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4 How Breastfeeding Works: Anatomy and Physiology of Human Lactation

Published onJul 01, 2018
4 How Breastfeeding Works: Anatomy and Physiology of Human Lactation

4 How Breastfeeding Works: Anatomy and Physiology of Human Lactation

Melinda Boss, MPS, B.Pharm, Senior Research Fellow; Peter E. Hartmann, E/Prof, PhD, BRurSc

Expected Key Learning Outcomes

  • The history of the understanding of the anatomy and physiology of lactation

  • The processes of lactation

  • The production and regulation of milk supply

  • How the complexity of lactation benefits both mother and baby

4.1 Introduction

In 1840, Astley Cooper published a book titled “On the Anatomy of the Breast”. His anatomical dissections of the lactating breast are still used in textbooks to this day. This is in part due to the difficulty in obtaining specimens (lactating women rarely donate their bodies to science) and partly due to a lack of scientific interest in this fascinating organ. Thus, Cooper’s work stands out as the exception and his book provides a sound foundation for the understanding of mammary anatomy and physiology. He rightly deserves to have the ligaments of the breast, Cooper’s ligaments, named in his honour. This chapter addresses historical as well as current knowledge of lactation, including a detailed review of Cooper’s work and how this developed our current understanding. His dissections remain the seminal work on the gross anatomy of the human breast and many of his preparations have been reproduced here to illustrate the structure of its parenchyma, together with its innervation, blood,and lymphatic supply. In addition, the anatomy of the lactating breast forms the basis for a detailed consideration of the physiology of human lactation. The historical development of the current knowledge of the mechanisms involved in the synthesis and secretion of milk are considered in a functional context. The removal of milk from the mammary gland is also reviewed, including milk ejection and the infant suck-swallow-breathe reflex. This chapter covers changes occurring over the lactation cycle from conception, secretory differentiation during pregnancy, secretory activation after birth, the endocrine and autocrine regulation of lactation, and finally involution and the return of the mammary gland to its resting state.

4.2 Background

In 1758 Carolus Linnaeus, the “father of taxonomy”, grouped into one class both aquatic and land animals with the capacity to produce milk for their young: Mammalia. The selection of this term was unusual because it was only directly applicable to half the animals in this class, namely females. Indeed, he ignored other biological traits (such as hair, sweat glands, and three ear bones) that are specific to all mammals. Wet nursing, the practice of mothers breastfeeding another mother’s infant, was widely practiced at that time. Specifically, rich families paid poor mothers to breastfeed their babies. Diaries of rich mothers suggest that they reluctantly accepted this “cuckoo-like” behaviour because they had been convinced that it was best for their babies. Wet nursing was prevalent in the “better classes” in Sweden and other European countries. Linnaeus was strongly opposed to wet nursing. It is said that he chose the term, Mammalia, because he wanted to emphasize that young mammals should be suckled by their own mothers. Today, our current knowledge of the importance of breastfeeding to both the mother and her infant reinforces the wisdom of Linnaeus’ choice of the term, Mammalia.

▶Fig. 4.1

Changes in the proportion of infants who were breastfed in high-income countries from 1938 to 1980. (Reproduced from Hartmann, P.E. et al. Human lactation: Back to nature. Physiological Strategies in Lactation. Symposia of the Zoological Society of London. 337–368, 1984)

The abandonment of breastfeeding in the 19th and 20th centuries seems to have been associated with the development of condensed cow’s milk in 1853 and evaporated cow’s milk in 1885. Pasteurisation and the home icebox also decreased the risk of contamination of infant formula with microbiological pathogens. By the 1920s and 1930s evaporated cow’s milk was widely available at affordable prices and several clinical studies suggested that infants fed evaporated cow’s milk formula thrived as well as those that had been breastfed. Importantly, these studies have not been supported by modern research. Indeed, Cowie, et al. concluded that ‘We may also surmise that had cow’s milk been tested by usual procedures that are now applied to new drugs it is unlikely, in view of its puzzling toxicity to infant rabbits, that it would have reached the stage of even a clinical trial in human infants!’[1].

The active marketing of “safe” infant formula under the erroneous belief that scientifically developed formula was either better or equivalent to breastmilk for the nourishment of babies, enabled the lower socioeconomic classes to use this “pocket wet nurse” and follow the example set by the richer classes. The decline in breastfeeding was arrested in 1972 in most high-income countries ▶Fig. 4.1 when for the first time in Western history affluent mothers began to breastfeed their own babies ▶Fig. 4.2. This example has filtered down all social classes and currently almost all mothers in some Western countries choose to breastfeed their newborn infants. The breast is unusual in that lactation is characterised by periods of high secretory activity followed by periods of quiescence. Indeed, lactation is the final phase of the reproductive cycle in mammals. In all of the 4000 plus species of mammal, maternal milk is essential for the survival of the young during early postnatal life. However, mammals are either hatched or born at very different stages of maturity. Species-specific lactation strategies and milk composition provide a unique environment for the maturation of each mammal’s young [2]. Therefore, it is not surprising that the milk of one species is not suitable for optimum physiological growth and development of the young of another. Human lactation is no exception; for example, human infants grow extremely slowly compared to most other mammals. The time to double birth-weight extends many months for human infants but is only a few days in piglets. Indeed, human milk has a very low concentration of protein relative to its energy content and therefore cannot support rapid infant growth. The proportion of energy derived from protein is lower in infants than that recommended for adults. It follows that the proportion of essential amino acids in human milk must exactly match the infant’s requirements. This is very difficult achieve with infant formula. To obtain the required intake of all essential amino acid(s), extra protein has been added to infant formula. Unfortunately, this higher protein intake is associated with adverse outcomes in infants such as obesity and increased renal solute load.

▶Fig. 4.2

Social rank of mothers and the proportion of mother’s breastfeeding in Australia from 6 weeks to 12 months postpartum in 1983.

The evolution of a large brain (i.e., one that requires ~25% of the mothers daily resting energy intake) has given humans a significant competitive intellectual advantage over all animals, including other mammals. Consequently, unlike other mammals, extensive brain growth in human infants occurs in the first one to two years after birth. This rapid postnatal growth is facilitated by many components present in breastmilk. Furthermore, the lactating breast is a very active metabolic organ (▶Fig. 4.3), with energy output in breastmilk representing ~30% of the daily resting energy requirements of the mother. It is also important to consider the duration of lactation. Other large primates breastfeed for years rather than months; for example, the orang-utan breastfeeds for 7 years. Therefore, it is also to be expected that women would breastfeed for a number of years and indeed rural Aboriginals in North Western Australia breastfed their babies into their 6th year of life. Modern traditional societies (i.e., those without access to manufactured contraceptives or prepared infant foods) usually wean between 2–3 years of age [3]. The World Health Organization recommends that all infants should receive breastmilk only (with no additional food, drink, or water) until 6 months after birth and then continue to be breastfed with the introduction of first foods up to 2 years of age and beyond [4]. Currently, most infants in developed countries are weaned before one year of age [5], [6], [7].

▶Fig. 4.3

Thermal images of the breasts of (a) non-lactating and (b) lactating women (red 38 °C, green 31 °C). (from Kent J.C., Hartmann, P.E. 1995 Unpublished data.)

The promotion of breastfeeding by community groups and health professionals in countries like Australia has been excellent, and 96% of mothers now choose to breastfeed their babies compared to only 48% in 1972 [5], [8]. Indeed, facilitation of breastfeeding (e.g., in coffee shops) is now beginning to be seen as providing an economic dividend (▶Fig. 4.4). Unfortunately, there is a rapid decline in breastfeeding with time after birth, with less than 16% of infants exclusively breastfed to 5 months and only 60% receiving any breastmilk at this time[5].

The commitment of such a large proportion of maternal energy intake to lactation over a long period of time (years), and the conservation of genes associated with lactation and milk composition strongly suggests that mothers are “hard-wired” to breastfeed. This conclusion is reinforced by the observation that mothers will endure hardships suchasseverebreastand nipple pain and still continue to breastfeed their infants. This begs the question, ‘Why have women in high-income countries found it difficult to breastfeed?’ Two reasons may be postulated. First, perhaps subtle uncertainties accumulate and diminish the mother’s confidence in her ability to produce enough milk for her baby. Secondly, mothers experience unacceptably high incidences of conditions, such as breast engorgement, mastitis, and severe nipple pain, which challenge the resilience of even the most committed mothers (▶Fig. 4.5).

