase in glucose uptake by the mammary gland. In ruminants, mammary glucose uptake consumes 60%–85% of the total amount of glucose that enters the maternal circulation.131 This dramatic increase in glucose uptake requires adaptations to provide enough glucose for milk synthesis and avoiding maternal hypoglycemia. These adaptations vary with the species, but they generally include some combination of increased gluconeogenesis, decreased maternal glucose utilization, and increased food intake.115,131,132 In ruminants, the glucose demands of lactation are met by a sharp increase in the rate of gluconeogenesis, and gluconeogenic precursors are supplied both from the diet and from maternal stores.131 In addition, glucose uptake by myocytes and adipocytes is suppressed during lactation, as is adipocyte lipogenesis.131 Maternal glucose metabolism in rodents has been studied less, although they also likely experience increased rates of gluconeogenesis, glycogenolysis, or both.108,109,133 Nursing women have lower blood glucose and insulin levels, despite having an increase in glucose production compared to postpartum women who are not lactating.115,116

Insulin sensitivity is also increased in lactating women, especially compared to the relative insulin resistance noted during pregnancy.115,116 Glucose tolerance testing suggests that stimulated insulin responses, as well as basal insulin secretion, are decreased in lactating women.115,134–137 Lactating women subjected to a short fast met the demands for milk production, primarily by increasing the rate of glycogenolysis by 50%.137 However, after a more prolonged fast, their rate of gluconeogenesis increased alongside that of lipolysis and ketogenesis.138 Glucose levels declined more rapidly with fasting in lactating women, leading to hypoglycemia after 30 h. While insulin levels were similarly suppressed in lactating and nonlactating women after fasting, glucagon levels were significantly higher in the lactating subjects.138

The endocrine control of adaptations in glucose metabolism during lactation is not fully understood. It is likely that lower levels of insulin and increased insulin sensitivity are prime drivers for the increased rates of glucose production, whether by stimulating increased glycogenolysis, gluconeogenesis, or both in target tissues.109,115,116,135–137 Both GH and PRL also modulate glucose metabolism, likely by increasing insulin resistance in peripheral tissues114,139–141 to direct glucose toward the mammary gland in support of milk production.115,131 Interestingly, oxytocin has been described to increase insulin sensitivity as well as insulin release, which seems at odds with the reported decreased insulin levels and responses in lactating women and rodents.142 An abundance of research literature highlights the correlations between maternal body mass and nutrition, the levels of milk adiponectin and other adipokines, and neonatal metabolic programming,115,131,143–145 although less emphasis has been placed on the potential role of these factors on maternal metabolism during lactation. Maternal adiponectin levels in cows and women are decreased in early lactation which, at least in ruminants, may help to retain insulin insensitivity.131,146,147 Furthermore, hepatic production of fibroblast growth factor-21 (FGF21) is increased during lactation,133,148,149 which theoretically might increase fatty acid oxidation and augment insulin sensitivity, thereby reducing gluconeogenesis.148 However, neither increased fat oxidation nor suppressed gluconeogenesis is typical of the maternal adaptations to lactation, and it has also been shown that hepatic FGF21 is transported into milk and affects neonatal gut function.150 Thus, a more dominant function of FGF21 during lactation may be to coordinate maternal and neonatal metabolism. Finally, concentrations of both GLP1 and GIP are elevated during lactation in ruminants and rodents, although the contribution of these gut peptides to insulin secretion is not clear, given that insulin levels are decreased in these species during lactation.131,151–153

Milk Volume

Daily milk production in women is relatively constant regardless of maternal nutritional status.2 Exclusively breast-fed healthy infants have a mean daily milk intake of 750 to 800 mL/24 hours from 1 to 6 months of lactation. However, a wide range of intake volumes from 450 to 1200 mL/24 hours has been reported.3 Despite these differences in milk intake, there is a significant relationship between milk intake and infant growth rate.4 Milk intake remains consistent from 1 to 6 months.3 This is not surprising considering that younger infants (1 to 3 months of age) grow more rapidly than older infants (4 to 6 months of age).5 Smaller infants also have a larger surface area to volume ratio and therefore have a higher metabolic rate per kilogram of body weight6 and utilize more of their nutrient intake for maintenance of body temperature than do older, heavier infants.

