Learning objectives
• To describe the anatomical structure of the breast.
• To outline the hormonal control of lactation.
• To describe how the physiology of lactation can be applied clinically.
• To describe the mechanisms of milk secretion.
• To discuss maternal adaptations during lactation: the effects on fertility, maternal behaviour and nutritional requirements.
• To explain why breastfeeding provides optimal nutrition of the neonate.
• To describe the non-nutritional advantages of breast milk.
Introduction
Infant feeding is the result of multifaceted interactions between infant nutritional demand and maternal physiology. The physiological basis of lactation is important in understanding and facilitating successful breastfeeding. Despite increased awareness of the health benefits of human milk, many women discontinue breastfeeding because they perceive that they have insufficient milk supply. Most breastfeeding problems have identifiable physiological, rather than pathological, causes and are best addressed by considering the interactions between the mother and the baby. Successful breastfeeding has nutritional, emotional, developmental and economic benefits. It can be argued that the nutrient requirement of the infant is one of the best understood areas of nutrition. Human milk, however, does not just provide the optimal balance of nutrients in a form appropriate to the developmental needs of the infant, it also compensates for the immature digestive capability and vulnerable immune status of the neonate. Breast milk is the most appropriate food for growth, development, and protection of the neonate. Short-term benefits are a result of the immunological properties of breast milk and protection against infectious diseases. Medium-term benefits are associated with the lower prevalence of inflammatory bowel diseases, type-1 diabetes and childhood cancers. In addition, there are long-term benefits; health in later life appears to be optimized for those individuals who were breastfed as infants. Breastfeeding is universally agreed to be one of the most effective preventative measures of reducing the death rate of children under 5 years old. There are also health benefits associated with breastfeeding; lactation contributes to birth spacing and women who have breastfed seem to have reduced incidence of breast and ovarian cancer.
Chapter case study
Almost immediately following his birth, Zara placed Zak in her arms and he instinctively latched onto the breast and started feeding before the cord was cut. Zak fed on the breast for over 45 min before detaching himself.
• What are the advantages of offering the baby the breast as soon as possible after delivery for both mother and baby?
• What factors could have a negative influence on the early establishment of breastfeeding and how can the midwife optimize breastfeeding?
Anatomy of the breast
The tissue of the breast extends from about the second to the sixth rib (depending on posture). The extension of the tail of the tissue into the axilla (Fig. 16.1) can result in discomfort in the early puerperium when it may become swollen. The mammary gland is made up of a branching network of ducts ending in lobular–alveolar clusters which are the sites of milk secretion. The breast also has a variable amount of adipose tissue and connective tissue. The breast is divided into sections or lobes by fibrous septae, which run from behind the nipple towards the pectoralis muscle. These septae are important in localizing infections, which are often visually evident as a wedge of red inflamed skin on the surface of the breast. Each of the 8–12 lobes, separated by connective tissue, contains glandular tissue composed of clusters of alveoli and small ducts (Fig. 16.2). The alveolar secretory cells are grouped in grape-like lobules around an extensive branching system of small ducts, which lead to the nipple. Fat is interspersed throughout the lobules. Ultrasound studies of babies feeding at the breast show that there are no discernible lactiferous sinuses in the human breast and that the ducts, even close to the nipple, can branch and be very small and compressible (Ramsay et al., 2005).
Fig. 16.1 The position of the breast. |
Fig. 16.2 Anatomy of the human breast. (Reproduced with permission from Ramsay et al., 2005.) |
The nipple is surrounded by the areola, a pigmented area of varying size, which darkens during pregnancy and has a rich vascular supply and sensory nerve inputs. Surrounding the nipple are Montgomery's tubercles which are sebaceous glands that hypertrophy and become prominent during pregnancy, providing lubrication and protection. Heavy use of soap can increase the risk of nipple damage, particularly drying and cracking. The sensitivity of the nipple and surrounding area increases markedly immediately after delivery. Suckling results in an influx of afferent nerve impulses to the hypothalamus controlling lactation and maternal behaviour.
Each lobe consists of 20–40 lobules, each containing 10–100 alveoli, the glandular physiological units. Alveolar cells are cuboidal in the resting non-pregnant breast and change remarkably to develop full secretory features during lactation. The alveolar cells secrete milk into the lumen of the small ducts. These secretory cells are surrounded by oxytocin-sensitive myoepithelial (contractile) cells, which are important in milk ejection. The ducts are also lined by contractile cells that open the ducts widely during the milk ejection reflex to assist flow.
Breast growth and development
Mammary growth and development can be divided into four phases: resting, development (pregnancy), milk secreting (lactation) and involution. At birth, the structure is simply the nipple and a few rudimentary ducts, with few or no alveoli, reflecting their evolutionary origin of modified apocrine sweat glands. Until puberty, the only degree of development may be a little branching of the ducts. There is a decreased incidence of breast cancer in populations with a high consumption of phytoestrogens (oestrogen-like compounds derived from plants). It is suggested that the phytoestrogens stimulate development of the mammary cells in childhood and puberty before pregnancy; these well-differentiated cells may be more resistant to tumour formation (Adlercreutz, 1995).
The human is unusual, even compared with other primates, having extensive breast development at puberty, rather than at pregnancy, resulting in an erotic significance. During puberty, the proliferation of the milk ducts, which elongate, sprout and branch, is primarily dependent on secretion of oestrogen with further contributions from growth hormone (GH) and adrenal hormones. The modest alveolar development at this stage is stimulated by progesterone, providing the tissue has been primed by oestrogen. Prolactin may also play a role although the interaction between the adrenal and pituitary glands and the ovaries is not fully understood. The hormonal fluctuations of the menstrual cycle give repeated exposure of the tissue to oestrogen and progesterone, which allow additional but limited growth. Many non-pregnant women experience cyclical changes, especially premenstrually, in breast volume, which is associated with water retention. Occasionally, some secretory activity may occur within the alveoli and a mammary secretion may be expressed premenstrually.
Once an adult woman has developed breasts, minimal stimulation is required to begin milk secretion (Box 16.1). Growth in breast size is most marked in early pregnancy (Hytten, 1995). The hormones required for breast development during pregnancy are less than those required for other species. In humans, neither human placental lactogen (hPL) nor GH is essential.
Box 16.1
Relactation
Relactation, or induced lactation, is the process whereby lactation is initiated at a time not associated with delivery. For instance, an adoptive mother who has not borne a child may wish to breastfeed her adopted baby or a mother may want to resume feeding her own child. Relactation is easier if the woman has previously lactated or been pregnant and if the infant is young. Hormonal support such as oxytocin nasal sprays may be used. The woman is advised to eat well and rest, and to stimulate the nipple and breast often, either by hand or with a breast pump. Supplementary formula milk is given to the baby by spoon or dropper; bottle teats and dummies are avoided. Use of a ‘Lact-Aid’ supplementer is often found helpful. This device allows the baby to feed on formula milk from a tube attached to the mother's nipple. As the baby feeds, it stimulates the nipple and increases endogenous prolactin secretion. The formula milk is in a bag maintained at body temperature because it is in contact with the mother's body. As breast milk production increases, the amount of formula milk can be reduced.
In early pregnancy, breast size and areolar pigmentation increase. The tubercles of Montgomery enlarge and the nipples become more erect. Blood flow to the breast doubles so blood vessels become more prominent and the skin may appear to have a translucent marbled appearance. There is a sharp increase in ductal and glandular elements so the breasts tend to feel slightly lumpy in early pregnancy. This initial hyperplasia is followed by alveolar cell hypertrophy and initiation of secretory activity in later pregnancy.
Oestrogen plays the dominant role in development of the ducts and progesterone in the development of glandular tissue, although insulin and other growth factors, such as epidermal growth factor (EGF) and transforming growth factor (TGFα), have a role in regulation. Changes in pregnancy depend on the lactogenic hormones, prolactin and hPL, with placental oestrogen and progesterone playing important modulatory roles. Under these hormonal influences, prominent lobules, resembling bunches of grapes, form in the breast so the alveolar lumen becomes dilated by mid-pregnancy and the secretory cells fully differentiated (Box 16.2). The areola becomes pigmented and a secondary patchily pigmented areola may develop. The nipple enlarges and becomes more mobile and protractile, as the connective tissue anchorages soften and become more stretchable with the oestrogen-driven increase in hydration (see Chapter 11). By the 4th month of pregnancy, the epithelial cells accumulate substantial amounts of secretory material and the mammary glands are fully developed. Prolactin levels progressively increase throughout the pregnancy and are maximal at term. Although it is possible to expel a breast secretion in pregnancy, this is not true colostrum. Full colostrum and milk production is inhibited by high progesterone levels so copious milk production is not established until after parturition. Placental hPL may also contribute to blocking of prolactin responses in pregnancy. Even if very small amounts of the placenta or fetal membranes are retained after delivery, lactation is inhibited (Neifert et al., 1981) (see Chapters 13and 14).
Box 16.2
Changes to the breasts in pregnancy
• Increased vascularization – may cause tingling
• Dilatation of superficial veins – fair skin appears ‘marbled’
• Hypertrophy – full development of lobules
• Dilatation of alveoli and ducts – may feel nodular
• Thickening of nipple skin
• Pigmentation of nipple and areolar – persists after pregnancy
• Secondary areola may appear in dark-skinned women
• Montgomery's tubercles become prominent
• Small quantity of clear colostrum can be expressed in latter half of pregnancy
The increase in glucocorticoids that occurs in association with the raised levels of free placental corticotrophin releasing hormone prior to the onset of labour (see Chapter 13) is also important for the breast secretory activity and milk synthesis and secretion (Casey and Plaut, 2007). Glucocorticoids play a significant role in the formation of cellular components such as rough endoplasmic reticulum and tight junctions which are required for milk synthesis and secretion. They are also involved in the regulation of milk protein gene expression and the maintenance of secretory cell differentiation and lactation by preventing the second phase of involution.
Physiology of lactation
Mammary differentiation and milk secretion are coordinated by the endocrine system and involve three categories of hormones: reproductive hormones which change during reproductive development and affect mammary gland development and coordinate milk delivery; metabolic hormones which regulate metabolic responses to nutrient intake or stress; and mammary hormones produced by the lactating mammary gland (Neville et al., 2002). Lactation can be considered as two phases: lactogenesis, the initiation of lactation; and galactopoiesis (sometimes referred to as lactogenesis stage 3), the maintenance of milk secretion. Lactogenesis itself has two stages. Stage 1 is the enzymatic and cellular differentiation of the alveolar cells, which result in colostrum formation, and uptake of immunoglobulins prior to parturition but very little milk synthesis and secretion. Lactogenesis stage 2 is the onset of copious secretion of all milk components about 2–4 days after parturition following the progesterone withdrawal at parturition and concurrent stimulation by prolactin and cortisol. Lactogenesis is normally robust but may be delayed with stressful deliveries and in poorly controlled diabetes (Neville and Morton, 2001) and in obese women, probably because adipose tissue abrogates the decrease in progesterone concentration (Rasmussen et al., 2001). Maternal obesity is associated with a lower breastfeeding rate but not solely related to physiological issues; obesity affects breastfeeding intention, initiation and duration (Amir and Donath, 2007). Other factors that may delay lactogenesis are increasing maternal age, infant birthweight (over 3.6 kg), use of formula milk (especially more than 60mL in the first 48 h of life), lower maternal educational status, low Apgar scores and caesarean section (Nommsen-Rivers et al., 2009), Once lactation is commenced, it is maintained by the removal of milk which is orchestrated by prolactin, which stimulates production of milk, and oxytocin, which is involved in milk ejection (Table 16.1, Fig. 16.4). Maternal perception of inadequate milk supply may influence mothers to augment breast feeding with formula milk and thus interfere with the establishment of lactogenesis and galactopoiesis (Huang et al., 2009). Women at risk of lactational failure will need careful support and encouragement in the initiation of breast feeding. Augmentation with formula milk should be discouraged unless there are medical indications and women whose babies suckle frequently must be reassured that this does not mean their milk supply is inadequate but is an important component in establishing lactation.
Table 16.1 Prolactin and oxytocin |
||
Source |
Anterior Pituitary Gland |
Posterior Pituitary Gland (but Synthesized in Hypothalamus) |
Primary control |
Lifting of dopamine inhibition |
Neural pathway |
Modulating factors |
Positively stimulated by oestrogen, TSH, VIP |
Neurotransmitters |
Peak response |
30 min |
30 s |
Stimulus |
Suckling |
Suckling, sound, sight and thought of baby |
Target cell |
Alveolar cell |
Myoepithelial cell |
Effect |
Milk synthesis |
Milk ejection |
Fig. 16.4 Suckling stimulates the release of prolactin and oxytocin. |
Prolactin
Suckling results in the firing of afferent impulses via the anterolateral columns of the spinal cord to the brain stem and hypothalamus. The hypothalamus subsequently decreases release of dopamine (formerly described as prolactin inhibitory factor) into the portal circulation to the pituitary gland. It was postulated that a dopamine-stimulating factor existed but, although several hormones positively modulate prolactin secretion, control is largely by the lifting of the tonic inhibition from dopamine. The abrogation of thedopamine inhibition stimulates the release of prolactin from the cells of the anterior pituitary. Secretion of prolactin is modified by oestrogen and thyroid-stimulating hormone (TSH). Studies in rats have demonstrated that vasoactive intestinal peptide (VIP), released from the pituitary gland, is an extremely potent prolactin-releasing factor and affects mammary blood flow. The number of signals affecting prolactin release indicates a complex neuroendocrine axis (Ben-Jonathan et al., 1991). β-Endorphin and melanocyte-stimulating hormone (MSH), which are co-released from the intermediate lobe of the pituitary gland, also seem to have a role. β-Endorphin blocks dopamine inhibition of prolactin and MSH stimulates the release of prolactin by lowering the threshold of the lactotrophs (Porter et al., 1994).
Levels of prolactin begin to rise within 10 min of suckling, peak about 30 min after initial stimulation and then progressively fall back to basal levels within a further 3 h. This delay in prolactin secretion following suckling led to the concept that the rise in prolactin was the ‘order for the next meal’. Areolar stimulation is essential for prolactin release; negative pressure alone is not adequate and denervation of the nipple prevents prolactin release in response to nipple stimulation.
Prolactin levels fall abruptly about 2 h before delivery then dramatically rebound. These fluctuations in prolactin level probably relate to changing oestrogen concentrations. The level of prolactin seems to be important in establishing lactation but levels are much diminished after 6 weeks at a rate dependent on suckling frequency and duration (Johnston and Amico, 1986). The peak prolactin levels in response to suckling also fall progressively.