Since there is only limited basic research on human lactation, evidence-based medical diagnosis and treatment of lactation dysfunction is very limited. For example, unlike other metabolically equivalent organs in the body, there are no clinical tests to assess the normal function of the lactating breast and no reference ranges for either milk production or milk composition. Consequently, family doctors do not have objective tests to assist with the diagnosis and treatment of mothers who experience breastfeeding difficulties. There are no clinical tests to measure 24-hour milk production, yet perceived low milk supply is one of the major causes of mothers ceasing to breastfeed.

Conventional medical care (that is, the availability of a lactology medical specialist to whom the family doctor can refer patients if necessary) does not exist and this is probably responsible for much of the current decline in breastfeeding with time after birth. This is appalling considering that the lactating breast requires a higher proportion of daily resting energy than the brain. Attention to this situation was succinctly stated in TIME magazine,

▶Fig. 4.4

A coffee shop advertisement in Perth, Western Australia featuring a mother breastfeeding her 6 month old baby and inviting other breastfeeding mothers to frequent the coffee shop in 2011. (STM 2011, Sunday Times Magazine, January 2016)

‘... lactation is probably the only bodily function for which modern medicine has almost no training, protocol or knowledge. When women have trouble breast-feeding, they’re either prodded to try harder by well-meaning lactation consultants or told to give up by doctors. They’re almost never told, “Perhaps there’s an underlying medical problem — let’s do some tests”’[9].

▶Fig. 4.5

Lactating mothers with (a) breast abscess and (b) mastitis. Both mothers breastfed their babies during the breast trauma and for several months after recovery. (from Hartmann, P.E. 1985. Unpublished data.)

Obviously a much deeper understanding of the anatomy and physiology of the human breast are required so that appropriate medical care can be provided for lactation.

4.3 Gross Anatomy

4.3.1 History

Any consideration of the anatomy of the non-lactating and lactating human breast is not complete without acknowledgment of the contribution of the brilliant Sir Astley Paston Cooper in 1840 [10] (▶Fig. 4.6). He was the greatest surgeon of his time and was much loved in the medical world [11]. His patients knew him for his sweetness of manner and courtesy. Against the practice of the time, Cooper always removed his top hat on entering the wards. He also took good care of his students; for example, he found accommodation for the poet Keats when he was a medical student. Cooper’s careful observations and meticulous dissections set the foundation for current knowledge of the gross anatomy of the lactating human breast. His findings have, in the main, stood the test of time.

‘My rule has been to publish that only which I could show to those who were sceptical, and were yet desirous of arriving at the truth.’

Subsequently, few scientists have followed his example and investigated this extremely interesting organ, the human mammary gland. Very few papers investigating the anatomy of the lactating human breast were published for the remainder of the 19th century and the entire 20th century. Thus, anatomical diagrams and descriptions of the gross anatomy of the lactating breast have changed little over the past 165 years.

Cooper obtained lactating breasts from the bodies of cadavers who were most likely provided by gangs of “resurrection men”. The bodies were from women in established lactation. The breasts from mothers who died soon after giving birth (presumably from puerperal fever) were decomposing from virulent septicaemia and unsuitable for his anatomical studies. Cooper studied the gross anatomy of the lactating breast including the ductal system, innervation, blood vessels, lymphatic system, fatty tissue, and the ligamenta suspensoria. These ligamenta suspensoria are now commonly referred to as “Cooper’s ligaments” in recognition of his contribution to the understanding of the anatomy of the lactating breast and in particular for being the first to provide a detailed description of these ligaments (▶Fig. 4.7). Cooper’s ligaments support the breast in its normal position.Cooper noted that without the internal support provided by these ligaments the breast tissue (which is heavier than the surrounding fat) would sag under its own weight, losing its normal shape and contour.

▶Fig. 4.6

Sir Astley Cooper, author of the seminal book “On the Anatomy of the Breast”, published in 1840. (Cooper, AP 1840. On the Anatomy of the Breast, Longman.)

‘The uses of the ligamenta suspensoria are to connect the nipple to the breast, the breast to the skin and to fold up the gland to increase the secretory organ, without spreading it more widely over the surface of the chest. They also enclose the adipose matter of the breast.’

Errors in interpretation of Cooper’s work have persisted over time and this suggests that few authors actually quoted from his original work.

4.3.2 Foetal and Pubertal Development

The normal growth and functional development of the breast may be either reduced or even abolished by trauma such as from cosmetic surgery. Therefore, the anatomy and physiology of lactation is concerned not only with breastmilk and the function of the breast during lactation, but also with development. Development must encompass maturation of the breast from foetal stages to sexual maturity, together with development to a secretory state during pregnancy and after birth.

The mammary ridge (milk line) appears as a raised portion of ectoderm on either side of the midline by the time the human embryo has attained a length of 4–6mm(4th week of gestation). Regression of the mammary ridge occurs except for the pectoral region (2nd to 6th rib), which forms the mammary buds that lead to the development of breasts. In 2–6% of women, mammary buds may develop anywhere along the mammary ridge and may either mature into accessary breasts (polymastia) or remain as accessory nipples (polythelia).

▶Fig. 4.7

(a) Section of the mammary gland through the nipple, showing ducts over a bristle, unravelled, and proceeding to the posterior part of the gland. (b) A preparation made to show the ligamenta suspensoria supporting the folds of the breast to the inner side of the skin. (c) A view of the gland, dissected and unravelled, to show the ducts over bristles, lobuli, and glandules. (Cooper, AP 1840. On the Anatomy of the Breast, Longman. Plate IV fig 1.)

By the end of gestation, epithelial cells in the mammary buds have elongated microvilli on the luminal surface, the cytoplasm is rich in organelles, and the rough endoplasmic reticulum has dilated cisternae containing fine granular material. The Golgi vesicles in these epithelial cells contain dense, dark granules and fat droplets that are discharged into the alveolar lumen. Therefore, by the end of gestation, the cells of the breast of the human foetus have reached a high degree ofdifferentiation and are secreting in response to the foetal hormonal milieu of late pregnancy.

The newborn breast consists only of rudimentary ducts that have small club-like ends, which regress soon after birth. Neonatal galactorrhoea, commonly referred to as witch’s milk, is a fluid secreted from the breasts of newborn infants. Indeed, witch’s milk is one of the few pre-scientific terms still in current medical usage. It was thought that the witches possessed infants that secreted such milk and these infants were not favoured. However, this physiological occurrence is found in 100% of term infants less than 3 weeks of age and is usually resolved before the infant reaches 4 months of age [6]. Witch’s milk is similar in composition to colostrum and when compared with extracellular fluid, the concentration of sodium is low. Thus, the ionic composition of the mammary secretion of the newborn infant can be used to distinguish between true neonatal galactorrhoea with low sodium and bacterial infection that has high sodium content. Bacterial infection increases the permeability of the breast epithelium and the ionic content of the secretion from the infant nipple under these circumstances tends to equilibrate with the higher sodium content of the extracellular fluid [12].

Throughout childhood only isometric growth of the breast occurs and the rudimentary breasts remain quiescent. Allometric growth of the human breast occurs at puberty and continues during the luteal phase of the menstrual cycle until maximum development is achieved between 20–30 years of age. During this period there is accelerated growth of the nipple and the development of sub-areolar tissue, leading to elevation of the areola and nipple. In the adult, the areola is a circular pigmented area of skin about 40mm in diameter, but the size of both the areola and nipple can vary greatly between women and with time (▶Fig. 4.8).

4.3.3 Non-Lactating Adult Breast

The non-lactating breast is composed of glandular and adipose tissue and is supported by a loose network of fibrous connective tissue (Cooper’s ligaments). Ultrasound imaging has identified an average of nine ductal openings (nipple pores) at the nipple. This is in close agreement with Cooper’s observations from his dissections of seven to ten functional ductal openings on the nipple. Larger numbers (15–20) are usually quoted in textbooks based on Cooper’s work. Careful reading of his work shows that he only observed a maximum of 12 functional ducts opening at the nipple. ‘The greatest number of lactiferous tubes I have been able to inject, has been twelve, and more frequently from seven to ten.’ However he did note up to 22 openings on the nipple but concluded that a number of these were just follicles and not open ducts.

▶Fig. 4.8

Size of the breast from 11 months to 20 years of age. (a) 11 months, (b) 3yr, (c) 4yr, (d) 6yr, (e) 9yr, (f) 11yr, (g) 12yr, (h) 13yr, (i) 14yr, (j) 16yr, and (k) 20yr. (Cooper, AP 1840. On the Anatomy of the Breast, Longman. Plate II.)