Similar levels of milk production have been reported for mothers in developing countries,7 although maternal nutritional status may be subject to seasonal variation and may be less than adequate based on industrial country standards. Increasing the intake of fluids does not seem to affect milk production; therefore lactating women should maintain adequate fluid intake, but they should be aware that “fluids consumed in excess of natural thirst have no effect on milk volume.”8

The measurement of daily milk production provides an objective measure of mammary gland function and has been shown to be useful to both the clinician9 and the mother without undermining the mother's confidence.10 In contrast, measurement of milk intake at a single incidence of breast-feeding is of little value because milk intake is controlled by the infant's appetite and can vary greatly from one breast feeding to the next.3

Dairy Products

Milk production exceeds 700 million tons annually, but about 10–20% of the initial milk and dairy production is lost worldwide. Europe is the main producer of dairy products. A large proportion of them found on the market are fermented, like cheese (20 million tons) or yogurt. Starter cultures, often used in the industrial production of fermented products, usually overgrow indigenous microbiota, lead to a pH drop, and thus limit the possibility of spoilage bacteria having a negative effect on the quality of the products. The addition of salt in cheese making also contributes to reducing spoilage. Nevertheless, dairy product spoilage is still reported, and some examples are listed in the succeeding text.

In fresh cheese, like cottage cheese, the relatively high pH may not be sufficient to inhibit the development of psychrotrophic species of Pseudomonas and coliforms. The spectacular ‘blue mozzarella cheese’ spoilage has been reported in Italy and Germany. It is caused by Pseudomonas fluorescens strains producing a blue pigment (i.e., pyocyanin) after mozzarella cheese packs are opened, changing the milky white balls typical of this product into inky blue balls. Pseudomonas fluorescens and other Pseudomonas species, such as Pseudomonas putida and Pseudomonas fragi, may also be responsible for the rancid flavors and odors caused by their lipid and fatty acid metabolism. In addition, several Pseudomonas and Bacillus species can produce proteases that may degrade caseins causing the bitterness of cheese and influencing milk coagulation. Extracellular lipase and protease activities produced by Pseudomonas can be heat-stable and therefore affect milk quality even after heat treatment, such as pasteurization or ultra-high-temperature treatment. Slime production by some lactic acid bacteria has also been reported. This property is considered beneficial for fermented yogurts since it contributes to their texture but undesirable in many other products. Slime production by Alcaligenes viscolactis in cottage cheese and by Pseudomonas putida or Pseudomonas fragi on cheese surfaces has been reported as spoilage. Moreover, the butter smell due to the diacetyl molecule participates in the quality of some dairy products but is undesirable in others. Diacetyl is produced by various bacteria, in particular lactic acid bacteria, but degraded by other species. Therefore, some lactic acid bacteria may be considered spoilers through diacetyl production in some products, whereas diacetyl degradation by some species may result in spoilage in other products requiring a buttery flavor. Propionibacterium freudenreichii contributes to the Swiss-type cheese taste and to the ‘eyes’ or holes typical of these cheeses by producing gas. This phenomenon is well controlled by cheese makers, but occasionally, lactic acid bacteria or Clostridia may produce a gassy defect in an uncontrolled manner, leading to holes of unwanted size. Clostridium tyrobutyricum may cause this spoilage and, by producing butyric acid, may also provoke a rancid taste. Early blowing in fresh cheese in the early ripening stage and late blowing occurring well into the ripening stage of hard and semihard cheeses are also important causes of spoilage. It results in considerable losses as large-volume productions can be spoiled. Gas (CO2) and butyric acid production by bacterial metabolism lead to balloon-like expansion of cheeses and to rancidity, respectively. Several gas-producing bacterial species belonging to Enterobacteriaceae can be responsible for early blowing, while Clostridia spp. are the main causes of late blowing. Clostridial spores, initially present in raw milk, can germinate and then grow during the cheese making process. Clostridium tyrobutyricum is the main species causing late blowing, but Clostridium butyricum and Clostridium sporogenes have also been reported as involved in this defect.

These examples show that bacterial spoilage of dairy products may affect the color, texture, odor, or appearance of the product and can be caused by various Gram-positive and Gram-negative species.

Lactation

Lactogenesis, or milk secretion, includes all the necessary changes that the mammary epithelium goes through to develop into a fully functional lactational gland after birth (Neville et al., 2001). This process begins during mid-pregnancy and continues until weaning (Neville et al., 2001). During the pregnancy–lactation cycle the breast matures from nonfunctional tissue into a mature milk-producing gland (Faupel-Badger et al., 2013). When breastfeeding is completed, there is apoptosis of the secretory epithelium to return the tissue to a resting state (Watson, 2006; Faupel-Badger et al., 2013).

