BREASTFEEDING AND BREASTMILK - FROM BIOCHEMISTRY TO IMPACT

A Multidisciplinary Introduction

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How Breastfeeding Works: Anatomy and Physiology of Human Lactation Peter E. Hartmann and Melinda Boss tghncollections.pubpub.org/pub/4-how-breastfeeding-works

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This book, including all parts thereof, is legally protected by copyright. Any use, exploitation, or commercialization outside the narrow limits set by copyright legislation with- out the publisher’s consent is illegal and liable to prosecu- tion. This applies in particular to photostat reproduction, copying, mimeographing or duplication of any kind, trans- lating, preparation of microfilms, and electronic data proc- essing and storage. 39 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

milk are considered in a functional context. The ! Expected Key Learning Outcomes removal of milk from the mammary gland is also

● Setting the Scene The history of the understanding of the reviewed, including milk ejection and the infant anatomy and physiology of lactation suck-swallow-breathe reflex. This chapter covers ● The processes of lactation changes occurring over the lactation cycle from ● The production and regulation of milk sup- conception, secretory differentiation during preg- ply nancy, secretory activation after birth, the endo- ● How the complexity of lactation benefits crine and autocrine regulation of lactation, and fi- both mother and baby nally involution and the return of the mammary gland to its resting state.

4.1 Introduction 4.2 Background In 1840, Astley Cooper published a book titled “On “ the Anatomy of the Breast”. His anatomical dissec- In 1758 Carolus Linnaeus, the father of taxono- ” tions of the lactating breast are still used in text- my , grouped into one class both aquatic and land books to this day. This is in part due to the diffi- animals with the capacity to produce milk for culty in obtaining specimens (lactating women their young: Mammalia. The selection of this term rarely donate their bodies to science) and partly was unusual because it was only directly applica- due to a lack of scientific interest in this fascinat- ble to half the animals in this class, namely fe- ing organ. Thus, Cooper’s work stands out as the males. Indeed, he ignored other biological traits exception and his book provides a sound founda- (such as hair, sweat glands, and three ear bones) tion for the understanding of mammary anatomy that are specific to all mammals. Wet nursing, the and physiology. He rightly deserves to have the practice of mothers breastfeeding another moth- ’ ligaments of the breast, Cooper’s ligaments, er s infant, was widely practiced at that time. Spe- named in his honour. This chapter addresses his- cifically, rich families paid poor mothers to breast- torical as well as current knowledge of lactation, feed their babies. Diaries of rich mothers suggest “ ” including a detailed review of Cooper’s work and that they reluctantly accepted this cuckoo-like how this developed our current understanding. behaviour because they had been convinced that it His dissections remain the seminal work on the was best for their babies. Wet nursing was preva- “ ” gross anatomy of the human breast and many of lent in the better classes in Sweden and other his preparations have been reproduced here to il- European countries. Linnaeus was strongly op- lustrate the structure of its parenchyma, together posed to wet nursing. It is said that he chose the with its innervation, blood, and lymphatic supply. term, Mammalia, because he wanted to emphasize In addition, the anatomy of the lactating breast that young mammals should be suckled by their forms the basis for a detailed consideration of the own mothers. Today, our current knowledge of the physiology of human lactation. The historical de- importance of breastfeeding to both the mother ’ velopment of the current knowledge of the mech- and her infant reinforces the wisdom of Linnaeus anisms involved in the synthesis and secretion of choice of the term, Mammalia. 4 – How Breastfeeding Works 40

▶ Fig. 4.1 Changes in the propor- tion of infants who were breastfed in 7 high-income countries from 1938 to 80% 1980. (Reproduced from Hartmann, 10 P.E. et al. Human lactation: Back to nature. Physiological Strategies in 60% 4 5 Lactation. Symposia of the Zoologi- 6 9 cal Society of London. 337–368, 40% 8 1984) 2 1 3 20%

Incidence of breastfeeding Incidence 11 12 0% 1940 1950 1960 1970 1980 Time (years)