Although prior to pregnancy the adult breast is in an inactive state, changes do occur in the breast during the menstrual cycle. In the proliferative phase of the menstrual cycle (when follicles are primed for ovulation) there is increased cell division. During the luteal phase (when follicles produce progesterone to prepare the uterus for the fertilised egg), the ducts become somewhat dilated and the alveolar cells contain some lipid droplets. From 3–4 days before the onset of menstruation, increased turgescence and tenderness are observed. Breast volume normally increases by 15–30mL but in some women this increase can be up to 300–400mL. Towards the end of menstruation the secretory tissue begins to regress and breast oedema decreases to reach a minimum breast volume by 5–7 days after menstruation.

During the non-lactating state the lobules consist of either tubules or ducts lined with epithelial cells and embedded in connective tissue. They are widely separated, with connective and adipose tissues predominating. At this stage of development there is only a small contribution from the glandular tissue. A few bud-like sacculations (terminal end buds) arise from the ducts, but the gland consists predominantly of interlobar and interlobular ducts. The few alveoli present consist of simple cuboidal epithelial cells without distinctive structural features. The milk ducts branch under the areola, are quite superficial, and are easily occluded with the application of light pressure. Differences in the morphology (external appearance) of the breast exist, even between different ethnic groups, but the internal structure of the glandular and supporting tissues is similar in practically all species of mammal [13].

The distribution of adipose tissue in the human breast is highly variable. It is situated beneath the skin (subcutaneous), between the glandular tissue (intra-glandular) and beneath the breast (retromammary fat pad). Unlike other mammals, women have significant amounts of intra-glandular adipose tissue. In other species studied, the mammary glands contain subcutaneous and retromammary adipose tissue but no intra-glandular adipose tissue. The variable amount of intra-mammary adipose tissue may be, in part, the reason why breast size does not correlate with milk production.As Cooper observed,

‘The quantity of milk which a woman is capable of secreting, cannot be estimated by the size of her breast, as it often is large and hard rather than secretory, or it is loaded with adeps, and produces but little milk.’

Knowledge of the innervation of the breast is relatively limited compared to that of other major organs in the body. Investigation of the innervation and sensitivity of the breast has predominantly focused on women who have undergone breast surgery such as reduction mammoplasty. Cooper showed that the 2nd to 6th intercostal nerves supply the breast (▶Fig. 4.9). These nerves divide into two branches. The deep branch supplies the glandular tissue and the other branch takes a relatively superficial course within the gland, supplying the nipple and areola. The areola also contains a dense intradermal nerve plexus supplying numerous sensory end organs, including Meissner’s corpuscles and Merkel’s discs (mechanoreceptors). This ensures it is receptive to mechanical stimuli, suchassuckling.

Innervation of the larger ducts has been observed but no nerves have been associated with the smaller ducts, and a lack of sensitivity of the epidermis of the nipple has been noted. Clinically, women recognise the overall fullness and distension of their breast as well as pain associated with some abnormalities, but are often unable to accurately localise either sensation.

4.3.4 Pregnancy

In some women, changes in the breast (e.g., tenderness related to growth) can provide the first indication of conception and the beginning of the lactation cycle with a progressive increase in breast volume (▶Fig. 4.10). The areola contains large sebaceous glands (Montgomery’s glands)

▶Fig. 4.9

Innervation of the breast. (a) The dorsal of posterior nerve going to the breast (white), (b) The 4th posterior nerve coming out of the chest below the fourth rib, and proceeding to the breast and the nipple. (Cooper, AP 1840. On the Anatomy of the Breast, Longman.)

▶Fig. 4.10

Increase in the volume of a breast from preconception to one-month postpartum. (Cox D.B. The morphological and functional development of the human breast during pregnancy and lactation. PhD Thesis: The University of Western Australia; 1996)

that hypertrophy and form papillae during pregnancy, as well as sweat glands and some hairs. Secretions of the Montgomery glands lubricate and protect the nippleand areoladuring lactation.Volatilisation ofcompounds in this secretion may also provide an olfactory stimulus for the infant. Ductal branching and lobular formation (alveolar development)exceeds the normal premenstrual growth by 3–4 weeks of gestation. A lactogenic complex of reproductive hormones (progesterone, oestrogen, and prolactin) and metabolic hormones (growth hormone, glucocorticoids, parathyroid hormone related protein, and insulin) influence alveolar development in women during pregnancy.

There is extensive lobular-alveolar growth during the first half of pregnancy. However, the glandular parenchyma of the breast does not respond to hormonal stimulation in a synchronous manner. Different areas in the same breast can develop to a greater or lesser degree at any particular time during pregnancy. In the latter stages of pregnancy there is a further increase in lobular size due to the hypertrophy of the cells and the accumulation of secretion in the lumen of the alveoli. The milk ducts have branched and form lobes and the lobes divide into lobules that consist of clusters of alveoli lined with lactocytes (mammary secretory epithelial cells) (▶Fig. 4.11).

The classic dissections of lactating cadavers by Cooper have also formed the basis for descriptions of the blood supply to the breast (▶Fig. 4.12). During pregnancy, blood flow to the breast doubles by 24 weeks and then remains constant during lactation. Along with the increase in blood flow, the superficial veins of the breast become more prominent during pregnancy and lactation. The blood supply to the breast arises from the anterior and posterior medial branches of the internal mammary artery (60%) and the lateral mammary branch of the lateral thoracic artery (30%) [14].

▶Fig. 4.11

Milk ducts injected with different coloured waxes. (a) showing the radiated direction and inter-ramification of the milk ducts injected with red wax. (b) milk ducts injected with red, yellow, black, green and brown wax with the lobes spread out over a stone. (c) at the lower part of the preparation the separate ducts are seen passing above and beneath each other, to render the breast a cushion; whilst at the upper part the ducts are single, (d and e) alveoli six times magnified, (f and g) alveoli injected with mercury and four times magnified. (Cooper, AP 1840. On the Anatomy of the Breast, Longman. Plate VI and VII.)

▶Fig. 4.12

(a) Arteries (red) and veins (yellow) of the breast from their anterior and posterior sources, (b) veins around the nipple, (c) distribution of arteries upon the breast and around the nipple, (d) veins injected in the areola and nipple. (Cooper, AP 1840. On the Anatomy of the Breast, Longman. Plate X.)

However, there is wide variation in the proportion of blood supplied by each artery between women. In women, as in lactating animals, the ratio of blood flow to milk production is approximately 500:1. No relationship was observed between blood flow and milk production.

4.3.5 Lactating Breast

Cooper concluded that the ligaments associated with the mammary fat pad also protected the lactating breast tissue. Indeed, throughout his book he makes numerous statements marvelling at how resilient the breast is to severe blows.

‘It is, then, a thick cushion of fat placed under the skin, which enables women of the lower class to bear the very severe blows which they often receive in their drunken pugilistic contests.’

In this connection, Cooper was first to report the vigorous sucking behaviour of the young of some mammals, noting that

‘… the lamb suckling for a short time to empty the large reservoir of the gland of accumulated milk, and then beating the udder of the ewe with its head as if to put it in mind of secreting more to supply its still pressing wants.’

It is of interest that fatty tissue is interspersed within the glandular tissue in women but not in other mammals. This suggests that the support from the ligaments may be more important than the pad of fatty tissue in protecting the breast against severe blows. On the other hand,

▶Fig. 4.13

Anatomy of the human breast. (Ramsay DT, Kent JC, Hartmann RA, et al. Anatomy of the lactating human breast redefined with ultrasound imaging. J Anat 2005; 206(6): 525–534)

‘Very thin women, whose breasts are unprotected by this mode of defence, sometimes show severe bruises; but these in a fortnight or three weeks disappear. Yet it is very certain that at distant periods women apply with tumours in their breasts, which they frequently impute toblows.’

In the literature up to 2005, Cooper’s description of the ductal system prevailed and was depicted as a cluster of alveoli joined to small ducts expanding to form larger ducts that drain the lobules. The larger ducts then merge into one milk duct for each lobe. These ducts then open through a pore to the surface of the nipple (▶Fig. 4.13). Cooper stated that the areola

‘form a surface which is embraced by the child, and received into its mouth, so that the large lactiferous tubes behind the areola (▶Fig. 4.14) are emptied by the pressure of the lips of the infant. The areola is, therefore, tobe considered as an extension of the nipple, the base of which latter is lost in the former: its structure is very similar to the nipple, or mammilla.’

▶Fig. 4.14

Milk ducts injected from the nipple. (a) Six milk ducts, (b) reservoirs or dilatations of the ducts below the nipple, (c) a single lobe. (Cooper, AP 1840. On the Anatomy of the Breast, Longman. Plate VII.)