Prolactin has a pulsatile release. A diurnal rhythm of prolactin secretion is apparent, with higher circulating levels during sleep. The exact quantitative relationship between prolactin levels and milk production is not clear. In the early puerperium bromocriptine, a dopamine D2 receptor agonist causes a fall in prolactin levels and abolishes milk secretion. Dopamine-receptor blockers (such as metoclopramide, haloperidol, domperidone and sulpiride) increase prolactin levels and milk production. The use of drugs which stimulate prolactin should be the last resort after excluding all the other factors which might negatively affect milk supply such as checking the positioning of the infant. All the drugs are a risk of side effects. Domperidone is usually preferred because it has a lower risk of toxicity as it crosses into the breast milk and brain to a lesser extent (it has a large molecular weight, is less soluble and is usually bound to proteins). Dopamine binds to receptors on the pituitary and is internalized resulting in the increased breakdown of prolactin within the secretory granules. However, women who have had pituitary surgery and have prolactin levels just above non-pregnant level can breastfeed. The evidence seems to suggest that a threshold prolactin level is required but then there is no correlation between prolactin level and milk production (Howie et al., 1980).
Prolactin binds to receptors on the secretory alveolar (acinar) cells acting at several sites to increase synthesis of several components of the milk including casein, lactalbumin and fatty acids. During pregnancy, secretory alveolar cells proliferate and acquire the characteristics of highly active secretory cells including numerous mitochondria, an extensive endoplasmic reticulum, well-developed Golgi apparatus and many secretory vesicles. Early suckling is important to stimulate prolactin to ensure that milk production is optimal and sustained. Infrequent and/or poor suckling in the early postnatal period may significantly reduce the optimal long term milk production as less prolactin receptor complexes are formed so stimulation of the acinar cells is sub-optimal and the potential for milk production is reduced (Manuel et al., 2007). It is important to support and reassure mothers whose infants frequently suckle in the early postnatal period to promote prolactin release and establish long term breast feeding (Case Study 16.1). Introduction of formula feeds in the belief that the infant is hungry will interfere with the establishment of lactation. In the first few hours of birth, spontaneous suckling may be facilitated by maternal–neonatal skin-to-skin contact (Bramson et al., 2010).
Case study 16.1
Almost immediately following his birth, Zara held Zak in her arms; he was naked and in direct contact with Zara's skin and he instinctively latched onto the breast and started feeding before the cord was cut. Zak fed on the breast for over 45 min before falling asleep.
• What are the advantages of offering the baby the breast as soon as possible after delivery for both mother and baby?
• What can the midwife do to encourage Zak to spontaneously suckle at the breast with future feeding?
• What factors could have a negative influence on the early establishment of breastfeeding and how can the midwife optimize breastfeeding?
As well as the dopamine-antagonist drugs, there are a number of herbal galactogogues which have been traditionally used to promote milk production; these include fenugreek seeds, fennel, brewer's yeast, alfalfa, asparagus, rescue remedy and ignatia 6x (Gabay, 2002). There is a lack of scientific evidence for the effectiveness of these herbal galactogogues. Smoking has been shown to reduce prolactin production (Andersen et al., 1984); in addition, psychosocial factors tend to result in lower rates of breastfeeding in women who smoke (Amir and Donath, 2003).
Biosynthesis of milk
The secretory cells of the alveoli (Fig. 16.3) synthesize or extract the components of milk, which are secreted into the alveolar lumen. The cells are joined near their apical surface by adherins and tight junctions. The apical plasma membrane has a smooth surface with few microvilli, in contrast to the tightly folded basal membrane, which facilitates uptake of substrates such as amino acids, glucose, acetate and fats from the extracellular space. Proteins, fats and lactose are synthesized in the cell and packaged into vesicles. The vesicles move to the apex of the cell where exocytosis takes place.
Fig. 16.3 The alveolar secretory cells of the breast. (Reproduced with permission from Pond, 1992.) |
The composition of the maternal diet can influence the components of breast milk, especially those passing from blood to milk with little modification by the alveolar cell, such as lipids. The alveolar cells have a unique mechanism for lipid secretion whereby microlipid droplets coalesce forming progressively larger lipid droplets that are eventually enclosed by a specialized milk fat droplet membrane prior to secretion (McManaman and Neville, 2003). Aqueous solutes including the proteins, oligosaccharides, lactose, citrate, phosphate and calcium are secreted into the milk by exocytosis after being packaged into secretory vesicles by the Golgi apparatus. Macromolecular substances derived from maternal serum, such as serum proteins (IgA, albumin and transferrin), endocrine hormones (insulin, prolactin and oestrogen), cytokines and lipoprotein lipase, are transported by a transcytosis pathway. Various membrane transport pathways transfer small molecules and ions such as glucose, amino acids and water. Large blood cells and serum follow a paracellular route, squeezing between the alveolar cells.
Oxytocin
Oxytocin levels control the milk ejection reflex, which is responsible for the transfer of the milk from the breast to the baby. Oxytocin stimulates the myoepithelial cells so the alveolar sacs are compressed, increasing the pressure, and the ducts shorten and widen. Although secretion of oxytocin is under a similar neuroendocrine reflex to prolactin, it is physiologically independent. Oxytocin synthesis in the hypothalamus, and its release from the posterior lobe of the pituitary gland, is increased in response to handling the baby, hearing cries or thinking about feeding as well as by tactile stimulation at the nipple. Oxytocin is released in short-lived bursts of less than a minute immediately in response to stimuli. Frequently, the largest response is to the baby crying before feeding so maximum release of oxytocin may occur before suckling even starts. Between feeds, isolated pulses of oxytocin are released (McNeilly, 2001) possibly in response to other babies' cries or fleeting images of the baby. Unlike prolactin secretion, the milk ejection reflex can be conditioned, as demonstrated by dairy farmers who clang their buckets to stimulate oxytocin and a good milk yield. Similarly, a baby's cry can often trigger oxytocin secretion, which is why the practice of babies ‘rooming-in’ with their mothers (sleeping close to their mother's bed) is often associated with successful breastfeeding.
The milk ejection reflex is very sensitive to inhibition by physical and psychological stresses such as pain and discomfort, anxiety, emotional swings, tiredness, embarrassment, worry and alcohol. Women who have had long labours, high levels of intervention and traumatic deliveries may be particularly at risk of impaired oxytocin production. In addition, the use of oxytocin to augment labour may reduce endogenous oxytocin levels in the early postnatal period and also affect the milk ejection reflex (Jonas et al., 2009). The limbic system, which coordinates the body's responses to emotions, is involved in oxytocin release. The likely mechanism is catecholamine inhibition of oxytocin release and adrenergic vasoconstriction of mammary blood vessels limiting access of the oxytocin to the myoepithelial cells. Women experiencing problems in establishing milk flow are often helped by covering their breasts with warm flannels which appears to aid blood flow and oxytocin access. Women may be embarrassed by exposing their breasts or being touched by practitioners helping them to establish breastfeeding and so a ‘hands-off’ approach is best adopted whilst focusing on maintaining privacy and dignity and minimizing inhibition. Stress reducing interventions such as relaxation therapies and skin-to-skin contact have been shown to improve lactation performance (Lau, 2001).
Surprisingly, denervation of mammary glands in experimental animals appears to have little effect on milk production (Williams et al., 1993). This suggests that the afferent nerve pathway may not be as important as the interactions of neurotransmitters. Transmitters that have been implicated in the control of the milk ejection reflex include noradrenaline, β-endorphin, serotonin and dopamine. As with control of prolactin secretion, the number of factors influencing oxytocin secretion suggests that the pathway is much more complicated than originally thought. Stimulation of the female reproductive tract, especially the vagina and cervix, increases oxytocin release so milk may be ejected from the breasts during coitus.
Oxytocin binds to specific receptors on the myoepithelial cells around the milk-secreting cells and to longitudinal cells in the duct walls. Contraction of the myoepithelial cells results in milk being expelled into the ducts, which shorten as the longitudinal cells contract. Oxytocin-induced contraction generates pressure waves within the breasts and is responsible for prickly sensations associated with breastfeeding. When the milk ejection reflex is well established, milk may be spontaneously ejected from both breasts.
Oxytocin pulses increase in amplitude during labour and are involved in the positive-feedback amplification in labour (see Chapter 1). Oxytocin is associated with changes in maternal behaviour and increased alertness at delivery. The pulses of oxytocin induced by feeding have an effect on the uterus, stimulating uterine contractions and involution. Multiparous women tend to feel these contractions or ‘after-pains’ with increased intensity. Women who do not want to breastfeed may find the physiological changes in the breasts at delivery uncomfortable; various techniques are recommended to inhibit lactation (Box 16.3).
Box 16.3
Methods for suppression of lactation
• Bromocriptine (dopamine agonist) (use with great caution)
• Treatment with sex steroids to antagonize prolactin effects
• Breast-binding
• Application of ice-packs
Suckling and milk transfer
In feeding from the breast, the baby takes the whole nipple into its mouth and places its tongue under the adjacent areola. When the baby's tongue moves down, ducts in the nipple fill with milk which is expelled when the tongue moves upwards. The milk is expressed from the nipple and sucking aids the process.
Babies exhibit two distinct patterns of suckling (Turgeon-O'Brien et al., 1996). Nutritive suckling is a continuous stream of strong slow sucks, which efficiently allows milk transfer. This occurs predominantly in theearly part of the feed. Non-nutritive suckling increasingly replaces nutritive suckling during the progression of the feed. It is characterized by alternation of rapid shallow bursts of suckling and rests. It is thought that patterns of thumb sucking may reflect these two conducts. Breastfed babies have two distinct rhythms of thumb sucking and tend to put more of the root of the thumb into their mouths. Although non-nutritive suckling is associated with a decreased transfer of milk, it is still very effective in stimulating prolactin release and so may be important in successful lactation. It has been suggested that odours from volatile compounds in the secretions from the Montgomery's tubercles may promote positive feeding behaviour such as rooting and contribute to the establishment of effective milk production and transfer (Doucet et al., 2009).
The amount of milk produced is extremely variable; that mothers can feed multiple babies and produce additional milk for banking or storage suggests that the mammary synthetic capacity exceeds the normal requirement of single infants. A demand-fed baby consumes irregular quantities of milk at irregular times. The suggestion that the baby determines milk yield by local control is supported by the strong correlation between degree of breast emptying and rate of milk synthesis. Some women feed exclusively from one breast (and not at all from the other). The autocrine factor capable of overriding the central hormone control, feedback inhibitor of lactation (FIL), was first identified in goats (Wilde et al., 1995). This protein inhibitory factor has also been found in the whey fraction of human milk. It is secreted from the alveolar cells and accumulates in milk. The factor inhibits secretion of lactose, probably by blocking the action of prolactin, and therefore provides the mechanism to adjust supply to demand. When milk is not removed from the breast, the concentration of the factor increases and blocks the action of prolactin thus reducing the rate of milk synthesis. It helps to explain why maternal dietary intake has relatively little influence on the amount of milk produced. Women in traditional societies have a much greater frequency of breastfeeding so their production of FIL is probably not enough to have an autocrine effect on lactation; milk synthesis is most likely to be influenced solely by metabolic and endocrine mechanisms (Hartmann et al., 1998). Ankyloglossia or tongue tie may interfere with the suckling reflex and the division of the tie (frenulotomy) may be effective in improving breastfeeding (Miranda et al., 2010).
Involution
After cessation of lactation, involution takes about 3 months. Milk accumulates in the alveoli and small lactiferous ducts, which causes distension and mechanical atrophy of the epithelial cells and rupture of the alveolar walls, creating large spaces. Milk secretion is therefore suppressed by local mechanical factors rather than by diminishing prolactin levels. Phagocytosis of the cells and glandular debris results in fewer and smaller lobular–acinar structures. The alveolar lumens decrease in size and may disappear. The alveolar lining changes from a single secretory layer to a non-secretory double layer. If breastfeeding is stopped suddenly, the process is more intense and painful. The breasts remain larger after lactation as the deposits of fat and connective tissue are increased. Involution after lactation is different to the structural atrophy and loss of adipose tissue occurring in postmenopausal mammary cells deprived of oestrogen.
Problems associated with lactation
Milk insufficiency
Most problems have an identifiable physiological basis; breast milk insufficiency is frequently over-diagnosed and is usually simply resolved (Woolridge, 1996). The majority of women with apparently insufficient milk supply have unsubstantiated worries and require confidence, improved technique (especially positioning), encouragement or advice. This can be supported by physiological strategies such as electric breast pumps and pharmacological (anti-dopamine) agents. Avoiding pressure on the breasts (such as that due to wearing a tight bra or other tight clothing or sleeping prone) is important as it can negatively affect milk supply. Iatrogenic low milk supply may be attributed to excessive down-regulation of supply probably during the calibration period. It is possible that baby milk manufacturers inadvertently exploit the importance of the calibration period by offering free milk samples early in lactation. If the initial calibrated volume cannot be increased, the mother will then be unable to increase her milk supply later and will be forced to provide alternative inferior sources of milk, which are expensive and can be harmful if water supplies are contaminated, as happens in a number of developing countries.
Behavioural problems that are acquired by the baby as coping strategies to avoid aversive events may also induce a low milk supply. These problems include discomfort during positioning at the breast and problems with breathing. Self-limitation of intake and lack of persistence may account for the condition described as ‘contented underfed babies’ (Woolridge, 1996). Pathophysiological failure is rare and probably affects less than 2% of women with apparent milk insufficiency. Rare causes include mammary hypoplasia, or absence of normal breast development at puberty or in pregnancy. Retained placental products affect lactation reversibly but Sheehan's syndrome, necrosis of the anterior pituitary due to acute hypovolaemic shock, as in antepartum haemorrhage (e.g. due to placental abruption) or postpartum haemorrhage, is more serious.
Drugs
Many drugs are secreted into breast milk, but the data on the effects of specific drugs on the breastfed infant is often not available. Of particular concern are those drugs with central nervous system (CNS) activity as the postnatal development of the infant's nervous system is vulnerable. The benefits of maternal treatment and the advantages of breastfeeding have to be balanced against the risk of exposure of the neonate to the medication. Passive diffusion of the unbound, unionized form of the drug into the breast milk is the major mechanism of transfer. Therefore, it is affected by maternal compartmentalization and molecular properties and the composition of the breast milk (McManaman and Neville, 2003). Assessment of adverse drug reactions in infants is difficult. Drugs that are minimally excreted into the breast milk, are metabolized quickly by the neonate and are not associated with adverse effects are obviously the preferred choice.