(1) at 3 months of age, Australia (from Wilmot, 1973) (2) at 2 months of age, Sweden (from Hofvander & Sjolin, 1971) (3) at 3 months of age, Poland (from Vahlquist, 1975) (4) at 1 week of age, U.S.A. (from Martinez & Nalezienski, 1981) (5) at 1 week of age, Canada (from M. E. Thomson & Brault-Dubuc, 1981) (6) at 1 week of age, United Kingdom (from Sloper, Elsden & Baum, 1977) (7) at 1 week of age, Australia (from Hartmann, Kulski, Rattigan, Prosser & Saint, 1981) (8) at 3 months of age, Sweden (from WHO, 1981) (9) at 3 months of age, Hungary (from WHO, 1981) (10) at 3 months of age, Australia (from Hitchcock & Owles, 1980) (11) at 2 months of age, Denmark (from Biering-Sørensen, Hilden & Biering-Sørensen, 1980) (12) at 3 months of age, United Kingdom (from Vahlquist, 1975)

The abandonment of breastfeeding in the 19th The active marketing of “safe” infant formula and 20th centuries seems to have been associated under the erroneous belief that scientifically de- with the development of condensed cow’s milk in veloped formula was either better or equivalent to 1853 and evaporated cow’s milk in 1885. Pasteur- breastmilk for the nourishment of babies, enabled isation and the home icebox also decreased the the lower socioeconomic classes to use this “pock- risk of contamination of infant formula with mi- et wet nurse” and follow the example set by the crobiological pathogens. By the 1920s and 1930s richer classes. The decline in breastfeeding was ar- evaporated cow’s milk was widely available at af- rested in 1972 in most high-income countries fordable prices and several clinical studies sug- ▶ Fig. 4.1 when for the first time in Western his- gested that infants fed evaporated cow’s milk for- tory affluent mothers began to breastfeed their mula thrived as well as those that had been own babies ▶ Fig. 4.2. This example has filtered breastfed. Importantly, these studies have not down all social classes and currently almost all been supported by modern research. Indeed, Cow- mothers in some Western countries choose to ie, et al. concluded that ‘We may also surmise that breastfeed their newborn infants. had cow’s milk been tested by usual procedures The breast is unusual in that lactation is charac- that are now applied to new drugs it is unlikely, in terised by periods of high secretory activity fol- view of its puzzling toxicity to infant rabbits, that lowed by periods of quiescence. Indeed, lactation it would have reached the stage of even a clinical is the final phase of the reproductive cycle in trial in human infants!’[1] mammals. In all of the 4000 plus species of mam- mal, maternal milk is essential for the survival of 4.2 Background 41

▶ Fig. 4.2 Social rank of mothers and the proportion of mother’s 100 breastfeeding in Australia from 6 highest weeks to 12 months postpartum in a 1983. b c 75 d lowest