▶Fig. 4.15

Ultrasound images of the milk ducts below the nipple. No reservoirs or dilatations of the ducts were detected and secretory tissue was present immediately below the nipple. (Ramsay, DT 2005 personal communication.)

Recent detailed studies by Ramsay, et al. using ultrasound imaging have not identified large lactiferous tubes behind the areola” (▶Fig. 4.15) [15]. It is likely that the dilation of the “tubes” was an artefact resulting from the injection of hot wax through the pores of the nipple to enable the identification of the milk ducts. In contrast to Cooper’s observations, ultrasound imaging clearly shows that the area immediately under the areola is densely packed with lobules containing alveoli. Since it was assumed that the pressure of the lips of the infant emptied the non-existent “large lactiferous tubes”, the mechanism by which the infant removed milk from the breast had to be reassessed.

4.4 Physiology

4.4.1 Origin of Milk

The genesis of milk has long intrigued scientists and theories have been recorded back to the time of the Ancient Greeks. Four observations were seminal in the formation of ideas on the origin of milk. Firstly, the absence of menstruation during pregnancy and early lactation; secondly, many women experienced peculiar sensations in the lower abdomen during breastfeeding; thirdly, milk was thought to be synthesised and actively secreted during milk ejection; and finally, lymphatic vessels draining the small intestine were thought to be the origin of milk because they contained a milky fluid. The first and second observations led to the uterine milk theory promoted by Galen, who claimed that the menstrual blood that nourished the foetus was diverted to the breast after birth in special vessels (vas menstrualis, ▶Fig. 4.16). This theory was rejected when it was found that no such vessels existed. Galen’s knowledge of the anatomy of the male body was probably more accurate than that of the female body because he was at one time a physician to the gladiators.

▶Fig. 4.16

Drawing by Leonardo da Vinci influenced by Galen’s teachings showing a vessel from the uterus to the breast that in fact does not exist. (Calder, R. 1970 Leonardo & the Age of the Eye, Heinemann. p176.)

The chyle theory of the origin of milk followed the observation that the lymphatic vessels draining the small intestine into the thoracic duct were white in appearance and, when pricked, a fluid resembling milk flowed out. This theory was soundly discredited by the experiments of Cooper who stated

▶Fig. 4.17

Lymphatic vessels of the female breast, (a and b) lymphatics draining from the nipple to the clavicle. The constrictions in the vessel are the valves in the lymphatic vessels that ensures that the lymph flows away from the breast to the lymph nodes. (c) The dense network of lymphatic vessels in the breast. (Cooper, AP 1840. On the Anatomy of the Breast, Longman. Plate XI.)

‘A most extraordinary opinion has been broached, that the absorbents (lymphatic vessels) carried chyle to the breast (▶Fig. 4.17) — an opinion at variance with the nature of the fluid, entirely inconsistent with every injection which I have made, and irreconcilable with the valvular structure of these vessels’ [10].

The idea that milk was rapidly synthesised in the breast during milk ejection was questioned in the early 20th century when a clear distinction was made between the continuous process of milk synthesis and the intermittent acute process of milk ejection. This provided the background for development of the current understanding of milk synthesis and secretion.

Human placental lactogen secreted from the placenta has an action similar to growth hormone. The increase in breast growth during pregnancy is closely related to the increase in this hormone (▶Fig. 4.18), which disappears within a few hours postpartum. On the other hand, the increasing prolactin concentration in maternal blood during pregnancy is closely related to the increase in amount of lactose excreted in urine. The bloodmilk barrier is not fully formed during pregnancy, allowing lactosetodiffuse into the maternal blood. Lactose is not metabolised in the blood but excreted via the urine; this means that lactose excretion in urine over a 24-hour period can be used as a measure of lactose synthesis during pregnancy. It should be noted that this increase in urinary lactose excretion during pregnancy is also closely related to secretory differentiation (▶Fig. 4.19).

4.4.2 Secretory Differentiation

We now know that the initiation of lactation occurs in two stages. The first stage (secretory differentiation) commences during mid pregnancy when the breast develops the capacity to synthesise unique milk constituents, such as lactose and milk specific proteins. At this time the stem cells within the breast have developed into progenitor cells that in turn have differentiated into lactocytes.

This transition is termed secretory differentiation (previously termed lactogenesis I) [16]. Due to the high levels of progesterone in women, the milk secretion rate (colostrum) is low; on average about 30mL per day. Secretory differentiation occurs at about 20–25 weeks of gestation and is very close to the time of viable preterm delivery. Thus, it is possible that incomplete maturation of secretory differentiation could be one of the factors limiting successful development of lactation in preterm mothers.

▶Fig. 4.18

Breast volume (mL), a measure of breast growth, and the concentration of human placental lactogen

(mg/L) at three-weekly intervals from conception to birth. (Czank C, Henderson JJ, et al. Hormonal control of

the lactation cycle. In: Hale TW, Hartmann P. Textbook of human lactation, New York: Springer; 2007)

▶Fig. 4.19

Concentration of prolactin (μg/L) in blood and the excretion of lactose (mmol/24h) in urine at three weekly intervals from conception to birth. Secretory differentiation commences at approximately 18 weeks of pregnancy. (Czank C, Henderson JJ, et al. Hormonal control of the lactation cycle. In: Hale TW, Hartmann P. Textbook of human lactation, New York: Springer; 2007)

4.4.3 Secretory Activation

Secretory activation (previously termed lactogenesis II) is the second stage in the initiation of lactation and occurs during the first 3 days after birth [16]. Secretory activation is characterised by the initiation of copious milk production and is arguably the most important phase of the lactation cycle. Unlike secretory differentiation, secretory activation has to be tightly coupled to the time of birth, so that the newborn can make a seamless transition from the protective environment of the uterus and continuous nourishment from the umbilical vein to the intermittent provision of protection and nourishment from the mother’s milk. Appropriate management of secretory activation is crucial for the successful development of optimal milk production. Only one study has investigated the sensitivity of the breast during pregnancy and lactation. This study showed that areola and nipplesensitivity increasedmarkedly within 24 hours postpartum and then declined in the following days [17]. Presumably sensitivity of the nipple at this time provides a signal to the mother (pain) if her infant is not appropriately attached to her breast when feeding.

▶Fig. 4.20

Milk production (mL/24h) in a woman with placental retention from 20 to 44 days postpartum.

Dilatation and curettage was carried out at day 23 to remove placental fragments.

It is of concern that little medical follow-up of lactation occurs after administration of pain relief to the mother. Analgesia can prevent the mother sensing when her baby is incorrectly attached during a breastfeed and thus predisposeher to nippletrauma.

Oestrogen withdrawal was once favoured as the stimulus for secretory activation because pharmacological doses of estrogenic hormones inhibited milk synthesis. These findings encouraged Gunther to recommend graded doses of diethylstilbestrol as a method of suppressing postpartum breast engorgement [18]. This practice has since been abandoned due to long-term unfavourable outcomes. The classic findings of Kuhn in 1969 clearly demonstrated that progesterone withdrawal was the lactogenic trigger in rats, but progesterone withdrawal has since been shown to be the universal trigger for secretory activation in all Eutherian mammals including women [19]. Indeed, Neifert, et al. found that secretory activation was inhibited after birth in a woman with retained placental fragments [20]. Milk secretion (secretory activation) rapidly increased from about 10mL/24 h to about 350mL/24 h on day 28 after curettage (▶Fig. 4.20) [20]. In this context it should be noted that progesterone synthesis occurs in the placenta in women but that oestrogen synthesis requires the presence of both placenta and foetus.

▶Fig. 4.21

Concentration of progesterone (% of maximum values) in blood and lactose (% of maximum values) in mammary secretion from –6 days prepartum to 5 days postpartum in women and rats. (Reproduced from Hartmann, P.E. 1990. Unpublished data.)

While precipitous progesterone withdrawal occurs just before birth in most mammals, this abrupt withdrawal occurs after birth in women following placental delivery. As a result, secretory activation occurs 30–40 hours after birth (▶Fig. 4.21). This seems counterintuitive to the high-energy requirements of the newborn infant. However, unlike the newborn of most other mammals, the human newborn has high levels of body fat (10–15%) to draw on for its energy requirements. This feature has facilitated the survival of newborn infants for days without nourishment, such as after earthquakes. It is likely that the protective role of human milk (innate immunity) and, in particular colostrum, is as important as its nutritional role. Therefore, the small volume of colostrum secreted after birth (~30mL/24h) [21] with its high concentration of protective glycoproteins, oligosaccharides, and fatty acids facilitates protection of the surfaces of the respiratory and gastrointestinal tracts against pathogenic microorganisms.