Research has shown that breastfeeding, especially for a longer time span, is protective against breast cancer development when compared to parous women who never breastfed (Bernier et al., 2000; Kobayashi et al., 2012). The mechanisms of how breastfeeding decreases breast cancer risk are unknown; however, theories generally focus on the fact that breastfeeding and sustained lactation decrease the number of menstrual cycles a woman has and therefore decrease the lifetime exposure to estrogen and that pregnancy and lactation change the TDLU morphology (Kobayashi et al., 2012; Faupel-Badger et al., 2013). Nulliparous women have fewer TDLUs per unit area of breast tissue than do parous women and parous women have more TDLU involution (Faupel-Badger et al., 2013). Increased amounts of TDLU involution is associated with decreased risk, especially for basal-like breast cancers, because the TDLUs are the site where most breast cancers originate (Faupel-Badger et al., 2013). Each year that a woman breastfeeds infers a decrease in relative breast cancer risk of 4.3% with an additional reduction in risk of 7% for each birth the woman completes (Collaborative Group on Hormonal Factors in Breast Cancer, 2002). Prolonged breastfeeding and subsequent gradual weaning may also provide protection by decreasing the inflammatory reaction caused by rapid involution of secretory epithelium (Kobayashi et al., 2012). However, it is hard to determine the effects of breastfeeding alone on breast cancer risk because the strongest reduction of risk is seen in multiparous women (Faupel-Badger et al., 2013).

Studies have also found protective effects of breastfeeding in high-risk groups such as those with genetic mutations and a family history of breast cancer. Women who carry the BRCA1 mutation are at a higher risk for early onset breast cancer; however, those with the mutation who breastfed for at least 1 year had a 32% risk reduction in the development in early- and late-onset cancers (Kotsopoulos et al., 2012). The same protection was not found in breastfeeding women with the BRCA2 mutation (Kotsopoulos et al., 2012). Breastfeeding, regardless of length of duration, was found to reduce the incidence of premenopausal breast cancer by 59% in women with a first-degree relative with breast cancer, which is a comparable reduction in risk to using hormonal treatments for those who are at high risk for developing breast cancer (Stuebe et al., 2009).

Breastfeeding, then, can be said to be protective against breast cancer development. Therefore, not-breastfeeding is linked to breast cancer risk. The Carolina Breast Cancer Study found that the strongest risk factors among premenopausal black women for basal-like breast cancers were “not breastfeeding” and increased waist-to-hip ratios (attributable fraction of 68%) (Millikan et al., 2008). Increased risk for estrogen receptor-negative/progesterone receptor-negative breast cancers in the Black Women’s Health Study and increased risk of triple-negative breast tumors in a predominantly white population were also linked with lack of breastfeeding in parous women (Gaudet et al., 2011; Palmer et al., 2011).

Galactagoges: Medication-Induced Milk Production

Stimulating milk production pharmacologically in mothers of LBW infants who are pumping to provide milk for their infants has been recommended by several authors, as reported by Ehrenkranz and Ackerman.54 They used 10-mg metoclopramide orally every 8 hours for 7 days, tapering during 2 days more. Milk production increased within 2 days, but after therapy decreased, milk production decreased. Prolactin levels also increased during the treatment.

Improved lactation occurred in 67% of mothers with no breast milk at onset and in 100% of mothers with poor supply given metoclopramide (10 mg three times per day for 10 days) by Gupta and Gupta.75 They reported that the improvement persisted when the drug was discontinued. None of the 32 women had any symptoms or side effects. This drug is a substituted benzamide, which has selective dopamine-antagonist activity.

Although growth hormone has been observed to enhance milk supply, no recommended protocol exists for its clinical use.74 A study of 20 healthy mothers with insufficient milk who delivered between 26 and 34 weeks were given growth hormone, 0.2 international units/kg/day subcutaneously for 7 days. A group of 10 mothers received a placebo. Milk volume increased in the treated mothers. No change was noted in plasma growth hormone levels, but an increase was seen in insulin-like growth factor. No other changes were noted during this short-term therapy.60

Other drugs have been noted to enhance milk production. Domperidone (Motilium) is currently unavailable in the United States because the FDA banned its distribution. It is widely available in Canada, Europe, and Australia. It is fully discussed in Chapter 12. A dosage of 10 mg three times per day is reported to increase milk supply in some women. The drug is not without side effects, however. Other galactagogues are discussed in Chapter 12.

Manufacture

The quality of cream depends on the physicochemical and microbiological properties and handling of the milk from which it is prepared. Milk should be handled carefully to prevent damage to the fat globules during pumping and agitation, since this may result in free fat, which may coalesce or ‘churn,’ making the separation difficult. General steps involved in industrial manufacture of cream follow.