50 Setting the Scene Proportion (%) of Mothers 25

0 6 wk 3 mo 6 mo 9 mo 12 mo Time after Birth

the young during early postnatal life. However, The evolution of a large brain (i.e., one that re- mammals are either hatched or born at very dif- quires ~25% of the mothers daily resting energy ferent stages of maturity. Species-specific lactation intake) has given humans a significant competitive strategies and milk composition provide a unique intellectual advantage over all animals, including environment for the maturation of each mammal’s other mammals. Consequently, unlike other mam- young [2]. Therefore, it is not surprising that the mals, extensive brain growth in human infants oc- milk of one species is not suitable for optimum curs in the first one to two years after birth. This physiological growth and development of the rapid postnatal growth is facilitated by many com- young of another. Human lactation is no excep- ponents present in breastmilk. Furthermore, the tion; for example, human infants grow extremely lactating breast is a very active metabolic organ slowly compared to most other mammals. The (▶ Fig. 4.3), with energy output in breastmilk rep- time to double birth-weight extends many months resenting ~30% of the daily resting energy require- for human infants but is only a few days in piglets. ments of the mother. It is also important to con- Indeed, human milk has a very low concentration sider the duration of lactation. Other large pri- of protein relative to its energy content and there- mates breastfeed for years rather than months; for fore cannot support rapid infant growth. The pro- example, the orang-utan breastfeeds for 7 years. portion of energy derived from protein is lower in Therefore, it is also to be expected that women infants than that recommended for adults. It fol- would breastfeed for a number of years and in- lows that the proportion of essential amino acids deed rural Aboriginals in North Western Australia in human milk must exactly match the infant’s re- breastfed their babies into their 6th year of life. quirements. This is very difficult achieve with in- Modern traditional societies (i.e., those without fant formula. To obtain the required intake of all access to manufactured contraceptives or pre- essential amino acid(s), extra protein has been pared infant foods) usually wean between 2–3 added to infant formula. Unfortunately, this higher years of age [3]. The World Health Organization protein intake is associated with adverse outcomes recommends that all infants should receive breast- in infants such as obesity and increased renal sol- milk only (with no additional food, drink, or ute load. water) until 6 months after birth and then contin- 4 – How Breastfeeding Works 42

▶ 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.)

ue to be breastfed with the introduction of first ably high incidences of conditions, such as breast foods up to 2 years of age and beyond [4]. Cur- engorgement, mastitis, and severe nipple pain, rently, most infants in developed countries are which challenge the resilience of even the most weaned before one year of age [5], [6], [7]. committed mothers (▶ Fig. 4.5). The promotion of breastfeeding by community Since there is only limited basic research on hu- groups and health professionals in countries like man lactation, evidence-based medical diagnosis Australia has been excellent, and 96% of mothers and treatment of lactation dysfunction is very lim- now choose to breastfeed their babies compared ited. For example, unlike other metabolically to only 48% in 1972 [5], [8]. Indeed, facilitation of equivalent organs in the body, there are no clinical breastfeeding (e.g., in coffee shops) is now begin- tests to assess the normal function of the lactating ning to be seen as providing an economic dividend breast and no reference ranges for either milk pro- (▶ Fig. 4.4). Unfortunately, there is a rapid decline duction or milk composition. Consequently, family in breastfeeding with time after birth, with less doctors do not have objective tests to assist with than 16% of infants exclusively breastfed to 5 the diagnosis and treatment of mothers who expe- months and only 60% receiving any breastmilk at rience breastfeeding difficulties. There are no clin- this time [5]. ical tests to measure 24-hour milk production, yet The commitment of such a large proportion of perceived low milk supply is one of the major maternal energy intake to lactation over a long pe- causes of mothers ceasing to breastfeed. riod of time (years), and the conservation of genes Conventional medical care (that is, the availabil- associated with lactation and milk composition ity of a lactology medical specialist to whom the strongly suggests that mothers are “hard-wired” family doctor can refer patients if necessary) does to breastfeed. This conclusion is reinforced by the not exist and this is probably responsible for much observation that mothers will endure hardships of the current decline in breastfeeding with time such as severe breast and nipple pain and still con- after birth. This is appalling considering that the tinue to breastfeed their infants. This begs the lactating breast requires a higher proportion of question, ‘Why have women in high-income coun- daily resting energy than the brain. Attention to tries found it difficult to breastfeed?’ Two reasons this situation was succinctly stated in TIME maga- may be postulated. First, perhaps subtle uncertain- zine, ties accumulate and diminish the mother’s confi- dence in her ability to produce enough milk for her baby. Secondly, mothers experience unaccept- 4.2 Background 43 Setting the Scene

▶ Fig. 4.4 Acoffee 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) 4 – How Breastfeeding Works 44

▶ 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.)

‘... lactation is probably the only bodily function sections set the foundation for current knowledge for which modern medicine has almost no train- of the gross anatomy of the lactating human ing, protocol or knowledge. When women have breast. His findings have, in the main, stood the trouble breast-feeding, they’re either prodded to test of time. try harder by well-meaning lactation consultants or told to give up by doctors. They’re almost never ‘My rule has been to publish that only which I told, “Perhaps there’s an underlying medical could show to those who were sceptical, and were problem — let’s do some tests”’[9]. yet desirous of arriving at the truth.’