The withdrawal of progesterone from the maternal blood is rapid, declining by more than 10 fold within 3 days postpartum, and the literature is quite consistent on the nature of this fall (▶Fig. 4.22). Due to this rapid decline, accurate timing between the delivery of the placenta and blood sampling would likely improve the precision of these values. In contrast to parturition, changes in the concentration of progesterone in maternal blood during established lactation do not appear

▶Fig. 4.22

Concentration of progesterone (μg/L) and prolactin (μg/L) in blood of women from birth to 8 days postpartum. (Boss M, Gardner H and Hartmann P. Normal Human Lactation: closing the gap [version 1; referees: 4 approved]. F1000Research 2018, 7(F1000FacultyRev):801 (doi: 10.12688/f1000research.114452.1))

to influence milk production, perhaps due to down-regulation of progesterone receptors in the breast. Once lactation is established, milk production is not coupled to progesterone levels during the menstrual cycle and progesterone-containing low dose contraceptives do not appear to inhibit lactation. Thus, the important role for progesterone centres on the early postpartum period. In view of the universality of the progesterone withdrawal mechanism, it is puzzling that more attention has not been given to the potential effects that subtle changes in progesterone withdrawal could have on the immediate and long-term synthesis of breastmilk, particularly as there are potential therapeutic options in relation to regulating progesterone receptors in the breast at this time.

The administration of Bromocriptine (to suppress prolactin secretion) inhibits secretory activation in women suggesting that prolactin is required for this stage of gland development [22]. Furthermore, a number of studies have concluded that milk production can be increased by the administration of galactogogues (e.g., domperidone and metoclopramide) that increase blood prolactin. Indeed, these medications are often prescribed when women present with either low milk supply or perceived low milk supply. Unfortunately, measurements of blood prolactin and milk production are rarely made prior to medication administration to justify their use.

▶Fig. 4.23

Circadian changes in the concentration of prolactin (μg/L) in the blood plasma of 8 normal women. (Reproduced from Yen, S., Jaffe, R. 1999. Prolactin in Human Reproduction. In: Reproductive Endocrinology. 4th ed. Philadelphia: WB Saunders Co.)

▶Fig. 4.24

Concentration of prolactin (μg/L) in the blood plasma of breastfeeding women from 60 minutes before to 180 minutes after the commencement of breastfeeds.

While the literature on progesterone withdrawal is quite consistent, the literature for prolactin is not (▶Fig. 4.23). Prolactin concentrations reported for mothers in the immediate postpartum period vary greatly and averages don’t make much sense. The reason for much of this variation is probably due to sample collection. It has been shown that the concentration of prolactin has a circadian rhythm, with the lowest concentrations during the day and high concentrations during sleep (▶Fig. 4.24). In addition, prolactin concentration increases at mealtimes and doubles when measured before a breastfeed to about 30–45 minutes after the commencement of the breastfeed. This response decreases from one to six months of lactation (▶Fig. 4.25). Much of the large variation between samples might be removed if care was taken to standardise blood-sampling procedures in relation to infant’s breastfeeds, time of day, and meal times. Obviously, with the wide use of domperidone and metoclopramide,it is very important to establish reference values for postpartum prolactin concentration in maternal blood. Although it is clear that prolactin is required for secretory activation, it probably does not playa rate-limiting role during normal secretory activation and in established lactation.

Glucocorticoid receptors are present in the cytosol of lactocytes. When bound with glucocorticoids, these receptors translocate to the nucleus and act synergistically with prolactin-activated transcription factors to enable the synthesis of milk proteins. While progesterone binds to the glucocorticoid receptor, it does not translocate to the nucleus and deactivate the milk synthesis genes.

▶Fig. 4.25

Concentration of prolactin (μg/L) in the blood plasma of 11 lactating women at 1, 2, 4, and 6 months of lactation. Blood samples were taken immediately before and 45 minutes after the commencement of the breastfeed. (Reproduced from Cox, D.B. 1996. The morphological and functional development of the human breast during pregnancy and lactation. PhD Thesis: The University of Western Australia; p3-6 3-7.)

Despite the obvious association between pregnancy and secretory differentiation and activation, pregnancy is not an essential prerequisite for lactation. There are numerous reports of the induction of mammary growth and lactation arising from repeated application of stimulation by either suckling or massage in non-pregnant women. Although responses are highly variable, there are reports of infertile women establishing exclusive breastfeeding by the application of suckling and massage for just a few weeks.

By definition, the ideal method for determining secretory activation is to measure milk production. However, this is quite difficult to do in the immediate postpartum period. Furthermore, milk synthesis at this time is greatly influenced by the ability of the infant to remove all of the available colostrum. In many women the onset of lactation is accompanied by a sudden feeling of breast fullness and leakage. If this is not managed properly it can lead to extremely engorged and painful breasts. Nevertheless, this is a subjective assessment of secretory activation. The metabolic changes that occur in the breast offer more precise objective assessments. The withdrawal of progesterone triggers the closure of tight junctions between lactocytes. Synthesis and secretion of lactose rapidly increases, drawing water with it to maintain osmotic equilibrium. As a result of these metabolic changes, the concentrations of sodium, chlorine, and total protein decrease. Conversely, lactose and citrate concentrations, and milk production increase as mammary secretion transitions from colostrum to milk over the first 5 days postpartum. Thus, analysis of mammary secretion for sodium, chloride, citrate, and total protein over this early postpartum period can be used to assess the progress of secretory activation (▶Fig. 4.26). Unfortunately, there is not sufficient appropriate research available to enable the establishment of reference values for these milk constituents during this crucial period in the lactation cycle.

▶Fig. 4.26

Milk production (mL/24h) and the concentrations of lactose (mM), total protein (g/L), citrate (mM) and sodium (mM) in mammary secretion from day 1 to day 5 of lactation, that is, during secretory activation.

▶Tab. 4.1 Prevalence of exclusive breastfeeding postpartum (%).

6 weeks

14 weeks

6 months

Group 1: Standard care




Group 2: Steps 1–9 alone




Group 3: Steps 1–10




The importance of secretory activation is clearly demonstrated from three recent rather subtle intervention studies that focused on the first 3 days postpartum. Yotebieng and colleagues randomly assigned clinics to three groups to investigate optimisation of the Baby Friendly Hospital Initiative (BFHI) ten steps to successful breastfeeding [23]. Steps 1–9 focus on promotion and establishment of breastfeeding in the clinical setting after birth. Step 10 promotes the establishment of breastfeeding support groups and referral of mothers to these on discharge from either hospital or clinic. The primary outcomes were initiation of lactation (commencing breastfeeding within 1 hour of birth) and exclusive breastfeeding. Exclusive breastfeeding was higher in groups 2 and 3 at 14 weeks but surprisingly was only significantly higher in Group 2 at 6 months (▶Table 4.1). Leaving aside the unexpected finding that the results for the 1–9 steps group (Group 2) were significantly better than those for the controls and the 1–10 steps group (Group 3), these findings clearly show that interventions at birth can have very significant long-term effects presumably associated with a critical learning period.

▶Fig. 4.27

Milk production (mL/ 24h) in three groups of mothers 33 to 38 preterm from birth to 14 days postpartum. One group used an experimental suction pattern that was designed to simulate the baby sucking, another group received the experimental pattern until secretory activation (~80h postpartum) and then the standard pattern and the final group only received the standard pattern. (Reproduced from Meier, P. P., et al. 2012. Breast pump suction patterns that mimic the human infant during breastfeeding: Greater milk output in less time spent pumping for breast pump-dependent mothers with premature infants. J Perinatol, 32, 103–110.)

Morton, et al. showed that combining hand massage techniques with electric pumping increased milk production in preterm mothers at 2 weeks and beyond [24]. The treatment was only applied in the immediate postpartum period and again emphasises the importance of the secretory activation period. Similarly, in another study of preterm mothers, Meier, et al. used an experimental suction pattern that was designed to resemble the suckling patterns of neonatal infants [25]. The pattern was applied until the onset of secretory activation (approximately for the first 80 hours postpartum). Mothers were then changed to the commercial pattern for the electric breast pump. Interestingly, this intervention in the first 80 hours after birth increased milk production significantly at 1 week postpartum and by 2 weeks postpartum. The experimental group were producing approximately 60% more milk than the standard electric breast pump group (▶Fig. 4.27).