Socially used drugs such as alcohol (Mennella and Beauchamp, 1991), nicotine and illicit drugs (heroin and cocaine) (Golding, 1997) also cross into the milk. How much these affect the baby is not clear. Women who smoke are less likely to want to breastfeed, or initiate breastfeeding, and more likely to breastfeed for a shorter duration (Amir and Donath, 2003). Drug metabolism and elimination by the neonate is often limited, so exposure to apparently low doses of the drug in milk can have a cumulative effect, particularly in premature babies and those who have prolonged exposure. Drugs tend not to accumulate in the milk but have a bidirectional transfer. Therefore, the amount of drug received by the infant will be reduced if the mother takes the drug immediately after a feed so the baby does not feed when the drug is at peak concentration in the maternal plasma and milk. Production of breast milk is also a method of excretion and contains drugs, viruses, food additives, chemical contamination (such as lead), volatile solvents, pesticides and radioactivity. Chemical residues of pollutants are detected in most human milk throughout the world. Heavy metals are of concern because of the susceptibility of the infant's nervous system. Mammals do not have a mechanism to excrete pesticide residues such as polychlorinated biphenyls and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). However, the residues do cross the blood–breast barrier so lactation is the only way to reduce the body load. The burden of persistent organic pollutants is then transferred to the breastfed infant (Nickerson, 2006). Usually, breastfeeding is not contraindicated but a slow and steady rate of maternal weight loss during lactation is important to limit the mobilization of maternal fat and release of the environmental contaminants which can then partition in the breast milk.
Psychological stress and breast diseases
Women often cease breastfeeding prematurely in the first 6 months after birth because they experience breastfeeding related problems such as pain, cracked nipples, milk stasis and mastitis (Abou-Dakn et al., 2009). These conditions may occur in isolation or may be compounded by anxiety about milk sufficiency. It is estimated that a significant proportion of breastfeeding women will experience some problem in the first few days of feeding. Women experiencing breastfeeding problems are likely to have a higher level of psychological stress. Although lactation may be protective against stress in the short-term, longer lasting psychological stress may negatively affect the endocrine, immune and nervous systems (Wöckel et al., 2010).
Viruses
Maternal viruses may enter the milk. Vertical transmission and subsequent infection of the infant via breast milk have been confirmed for human immunodeficiency virus (HIV), tuberculosis (TB), cytomegalovirus (CMV) and hepatitis B. It is probably inadvisable for mothers with TB to breastfeed as the infection tends to be reactivated by maternal tiredness and stress (Box 16.4). However, advice for HIV-positive mothers is unclear. The immunological properties of breast milk are probably important in protecting against illnesses that accelerate the development of AIDS (acquired immune deficiency syndrome), particularly in areas of the world where it is endemic (Van de Perre, 1995). The likelihood of HIV transmission is affected by maternal viral load, the volume of the milk consumed, the duration of breastfeeding, inflammation of the breast (e.g. caused by cracked nipples), the presence of oral thrush and the introduction of formula milk (Warner and Sapsford, 2004). (Note that several medications used in HIV prophylaxis can transfer to the breast milk and have potentially serious side effects, including anaemia, seizures, hepatitis and feeding difficulties.) The WHO recommends exclusive breastfeeding for the first 6 months of life (and breastfeeding with complementary feeding for the first 2 years of life). The rationale for this is the protective effect of breastfeeding on infection rate. However, in developed countries where the water supply is clean and good quality, alternatives to breast milk are feasible and affordable, it may be preferable for mothers with serious infections not to breastfeed to prevent vertical transmission. However, it should be noted that whatever method is chosen, it should be exclusive as mixed feeding is thought to increase the risk of transmission of HIV.
Box 16.4
Contraindications to breastfeeding
• Maternal illness
• Maternal drug consumption
• Congenital abnormalities, for example, cleft palate
• HIV-positive – controversial
• TB infection (depending on strain and treatment)
Case study 16.2 is an example of concerns about breastfeeding.
Case study 16.2
Elma expressed concerns about breastfeeding throughout her pregnancy. She complained that the midwives running the antenatal classes were biased towards breastfeeding and that bottle-feeding was just as good. Elma described her own family as an example; she is the oldest of five children all of whom were bottle-fed by her mother and were well and healthy. Two days after delivery, Elma experienced breast discomfort and tentatively asked a midwife whether it was too late to try breastfeeding.
• How would you as the midwife explain and encourage Elma to breastfeed throughout the antenatal period?
• What are the health advantages for mothers and their babies who choose to breast feed? Do you think women should be informed of the higher risks of infection for the baby if the mother chooses to feed with formula milk? If so, remember it is not just because of the need to ensure sterilization of feeding equipment but formula milk lacks many of the components of breast milk that actively reduce infection in the newborn.
• What factors would increase her chances of being successful in breastfeeding?
• What support would she require from the midwives?
• Would breastfeeding or anything else help to relieve the breast discomfort?
Inhibition of fertility
Breast milk is also important to the infant because suppression of fertility is an advantage. An adequate birth interval is important for both maternal and child health. Lactational amenorrhoea may last from 2 months to 4 years. It is particularly important in developing countries where breastfeeding prevents more pregnancies than all the other methods of contraception put together. The variability in duration of suppressed fertility seems to be related to a number of factors; the most important seems to be frequency of suckling. At the end of pregnancy, levels of gonadotrophins are very low because high levels of oestrogen continue to impose negative feedback. At delivery, the placental hormones begin to disappear, at different rates depending on their half-life. hPL disappears from the plasma within hours. Oestrogen and progesterone levels fall to pre-pregnant levels within a week of the placental loss (Hytten, 1995). Levels of human chorionic gonadotrophin (hCG) are negligible about 3 weeks after delivery. There is a gradual recovery in the ovarian–pituitary axis over the first 4 months after delivery; this recovery is delayed by regular suckling.
In non-lactating women, body temperature measurements and the first menstrual bleeding suggest that the earliest ovulation may occur at 4 weeks after delivery but is usually delayed until 8–10 weeks (McNeilly, 2001); most women have resumed normal menstrual patterns by 15 weeks. The first menstrual cycle is often anovulatory or associated with an inadequate luteal phase. Most women ovulate by the third cycle. Fifty percent of non-lactating women who do not use contraception conceive within 6–7 months.
Menstruation and ovulation return more slowly in a lactating woman. Ovarian activity usually returns before the end of lactational amenorrhoea. Therefore, menstruation is a poor indicator of fertility; conception can occur before the resumption of menstrual cycles. Neither ovulation nor menstruation normally occurs within 6 weeks, but about half of all contraceptive-unprotected breastfeeding mothers conceive within 9 months of lactation, 1–10% during lactational amenorrhoea. Between 30% and 70% of first cycles are ovulatory; the longer the period of lactational amenorrhoea, the more likely the woman is to ovulate prior to the first menstruation.
The precise mechanisms involved in lactational amenorrhoea are not clear. High prolactin levels abolish the pulsatile luteinizing hormone (LH) secretion and decrease the pituitary response to gonadotrophin-releasing hormone. The mid-cycle positive feedback in response to oestrogen is absent. The sensitivity to negative feedback is enhanced and that to positive feedback is decreased. So, even if enough LH and follicle-stimulating hormone (FSH) are present to stimulate follicular development, the inhibitory effect of oestrogen results in an inadequate luteal phase. Prolactin is inhibitory at the level of the ovary, blocking the effects of LH and FSH. It also has a direct effect on the brain, possibly affecting libido.
As prolactin secretion has a pulsatile rhythm with larger amounts being released at night, the frequency of stimulation by suckling and the night-time feeds are particularly important in maintaining prolactin levels high enough to suppress fertility (McNeilly, 2001). The duration and number of feeds are important because the prolactin levels are augmented before they return completely to the basal secretory level. Prolonged amenorrhoea is associated with maternal malnutrition (Rogers, 1997). Poor nutrition is associated with suppression of fertility in non-lactating women. The extra nutrient requirement for milk production can increase the degree of maternal malnutrition. Also, although women receiving less than optimal nutrition can breastfeed their babies adequately, they secrete milk more slowly so the infants feed more often and for longer which raises their circulating prolactin levels.
Maternal behaviour
Maternal commitment to reproduction is more than pregnancy; it involves the establishment of lactation and appropriate maternal behaviour (Grattan, 2002). The demands of the parents and offspring during lactation may conflict. It is suggested that parents will tend to maximize the survival of their young but not to the extent that would limit investment in other offspring, including those as yet unborn (Peaker, 1989). This theory means that, although mothers will try to recoup the investment of pregnancy by favouring the offspring's survival, should this cost compromise their future reproductive ability there are definite advantages in discontinuing this investment in favour of a more favourable future offspring. There may be genetic components affecting the time course of lactation or the upper limit of milk production. The rate of milk secretion and duration of lactation vary with nutritional state. Some mammals respond to decreased food supply in ways that favour the succeeding pregnancies, such as killing some or all of the litter. Species with long gestation and long-term commitment to the offspring, such as humans, tend to favour the well being of live offspring.
Behavioural changes include preparatory behaviour such as nest building and increased aggression. Care and protection are associated with lactation, particularly the maternal level of oxytocin (Gordon et al., 2010). These behavioural patterns are associated with the progressive independence of the young. In humans, this behaviour is more difficult to observe than in other species.
The nutritional status of the mother may affect feeding and interaction with her infant (Britton, 1993). The effect of maternal malnutrition can affect infant development, depending on its duration and the timing. Infants malnourished in utero may have decreased capacity to respond to appropriate cues and therefore an increased likelihood of social and further nutritional deprivation. Malnourished infants have poorer muscle tone, increased lethargy, irritability and frequency of illness, decreased attention and responsiveness and altered sleep–wake states. Malnourished mothers experience more fatigue, which can affect their own sensitivity to cues from the baby, such as responses to stress and attention–behavioural patterns.
Nutrition of the lactating mother
Human growth rate is much slower than that of other animals. Neurological development is relatively late and the duration of human lactation is longer. During lactation, daily nutrient input and reserves laid down in pregnancy are juggled. Milk output is largely independent of the mother's ethnic origin and nutritional status. A balanced diet in lactation appears to favour the health of the mother. However, it should be noted that substrates required for milk synthesis are not flexible. Mammary glands are not able to synthesize essential amino acids or long-chain polyunsaturated fatty acids (LC-PUFAs); they also require non-essential amino acids for protein synthesis and glucose or glucose precursors for lactose and oligosaccharide synthesis. These have to be provided from the maternal diet or from maternal body reserves. Indeed, it has been suggested that the maternal brain may act as a reservoir of PUFAs for both fetal and neonatal brain requirements (Dewar and Psych, 2004) and that increased transfer of nutrients to the developing brain during pregnancy and lactation might contribute to postnatal depression.
Energy requirements for milk production
The energy output of milk is a significant proportion of the total energy output of the lactating woman; it is suggested that peak lactation requires an increase of energy intake of about 25%. In dairy animals, the level of food intake strongly correlates with milk yield. In a number of species, lactation results in a significant increase in size and complexity (such as villus size) of the maternal intestine (Hammond, 1997), but it is obviously not possible to study any such adaptive changes in lactating women. It may not be valid to apply knowledge of nutrition and physiology of dairy animals, which are completely milked twice a day, to mammals that suckle their young according to natural patterns of behaviour. Anthropological studies on human hunter–gatherer communities suggest that babies feed every half hour at 2 weeks and every 4 h at 4 months. The characteristics of mammalian milk relate directly to the interaction between the mother and child. Marsupials and animals that bear their young during hibernation are always present and produce milk that is dilute and has a low fat content. In contrast, in animals where the mother nurses her young at widely spaced intervals, for instance a hunting lioness, the milk is very concentrated and high in fat. Human milk has most resemblance to the former; it is dilute with a low fat content suggesting that humans have evolved as a species where the young have unlimited access to milk and there is high attentiveness shown by a constantly present mother (Prentice and Prentice, 1995). The stress of human lactation is relatively low compared with species with faster growing or multiple young, but this is countered by the high cost of maintaining a dependent infant for a prolonged period. The high level of maternal investment in pregnancy and slow reproductive cycle mean that humans are committed to sustain a conception.
There is a discrepancy between the theoretical calculated energy requirement for milk production and the actual intake of lactating women, even taking into account the fat reserves laid down in pregnancy. Current recommendations are that an exclusively breastfeeding woman requires an additional 2700 kJ (650 kcal) per day and an increase of 20 g of protein per day (Dewey, 1997). However, it is thought that about 600 kJ (150 kcal) per day will be provided by the maternal fat stores for the first 6 months so the net increment needed is 2100 kJ (500 kcal) per day. In practice, these requirements are much higher than the observed intakes in successfully lactating women even when offered unlimited access to food. Lactational performance is particularly resilient in humans as demonstrated by the efficiency of lactation in undernourished and impoverished communities. In animals, a decrease in non-shivering thermogenesis (inhibition of brown-fat heat generation) (NST) and therefore the provision of extra energy for milk production are suggested to account for this difference. The mechanism in humans is not thought to be mediated by changes in NST but the lactating woman has increased sensitivity to insulin (Illingworth et al., 1986). This energy-sparing effect and efficient energy utilization of lactating women have a particularly big implication in developing countries.
Increased incidence of obesity in Western societies is of concern with about a third of women having a body mass index (BMI) greater than 25 kg/m2. Pregnancy is a risk factor for the development of obesity; it is suggested that postpartum weight loss may not be inevitable and gestational weight gain may not be lost postpartum (Chin et al., 2010). Possibly, the changes in energy metabolism associated with pregnancy and lactation may remain after weaning. If so, lactation could contribute to the problem. Different species of mammal lay down body fat during pregnancy to different degrees. In lactation, mammals rely on the deposited fat to different extents. Whales and seals, for instance, rely entirely on body fat and protein reserves to sustain lactation whereas dairy cows and laboratory rats are very dependent on increased intake to provide energy for milk yield. Pregnant women deposit fat and have a changed hormonal environment. The reported studies tend to conflict and do not show significant differences in weight loss with different patterns of infant feeding. However, interpretation of the studies is confused by confounding factors such as different duration and extent of feeding and the increased tendency of women who are not breastfeeding to reduce their weight deliberately. There is also a large variation in the energy content of the milk produced (see below). Lactating women produce adequate-to-abundant quantities of milk of sufficient quality to promote growth of healthy infants, even when maternal nutrition is not adequate. Whereas the health of the breastfeeding infant is apparently protected should maternal nutrition be compromised, it is probably at the cost of depletion of maternal nutrient stores and potential effects on subsequent pregnancies. Deliberate weight loss in well-nourished healthy breastfeeding woman has no effect on the yield or composition of breast milk. However, it is recommended that weight loss should not be more than 1–2 kg per month (Institute of Medicine, 2002). Although reduction in energy intake does not affect milk synthesis, lower intakes of food mean that micronutrient intake, particularly calcium and vitamin D, might be compromised (Lovelady et al., 2006). As energy intake falls, the likelihood of a number of nutrients failing to reach the recommended intake progressively increases. In order of vulnerability, the nutrients most likely to be affected are calcium, zinc, magnesium, thiamin, vitamin B6, vitamin E, riboflavin, folate, phosphorus and iron (Lawrence, 2010). Overweight lactating women are advised to restrict their energy intake by decreasing consumption of foods high in simple sugars and fat and by increasing their intake of calcium-rich foods, vegetables and fruit.