Obviously a much deeper understanding of the Subsequently, few scientists have followed his ex- anatomy and physiology of the human breast are ample and investigated this extremely interesting required so that appropriate medical care can be organ, the human mammary gland. Very few pa- provided for lactation. pers investigating the anatomy of the lactating hu- man breast were published for the remainder of the 19th century and the entire 20th century. Thus, 4.3 anatomical diagrams and descriptions of the gross Gross Anatomy anatomy of the lactating breast have changed little over the past 165 years. 4.3.1 History Cooper obtained lactating breasts from the Any consideration of the anatomy of the non-lac- bodies of cadavers who were most likely provided tating and lactating human breast is not complete by gangs of “resurrection men”. The bodies were without acknowledgment of the contribution of from women in established lactation. The breasts the brilliant Sir Astley Paston Cooper in 1840 [10] from mothers who died soon after giving birth (▶ Fig. 4.6). He was the greatest surgeon of his (presumably from puerperal fever) were decom- time and was much loved in the medical world posing from virulent septicaemia and unsuitable [11]. His patients knew him for his sweetness of for his anatomical studies. Cooper studied the manner and courtesy. Against the practice of the gross anatomy of the lactating breast including the time, Cooper always removed his top hat on enter- ductal system, innervation, blood vessels, lym- ing the wards. He also took good care of his stu- phatic system, fatty tissue, and the ligamenta sus- dents; for example, he found accommodation for pensoria. These ligamenta suspensoria are now the poet Keats when he was a medical student. commonly referred to as “Cooper’s ligaments” in Cooper’s careful observations and meticulous dis- recognition of his contribution to the understand- 4.3 Gross Anatomy 45 Setting the Scene

▶ 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.)

ing of the anatomy of the lactating breast and in 4.3.2 Foetal and Pubertal particular for being the first to provide a detailed Development ▶ description of these ligaments ( Fig. 4.7). Coop- The normal growth and functional development of ’ er s ligaments support the breast in its normal po- the breast may be either reduced or even abol- sition. Cooper noted that without the internal sup- ished by trauma such as from cosmetic surgery. port provided by these ligaments the breast tissue Therefore, the anatomy and physiology of lacta- (which is heavier than the surrounding fat) would tion is concerned not only with breastmilk and the sag under its own weight, losing its normal shape function of the breast during lactation, but also and contour. with development. Development must encompass maturation of the breast from foetal stages to sex- ‘ The uses of the ligamenta suspensoria are to con- ual maturity, together with development to a se- nect the nipple to the breast, the breast to the skin cretory state during pregnancy and after birth. and to fold up the gland to increase the secretory The mammary ridge (milk line) appears as a organ, without spreading it more widely over the raised portion of ectoderm on either side of the surface of the chest. They also enclose the adipose midline by the time the human embryo has at- ’ matter of the breast. tained a length of 4–6mm(4th week of gestation). Regression of the mammary ridge occurs except Errors in interpretation of Cooper’s work have per- for the pectoral region (2nd to 6th rib), which forms sisted over time and this suggests that few authors the mammary buds that lead to the development actually quoted from his original work. of breasts. In 2–6% of women, mammary buds may develop anywhere along the mammary ridge 4 – How Breastfeeding Works 46