Although there is compelling evidence that human lactation is “hard-wired” and essential for the healthy growth and development of infants, these studies show that even subtle intervention in the first 3 days after birth can have major influences on the success of lactation. It is likely that, as in other mammals,the period from just before parturition to the immediate postpartum period is vitally important for both birth and lactation. Perhaps Michel Odent’s non-intervention approach in relation to childbirth may also apply to successful secretory activation and the establishment of breastfeeding [26]. Nevertheless, it is indisputable that removal of colostrum and then mature milk from the breast is essential for the continuation of milk production. Thus, milk removal is essential for secretory activation as well as established lactation. Two physiological processes, maternal milk ejection and infant breastfeeding, are required for the removal of milk from the lactating breast and normal lactation.

4.4.4 Milk Ejection

The history of the understanding of the milk ejection reflex is important because it illustrates how a simple misunderstanding of a physiological process can impact on the understanding of a whole physiological process — in this case, the physiology of lactation. In the 19th century it was generally accepted that milk was synthesised in the breast from components carried to it in the blood. First, it was thought that blood components were filtered off to form milk. However, some milk components were found not to be present in blood and therefore it was concluded that active synthesis of some components occurred in the breast. Then a stalemate existed for more than a century in the understanding of milk synthesis and secretion. This arose because of the erroneous conclusion that milk ejection (milk let down) resulted from very active synthesis and secretion of milk (due to stimulation by the infant’s sucking) with either little or no synthesis of milk at all other times. Cooper was on the right track when he stated that

‘The secretion of milk may be said to be constant or occasional; by the first, the milk tubes and reservoirs are constantly supplied by means of a slow and continuous production of fluid, so that the milk is thus, in some degree, prepared for the child. By the occasional, is to be understood that secretion which is called by mothers and nurses, the draught of the breast, by which is meant a sudden rush of blood to the gland, during which the milk is so abundantly secreted, that if the nipplebe not immediatelycaught by the child, the milk escapes from it, and the child when it receives the nipple is almost choked by the rapid and abundant flow of fluid; if it lets go its hold, the milk spurts into the infant’s eyes.’ [26].

More than 100 years later it was still claimed that milk secretion was mostly confined to the periods of sucking. Finally, in 1941 Ely & Petersen carried out studies in cows and correctly concluded,

The letting down of milk is a conditioned reflex operated by sensory stimuli associated with milking. Afferent impulses reach the central nervous system and release oxytocin from the posterior pituitary, which in timecauses arise in milk pressure probably because of the contraction of muscular tissue which is believed to surround the alveoli and small ducts’ [27].

It is now known that myoepithelial cell processors surround the alveoli (▶Fig. 4.28) and contract when stimulated by oxytocin, forcing the milk along the milk ducts towards the nipple.

▶Fig. 4.28

Myoepithelial cells surrounding contracted alveoli from the mammary gland of a lactating goat. (Cowie, A. T., Forsyth, I. A., Hart, I. C. 1980. Lactation. Hormonal control of lactation. Springer. p194.)

▶Fig. 4.29

Ultrasound image of a milk duct (a) prior to milk ejection and, (b) one minute after milk ejection. White flecks in the ducts in the image (b) are fat globules.

▶Fig. 4.30

Rate of milk flow and accumulated weight of milk in left and right breasts during breast expression. The peaks in milk flow relate to the number of milk ejections that occurred during the expression period. (Reproduced from Prime, D. K., et al. Using milk flow rate to investigate milk ejection in the left and right breasts during simultaneous breast expression in women. Int Breastfeed J. 4, 10.)

Milk ejection can be measured either by the increase in milk duct diameter viewed by ultrasound imaging (▶Fig. 4.29) or by the change in milk flow rate when milk is expressed using an electric breast pump. Mothers have several milk ejections during a breastfeed (▶Fig. 4.30). Each mother has a particular pattern of milk ejections during a breastfeed, and this pattern holds throughout the lactation and for subsequent lactations. Thus, the initial sucking of the infant is important in initiating the first milk ejection but subsequent milk ejections are intrinsic to the mother. Failure to release oxytocin is rare for breastfeeding mothers. Milk ejection may be identified by changes in the infant’s sucking pattern (from rapid initial sucking to a slower suck and swallowing pattern). Although 88% of mothers sense the first milk ejection, almost all mothers fail to sense subsequent milk ejections.

Maternal sensation of milk ejection varies. Mothers have reported sensations such as a pleasant tingling, pins and needles, sharp nipple pain, warmth, thirst, sleepiness, and mild nausea before milk flow increases. In addition, as noted by Cooper, milk can spurt from the breast for a distance of a meter or more in some women. These sensations are more common in early lactation. Milk ejection usually occurs within one minute of putting the baby to the breast but can occur at other times (for example when the mother thinks about her baby) because milk ejection is a conditioned reflex. Like other conditioned reflexes it can be inhibited by stress. However, women successfully breastfeed through severe stresses such as injury, wars, and famine. Stresses that inhibit milk synthesis are the less obvious stresses that undermine maternal confidence, such as either concerns about the adequacy of her milk supply or the quality of her milk. Again, Cooper commented on this anomaly:

‘A female of luxury and refinement is often in this respect a worse mother than the inhabitant of the meanest hovel, who nurses her children, and brings them up healthy under privations and bodily exertions to obtain subsistence, which might almost excuse her refusal.’ [10]

4.4.5 Infant Suck, Swallow, and Breathe

The finding that lactiferous sinuses were not present in the lactating human breast led to the reassessment of the suck-swallow-breathe reflex. When considering the nature of infant sucking, it is important to ensure that only breastfeeding infants are considered because the dynamics of suckling are different in bottle-fed infants. Breastfeeding is a very complicated process in that it requires the coordination of sucking, swallowing, and breathing. This is reflected by the attention that clinicians give to positioning and attachment of the baby at the breast. However, this intervention is very subjective, and advice has changed with time without support from evidence-based research. For the development of an evidence based assessment of breastfeeding, it was important to develop synchronized continuous measurements to describe this complex behaviour. Information was gathered from synchronised ultrasound imaging of tongue movement and milk flow, the intraoral vacuum generated by the downward movement of the tongue, and respiratory-inductive plethysmography to identify sucking,breathing,and swallowing (▶Fig. 4.31).

▶Fig. 4.31

Sagittal mid-line images of an infant’s oral cavity during breastfeeding showing stylised overlay of ultrasound images showing the soft palate, hard palate, nipple and tongue, (a) tongue up (baseline vacuum), (b) tongue down (peak vacuum). (Geddes, D., Sakalidis V. 2015. Breastfeeding: How do they do it? Infant sucking, swallowing and breathing. Infant, 11; 146–150.)

First, it was important to define nutritive and non-nutritive sucking. Nutritive sucking showed milk flow coupled with frequent swallowing. In non-nutritive sucking, little milk was removed from the breast and swallowing occurred only occasionally due to the accumulation of saliva. Non-nutritive sucking bursts were shorter with a tendency to occur towards the end of a breastfeed compared with nutritive sucking.

Nutritive sucking is achieved by an intraoral vacuum(negative pressure),which is generated by the downward movement of the infant’s tongue during feeding and intermittent positive pressure generated within the milk ducts at milk ejection. Infants attach to the breast and generate a baseline vacuum that stretches the nipple to within 5– 7mm of the junction between the hard and soft palates. Under the influence of this vacuum, milk ducts in the nipple expand and milk flows into the oral cavity space bounded by the tip of the tongue, the hard-soft palate junction, and the oral epithelial lining of the cheeks. The vacuum is released as the tongue rises, and compression of the nipple allows the milk to be cleared from the oral space to the pharyngeal area at each suck. The milk bolus may remain in this area for a number of sucks before it is swallowed (▶Fig. 4.32).

▶Fig. 4.32

Simultaneous recordings of infant intra-oral vacuum and respiration (respiratory inductive plethysmography, RIP) during a breastfeed. The intra-oral vacuum shows a variable baseline vacuum (latch vacuum) and a peak vacuum (sucking vacuum). The respiratory trace measures respiration as inspiration effort and expiration effort and absence of a signal indicates a swallow. The inspiratory phase of swallowing can be identified (E-S-I, expiration-suck-inspiration; I-S-I, inspiration-suck-inspiration).

Sakalidis and Geddes found that infants were able to simultaneouslysuck and swallow, and suck and breathe, but not breathe and swallow [28]. Breastfeeding infants did not have a consistent suck-swallow-breathe pattern. Respective ratios can range from 1:1:1 to 12:1:4 during nutritive sucking to from 2:0:1 to 23:1:23 for non-nutritive sucking. This rangefor nutritivesuckingis not surprising as the rate of milk flow rapidly increases and decreases at each milk ejection, particularly during the first few minutes of a breastfeed. In addition, there is large variation in the pattern of release of oxytocin between mothers.