Minerals
Both pregnancy and lactation present a tremendous challenge to maternal calcium status (Prentice, 2000). The fetal skeleton requires 5 mmol of calcium per day. The lactational drain of calcium is greater; average daily production of 800mL milk contains 6.25 mmol of calcium. It is estimated that about 10% of total maternal calcium stores (about 105 g) is transferred to the fetus/neonate, predominantly duration lactation (Wysolmerski, 2002). One or more of the following can meet demand for calcium: increased dietary calcium, increased absorption, decreased excretion or increased bone demineralization (net loss of bone). In the third trimester, absorption of calcium increases together with a modest increase in bone resorption. This increase in calcium absorption appears to be independent of vitamin D status (Fudge and Kovacs, 2010). Calcium demands of lactation are met by an increase in the rate of bone resorption and a decrease in renal calcium excretion which are speculated to have evolved from the adaptations in bone and mineral metabolism that supply calcium for egg production in lower vertebrates (Wysolmerski, 2002). The oestrogen level during lactation is relatively low so the bone mass is not protected to the same extent.
Lactation is the period of most rapid bone loss in a woman's life; there is a net drain of calcium from the body, with a selective decrease in trabecular bone. This reduction is independent of parathyroid hormone and vitamin D levels. So lactation may appear to increase future risk of osteoporosis, but risk factors shown to be associated with fractures do not necessarily include breastfeeding (Sowers, 1996). During weaning, an imbalance between bone resorption and bone formation results in a rapid and complete recovery of bone mass. The implications for birth spacing and prolonged breastfeeding are not clear. Modern practices of delaying childbearing resulting in decreased time for recovery before menopause are probably countered by the cumulative effect of having fewer children. Prolonged lactational amenorrhoea may help to restore maternal iron status.
The mammary gland homeostatically controls milk concentration of essential nutrients; levels of major minerals including calcium, sodium, potassium, phosphorus and magnesium are not affected by the diet. The mammary gland can adapt to maternal deficiency (or excess) of iron, zinc and copper (Lönnerdal, 2007) suggesting there are active transport mechanisms for these nutrients in the mammary gland. When milk production falls during weaning, milk iron levels decrease and milk zinc levels increase. However, maternal intakes of iodine and selenium do affect levels in milk. As iodine is so important for fetal and neonatal brain and nervous system development and many women do not have an optimal intake of iodine (partly because salt use is decreasing and fewer iodine-containing cleaning agents are used in the dairy industry), iodine supplements are widely recommended for pregnant and lactating women and for women considering pregnancy (Zimmermann, 2009).
Water and fluids
The volume of milk produced is robust; only very severe dehydration and extreme malnutrition affect the volume of milk produced. There is no evidence that increasing fluid intake increases the volume of milk produced or that reducing fluid intake prevents engorgement. When fluids are restricted, urine output decreases and the woman is at risk of dehydration. Breastfeeding women should be advised to drink when they are thirsty and to be aware that they will need more fluid than normal.
Infant nutrition and the composition of human milk
Human milk optimally fulfils the nutritional requirements of the human neonate. It has a unique composition that is particularly suitable for the rapid growth and development of the infant born with immature digestive, renal and hepatic systems. Unique features of human milk are able to compensate for the underdeveloped neonatal capabilities. Human milk contains not only the macronutrients, vitamins and minerals but also non-nutrient growth factors, hormones and protective factors.
There are at least 100 components of human milk, including substances yet to be identified and their roles elucidated. In the Koran, breast milk is described as ‘white blood’. This is a particularly apt description, because the early milk has more white blood cells than blood itself. Milk is a solution in which other substances are dissolved, emulsified or colloidally dispersed. The value of breast milk is undisputed; rarely should breastfeeding be discouraged.
Both the volume and composition of human milk are extremely variable. Some of this variability is genetic (any genetic mutation leading to inadequate mammary development in humans would no longer be eliminated as alternatives to human milk are available). Postponing childbearing until long after sexual maturity has an effect on breast development as advancing age causes some atrophy of the mammary tissue (Hytten, 1995). However, there is little relationship between the size of the breast and milk output.
The unique characteristic of humans is the large complex brain, which undergoes much development in the first 2 years of life. Human milk provides levels of lactose, cysteine, cholesterol and thromboplastin, which are required for CNS tissue synthesis. However, as breast milk provides a model of optimum nutrition, analysis of its composition has allowed good substitutes to be produced as formula feeds. Infant formula milk will never completely mimic human milk, however, as the quality of the nutrients is not reproducible and the immunological aspects of the milk make it superior.
Although breast milk may be considered perfect nutrition, its composition is variable. It varies from woman to woman, from one period of lactation to another, and hourly through the day. Its composition is related to the timing of the feed, how much is produced and parameters relating to the last feed (Emmett and Rogers, 1997); it has also been suggested that maternal age, parity, health and social class affect the composition of the milk. Mothers of premature infants produce milk that has a higher concentration of some nutrients, but this probably reflects the small volumes produced for small infants. Except for vitamin and fat content, the composition is largely independent of maternal nutrition unless the mother experiences severe malnutrition. Supplementation may improve maternal health rather than affect milk composition and volume.
There are many difficulties encountered in the estimation of the volume of milk produced. Weighing either the mother or baby before and after the feed is fraught with problems. Although double-labelled water measurements have allowed more accurate estimations (Lucas et al., 1987), the variability within a feed and from feed to feed makes it very difficult to ascertain precisely the nutrient consumption of a healthy growing baby. These estimates of about 60 kcal per 100mL are lower than UK food composition tables (69 kcal per 100mL). The volume of daily milk intake by healthy infants has a wide range. Factors that influence frequency, intensity or duration of feeds will affect volume consumed. Breastfed infants appear to self-regulate their energy intake and consume more milk if it has a lower energy level. This is thought to be related to the lower incidence of obesity in individuals who were breastfed as infants (Dewey, 2003). Breastfeeding allows infants to learn self-regulation of energy intake whereas bottle-fed infants may be encouraged to finish the bottle which suppresses their autoregulatory mechanism. Breast milk may also contain appetite inhibitors and stimulators. It is suggested that different modes of infant feeding have different metabolic programming effects. Formula-fed infants tend to receive more protein which results in an increased insulin response. Insulin stimulates adipose tissue deposition (increased number and fat content of adipocytes) which is associated with weight gain and obesity. Alternatively, breastfeeding may affect leptin metabolism; the higher level of fatness in formula-fed infants may programme reduced sensitivity to leptin in later life. However, it should be noted that there is confounding by parental attributes and the family environment. Parents who choose to breastfeed tend to have a healthier lifestyle with more optimal dietary habits and higher levels of physical activity; they also exert less parental control over child-feeding practices (Dewey, 2003).
The low levels of gastric secretion and other immature digestive characteristics of the neonatal gut confer a number of immunological advantages which were described in Chapter 15 (p. 397).
Colostrum
In the first 3 days postdelivery, the mother produces about 2–10mL of colostrum per day. More colostrum is produced sooner if the woman has had previous pregnancies, particularly if she has lactated before. In some cultures, colostrum is thought to be old milk or ‘pus’ and is discarded rather than fed to infants.
Colostrum is transparent and is yellow from the high β-carotene content. Mature milk in contrast looks less viscous and slightly blue. Colostrum has more protein and vitamins A and K and less carbohydrate and fat than mature milk. It is easily digested and well absorbed. It has a lower energy content of 58 kcal per 100mL compared with 70 kcal per 100mL in mature milk. Levels of sodium, potassium, chloride and zinc are high in colostrum but these reflect the low volume produced rather than the infant's requirements for a bolus dose of certain nutrients. The composition is extremely variable, which reflects its unstable secretory pattern.
Colostrum facilitates the colonization of the gut with Lactobacillus bifidus (Wharton et al., 1994). Meconium also contains growth factors for L. bifidus. Colostrum seems to have a laxative effect, stimulating the passage of meconium. The high protein content is largely due to the abundant antibodies, which protect against gastrointestinal tract infection. IgA forms 50% of the protein content of colostrum, falling to 10% by 6 months. In the first few days of life, priming and maturation of the mucosal immune system is maximal and the gut is permeable and able to absorb macromolecules; colostrum contains many immunomodulatory molecules particularly anti-inflammatory agents which help to protect the vulnerable immature gut from mucosal damage.
During the first 30 h or so, the secretion (colostrum) has a high protein:lactose ratio. In the following days, as the baby suckles more and stimulates milk production, the resulting increase in prolactin secretion stimulates production of the major whey protein α-lactalbumin, which is a specific component of the enzyme lactose synthetase and so regulates lactose production. The effect of increasing lactose production is that water is drawn into the secretion to maintain osmotic equilibrium so the volume increases thus diluting the protein content. The absolute amounts of protein secreted into the milk are maintained or increased even though the concentration falls.
The composition of the milk becomes relatively stable from about day 5 but is variable in volume. The amount of breast milk produced is related to the weight and requirement of the infant; there is a steady increase in volume in the first few weeks. Milk production appears to get under way regardless of the size and requirements of the baby, although hPL levels may play a role in the increased production of milk in mothers of twins. The early weeks of lactation can be considered to be a time of calibration between maternal production and the infant's demand. The volume of milk produced is usually increased to match demand. Down-regulation may be irreversible. It is suggested that mothers of small or preterm babies should express as much milk as they can (i.e. peak yield rather than only enough for the baby's transiently limited requirement).
Milk secretion in women who do not suckle their baby may persist scantily for 3 or 4 weeks while prolactin levels are still high. The effect of suckling is to stimulate the release of prolactin and oxytocin, which are essential for the maintenance of lactation (Fig. 16.4). Provided breastfeeding is regular, lactation can last for several years. Most studies suggest that the average daily volume of milk produced is about 800mL. Measurement of the milk produced is notoriously difficult but it is clear that there is much variation depending on demand: mothers of twins produce about twice as much milk (Saint et al., 1986) (see Box 16.5).
Box 16.5
Breastfeeding twins and multiples
Human milk is nutritionally and immunologically superior to formula milks which is particularly important for twins as multiple pregnancies have a relatively high incidence of prematurity and low birthweight infants. There is no physiological reason for not breastfeeding multiple infants; milk supply will be increased in response to increased demand. Mothers feeding multiple infants are advised to increase their nutrient intake and to rest more. Advice about simultaneous feeding or feeding the infants individually will need to be given (Flidel-Rimon and Shinwell, 2006). Simultaneous feeding saves time and can mean that a more vigorous infant on one breast can stimulate the let-down reflex for the other infant. There are three commonly used positions for feeding twins: ‘double cradle’ (where the two infants' bodies cross on the mother's abdomen), ‘double football’ (where the infants' bodies are tucked under the mother's arms) and a cradle-football combination. Mother feeding triplets or quadruplets choose between the various combinations; these mothers often intend to provide their infants with some exposure to human milk rather than feeding them exclusively.
Energy
The energy requirements of infants can be estimated from total energy expenditure and the energetic cost of tissue deposition during growth (Butte, 2005). Energy expenditure includes basal metabolism, thermic effect of feeding, thermoregulation and physical activity. The energy requirement to maintain the tissue takes precedence over the energy requirements to synthesize new tissue. So satisfactory growth is a sensitive indicator of whether energy needs are met. Infectious diseases increase energy requirement because there is an increased protein turnover, production of cytokines and phagocytotic cells and repairing tissue are costly and lipids are metabolized less efficiently. Originally, infant energy requirements and recommendations were based on a compilation of energy intakes of well-nourished infants. Measurement of infant energy expenditure using doubly labelled water was subsequently used as the basis for revised energy requirements which were lower than the original recommendations.
Total energy requirements increase with age. Energy requirements are higher in male infants because male infants are heavier. This has an influence on lactation; increased energy content of milk is associated with a male infant. It is proposed that this increased nutritional investment may account for the often observed greater growth rates in male infants (Powe et al., 2010).
Protein
Protein is the limiting nutrient for growth and development. It also provides nitrogen and amino acids required for membrane and transport proteins, hormones, enzymes, growth factors, neurotransmitters and immunoglobulins. Human neonates have a slow growth rate compared with other species which is reflected in the low protein concentrations (0.7–0.9 g protein per 100mL compared with 3.5 g per 100mL in cow's milk). (Note that early estimates of protein neglected the high concentration of non-protein nitrogen (NPN) thus significantly overestimating protein level; see below.) Excess protein intake can present an excessive solute load to the immature kidneys, which results in acid–base imbalance and metabolic acidosis. The faster growth rates of formula-fed infants is probably related to the higher level of protein and different ratio of amino acids in formula milks compared to breast milk; as appropriate infant growth has short- and long-term health implications, reducing the protein content and improving the protein quality of formula milks may be desirable. The growth rate of infants fed formula milk or breast milk is different from the first days of life and diverges markedly after 2–3 months. Breastfed infants have lower weight-for-length (Nommsen-Rivers and Dewey, 2009) but it is evident that this is not related to insufficient breast milk. Breastfed infants are also taller as adults (Schack-Nielsen and Michaelsen, 2007).
Chronic maternal protein undernutrition or prolonged lactation may result in changes in the protein composition of milk. Protein supplementation of the mother's diet tends to increase milk volume rather than affecting protein concentration but has an important role in supplementing maternal health.
When milk proteins are exposed to the relatively acidic environment of the neonatal stomach they separate into casein (proteins that precipitate, forming curds) and whey (those proteins that remain soluble). This means that there is a continuous flow of nutrients, initially as soluble lactose and whey proteins, and later from digested curd. Whey proteins include serum albumin, α-lactalbumin, lactoferrin, secretory IgA and some enzymes and protein hormones transported from the maternal circulation. Whey proteins are easy to digest by a human neonatal gut, which has particularly low levels of trypsin and pepsin. The whey-dominant content of milk reduces the risk of lactobezoars (obstructive milk curd balls) forming in the stomach. Human α-lactalbumin is easier to digest than bovine β-lactalbumin.
The ratio of whey to casein in human milk is 60:40 (1.5). The β-casein in human milk forms curds that are soft and flocculent with a low curd tension, which are easily digested. Bioactive peptides formed from partial hydrolysis of human milk casein may be important in stimulating the neonatal immune system (Ebrahim, 1990). In contrast, cow's milk has a whey:casein ratio of 20:80 (0.25). Bovine casein is predominantly α-casein, which forms a tough rubbery precipitate unless heat treated, which is more difficult for human infants to digest and decreases the bioavailability of calcium and other cations. Human β-casein tends to form smaller micelles incorporating minerals that are easier for the neonate to digest. κ-Casein in cow's milk has a marked effect on the development of the bovine gastrointestinal physiology, stimulating the secretion of chymosin, which is the dominant protease of the fourth stomach. Casein associates with calcium, phosphate and magnesium in the micelles.