gress soon after birth. Neonatal galactorrhoea, commonly referred to as witch’s milk, is a fluid se- creted from the breasts of newborn infants. In- deed, 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 com- position 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 dis- tinguish 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 nip- ple under these circumstances tends to equilibrate with the higher sodium content of the extracellu- ▶ Fig. 4.7 (a) Section of the mammary gland through the lar fluid [12]. nipple, showing ducts over a bristle, unravelled, and pro- Throughout childhood only isometric growth of ceeding to the posterior part of the gland. (b) A prepara- the breast occurs and the rudimentary breasts re- tion made to show the ligamenta suspensoria supporting the folds of the breast to the inner side of the skin. (c) A main quiescent. Allometric growth of the human view of the gland, dissected and unravelled, to show the breast occurs at puberty and continues during the ducts over bristles, lobuli, and glandules. (Cooper, AP luteal phase of the menstrual cycle until maxi- 1840. On the Anatomy of the Breast, Longman. Plate IV mum development is achieved between 20–30 fig 1.) years of age. During this period there is acceler- ated growth of the nipple and the development of sub-areolar tissue, leading to elevation of the are- and may either mature into accessary breasts ola and nipple. In the adult, the areola is a circular (polymastia) or remain as accessory nipples (poly- pigmented area of skin about 40 mm in diameter, thelia). but the size of both the areola and nipple can vary By the end of gestation, epithelial cells in the greatly between women and with time (▶ Fig. 4.8). mammary buds have elongated microvilli on the luminal surface, the cytoplasm is rich in organ- 4.3.3 Non-Lactating Adult Breast elles, and the rough endoplasmic reticulum has di- lated cisternae containing fine granular material. The non-lactating breast is composed of glandular The Golgi vesicles in these epithelial cells contain and adipose tissue and is supported by a loose net- dense, dark granules and fat droplets that are dis- work of fibrous connective tissue (Cooper’s liga- charged into the alveolar lumen. Therefore, by the ments). Ultrasound imaging has identified an end of gestation, the cells of the breast of the hu- average of nine ductal openings (nipple pores) at man foetus have reached a high degree of differen- the nipple. This is in close agreement with Coop- tiation and are secreting in response to the foetal er’s observations from his dissections of seven to hormonal milieu of late pregnancy. ten functional ductal openings on the nipple. Larg- The newborn breast consists only of rudimenta- er numbers (15–20) are usually quoted in text- ry ducts that have small club-like ends, which re- books based on Cooper’s work. Careful reading of 4.3 Gross Anatomy 47 Setting the Scene

▶ 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.) 4 – How Breastfeeding Works 48