Sale – Possibly a Multistage Operation

Cream presents more problems than milk owing to distribution methods and the requirements for longer keeping quality. Sales are erratic, depending on the weather, holiday seasons, local activities, and so on. Cream should be dispatched throughout the distribution chain from manufacturing dairies to smaller retailers under chilled conditions.

A typical flow sheet for manufacture of sterilized and clotted creams is shown in Figures 1 and 2, respectively. Apart from clotted cream, most creams are produced by mechanical separators. Clotted cream has a very high viscosity, a golden creamy color, and granular texture.

Figure 1. Flow sheet of typical manufacturing process for sterilized cream.

Figure 2. Flow sheet of typical manufacturing processes for clotted cream. (a) Traditional process. (b, c) Commercial processes.

In whipping creams, air is incorporated at the air–water interface and there is a disruption of the milk-fat globule membrane. Whipping using nitrogen reduces the chances of microbial growth.

Some important factors for whipping cream are as follows:

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Extent of beating required to form a stable aerated structure

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Overrun, expressed as percentage volume increase of cream due to air incorporation

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Stiffness and serum leakage from whipped cream due to overwhipping leading to sogginess if used in cakes

Factors affecting whipping properties of cream apart from rebodying are the fat content, temperature (should be <10 °C), distribution, and size of fat globules and membrane structure. Whipping creams can also be foamed by aerosols. In this process, cream is filled into hermetically sealed cans that are prefilled with an inert gas, such as nitrogen. Low foam stability in aerosol-foamed creams can be compensated for with stabilizers; this also prevents microbial spoilage.

Sour cream is made by inoculating cream with cultures of lactic acid–producing bacteria, such as Lactococcus lactis subspp. lactis and cremoris, and flavor-producing bacteria, such as Leuconostoc mesenteroides subspp. cremoris and dextranicum. Souring takes place at 20 °C and avoids spoilage by thermophilic organisms.

Creams are processed in different ways and sold accordingly. For example, sterilized cream has a distinct caramelized flavor due to the in-can sterilization process and has a shelf life of about two years. Temperatures employed are 110–120 °C for 10–20 min. This severe heating brings about protein denaturation, Maillard browning, and fat agglomeration, which collectively modify the texture and flavor of the cream. A process for rapid sterilization of cream, known as autothermal thermophilic aerobic digestion (ATAD) friction process, consists of preheating the cream to about 70 °C and then heating to 140 °C for 0.54 s. This process can be applied successfully to creams ranging in fat content from 12 to 33%. Double, whipping, single, and half cream may be UHT treated or frozen after adequate pasteurization. UHT sterilization at 135–150 °C for 3–5 s followed by aseptic packaging does not induce chemical changes, but creaming and fat agglomeration does take place on storage. In this process, the shelf life is limited by biochemical rather than microbiological considerations. Since all forms of microorganisms are destroyed, the cream can be stored indefinitely without refrigeration. Calcium–casein interactions destabilize the emulsion, and any proteases surviving the heat treatment may bring about gelation. Development of a stale or ‘cardboardy’ flavor generally limits the shelf life to 3–6 months. Problems arise in controlling the UHT method for high-fat creams.

Bulk storage of surplus cream may be done by freezing at −18 to −26 °C after pasteurization. A shelf life of 2–18 months (average 6 months) is achieved. Cream is frozen in rotary drum freezers or plate freezers or is frozen cryogenically using liquid nitrogen. Every technique has its advantages and disadvantages; however, for a good freeze-thaw stability of frozen creams, care must be taken to preserve the natural milk-fat globule membrane. Hence, frozen creams are not homogenized.

Additives for stabilization and improvement of whipping properties of cream are permitted in many countries. Gelatin and carboxymethylcellulose mainly increase the viscosity, while alginates and carrageenan interact with calcium–casein–phosphate complex to enhance whipping properties. Emulsifiers and stabilizers improve the freeze-thaw stability of cream. Sugars such as glucose and sucrose also impart freeze-thaw stability. Nutritive sweeteners and characteristic flavoring and coloring ingredients are also used sometimes. Cream powders and imitation creams, produced by emulsifying edible oils and fats in water, are other products available for industrial use.

Keeping quality of creams can be enhanced by following good manufacturing practices. Steps that can ensure this quality assurance to the manufacturer and the consumer are as follows:

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Sanitizing all items coming in contact with cream at any stage by heat or chemical disinfectants, such as chlorine compounds

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Ensuring good supervision

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Controlling air contamination around the fillers (this often is neglected)

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Packaging creams in rooms away from processing activities

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Using water containing 5 ppm available chlorine

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In-line testing of cream equipment