Colonization of the neonatal gut
The infant at birth has a sterile gut and lacks a fully functional immune system. The neonate is quickly colonized; in a vaginal delivery, the neonate comes into close proximity to its mother's vagina, skin and faeces. Infants born by caesarean section have a reduced number of bacteria. Breast milk also provides a source of bacteria; there are up to 109 microbial cells per litre of human milk. Initially, the gut is colonized with aerobic species of bacteria such as Enterobacteriaceae, streptococci and staphylococci (Morelli, 2008). Although these are potentially pathogenic species, their metabolism optimizes subsequent colonization by beneficial enteric bacteria within a couple of days.
The intestinal microbiota or microflora of breastfed and formula fed infants are distinctively different. Breastfed infants have a high preponderance of lactobacilli (especially Bifidobacterium bifidum formerly known as L. bifidus) which generates a lower pH and inhibits enteric pathogens. Human milk contains large amounts and numbers of complex carbohydrates such as glycans and oligosaccharides. Some glycans inhibit pathogens binding to the gut; there is structural homology between the milk glycan and the gut cell so the pathogen binds to the glycan which effectively acts as a decoy binding site. The glycans are indigestible and so arrive in the colon in an undigested state where they have a prebiotic effect and influence the composition of the intestinal microbiota. This may be particularly important as modern day hygiene practices limit exposure of the neonatal gut to environmental microbiota. Optimizing gut colonization is thought to be important in developing a stable microbial ecosystem which promotes the growth of symbiotic microorganisms and inhibits the colonization by enteric pathogens. The intestinal bacteria also appear to have a role in reducing the risk of developing allergy (Kalliomäki and Isolauri, 2003).
The immune response to cow's milk
A high proportion of dietary casein of bovine origin is associated with an increased incidence of intestinal allergy and inflammation and is implicated as one of the possible triggers of necrotizing enterocolitis (NEC). As the neonatal gut is permeable, large proteins can be absorbed intact across the gut. Some of these proteins stimulate maturation of the gut and immune system. However, others may present an immunological challenge that produces a response which can cause problems later in life. It has been controversially hypothesized that proteins in cow's milk formula are associated with an increased incidence of diabetes (Karjalainen et al., 1992). The hypothesis suggests that a large bovine protein crosses the infant's gut and stimulates the immune system (Monte et al., 1994). Because of similarities between this protein and proteins of the endocrine pancreas, the immune system may direct an autoimmune response against the cells of the pancreas destroying the insulin-producing β-cells. For whatever reason, the incidence of insulin-dependent diabetes mellitus is lower in children who have been breastfed.
Protein
Proteins are formed of chains of 20 amino acids. Some of the amino acids cannot be made in the body; these are essential or indispensable amino acids (see Table 12.1). Non-essential amino acids can be synthesized from glucose and ammonia via the Krebs cycle or from free amino acids by transamination. Some amino acids are conditionally essential for the neonate because the neonate has limited synthetic capability. The amounts and proportions of essential amino acids determine the quality of a protein. A protein that is rich in all essential amino acids has a high biological value or net protein utilization which means all the amino acids supplied are converted into proteins. A food with a deficiency of an amino acid has a low biological value. Human milk has a very high biological value because it is fully utilized by the neonate as its amino acids are exactly in proportion to requirement. Few other foods have such a high value. By the end of the second week of life, 90% of the ingested nitrogen-containing substances in milk are absorbed, suggesting that milk contains the optimal pattern of amino acids.
The amino acid content of human milk, especially whey proteins, is ideal for the growth requirements of the human infant. Neonatal metabolism of certain amino acids (e.g. phenylalanine, tyrosine and methionine) is initially limited because the enzymes involved in their metabolism are expressed late in development. If these amino acids reach high concentrations, they can cause damaging effects. Human milk is relatively low in tyrosine, phenylalanine and methionine but high in amino acids that the infant cannot synthesize in adequate amounts. The inability to synthesis adequate quantities of histidine, cysteine and taurine means that these amino acids become conditionally essential for infants and need to be provided in the diet. The enzyme that converts methionine to cysteine, cystathionase, is low or undetectable in the neonate. Cysteine is required for growth and development. Infants, especially preterm infants, fed unmodified cow's milk may develop hyperphenylalaninaemia and hypertyrosinaemia, which can increase the net acid load and adversely affect development of the CNS.
Taurine is the second most abundant free amino acid in human milk. Infants use taurine for bile acid conjugation (in contrast to adult conjugation by glycine) so this amino acid is important in the digestion and metabolism of cholesterol and fats. There are also high levels of taurine in fetal brain tissue where it may act as a neurotransmitter or neuromodulator, and be involved in myelinization of nerves and the optimal maintenance of retinal integrity (Chesney et al., 1998). The absolute requirement for taurine is unknown but it is added to formula milk at the levels found in human milk.
Aspartame is a sweetener composed of aspartic acid and phenylalanine. If maternal consumption of foods containing aspartame is increased, there is an increase in plasma levels of phenylalanine but levels in milk only increase marginally suggesting that the mammary gland regulates the transfer of amino acids into the milk.
Non-protein nitrogen
More than 25% of the nitrogen found in human milk comes from sources other than protein. This is the NPN fraction (Box 16.6). Methods for protein determination usually rely on measuring the total nitrogen in a foodstuff and calculating the average amount of protein that would contain that much nitrogen. Therefore, the protein content of human milk was overestimated before it was clear how large the proportion of NPN was. Each mammalian species has a characteristic amount and profile of NPN, which is of nutritional significance. The NPN of human milk includes a variety of compounds such as peptides and free amino acids (such as those that are conditionally essential), nucleotides, traces of inorganic compounds, urea, creatinine, N-acetyl sugars and glycosylated amines. Some of the NPN compounds are of developmental importance but the biological significance of others is uncertain. Urea is high in early milk, reflecting high plasma levels due to uterine involution (see Chapter 14).
Box 16.6
Non-protein nitrogen
The protein content of human milk was initially overestimated because it was based on the assumption that the nitrogen fractions within the milk would all be components of protein. In fact, about 25% of the nitrogen-containing components in the milk are not within proteins. This is high compared with other species; for instance, cow's milk contains only 5% of the total nitrogen as NPN.
NPN includes:
• Amino sugars: which promote the growth of Lactobacillus bifidus and are also incorporated into neural tissue and gut epithelial membrane
• Taurine: a free amino acid that is a component of bile salts and therefore contributes to fat digestion
• Peptides: these have roles as growth factors and hormones
• Cysteine: a free amino acid that is conditionally essential in the infant because the conversion of methionine to cysteine is limited
• Binding factors: these facilitate absorption of other nutrients
• Urea
• Creatine: the role of these factors is not clear
• Creatinine
• Uric acid
Fat
Fat is the main source of energy in the milk. The nutritional status of the mother can affect the fat concentration of the milk and therefore the energy content, fatty acid composition and immunological properties. Of all the macronutrients in milk, fat is the most variable component; it is influenced by the maternal diet, parity, the season of the year and amount of milk removed at the last and current feed, the length of the time between feeds and the fat content of the last feed (Mitoulas et al., 2002). The sampling method used to measure fat is important as hindmilk has three to five times the fat content of foremilk. Averaging foremilk and hindmilk is unlikely to produce a good estimate of the overall composition. The fat content of milk is lowest in the early morning (about 6 a.m.) and then rises to a peak midmorning (about 10 a.m.) before falling during the day (Hytten, 1995). There is also a progressive decline in the average fat content with increasing maternal age but with much individual variability. The diurnal rhythm of milk composition is related to GH secretion. The fatty acid pattern is variable, reflecting maternal energy intake and dietary fat consumption (Innis, 2007). It is possible to discriminate between the milk of vegetarian and non-vegetarian mothers. The concentration of the LC-PUFAs (such as docosahexaenoic acid (DHA), a component of membrane phospholipids of the brain and retina) in human milk is related to maternal intake and status (Jensen and Lapillonne, 2009). DHA supplementation of lactating women to optimize their status may confer neurodevelopmental and immunological benefits to the breastfed infants and, in addition, may possibly affect postnatal depression and cognitive function of the mothers. If maternal energy and fat intake fall, the fat composition of the milk resembles maternal adipose fat composition as fat stores are mobilized. If the maternal diet is high in energy but low in fat, milk triglycerides are higher in medium-length fatty acids (lauric acid, C12, and myristic acid, C14) indicating synthesis of fatty acids from carbohydrates is increased (Lawrence, 2010). Women of high parity (greater than 10) may have decreased capacity for milk synthesis and therefore produce milk of lower fat (and energy) level.
As fat concentration affects the energy content of the milk, these variations in fat content make it particularly difficult to arrive at the average energy content of human milk. Previous overestimation of energy levels in breast milk resulted in formula milk providing too high an energy level which may have led to overfeeding and potential obesity problems of previous generations.
Ninety percent of fat is present as triacylglycerides. The remaining 10% is made up of free fatty acids, phospholipids, cholesterol, diglycerides and monoglycerides, glycolipids and sterol esters. Fat provides the vehicle for fat-soluble vitamins and essential fatty acids required for brain development. Phospholipids are critical components of cell membranes and are a component of surfactant. The fatty acid composition of human milk is very different to that of cow's milk. Human milk has more essential fatty acids (linoleic and α-linolenic acids), has a higher proportion of unsaturated fatty acids and is rich in long-chain fatty acids. Cow's milk has more short-chain fatty acids (C4–C8) and a higher content of saturated fatty acids. The products of lipase digestion are predominantly 2-monoglycerides and free fatty acids, which can be absorbed. Free fatty acids, such as linoleic and lauric acid, and monoglycerides at the concentrations found in the stomachs of breastfed babies are toxic to many pathogens including viruses and some parasites. Monoglycerides act as detergents damaging the membranes of pathogens. Free oleic acid converts the α-lactalbumin in human milk to an altered complex known as HAMLET which induces apoptosis specifically in tumour and virus cells and promotes their regression (Svensson et al., 2002). Most of the triacylglycerides in human milk have palmitic acid (16:0) or oleic acid (18:0) at position 2 of the molecule. Bovine triacylglycerides usually have palmitic acid at position 1 or 3 so digestion of cow's milk fat can release free palmitic acid, which is precipitated by calcium as soap. This can result in the loss of absorption of both fat and calcium.
Human milk and vegetable oil fats are better absorbed than is the saturated fat of cow's milk. Long-chain fatty acids require bile salt micelle formation and lipase activity. Short- and medium-chain fatty acids can be absorbed intact.
Human milk has a high content of cholesterol, which is required for myelin synthesis (important for the CNS development). The cholesterol content of breast milk is not affected by maternal diet. There may be a connection between cholesterol exposure early in life and the development of enzymes for cholesterol degradation and amounts of endogenous cholesterol synthesized (Bayley et al., 1998), which results in lower cholesterol levels in individuals who were breastfed as infants.
As lactation progresses, triacylglyceride levels increase and cholesterol levels fall but phospholipid content remains stable. Usually, 20% of the milk in a feed remains in the breast; this contains about half of the fat. This effect may be due to absorption of fat globules on the surface of the alveolar cells in the secretory and ductal surfaces of the breast. It has been observed that babies suck in longer bursts and decrease the rest intervals when they are feeding on hindmilk (Woolridge and Fisher, 1988).
Essential fatty acids
Human milk provides all the dietary essential fatty acids (see Chapter 12) (Table 16.2) which are required for cell proliferation, retinal development and myelinization of the CNS. The LC-PUFAs DHA and arachidonic acid (AA) are essential constituents of cell membranes, particularly of the nervous system, occurring at notably high concentrations in the brain and retina. The brain undergoes a brain growth spurt in late gestation and early neonatal life when the brain weight increases about 60-fold from 20 g in the second trimester to about 1200 g by the age of 2 years (Dobbing and Sands, 1979). The neonate has a limited ability to desaturate and elongate fatty acid chains thus limiting the conversion of linoleic acid into AA and α-linolenic acid into DHA, so these PUFAs may be conditionally essential in the neonatal diet. Infants acquire PUFAs prenatally via the placenta and postnatally in milk. Human milk is particularly rich in DHA which is suggested to be associated with the raised IQ levels and better visual perception of breastfed infants (Lucas et al., 1992). Maternal PUFA status, and therefore milk levels, varies with fish and fatty acid intake but there is a lack of specific dietary fat recommendations for pregnancy and lactation. As the raised levels of oestrogen in pregnancy would increase the conversion of dietary essential acids to long chain fatty acids, the most vulnerable time seems to be lactation when oestrogen levels are low. It is suggested that lactating women who do not consume the currently recommended intakes of oily fish (two portions per week) should use a supplement (1 g fish oil per day) to achieve the equivalent breast milk levels of DHA (Innis, 2007).
Table 16.2 Long-chain polyunsaturated fatty acids |
||
Omega-6 (n − 6) |
Omega-3 (n − 3) |
|
Predominant source |
Vegetable oils |
Marine oils |
Essential fatty acid |
Linoleic |
α-Linolenic |
Converted to |
Arachidonic acid |
Docosahexaenoic acid |
LC-PUFAs are important for synaptogenesis in the visual system which is assessed by measuring visual acuity and speed of processing in infants. Breastfed infants appear to have a slight neurodevelopment advantage which is attributed to the high PUFA level of human milk. However, it should be noted that there are a number of selection biases, as women who choose to breastfeed tend to have higher IQ, educational level and socioeconomic status. Patterns of parent–child interactions may also be different.
The variation in milk fat reflects the variation in maternal diet. A low-fat maternal diet may maximize de novo synthesis of fatty acids for milk triacylglycerols but should contain adequate quantities of LC-PUFAs. As a species, humans have a uniquely large brain, which is composed of about 60% lipid. The essential dietary requirement for LC-PUFAs required for the development of the human cerebral cortex has some interesting evolutionary aspects. It has been proposed that the freshwater lakes of the Rift Valley in East Africa provided the optimal environment to promote development of Homo sapiens (Broadhurst et al., 1998). Freshwater fish and shellfish are particularly rich in LC-PUFAs and have an AA:DHA ratio similar to that of the human brain.
The importance of the long-chain fatty acid ratios may explain some of the observed benefits of breast milk such as the decreased incidence of multiple sclerosis (Pisacane et al., 1994). Animal fats, including human milk, tend to be rich in omega-6 fatty acids (Crawford, 1993). Formula milks are supplemented with fat derived from vegetable sources so tend to be far richer in linoleic acid than the omega-3 family of long-chain polyunsaturated fats. Milk intended for preterm babies is now supplemented with AA and DHA because premature babies have a very limited capability in elongating and desaturating fatty acids and have not experienced as much transfer of fatty acids in the third trimester. As premature infants have a high requirement, optimal levels of these LC-PUFAs in breast milk of mothers of preterm infants can be achieved by giving the mothers a supplement or by adding DHA directly to expressed milk (Lapillonne and Jensen, 2009).