his work shows that he only observed a maximum en have significant amounts of intra-glandular of 12 functional ducts opening at the nipple. ‘The adipose tissue. In other species studied, the mam- greatest number of lactiferous tubes I have been mary glands contain subcutaneous and retro- able to inject, has been twelve, and more fre- mammary adipose tissue but no intra-glandular quently from seven to ten.’ However he did note adipose tissue. The variable amount of intra-mam- up to 22 openings on the nipple but concluded mary adipose tissue may be, in part, the reason that a number of these were just follicles and not why breast size does not correlate with milk pro- open ducts. duction. As Cooper observed, Although prior to pregnancy the adult breast is in an inactive state, changes do occur in the breast ‘The quantity of milk which a woman is capable during the menstrual cycle. In the proliferative of secreting, cannot be estimated by the size of phase of the menstrual cycle (when follicles are her breast, as it often is large and hard rather primed for ovulation) there is increased cell divi- than secretory, or it is loaded with adeps, and sion. During the luteal phase (when follicles pro- produces but little milk.’ duce progesterone to prepare the uterus for the fertilised egg), the ducts become somewhat di- Knowledge of the innervation of the breast is rela- lated and the alveolar cells contain some lipid tively limited compared to that of other major or- droplets. From 3–4 days before the onset of men- gans in the body. Investigation of the innervation struation, increased turgescence and tenderness and sensitivity of the breast has predominantly fo- are observed. Breast volume normally increases by cused on women who have undergone breast sur- 15–30 mL but in some women this increase can be gery such as reduction mammoplasty. Cooper up to 300–400 mL. Towards the end of menstrua- showed that the 2nd to 6th intercostal nerves sup- tion the secretory tissue begins to regress and ply the breast (▶ Fig. 4.9). These nerves divide into breast oedema decreases to reach a minimum two branches. The deep branch supplies the glan- breast volume by 5–7 days after menstruation. dular tissue and the other branch takes a relatively During the non-lactating state the lobules con- superficial course within the gland, supplying the sist of either tubules or ducts lined with epithelial nipple and areola. The areola also contains a dense cells and embedded in connective tissue. They are intradermal nerve plexus supplying numerous widely separated, with connective and adipose tis- sensory end organs, including Meissner’s cor- sues predominating. At this stage of development puscles and Merkel’s discs (mechanoreceptors). there is only a small contribution from the glandu- This ensures it is receptive to mechanical stimuli, lar tissue. A few bud-like sacculations (terminal such as suckling. end buds) arise from the ducts, but the gland con- Innervation of the larger ducts has been ob- sists predominantly of interlobar and interlobular served but no nerves have been associated with ducts. The few alveoli present consist of simple cu- the smaller ducts, and a lack of sensitivity of the boidal epithelial cells without distinctive structur- epidermis of the nipple has been noted. Clinically, al features. The milk ducts branch under the areo- women recognise the overall fullness and disten- la, are quite superficial, and are easily occluded sion of their breast as well as pain associated with with the application of light pressure. Differences some abnormalities, but are often unable to accu- in the morphology (external appearance) of the rately localise either sensation. breast exist, even between different ethnic groups, but the internal structure of the glandular and 4.3.4 Pregnancy supporting tissues is similar in practically all spe- cies of mammal [1]. In some women, changes in the breast (e.g., ten- The distribution of adipose tissue in the human derness related to growth) can provide the first in- breast is highly variable. It is situated beneath the dication of conception and the beginning of the skin (subcutaneous), between the glandular tissue lactation cycle with a progressive increase in (intra-glandular) and beneath the breast (retro- breast volume (▶ Fig. 4.10). The areola contains mammary fat pad). Unlike other mammals, wom- large sebaceous glands (Montgomery’s glands) 4.3 Gross Anatomy 49 Setting the Scene

▶ 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.) 4 – How Breastfeeding Works 50

▶ Fig. 4.10 Legend on the opposite side. 4.3 Gross Anatomy 51 Setting the Scene

▶ Fig. 4.10 Increase in the volume of a breast from preconception to one-month postpartum. (Cox D.B. The morpholog- ical and functional development of the human breast during pregnancy and lactation. PhD Thesis: The University of West- ern Australia; 1996) 4 – How Breastfeeding Works 52 that hypertrophy and form papillae during preg- during pregnancy. In the latter stages of pregnancy nancy, as well as sweat glands and some hairs. Se- there is a further increase in lobular size due to cretions of the Montgomery glands lubricate and the hypertrophy of the cells and the accumulation protect the nipple and areola during lactation. Vol- of secretion in the lumen of the alveoli. The milk atilisation of compounds in this secretion may also ducts have branched and form lobes and the lobes provide an olfactory stimulus for the infant. Ductal divide into lobules that consist of clusters of alveoli branching and lobular formation (alveolar devel- lined with lactocytes (mammary secretory epithe- opment) exceeds the normal premenstrual growth lial cells) (▶ Fig. 4.11). by 3–4 weeks of gestation. A lactogenic complex of The classic dissections of lactating cadavers by reproductive hormones (progesterone, oestrogen, Cooper have also formed the basis for descriptions and prolactin) and metabolic hormones (growth of the blood supply to the breast (▶ Fig. 4.12). Dur- hormone, glucocorticoids, parathyroid hormone- ing pregnancy, blood flow to the breast doubles by related protein, and insulin) influence alveolar de- 24 weeks and then remains constant during lacta- velopment in women during pregnancy. tion. Along with the increase in blood flow, the There is extensive lobular-alveolar growth dur- superficial veins of the breast become more prom- ing the first half of pregnancy. However, the glan- inent during pregnancy and lactation. The blood dular parenchyma of the breast does not respond supply to the breast arises from the anterior and to hormonal stimulation in a synchronous man- posterior medial branches of the internal mam- ner. Different areas in the same breast can develop mary artery (60%) and the lateral mammary to a greater or lesser degree at any particular time 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 magni- fied, (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.) 4.3 Gross Anatomy 53 Setting the Scene