In summary, these studies clearly show that the application of vacuum by the infant is critical for successful milk removal. Sucking dynamics with good coordination of the suck-swallow-breathe reflex are evident in the early postnatal period for term babies. However, changes in oxygen saturation, heart rate, feed duration, and the applied vacuum change in relation to neurological maturation and conditioning as lactation proceeds.

4.4.6 Established Lactation

In the 1970’s, the slowing of infant growth at 2–3 months of age in low and middle-income countries was of great concern. Maternal diets in these countries were very poor compared to international recommendations. As such, it was concluded that poor infant growth was due to infants receiving insufficient breast milk from their mothers. This conclusion was consistent with research on dairy cows, dairy goats, and sows that showed that increased food intake was required to support milk production. The summation of these factors resulted in the slogan, ‘Feed the nursing mother and thereby feed the child’ [29]. This slogan was readily accepted at the time because it was logical and consistent with contemporary nutritional knowledge. Nevertheless, Ann Prentice and her colleagues studied poorly-nourished lactating women in The Gambia and well-nourished lactating women in the UK [30]. They concluded that

‘the processes controlling lactation performance are remarkably similar and that the same control mechanisms will be revealed in most other communities’.

They also concluded that

‘there is a strong drive towards milk production in lactating women, often to the detriment of maternal tissues, and that even low dietary intakes observed in most countries in the developing world do not fall below the threshold at which lactation performance is compromised’.

This was surely a seminal finding as it not only supported the concept that human lactation is “hard-wired” but totally reversed the mindset of scientists investigating the control of the synthesis of human milk. The question then became “How does the mother regulate her milk synthesis to meet the unpredictable appetite of her baby?”

Many studies have shown that the infant only consumes enough milk to satisfy its appetite and that variable milk volumes are taken at each breastfeed regardless of whether the feeds are unpaired or paired (▶Fig. 4.33). Studies in dairy animals have also found that goats milked three times per day produced more milk than if milked twice daily. Furthermore, if half the udder was milked three times per day while the other half was milked twice per day, the udder-half milked three times per day consistently produced more milk. This effect was clearly shown in women by the finding that when the breast was drained of milk, the rate of milk synthesis was high and when the breast was filled with milk the rate of milk synthesis was low (▶Fig. 4.34). Conclusions drawn from these studies were that the regulation of milk synthesis was local within each breast (autocrine), and that the hour-to-hour regulation of milk synthesis was relatively independent of endocrine influences.

However, a compensatory response was also found in dairy animals. That being, if the rate of milk removal was reduced in one udder-half, a compensatory increase in milk production occurred in the other udder-half without a change in the frequency of milk removal.These findings have important implications for human lactation. If a mother can store a lot of milk in her breasts then she could breastfeed at less frequent intervals. On the other hand, if she has a small storage capacity the breast will fill with milk more quickly and down-regulate milk synthesis sooner. This means that more frequent breastfeeds are required to maintain milk production in mothers with low storage capacity.

▶Fig. 4.33

Volume of milk consumed at each breastfeed from left and right breasts over a period of 24h, (30% of babies consistently fed from only one breast at each breastfeed and only 13% of babies fed from both breasts at each breastfeed; n=70).

▶Fig. 4.34

(a) Changes in breast volume for each breast at each breastfeed over a 24h period. (b) The rate of milk synthesis between each breastfeed for each breast over a 24h period.

▶Fig. 4.35

Part of a lobule from the left half of the mammary gland of a lactating goat fixed while distended with milk (a). The right half of the mammary gland of the same goat which was milked out as completely as possible before autopsy (b); note the contracted lobules with collapsed alveoli and ducts lined with a thick folded epithelium. (Folley, S. 1956. The Physiology and Biochemistry of Lactation, London, Oliver and Boyd. p90.)

It has been proposed that the down-regulation of milk synthesis is controlled by a feedback inhibitor of lactation [31]. However, identification of such a compound remains elusive. Alternatively, it is possible the down-regulation of milk synthesis is related to major morphologic changes in the secretory parenchyma during transition from full to drained gland (▶Fig. 4.35). This change could expose or mask receptors in the lactocytes to either up regulation or down regulation depending on whether the alveoli were distended or drained of milk, thereby regulating the lactocytes’ response to lactocrine hormones.

▶Fig. 4.36

Death of babies in summer from diarrhoea 1895–1904. Deaths of babies in summer from diarrhoea and high incidence of tuberculosis in army recruits prompted the Government to establish Child Health Nurses who were trained by free immigrants who, in turn, learnt hygiene on sailing boats coming to Australia. (Muslett, P. 1903. Australian Medical Guide, Sydney, William Brooks and Co.)

Healthy exclusively breastfed infants have a mean daily intake of 750–800mL/24 h from one to six months of lactation; however, the range is wide (from 500 to 1200mL/24 h) [32]. There is a relationship between infant growth and milk production but, unexpectedly, no relationship between infant growth and total energy, protein, fat, or lactose intake from breastmilk. The relatively constant milk production from one to six months of lactation is most likely explained by the relatively slow growth of the human infant. The energy saving from the decrease in the ratio of surface area to body mass is probably sufficient to sustain infant growth over the first six months of life.

Fluid intake during lactation is also important for both mother and her baby. Lactating women should maintain adequate fluid intake but be aware that fluid consumed in excess of natural thirst does not increase milk synthesis. Additionally, the infant has limited capacity to concentrate its urine, and therefore any increase in the osmotic load (for example, from the consumption of cows milk that has a much higher sodium content than human milk) will lead to an increase urine output. This explains why summer diarrhoea, resulting from dehydration in hot, dry climates, was a problem 100 years ago. For this reason, early last century, mothers in Australia were advised not to wean their babies in the summer months (▶Fig. 4.36).

4.4.7 Reference Ranges

The biochemical composition of human milk is spectacularly complex. It contains 900 proteins, 200 oligosaccharides, 1,000s of triacylglycerols, ~100 metabolites, and many bioactive peptides, hormones, cytokines, and cells, together with a full complement of minerals and vitamins. Some of these components (e.g., milk fat) vary from beginning to end of both a breastfeed and breast expression (▶Fig. 4.37), over the day, with diet, and during the lactation period. Unfortunately, with the notable exception of breastfed infant growth (▶Fig. 4.38, ▶Fig. 4.39), there are no reference ranges for normal values (i.e.,predicted values that cover 95% of individuals) for milk production and milk composition. Thus, values currently given for milk production and concentrations of breast milk components are flawed.

Standardised experimental inclusion and exclusion criteria are required for development of protocols to define normal ranges carefully for human lactation in the mother and her infant. This is an important prerequisite for establishing an objective evidence-base for the diagnosis of problems associated with human lactation.

▶Fig. 4.37

Serial samples of breastmilk collected during breast expression. The samples were centrifuged to separate the cream showing the increase in the fat content of breastmilk from a low concentration in milk from a full breast and a higher concentration of fat in milk from a drained breast. (from Hartmann, P.E. 1985. Unpublished data.)

▶Fig. 4.38

Reference ranges for the growth of breastfed boys. (from WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age.)

▶Fig. 4.39

Reference ranges for the growth of breastfed girls. (from WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl 2006; 450: 77–86.)

Measurement of 24-hour milk production provides an objective measure of breast function and has been shown to be useful to both mother [33] and clinician (Kent, personal communication 2016). Conversely, the measurement of milk intake at a single breastfeed is of less value because milk intake is controlled by the infant’s appetite and can vary greatly from one breastfeed to the next. The measurement of 24-hour milk production is useful in tracking changes within the mother-infant dyad but is not useful in determining whether the level of milk production is normal. More stringent assessment of the recruitment of mother-infant dyads would likely reduce the current wide range for normal milk production. Similar concerns are valid for maternal and infant endocrine and metabolic parameters. This highlights the urgent need to establish reference ranges for objective diagnosis and treatment of problems associated with human lactation.

4.5 Changes to Physiology in Mother and Infant

Physiologically, there are two very important aspects to human lactation. First, lactation is important for the mother and her baby and secondly, the importance of lactation in relation to breastfeeding behaviour and breastmilk composition must be considered. This is a very large topic and therefore only some pertinent points can be discussed here. Much of the importance of lactation has focused on the infant(Table 2a) but the importance to the mother (Table 2b) must also be considered.