Lipases
Human milk contains lipases, which are supplemented by unique production of neonatal lipases; these together compensate for limited pancreatic lipase activity. Lipoprotein lipase (serum-stimulated lipase) may appear in milk because of leakage from mammary tissue. Refrigerated and frozen milk undergo lipolysis. The enzyme responsible for this appears to have activity similar to that of pancreatic lipase; it is present in the fat fraction of the milk and is inhibited by bile salts. The most important lipase is the bile salt-stimulated lipase, which occurs in milk of humans and other primates. This enzyme, which is stable and active in the gut, has a significant effect on hydrolysis of milk triacylglycerides and is activated by concentrations of bile salts even lower than those required for micelle formation.
Lipase activity occurs in the saliva (and there may be additional gastric lipase activity). This lingual lipase is stimulated by the presence of milk in the mouth and by suckling, even non-nutritive suckling. Human milk fat digestion is 85–90% efficient compared with less than 70% efficiency of the fat digestion in cow's milk-derived formulas. Human milk fat globules are enclosed in maternal alveolar cell membranes, which aid in maintaining optimal surface area for emulsification and absorption and also protect the fat from lipolysis and oxidation. These factors mean that human milk stores well.
Carnitine
Human milk contains carnitine, which has an important role in facilitating the entry of long-chain fatty acids into mitochondria where they are oxidized. Carnitine is synthesized from the essential amino acids, lysine and methionine, but neonates may have limited synthetic capacity. Carnitine also is involved in the initiation of ketogenesis and in the regulation of heat generation from brown adipose tissue. As infants use fat as a major source of energy and have limited ability to synthesize carnitine, they have an increased need for carnitine.
Carbohydrate
Lactose, which is unique to mammalian milk (and probably therefore important in the development of the mammalian order), is the principal carbohydrate of milk, present at about 7 g per 100mL. The lactose concentration of mature human milk is thought to be related to the size of the adult brain. Levels of lactose are stable as lactose drives the volume of milk produced. There is no evidence that maternal nutrition affects lactose concentration. As well as lactose, there is also a significant amount of 130 other sugars, the most prevalent of which are glucose, galactose, glucosamine and other oligosaccharides (see below). Some of the non-lactose sugars may contribute to favourable gut colonization. Nitrogen-containing oligosaccharides, including the complex sugar l-fucose, promote the growth of L. bifidus resulting in increased gut acidity, which suppresses the growth of pathogenic bacteria and may facilitate calcium absorption.
Lactose is a disaccharide that is digested by the enzyme lactase into its component monosaccharides, glucose and galactose. Lactase activity develops rapidly in late gestation and is adequate from 36 weeks; its activity cannot be prematurely induced by exposure. Most mammals and many humans do not produce lactase after infancy. The ability to produce lactase throughout life seems to be related to continual exposure to lactose in communities that have a strong economic dependence on dairy farming.
Lactose is relatively insoluble and is slowly digested and absorbed in the small intestine. It promotes the growth of microorganisms that produce organic acids and synthesize many B vitamins. The acidic environment is inhospitable to many pathogenic bacteria. Lactose forms soluble salts so the absorption of calcium, phosphorus, magnesium and other metals is increased in the presence of lactose.
Clinical application: nutritional problems of preterm infants
Human milk is nutritionally inadequate for preterm infants, leading to poor growth rates and osteopaenia. However, it does have clear advantages. It has valuable immunological properties, protecting against NEC; 90% of infants affected by NEC have not been exposed to any human milk. Human milk is associated with improved cognition and it stimulates gut maturity and immunomodulation. The ideal food for a preterm infant able to tolerate lactose is the baby's own mother's milk fortified with additional calories, protein and minerals. Babies requiring parenteral feeding benefit from receiving some milk in the gut. One of the problems of tube feeding is the loss of energy, as the fat tends to stick to the tubes. If the mother has a good supply of milk, fractionating the milk and feeding the baby the fat-rich hindmilk can increase the energy content. Skin-to-skin contact has also been found to be important for premature babies and it helps to stimulate the mother's lactational capabilities. It also increases the maternal IgA in the milk, which will be specific to the nocosomial flora of the hospital environs or other environment that the mother and infant have been exposed to.
In preterm babies, with low lactase activity, a large proportion of lactose reaches the large intestine in an undigested form. Here, it is metabolized by colonic bacteria to produce organic acids, hydrogen and carbon dioxide. The organic acids are absorbed across the intestinal mucosa and a proportion of the energy is recovered. This means that preterm babies are able to utilize a large proportion of the energy contributed from lactose. The extent of colonic salvage can be determined by measuring the amount of hydrogen in the baby's breath and can be severely compromised by antibiotics or surgery disrupting the colonic flora. It is suggested that over-accumulation of organic acids in the lower gut may be a factor in the initiation of NEC (Lucas and Cole, 1990) (Box 16.7).
Box 16.7
Necrotizing enterocolitis
• Seen predominantly in premature infants
• Associated with infection, hypertonic feeds, hypovolaemia and perinatal asphyxia
• Most prominent in jejunum, ileum and colon
• Clinical signs usually appear at 3–10 days old
• Symptoms may include abdominal distension, blood in stools, vomiting, lethargy, respiratory distress and poor thermoregulation
• Human milk fed enterally is protective, possibly by stimulating gut maturity and integrity, providing substrates for enzymes and increasing perfusion
Although the evolution of mammalian species has obviously depended on the unique properties of lactose, intolerance to lactose may occur. Although galactose is directly involved in the synthesis of glycoproteins and glycolipids of the CNS, it is not essential in the diet. Galactose can be synthesized from glucose in the liver so glucose can substitute for lactose in a lactose-free diet. Alternatively, lactase can be added directly to bottles or milk can be fermented prior to ingestion.
Table 16.3 compares the composition of human colostrum, mature human milk and cow's milk.
Table 16.3 Compares the composition of human colostrum, mature human milk and cow's milk |
||||
Colostrum (100ml) |
Mature Human Milk (100ml) |
Cow's Milk |
Comments |
|
Energy water |
70 (kcal) |
66 (kcal) |
Colostrum is produced in small but easier digest amounts – produced during first 3 days of life; neonate may feed frequently as metabolic process adapts from the constant feed environment of the uterus to an extrauterine fast/feed cycle |
|
Protein |
Immunoglobulins account for increased protein content |
1.3 g (mostly whey); lactalbumin; immunoglobulins; lactoferrin; lysozyme; enzymes; hormones |
3.5 g (high casein content) |
Colostrum rich in passive immunity factors to provide initial protection to infant; cow's milk harder to digest owing to increased casein, also contains lactoglobulin not found in breast milk (may be responsible for cow's milk allergy); protein ratios differ owing to the calf having a faster growth trajectory than the human infant |
Lactose |
Less lactose |
7.0 g provides 37% of energy requirement |
4.9 g |
Breast milk tastes sweeter than cow's milk |
Fat |
Less fat |
4.2 g (98% triglycerides) provides approx. 50% of energy requirements |
3.7 g |
All mammalian milks are rich in fats owing to the high-yielding energy from fat metabolism |
Sodium |
15 mg |
22 mg |
Higher concentrations of organic ions in cow's milk; the neonatal kidney may be unable to regulate higher ion concentrations owing to immaturity |
|
Potassium |
60 mg |
35 mg |
||
Chloride |
43 mg |
29 mg |
||
Calcium |
35 mg |
117 mg |
||
Phosphorus |
15 mg |
92 mg |
||
Magnesium |
2.8 mg |
|||
Vitamin A |
Increased level |
60 μm |
less |
|
Vitamin D |
0.01 μm |
|||
Vitamin E |
Increased level |
0.35 μm |
||
Vitamin K |
Increased level |
0.21 μm |
6 μm |
|
Thiamin |
16 μm |
44 |
||
Riboflavin |
30 μm |
175 μm |
||
Nicotinic acid |
230 μm |
|||
B12 |
0.01 μm |
0.4 μm |
||
B6 |
6 μm |
|||
Folate |
5.2 μm |
5.5 μm |
||
Pantothenic acid |
260 μm |
|||
Biotin |
3.8 μm |
|||
Vitamin C |
3.8 mg |
1.1 mg |
||
Iron |
76 μm |
5 mg |
Breast milk has low levels of iron; however, it is absorbed approx. 20 times more efficiently than iron supplements |
|
Copper |
76 μm |
|||
Zinc |
295 μm |
|||
Iodine |
7 μm |
Starch
Starch digestion in young babies is possible. Infant saliva contains some amylase activity but levels rapidly increase from 3 to 6 months. Pancreatic amylase activity is minimal in the first 3 months and remains low until about 6 months. Mammary amylase in human milk has a high activity in colostrum, which is retained for about 6 weeks. Intestinal mucosa has both disaccharidases and glucoamylase, which hydrolyse oligosaccharides and disaccharides. Glucoamylase is a brush-border enzyme that can hydrolyse glucose polymers in formula milk. Formula feeds derived from cow's milk often contain maltodextrin, a polymer of maltose and glucose. This has the advantages of being easily digested and increasing the viscosity and mineral content of the formula. Babies are born with relatively high levels of glucoamylase activity, which further increases after birth. Glucoamylase is less susceptible to being affected by intestinal mucosal damage and is distributed along the length of the small intestine, which increases the efficiency of hydrolysis and uptake of its products.
There is evidence that the ability to digest starch can be induced if starch is present in the diet. Adaptation is not quick and may take days to weeks. Undigested starch causes gastrointestinal disturbances, such as diarrhoea, interfering with the absorption of other nutrients, so affected infants may exhibit symptoms of failure to thrive. Hypoxia and ischaemia result in decreased intestinal perfusion, which alters the structure of the epithelial cells affecting uptake of monosaccharides.
Oligosaccharides
Milk contains about 130 different oligosaccharides. Human milk seems to have a particular diverse profile of oligosaccharides, which vary genetically and with the duration of lactation and the time of day. The concentration of unbound human milk oligosaccharides (HMO) is about 5–10 g per litre (similar to the amount of protein in human milk and more than the amount of lipid; Bode, 2006). The role of oligosaccharides in milk is protective. They are not absorbed and appear to act as substrates for beneficial bacteria in the colon and to bind pathogens, so the pathogens do not bind to the cells lining the gut (Bode, 2006). HMO thus promote a particular bacterial flora in the gut of breastfed babies, which results in a characteristic pH; they also serve as receptor analogues for urinary pathogens and thus protect against urinary infections. In the infant's circulation, HMO participate in interactions in the immune system, protecting breastfed infants against NEC and other inflammatory diseases. Breast milk has high concentrations of gangliosides, sialic acid-containing glycosphingolipids (McJarrow et al., 2009). Gangliosides are found in high concentrations in the brain; they are deposited in the developing brain in fetal and early neonatal life and play a role in the development and maturation of the brain such as neuronal growth and myelination. They may influence cognitive function and development of the gut.
Vitamins
A plentiful supply of breast milk from a well-nourished woman contains all the vitamins required by a term neonate, with the possible exceptions of vitamins D and K. Dietary taboos practised during lactation in some cultures may affect the vitamin content of breast milk. As fat is the most variable constituent of the milk, the level of fat-soluble vitamins is relatively unstable. There is a seasonal variation in the vitamin A content of cow's milk. Water-soluble vitamins in breast milk fluctuate with maternal intake as they move readily from maternal serum to milk. Human milk has a high level of vitamin C; there may be a seasonal variation in vitamin C content and both infant and maternal requirements for vitamin C increase with stress (including lactation). B vitamin levels in milk are acutely affected by maternal diet. Vitamin B12, which is found in animal protein, is likely to be deficient in the milk from strict vegetarian or vegan women who should take vitamin B12 supplements during pregnancy and lactation. Transfer of folate from maternal plasma into milk occurs against a steep concentration gradient so the nursing infant is well protected against maternal folate deficiency. However, maternal folate reserves may be depleted during lactation which would have important consequences for the mother and her own folate status, especially if the interpregnancy interval is short.
Vitamin D
Breastfed babies rarely develop rickets although the level of vitamin D in breast milk is low. The vitamin D content of foods is measured by assessing the vitamin D content of the fat fraction. However, breast milk may contain an aqueous vitamin D sulphate, which is not included in the fat fraction, so the vitamin D content of breast milk may be underestimated. Although the vitamin D level in breast milk has been reported to be low, it is not low if the mothers have had optimal vitamin D status themselves throughout pregnancy and lactation. Neonates have stores of all fat-soluble vitamins, including vitamin D, and they are able to synthesize vitamin D on exposure to sunlight from an early age. Vitamin D-deficient milk is associated with low exposure to sun, long winters, Northern climes, use of sun screen, dark skins and cultural practices such as covering the skin, all factors which compromise maternal vitamin D status. Increased levels of pollution may also affect vitamin D synthesis in the skin. Certain ethnic groups, such as Rastafarians in the UK, have an increased risk of vitamin D deficiency.
Vitamin E
Vitamin E, mostly in the form of α-tocopherol, is an antioxidant. Deficiency compromises the integrity of the red blood cell membrane and can lead to microhaemorrhages if severe. In formula feeds, the α-tocopherol:polyunsaturated fat ratio is held constant (1 IU vitamin E per gram of linoleic acid).
Vitamin K
Vitamin K deficiency is associated with haemorrhagic disease of the newborn (see Chapter 15) and is usually due to low stores of vitamin K rather than low levels in the milk. There is a critical need for vitamin K during birth and in the first days of life when the risk of bleeding, particularly intracranially, is high. Vitamin K is not efficiently transferred across the placenta. The major source of vitamin K in postnatal life is from the by-products of bacterial metabolism, but the baby is born with a sterile gut, and gut colonization capable of producing vitamin K is not adequate until the baby is at least 6 weeks old as lactobacilli do not synthesis menaquinones. Concentrations of vitamin K are higher in colostrum and early milk, particularly the hindmilk as the vitamin is fat-soluble. Breast milk stimulates colonization of the gut by vitamin K-producing bacteria. A prophylactic dose of vitamin K is routinely given at birth to protect against haemorrhagic disease of the newborn.
Vitamin A
Vitamin A requirement is increased if stores are inadequate or there are problems with fat absorption. A deficiency of vitamin A in infancy is associated with bronchopulmonary dysplasia. This may result from a low intake or increased requirement for the vitamin in healing the damaged lung epithelium. Breastfeeding women are advised to select plenty of vegetables and fruit rich in provitamin A.