▶ 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.) 4 – How Breastfeeding Works 54

However, there is wide variation in the proportion In this connection, Cooper was first to report the of blood supplied by each artery between women. vigorous sucking behaviour of the young of some In women, as in lactating animals, the ratio of mammals, noting that blood flow to milk production is approximately 500:1. No relationship was observed between ‘… the lamb suckling for a short time to empty blood flow and milk production. 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 4.3.5 Lactating Breast supply its still pressing wants.’ Cooper concluded that the ligaments associated with the mammary fat pad also protected the lac- It is of interest that fatty tissue is interspersed tating breast tissue. Indeed, throughout his book within the glandular tissue in women but not in he makes numerous statements marvelling at how other mammals. This suggests that the support resilient the breast is to severe blows. from the ligaments may be more important than the pad of fatty tissue in protecting the breast ‘It is, then, a thick cushion of fat placed under the against severe blows. On the other hand, skin, which enables women of the lower class to bear the very severe blows which they often re- ceive in their drunken pugilistic contests.’

▶ Fig. 4.13 Anatomy of the human breast. (Ramsay DT, Kent JC, Hart- mann RA, et al. Anatomy of the lac- tating human breast redefined with ultrasound imaging. J Anat 2005; 206(6): 525–534) 4.3 Gross Anatomy 55

‘Very thin women, whose breasts are unprotected to the surface of the nipple (▶ Fig. 4.13). Cooper by this mode of defence, sometimes show severe stated that the areola bruises; but these in a fortnight or three weeks disappear. Yet it is very certain that at distant pe- ‘form a surface which is embraced by the child, riods women apply with tumours in their breasts, and received into its mouth, so that the large lac- which they frequently impute to blows.’ tiferous tubes behind the areola (▶ Fig. 4.14) are emptied by the pressure of the lips of the infant. In the literature up to 2005, Cooper’s description The areola is, therefore, to be considered as an ex- of the ductal system prevailed and was depicted tension of the nipple, the base of which latter is as a cluster of alveoli joined to small ducts expand- lost in the former: its structure is very similar to ing to form larger ducts that drain the lobules. The the nipple, or mammilla.’ larger ducts then merge into one milk duct for Setting the Scene each lobe. These ducts then open through a pore

▶ 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.) 4 – How Breastfeeding Works 56

▶ 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 be- low the nipple. (Ramsay, DT 2005 personal communica- tion.)

Recent detailed studies by Ramsay, et al. using ul- ▶ Fig. 4.16 Drawing by Leonardo da Vinci influenced by trasound imaging have not identified large lactif- Galen’s teachings showing a vessel from the uterus to the erous tubes behind the areola” (▶ Fig. 4.15) [15]. It breast that in fact does not exist. (Calder, R. 1970 Leonardo & the Age of the Eye, Heinemann. p176.) is likely that the dilation of the “tubes” was an ar- tefact resulting from the injection of hot wax through the pores of the nipple to enable the iden- tification of the milk ducts. In contrast to Cooper’s was thought to be synthesised and actively se- observations, ultrasound imaging clearly shows creted during milk ejection; and finally, lymphatic that the area immediately under the areola is vessels draining the small intestine were thought densely packed with lobules containing alveoli. to be the origin of milk because they contained a Since it was assumed that the pressure of the lips milky fluid. The first and second observations led of the infant emptied the non-existent “large lac- to the uterine milk theory promoted by Galen, tiferous tubes”, the mechanism by which the in- who claimed that the menstrual blood that nour- fant removed milk from the breast had to be reas- ished the foetus was diverted to the breast after sessed. birth in special vessels (vas menstrualis, ▶ Fig. 4.16). This theory was rejected when it was found that no such vessels existed. Galen’s knowl- 4.4 edge of the anatomy of the male body was prob- Physiology ably more accurate than that of the female body because he was at one time a physician to the 4.4.1 Origin of Milk gladiators. The genesis of milk has long intrigued scientists The chyle theory of the origin of milk followed and theories have been recorded back to the time the observation that the lymphatic vessels drain- of the Ancient Greeks. Four observations were ing the small intestine into the thoracic duct were seminal in the formation of ideas on the origin of white in appearance and, when pricked, a fluid re- milk. Firstly, the absence of menstruation during sembling milk flowed out. This theory was pregnancy and early lactation; secondly, many soundly discredited by the experiments of Cooper women experienced peculiar sensations in the who stated lower abdomen during breastfeeding; thirdly, milk 4.4 Physiology 57 Setting the Scene