  • Importance of lactation for the infant:

    • Immunological protection (both innate and acquired)

    • Optimal nutrition

    • Optimal metabolic development

    • Optimal neurological development

    • Prebiotic components that promote favorable microbiota in the infant

    • Probiotic transfer of a favourable microbiome to infant

  • Importance of lactation for the mother:

    • Recovery from childbirth

    • Cholesterol clearance

    • Suppression of maternal fertility

    • Glucose control in diabetic mothers

    • Improved bone mineralisation

    • Reduced obesity

    • Reduced risk of breast and ovarian cancer

    • Reduced risk of cardiovascular disease

    • Increased self esteem

    • Improved IQ

A good illustration of the complexity of human lactation in relation to the mother can be illustrated by examining calcium metabolism during pregnancy and lactation. In the past, nutritionists were aware of the high levels of calcium in breastmilk and thus it was concluded that breastfeeding was an impost on calcium metabolism. To emphasise this, textbooks claimed “for every child a tooth” and high calcium diets were recommended for pregnant and lactating women. Research from Ann Prentice’s group challenged this orthodoxy by showing that increasing calcium supply to international recommendations in the diet of mothers in populations with low calcium intake was neither beneficial for mothers during pregnancy and lactation nor for their children [34]. She showed that intuitive thinking is not always supported by research. Thus, studies in The Gambia showed that breastfeeding Gambian mothers who received calcium supplements during pregnancy had accentuated bone mobilisation during lactation, and that their lower bone mineral density persisted long term. These unexpected findings raise mechanistic questions about the underlying physiology of calcium metabolism during pregnancy and lactation, and illustrate the importance of a complete basic understanding of calcium metabolism before clinical intervention. Presently, the nutritional advice offeredbyJames in 1912 seems appropriate.

‘There is no special food for the production of milk: That which is best for the general health of the mother is the best for the child.’ [35]

The importance of the intimate but fragile metabolic relationship between mother and infant is clearly illustrated in Hofer’s studies [36]. Breastfeeding is related to complex signals that pass from mother to infant and from infant to mother. There are significant subtle interchanges that occur during human lactation. Hofer determined that the mother-infant relationship is built on many layers of sensory complexity. What seems to be a single physical function, such as either grooming or nursing, is actually a kind of umbrella that covers stimuli of touch, balance, smell, hearing, and vision, each with specific effects on the infant. He identified a ‘private realm of sensory stimulation constructed by the mother and infant from numberless exchanges of subtle cues’. Hofer discovered that a mother precisely controls every element of her infant’s physiology, from heart rate to release of growth hormones, and from appetite to the intensity of activity. Hofer says:

‘The mere presence of the mother not only ensures the infant’s well being, but also creates a kind of invisible hot house in which the infant’s development can unfold. Mother and offspring live in a biological state that has much in common with addiction. When they are parted, the infant does not just miss its mother, it experiences a physical and psychological withdrawal from a host of her sensory stimuli, not unlike the plight of a heroin addict who goes cold turkey. For a baby, the environment is the mother,’

Furthermore, it was known that a mother must keep her infant warm for its body and brain to mature; however, Hofer discovered that thermal contact with the mother regulated the infant’s behaviour and activity as well. Conversely, it has also been shown that the infant influences the mother’s metabolism and cycle of activity primarily through the act of breastfeeding. These findings provide a basis for understanding the beneficial effects of skin-to-skin contact. In addition, recent research has shown that breastfeeding and vaginal birth are physiologically important because they facilitate optimal passage (inoculation?) of maternal symbiotic microorganisms to the infant.

This is of particular importance when considering the composition of human milk and function of the components in the infant. Transfer of nutrient and bioactive components from mother to infant occurs though colostrum and milk after birth. The substitution of infant formula for human milk deprives the infant of the nutrients in human milk (e.g., essential amino acids and human casein) and of the many bioactive and immunoprotective factors (e.g., oligosaccharides, lactoferrin, and lysozyme) directed specifically against pathogens in the infant’s environment. Human milk components also compensate for the immature functioning of infant metabolism, in which endogenous digestive enzymes, secretory immunoglobulin A, taurine, choline, nucleotides, and long-chain polyunsaturated fatty acids are insufficient. The importance of these nutritive and bioactive components makes human milk superior to even the best infant formula.

4.5.1 Menstrual Cycle

Postpartum amenorrhoea lasts for approximately 55–60 days in non-breastfeeding women. However, this period is much more variable in breastfeeding women and can extend up to 2 years and beyond. The long period of lactation in traditional societies increases the duration of amenorrhoea and child spacing, with associated benefits to the mother and child. While lactational amenorrhoea is evident on a population basis, variation between mothers in the timing of the return of menstruation indicates that lactational amenorrhoea does not alone provide a reliable method of birth control.

4.5.2 Weaning and Involution

Weaning after six months of lactation is normally a gradual process, commencing with the baby having fewer breastfeeds while consuming additional foods. This is coupled with the gradual involution of the secretory and ductal tissue in the breast by apoptosis (programmed cell death), an increase in prominence of fatty tissue, and mammary parenchyma slowly returning to ducts and terminal end buds containing a colostrum-like fluid with very high concentrations of innate protective compounds. Once milk removal has completely stopped, mammary secretion takes more than 4 weeks to stabilise in women compared with about a week in most other mammals(▶Fig. 4.40).

▶Fig. 4.40

Concentration of lactose (% of day zero value) in the mammary secretion of (a) women, (b) cow, (c) sows, and (d) rats from 0 to 30 days after removal of milk had ceased. (By permission of Oxford University Press. Reproduced from Hartmann, PE et al. 1985. Variation in the yield and composition of human milk. Oxford Reviews Reproductive Biology, 7, 118–167.)

In some mothers, breastfeeding may continue into the next pregnancy and even to the next lactation (tandem feeding). It is unlikely that breastfeeding into a new pregnancy has any undesirable effect on either the infant or the mother, as two thirds of all cows milk that we drink is from pregnant cows.

Complete weaning of the infant marks the end of the lactation cycle and the breast returns to its non-lactating (resting) state. Studies have monitored the changes in breast volume over the entire lactation cycle(▶Fig. 4.41). The first significant reduction in breast volume occurs after six months of lactation and precedes the first significant decrease in milk production. After milk production has ceased, there is no significant difference between breast volume prior to conception and that measured after complete weaning.

▶Fig. 4.41

Relative change in breast volume (mL) from pre-conception (relative volume, zero), through pregnancy, lactation and weaning. (Reproduced from Czank C, Henderson JJ et al. Hormonal control of the lactation cycle. In: Hale TW, Hartmann P. Textbook of human lactation, New York: Springer; 2007)

4.6 Conclusion

Finally, it is appropriate to conclude this chapter with another quote from Cooper:

“If a woman be healthy and she has milk in her breasts, there can be no question of the propriety of her giving suck. If such a question be put, the answer should be, that all animals, even those of the most ferocious character, show affection to their young, do not forsake them, but yield them their milk, do not neglect, but nurse and watch over them; and shall woman, the loveliest of nature’s creatures, possessed of reason as well as instinct, refuse that nourishment toher offspring which no other animal withholds, and hesitate to perform that duty which all animals of the Mammalia class invariably discharge? Besides it may be truly said that nursing the infant is most beneficial both to the mother and the child, and that women who have been previously delicate, become strong and healthy whilst they suckle.” [10].

Key Points

  • Astley Cooper in 1840 was the first person to focus on the physiology of the lactating breast but it was not until a 150 years later that modern ultrasound technology provided a new insight into the workings of this amazing organ

  • Today it is understood that lactation occurs in several stages. Beginning with alveolar development and secretory differentiation during pregnancy, followed by secretory activation during the first 3 days after birth and ending with involution during weaning

  • Lactation is intricately controlled by endocrine and autocrine processes requiring the removal of milk to sustain it

  • Complex signals pass between mother and infant during breastfeeding which have subtle influences on the infants’ physiological well-being

Ms Melinda Boss, MPS, B.Pharm, is the team leader of a multidisciplinary group developing evidence-based protocols for the medical assessment and management of lactation dysfunction. She graduated from Curtin University and became a registered pharmacist in 1993. She has gained experience in both community pharmacy and research, most recently publishing, “Normal human lactation: closing the gap”. Interrupting her career to have her family, she returned to work part-time in 2011 as a senior research fellow at The University of Western Australia.

Emeritus Professor Peter E. Hartmann, E/Prof, PhD, BRurSc is a Senior Honorary Research Fellow at The University of Western Australia. He has published more than 200 research papers and numerous reviews and book chapters on lactation in dairy animals and women. He has received numerous awards including the MacyGyorgy award, La Leche League International Award of Excellence for contribution to supporting breastfeeding, and the Rank Prize for Nutrition. He is a Fellow of Nutrition Society of Australia, co-editor of a Hale & Hartmann’s Textbook of Human Lactation, and a Member of the Order of Australia.

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