Minerals
The mineral content of milk is slightly affected by maternal diet but milk provides all the major minerals and trace elements required by the normal term infant. Usually the mother's dietary deficiency or excess intake of mineral does not affect the composition of her milk very much as maternal homeostasis protects the infant against fluctuations of most minerals in the maternal diet. Parenteral feeding of infants, rather than frank deficiencies, has elicited most information about mineral requirements. Deficiencies are usually associated with short gestation or severe placental insufficiency.
The concentration of most minerals remains generally low but the bioavailability is high. Human milk has a number of binding proteins, notably for iron, calcium and zinc. Although the level of iron in breast milk is low, absorption of iron from human milk is particularly efficient, aided by the lactoferrin and transferrin content of milk and its low pH. Iron requirement in infants are relatively low for the first few months of life because there is recycling of the senescent red blood cells from the higher number circulating in the fetus.
The sodium content of human milk is inversely related to the volume of milk produced so it is higher initially and at weaning. Cow's milk has four times the sodium content of human milk. Hypernatraemia, caused for instance by hot weather, mild infection or over-concentrated formula reconstitution, can result in dehydration.
Calcium absorption is affected by vitamin D, calcium and phosphorus concentrations, fatty acids and lactose. It is particularly enhanced by the acid environment and low phosphorus content of human milk. The concentration of calcium in the blood is tightly regulated; there seems to be similar homeostatic mechanisms ensuring a relatively constant concentration of calcium in breast milk (Kent et al., 2009). The calcium:phosphorus ratio of human milk is 2:4 (compared with 1:3 in cow's milk). If phosphorus levels are high, there is increased phosphorus absorption at the expense of calcium absorption as they compete for the same mechanism of transfer across the gut wall. The resulting fall in plasma calcium concentration can cause hypocalcaemia with symptoms of jitteriness, tetany and convulsions.
Milk-borne trophic factors
As well as nutritive and immunological factors, human milk contains a group of biologically active factors that affect nutritional status and somatic growth. The immature neonatal mucosa can allow potentially immunogenic molecules to cross the gut; human milk accelerates maturation of the gut barrier function. Human milk contains products of the maternal adaptive immune system such as antibodies and components of the innate immune system; in addition components in human milk attenuate early inappropriate inflammatory responses. The biologically active factors in human milk can be classified into four groups: hormones and peptide growth factors, nucleotides and nucleosides, polyamines and digestive enzymes. The hormone group includes insulin, GH, insulin-like growth factors (IGF-I and IGF-II), somatostatin, EGF, prolactin, erythropoietin and GH-releasing factor. Some of these hormones and growth factors are absorbed across the permeable neonatal gut into the body where they affect metabolism and promote growth and differentiation of organs and tissues. Other hormones, such as somatostatin, appear not to be absorbed but resist proteolysis, having an effect directly on the wall of the gut. The growth factors in human milk may modulate the development of the infant gut (Goldman, 2000), protecting gastrointestinal cells and therefore reducing the risk of NEC.
Both human and bovine colostrum are rich in nucleotides, which are precursors of nucleic acids. Nucleotides appear to have a role in enhancing growth and differentiation. They are particularly involved in liver cell function, lipid metabolism and lipoprotein synthesis. They also affect the development of the gut-associated lymphoid tissue (GALT). Unlike cow's milk, mature human milk maintains high levels of nucleotides. Up to a fifth of the breastfed neonate's requirement for nucleotides is derived from milk. Dietary nucleotides may facilitate iron absorption and promote development of the immune response.
The polyamines, spermine and spermidine, are present in all cells but human milk has about 10 times as much polyamine content as cow's milk. Levels of polyamines are particularly high in the first days of lactation. They may have mitogenic, metabolic and immunological effects promoting gut development of the newborn. Enzymes include amylase, lipase and proteases which aid digestion.
Case study 16.3 is an example of concerns about newborn nutrition.
Case study 16.3
Isla is 11 days old and has just regained her birth weight. She has been breastfed since birth and appears to be very healthy and alert. Julia, her mother, contacts the midwife because she is concerned about Isla who is sleeping 12 h at night and feeds only four times a day. Julia's elder sister also gave birth recently and her 21-day-old baby feeds every 2 h, day and night, and has been progressively gaining weight. Julia's sister reported that her midwife told her that this is how a newborn baby normally behaves and advises Julia to stop breastfeeding because her baby is not growing properly.
• How can the midwife reassure Julia that Isla is well, feeding normally and gaining adequate nutrition?
• What concerns, if any, would you have for Julia's niece or how would you reassure Julia that all was normal?
• Why do some babies have different patterns of feeding and weight gain?
Special considerations
Breast milk can vary in taste and colour and can affect the infant's digestive system. Some components of the mother's diet such as artichokes, asparagus, peppers, legumes, brassica (vegetables from the cabbage family) and alliums (vegetables from the onion family) may occasionally result in a reaction from the infant though the evidence that maternal diet is the cause of infant colic is inconsistent. The taste and flavour of breast milk can be altered by components of maternal diet such as garlic (Mennella et al., 2001). When the breastfeeding mother consumes garlic, the infant consumes more milk. These early flavour and odour experiences may programme later food preferences including those at weaning. Rarely, breast milk colour has been reported to be affected by excessive maternal consumption of food colouring (usually in soft and sports drinks) and drug therapy (Lawrence, 2010).
It has been suggested that susceptible infants might be exposed to environmental allergens and dietary antigens via their mother's breast milk. In some cases, where there is a history of allergy, mothers may be advised to avoid potential allergens whilst breastfeeding such as nuts, eggs, cow's milk, berries and tropical foods. However, responses vary widely and foods should not be eliminated without medical supervision.
Caffeine and alcohol both pass into breast milk. With all substances including caffeine, nicotine, alcohol and drugs, the levels are reduced in the milk if maternal consumption is timed immediately after a feed with the longest possible time before the next feed.
Breastfeeding women are encouraged to exercise, time providing. Exercise increases blood lactic acid levels and there may be some transfer of lactic acid into breast milk. Human milk is sweet and lactic acid has a sour bitter taste which may result in infants displaying puckering facial expressions and even rejecting milk if they are offered it close to exercise. However, not all infants are sensitive to the taste of lactic acid and discarding the first few millilitres of milk by manual expression often remedies the situation (Lawrence, 2010). Physical activity and energy intake must be balanced.
Immunological properties of human milk
Neonates are particularly susceptible to infection (see Chapter 15). Milk has an important non-nutritive protective role. In addition, some of the nutrient components of human milk can be multifunctional in that either in their native or partially digested state, they are immunologically active. Human milk discourages bacterial growth whereas cow's milk promotes bacterial growth in the upper small bowel, which is optimal for ruminants (Jackson and Golden, 1978). Breastfed infants have fewer infections (Box 16.8), but some of this effect may be due to a decreased exposure to other foods bearing microorganisms (Golding et al., 1997). Breast feeding appears to be protective for Sudden Infant Death Syndrome (SIDS) possibly because as well as the immunological advantages of human milk, breast fed infants have different sleeping practices and are more easily aroused from active sleep (Horne et al., 2004). (Note that there are several significant risk factors for SIDS including not being breastfed, sleeping in a prone position, overheating and exposure to smoke.) The protective properties of milk are also important in protecting the breasts themselves from infection. Many cultures use breast milk topically, for instance to treat eye infections. Immunological properties of human milk are increased with better maternal nutrition (Chang, 1990). Human milk has a high antioxidant capacity because it is rich in ascorbic acid, uric acid, α-tocopherol and β-carotene (Labbok et al., 2004); this may be particularly important for preterm infants who have an immature antioxidant defence system and so are more prone to oxidative stress (Ledo et al., 2009).
Box 16.8
Advantages of breastfeeding
• Optimal infant nutrition
• Convenience, cost and lack of contamination
• Reduced risk of mortality from necrotizing enterocolitis and sudden infant death syndrome
• Reduced infection: gastrointestinal, respiratory, urinary tract, ear, meningitis, intractable diarrhoea
• Reduced atopic disease and allergy: eczema, asthma
• Increased intelligence
• Reduced overweight and obesity in childhood and adulthood
• Reduced risk of autoimmune disease
• Enhanced immunity
• Reduced risk of maternal cancer: breast, ovarian
• Increased maternal oxytocin levels: promote expulsion of placenta, minimize postpartum blood loss, and facilitates rapid uterine involution (see Chapter 14)
• The promotion of exclusive breastfeeding for at least the first six months of life –
– may significantly reduce the health care costs within the population both short and long term (Bartick and Reinhold, 2010)
– may reduce the incidence and severity of mental health for the neonate in later life (Oddy et al., 2010)
– may reduce the risk of maternal late onset diabetes (Gunderson et al., 2010)
Immunoglobulins
The immunoglobulins (antibodies) in milk are distinct from those found in maternal serum. The major immunoglobulin is secretory IgA which is produced from plasma cells in the breast; milk also contains minor amounts of monomeric IgA, IgG and IgM. Secretory IgA is at very high concentrations in the colostrum but declines to lower levels by day 14 as milk volume increases. The mother will produce specific immunoglobulins to every pathogen she encounters. The transfer of IgA into the milk is a form of passive immunity (see Chapter 10), augmenting the placental transfer of IgG to the fetus. The baby's own immune system is further stimulated by factors in the milk. Breastfed babies have superior responses to vaccination programmes and have higher IgA in their saliva, nasal secretions and urine (Prentice, 1987 and Prentice et al., 1987).
IgA is stable at low pH and resistant to proteolytic enzymes (because its structure has an additional secretory component that confers resistance to digestion by trypsin and chymotrypsin) so it survives in the gastrointestinal tract. IgA has an important role in the defence against infection, slowing bacterial and viral invasion of the mucosa by neutralising toxins. It adheres to the gastric mucosa and binds to antigens on the pathogen so preventing adhesion of microorganisms to the gut wall. IgA promotes closure of the gut and so decreases its permeability to allergens such as cow's milk β-lactoglobulin and serum bovine albumin.
Binding proteins
Lactoferrin is an iron-binding protein that facilitates the absorption of iron from milk. In binding iron, it reduces the amount of free iron available for microorganisms in the gut, thus inhibiting the growth of certain pathogenic bacteria and having a broad bacteriostatic effect. It is suggested that lactoferrin in breast milk helps to reduce the incidence of gastrointestinal tract infections. Excess free iron is associated with increased bacterial pathogens in the gut. These bacteria have a high iron requirement and can cause gut damage and microhaemorrhages, which themselves can lead to iron-deficiency anaemia. Lactoferrin also inhibits the pathological activity of several bacteria, stimulates macrophage phagocytotic activity and inhibits viruses such as HIV, CMV and herpes virus (Newburg and Walker, 2007). Partial digestion of lactoferrin produces lactoferricin B, a peptide which has antibacterial activity against gram-positive and gram-negative bacteria. Some lactoferrin and lactoferricin are absorbed and excreted in the urine where they probably also protect against urinary tract infections (Labbok et al., 2004). Haptocorrin, the binding protein for vitamin B12, is similarly resistant to digestion; haptocorrin inhibits the enterotoxigenic Escherichia coli.
Other protective properties
Breast milk contains high levels of lysozyme, an enzyme which is protective against Gram-positive bacteria and viruses because it breaks down the complex polysaccharides in bacterial cell walls. It is produced in the secretions protecting the mucosal surfaces of the gut and respiratory tract in later life but levels are very low in infancy. Lysozyme has a bacteriostatic effect against E. coli and can also inhibit growth of fungus such as Candida albicans. Breast milk contains prebiotic substances, called bifidogenic or bifidus factors, which together with lactose stimulate the growth of lactobacilli which produce organic acids thus promoting an acidic and protective environment. Bifidus factors are human milk glycans (glycopeptides and glycoproteins). Fibronectin, which is present in high concentrations in human milk, is a non-specific opsonin (see Chapter 10) that increases phagocytosis of bacteria. Milk also contains other protective factors (Table 16.4).
Table 16.4 Protective factors in milk |
|
Factor |
Function |
Cells |
|
B lymphocytes |
Produce antibodies against specific microbes |
T lymphocytes |
Kill infected cells |
Macrophages |
Produce lysozyme and activate parts of the immune system |
Neutrophils |
Phagocytose bacteria |
Lacto bifidus factor |
Promotes an acidic environment favourable for the growth of Lactobacillus bifidus and inhibits the growth of pathogenic microorganisms |
Immunoglobulins (antibodies IgA, IgG, IgM, IgD and IgE) |
Active against specific organisms, that is, poliomyelitis, salmonella |
Immunoglobulin A (IgA) |
Lines the gut to discourage adhesion of pathogenic microorganisms and limits allergen entry |
Lactoferrin |
Decreases iron available by binding to iron for bacterial growth |
Acts as a bacteriostatic agent |
|
Lysozyme |
Act in a non-specific way by damaging the cell walls of microorganisms |
Lactoperoxidase |
|
Complement |
|
Lipids |
Inhibit growth of staphylococcus and viruses by disrupting cell membranes |
Fibronectin |
Promotes macrophage activity and aids repair to damaged gut tissue |
γ-Interferon |
Promotes activity of immune cells |
Mucins |
Adhere to microorganisms inhibiting attachment to the gut wall |
Oligosaccharides |
Inhibit attachment of microorganisms to mucosal surfaces, promotion of optimal profile of microbiota in colon |
Bile salt-stimulated lipase |
Acts as an antiprotozoal |
Bile salt-stimulated lipase |
Promote fat and protein digestion |
Lipoprotein lipase, α-amylase |
|
α1-Antitrypsin |
Prevent breakdown of protective factors |
α1-Antichymotrypsin |
|
Epidermal growth factor |
Promotes maturation of the gut wall |
Binding proteins |
Increase absorption of nutrients and limit availability of nutrients utilized by bacteria |
B12-binding protein (haptocorrin) |
|
Lactoferrin |
|
Transferrin |
|
Folate-binding protein |
|
Somatomedin C |
Milk is not sterile but contains about 4 ∞ 109 cells per litre including lymphocytes from maternal Peyer's patches and scavenger macrophages and neutrophils. Levels of cells are particularly high in the colostrum. Proteins and mucins of the milk lipid globule membrane itself may also confer immunological advantages (Keenan, 2001). Other factors in human milk with anti-infective or immunological properties include anti-proteases, which inhibit the breakdown of anti-infective immunoglobulins and enzymes, free fatty acids which have antiviral properties and cytokines which stimulate an inflammatory response from the immune cells.
Formula feeding
Human milk substitutes existed before the modern age of infant formulas. There were two approaches, either using a surrogate mother or wet nurse, or feeding milk from another mammal. In Western countries, where dairy farming is established, cow's milk is modified and processed into the formula feeds, which are the basis of bottle feeding. Human children in other cultures are reared on buffalo, goat, horse, camel and yak milk. Mammalian milks may be quantitatively similar but the quality is variable, being species-specific.
Cow's milk is supplemented with carbohydrate, either lactose or maltodextrin, which dilutes the higher mineral and protein content. Cow's milk fat (which has a high commercial value as butter and cream) is substituted with vegetable oil-fat blends. This increases the absorption efficiency; unabsorbed fat decreases the energy content, lowers calcium absorption and produces steatorrhoea.
For whey-dominant formulas, demineralized whey (which is expensive) is blended with skimmed milk to increase the whey:casein ratio and decrease the electrolyte content. The profit margin of whey-dominant formulas is lower than that of casein-dominant formulas. Casein-dominant formulas are marketed for the ‘hungrier baby’ and, although the energy content is constant, are considered to be a progressive step in feeding. Mothers often demonstrate a strong brand loyalty when choosing formula milk. Many formula milks for term infants, particularly the prestige or ‘gold’ versions, are supplemented with long chain polyunsaturated fatty acids, DHA and AA (Heird, 2007), to benefit brain growth and optimize the immune system. The source of these fatty acids is often algae rather than marine oils which may result in fishy odour.
Hydrolyzed protein formula milks are produced for infants with gastrointestinal or allergy problems; the hydrolysis of the bovine milk proteins into smaller protein fragments appears to facilitate absorption and the smaller particles are less allergenic. Soy-based formulas were originally designed for infants intolerant of cow's milk protein-based formula milks. The early problems of loose malodorous stools, nappy rash and stained clothing associated with soy milk have been remedied by the use of isolated soy protein rather than soy flour. Concerns have been raised about the high levels of aluminium and phytoestrogens in soy formula milk; phytoestrogens may affect sexual development, immune and thyroid functions and neurobehavioural development (Bhatia and Greer, 2008). Soy-based formula milks are suitable for infants with the rare inborn errors of metabolism such as galactosaemia and hereditary lactase deficiency or where a vegetarian diet is preferred. Many infants with diagnosed allergy to cows' milk protein also have an allergy to soy so the extensively hydrolyzed protein formula is unusually the preferred option (Hays, 2006). Soy-based formula milks are not appropriate for preterm infants.
Trace minerals and vitamins are added in line with legal limits. Taurine is added to formula milk and, more recently, nucleotides have been added; they probably act as growth factors and may have immune effects, strengthening responses to immunization and reducing diarrhoea. Carnitine may also be added to formula milks (Heird, 2007). Carnitine is required for oxidation of fatty acids; levels in unsupplemented soy-based and protein hydrolysate formula milks are particularly low. Packaging of formula feed is important. Anaerobic storage and copper supplementation help to reduce fatty acid oxidation. Scoop and granule size are carefully designed to optimize precision in reconstitution. Current research into the optimal (and most profitable) formulations includes adding specific proteins such as α-lactalbumin, adjusting the ratio of amino acids such as glycine, leucine, arginine, cysteine and tryptophan, and adding probiotics and prebiotics such as synthetic HMO.
Breastfed infants grow at a slightly slower rate and have a different body composition than formula-fed infants. They consume less milk (about 85% of that consumed by formula-fed infants) and have lower energy expenditure. Breastfed infants have a lower risk for later obesity and possibly insulin resistance, obesity and type II diabetes mellitus. Gastric emptying is faster in breastfed infants and there is less gastro-oesophageal reflux and loss of intake in breastfed infants. They also have less infectious disease (see below) and a lower rate of necrotizing colitis. Concerns have been raised about rapid rates of weight gain in infancy, particularly in formula fed infants, being associated with later obesity. Breastfed infants self-regulate their appetite whereas formula-fed infants are often encouraged to finish their bottle. In addition, there may be factors in breast milk which affect satiety. Breastfed infants are often introduced to complementary feeding at a slightly older age which seems to protect against later weight gain (Schack-Nielsen et al., 2010). Growth charts derived from data from formula-fed infants are not appropriate to assess growth in breastfed infants.
Weaning
Weaning can be defined as the progressive transition from milk to a normal family diet. Before 4 months, it is considered unnecessary, being associated with increased incidence of diarrhoea and interference with the maintenance of breastfeeding (the nutritional value of most complementary foods is usually lower than that of breast milk). An increase in dietary cereals and vegetables tends to affect the absorption of iron, which can be delicately balanced in younger infants. By 6 months, many babies may require complementary feeding and will have sufficiently developed to cope with it. Deciduous teeth erupt at about 6 months. Incisors, which cut food, are the first teeth to appear, followed by molars at about 12 months, which allow grinding of food. Although it is not the current practice in many developed and developing countries, there is a call for meat to be introduced as an early complementary food as it provides essential micronutrients (Krebs, 2007).
Determination of the appropriate time to introduce foods other than milk is not just by age but should also take into consideration the food available, conditions to prepare it, the growth velocity and the neuromuscular development of the infant. It is not clear which pattern of growth is optimal. Growth charts are based on weight and height data from clinical surveillance. Ethnicity and both environmental and genetic factors affect growth. Practically, the high weight velocity, which is seen in the first 3 months of life, is not related to overfeeding. The deceleration of growth after 3 months is not in itself an indicator to wean. Early weaning is associated with an increased number of respiratory symptoms (Forsyth et al., 1993).
By 6 months, normal physiological development can support the introduction of alternative foods. The baby is able to hold its head erect and can control the movement of its hands to mouth. The tongue extrusion reflex is waning and can be overcome. Indeed, it is suggested that there is a critical window for introducing solid food, and if it is not done within this window, the baby tends to develop a preference for liquid feeds and may become a child with feeding problems. The kidneys are mature enough to cope with a solute load.
Although the health benefits of breastfeeding are not disputed, opinions and recommendations are divided on the optimal duration of exclusive breastfeeding. In March 2001, the World Health Organization convened an expert consultation committee to systematically review the evidence and make recommendations about the optimal duration of exclusive breastfeeding. The committee called for exclusive breastfeeding of infants until 6 months old and continued breastfeeding with appropriate complementary feeding until 2 years old. These recommendations would reduce deaths of children under 5 years by about 30% worldwide (Bryce et al., 2005). Despite this, many authorities argue that there is a lack of clear evidence to either support or refute recommendations for the age of introduction of complementary foods to the breastfed or formula-fed infant to be between 4 and 6 months. Although exclusive breastfeeding for the first 6 months of life can support growth and development in some infants, subgroups have been identified within certain populations who may require complementary feeding prior to this age, particularly larger, and often male, infants (Lanigan et al., 2001). To be confident that exclusive breastfeeding does not increase the risk of undernutrition (growth faltering) in healthy term infants, it may be necessary to make recommendations per infant weight rather than infant size.
Weaning is an important biological and social learning process as well as offering foods of higher nutrient and energy density than milk. Exposing different tastes to children has already begun in utero with amniotic fluid and is consolidated by breast milk feeding because compounds ingested by the mother are transported into the milk (Mennella, 2009). This develops the inherent taste variation of breastfed infants, affecting the development of food preferences; this important learning experience is not received by bottle-fed babies.
Key points
The physiological unit of the mammary gland is the alveolus. Prolactin, from the anterior pituitary, stimulates milk production from the alveolar cells. Oxytocin, from the posterior pituitary, stimulates contraction of the myoepithelial cells lining the alveoli and the ducts, resulting in milk ejection or ‘let-down’.
Prolactin secretion slowly reaches a peak following stimulation at the nipple. Secretion is pulsatile and circadian and is controlled by the abrogation of tonic inhibition from dopamine produced by the hypothalamus. Prolactin inhibits ovulation thus suppressing fertility.
Oxytocin release is stimulated by nipple stimulation and by thinking about or hearing the baby. Secretion of oxytocin immediately follows stimulation and can be inhibited by stress.
The effects of prolactin are locally controlled by the production of FIL in the milk. Increased concentrations of FIL suppress the response to prolactin thus inhibiting milk production. This is important in mammary gland involution when breastfeeding is curtailed.
Lactating women appear to have increased efficiency of energy utilization. The nutritional composition of the milk is not affected greatly by maternal diet unless the mother is extremely undernourished; however, concerns have been expressed about effects on maternal calcium balance and the tendency to develop obesity. Breastfeeding is associated with a reduced risk of maternal breast and ovarian cancer.
Human milk provides optimal nutrition for the human neonate, which has immature renal, hepatic and gastrointestinal functions and a rapidly developing nervous system. Breastfed babies have a lower incidence of infection.
Colostrum is the early secretion from the breast; it provides important anti-infective properties and promotes favourable colonization of the gut.
Protein requirements are relatively low as the human neonate has a relatively slow growth rate. Human milk has a high concentration of whey proteins and non-protein nitrogen components, which include growth factors. The amino acid composition of human milk protein compensates for the neonate's limited ability to convert essential amino acids to non-essential amino acids; the net protein utilization of human milk is high.
Fat is the main energy source in milk and the most variable constituent. The proportion of fat is higher in hindmilk. The fatty acid composition of human milk allows optimum absorption. Human milk fat is rich in polyunsaturated fatty acids required for development of the brain and nervous system.
Lactose is the major carbohydrate of milk; it provides energy, aids absorption of other nutrients and promotes an environment favourable to beneficial microorganisms.
Human milk has important immunological properties and is associated with a lower incidence of infections and a persistently more responsive immune system in breastfed babies.
Application to practice
It is consistently shown that breastfeeding is influential in the reduction of many disease states and thus should be encouraged. The midwife is uniquely placed to influence the overall health of the nation. Midwives must ensure women are aware of what the health benefits of breast feeding are for both them and their babies.
Knowledge of lactation and its benefits are important if the midwife is to promote breastfeeding in practice.
Following birth mother's should be encouraged to offer the breast as soon as possible after delivery. By placing the naked baby on the abdominal wall of the mother in close proximity of the breasts will enable the baby to spontaneously fix and suckle. This is important if the baby is cold following delivery and/or required initial resuscitation following birth. Cold, shocked babies are less likely to feed spontaneously and so skin to skin not only is efficient in warming babies up it also gives them comfort.
Women who have received pharmacological drugs during labour will need extra help and support as the baby's spontaneous urge to feed may be reduced.
If mother and baby are well and the mother has chosen to breast feed there are no reasons why exclusive breast feeding cannot be achieved.
If babies are drowsy or seem disinterested in the breast then the mother should be encouraged to keep offering the breast. The introduction of formula milk or bottles should be avoided as this will interfere with the establishment of lactation.
In the rare cases where the baby has difficulty latching on the mother should be encouraged to hand express and the expressed milk offered to the baby via a small cup or spoon.
The midwife must ensure that women who have chosen to bottle feed are aware of the need to ensure all equipment used is sterilized and milk made up is appropriately stored to minimize the risk of infection. The milk must be prepared as directed by the manufacturers as diluted or concentrated mixes are potentially harmful to the neonate.
Annotated further reading
Fomon, S., Infant feeding in the 20th century: formula and beikost, J Nutr 131 (2) (2001) 409S–420S.
A history of changing infant feeding practices in the 20th century, including the effects of sanitation, dairying practices and milk handling on home- and commercially prepared formulas.
In: (Editors: Goldberg, G.R.; Prentice, A.; Prentice, A.; Filteau, S.; Simondon, K.) Breast feeding: early influences on later health (advances in experimental medicine and biology) (2008) Springer.
This book comprises several papers which examine early life programming of adult health, particularly the influence of infant feeding practices on early metabolism and behaviour and thus later function including risk of disease.
Howard, B.A.; Gusterson, B.A., Human breast development, J Mammary Gland Biol Neoplasia 5 (2000) 119–137.
A comprehensive well-illustrated review of physiological states of the human breast including prenatal, prepubertal and pubertal development, adult resting state, pregnancy, lactation and postinvolution.
Joeckel, R.J.; Phillips, S.K., Overview of infant and pediatric formulas, Nutr Clin Pract 24 (2009) 356–362.
A clear summary of the differences between various types of infant and paediatric formula milks and their indications for use.
Levy, O., Innate immunity of the newborn: basic mechanisms and clinical correlates, Nat Rev Immunol 7 (2007) 379–390.
A beautifully written description of the complex immunological challenges faced by the fetus and neonate, particularly the demands of projection against infection, avoiding harmful inflammatory immune responses and balancing the transition from a sterile uterine environment to an extrauterine environment rich in foreign antigens.
Manuel, R.; Martens, P.J.; Walker, M., Core curriculum for lactation consultant practice (ICLA). ed 2 (2007) Jones and Bartlett .
This is essential reading for practitioners who want to extend their knowledge of breastfeeding and lactation and support women in the establishment of breastfeeding.
Newburg, D.S.; Walker, W.A., Protection of the neonate by the innate immune system of developing gut and of human milk, Pediatr Res 61 (2007) 2–8.
A well-balanced discussion of the neonatal innate immune system and its interaction with components of human milk which act to both protect the neonatal gut and compensate for the immature state of neonatal adaptive immunity.
Palmer, G., The politics of breastfeeding: when breasts are bad for business. ed 3 (2009) Pinter & Martin Ltd .
This book explores the influence of artificial feeding on the population from a global perspective. It discusses social, historical and economic factors affecting a woman's decision to breastfeed and the implications of the type of infant feeding method on health, the environment and the global economy with a particular focus on the pressures put on parents to use alternatives to breastmilk.
Riordan, J.; Auerbach, K.G., Breastfeeding and human lactation. ed 4 (2008) Jones & Bartlett, London .
A comprehensive text on breastfeeding aimed at midwives, breastfeeding consultants, antenatal teachers, dietitians and nutritionists. Covers cultural aspects, anatomy and physiology, breastfeeding education and practical considerations such as breast pumps, donor milk and breastfeeding the ill child.
Rogers, I.S., Relactation, Early Hum Dev 49 (1997) S75–S81.
This article discusses the possibility of re-establishing lactation in certain situations and includes information on promoting lactation in women who have never been pregnant.
Sellen, D.W., Evolution of infant and young child feeding: implications for contemporary public health, Annu Rev Nutr 27 (2007) 123–148.
A framework for understanding prehistoric, historic and contemporary variations in human lactation and infant feeding patterns which suggests complementary feeding evolved as a trade-off between the maternal cost of lactation and the risk of poor infant outcome.
West, D.; Marasco, L., The breastfeeding mother's guide to making more milk. (2008) McGraw-Hill .
Written by lactation consultants, this book is aimed at mothers to help promote and establish breastfeeding but practitioners will also find this text useful.
Winberg, J., Mother and newborn baby: mutual regulation of physiology and behavior – a selective review, Dev Psychobiol 47 (2005) 217–229.
An interesting review of the interactions between the mother and newborn infant in the period just after delivery and how these influence the physiology and behaviour of both.
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