▶ Fig. 4.17 Lymphatic vessels of the female breast, (a and b) lymphatics draining from the nipple to the clavicle. The con- strictions 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.) 4 – How Breastfeeding Works 58

‘A most extraordinary opinion has been broached, Lactose is not metabolised in the blood but ex- that the absorbents (lymphatic vessels) carried creted via the urine; this means that lactose excre- chyle to the breast (▶ Fig. 4.17) — an opinion at tion in urine over a 24-hour period can be used as variance with the nature of the fluid, entirely in- a measure of lactose synthesis during pregnancy. consistent with every injection which I have It should be noted that this increase in urinary lac- made, and irreconcilable with the valvular struc- tose excretion during pregnancy is also closely re- ture of these vessels’ [10]. lated to secretory differentiation (▶ Fig. 4.19).

The idea that milk was rapidly synthesised in the 4.4.2 Secretory Differentiation breast during milk ejection was questioned in the early 20th century when a clear distinction was We now know that the initiation of lactation oc- made between the continuous process of milk curs in two stages. The first stage (secretory differ- synthesis and the intermittent acute process of entiation) commences during mid pregnancy milk ejection. This provided the background for when the breast develops the capacity to synthe- development of the current understanding of milk sise unique milk constituents, such as lactose and synthesis and secretion. milk specific proteins. At this time the stem cells Human placental lactogen secreted from the within the breast have developed into progenitor placenta has an action similar to growth hormone. cells that in turn have differentiated into lacto- The increase in breast growth during pregnancy is cytes. closely related to the increase in this hormone This transition is termed secretory differentia- (▶ Fig. 4.18), which disappears within a few hours tion (previously termed lactogenesis I) [16]. Due postpartum. On the other hand, the increasing to the high levels of progesterone in women, the prolactin concentration in maternal blood during milk secretion rate (colostrum) is low; on average pregnancy is closely related to the increase in about 30 mL per day. Secretory differentiation oc- amount of lactose excreted in urine. The blood- curs at about 20–25 weeks of gestation and is very milk barrier is not fully formed during pregnancy, close to the time of viable preterm delivery. Thus, allowing lactose to diffuse into the maternal blood. it is possible that incomplete maturation of secre-

180 7 350 2.5 Birth Birth 160 6 300 2 140 250 5 Blood prolactin 120 1.5 Breast growth 200 4 100 Secretory Lactose Placental 150 excretion 80 differentiation 1 lactogen 3 100 60 2 0.5 40 50 Average placental lactogen placental Average

1 (mg/l) volume concentration 20 0 0 Average lactose excreted (mmol/24h) lactose excreted Average

Average prolactin concentration (μg/l) prolactin concentration Average 010203040 Average change in breast volume (ml) in breast volume change Average 0 0 010203040 Gestational age (weeks) Gestational age (weeks)

▶ Fig. 4.19 Concentration of prolactin (μg/L) in blood and ▶ Fig. 4.18 Breast volume (mL), a measure of breast the excretion of lactose (mmol/24h) in urine at three growth, and the concentration of human placental lacto- weekly intervals from conception to birth. Secretory differ- gen (mg/L) at three-weekly intervals from conception to entiation commences at approximately 18 weeks of preg- birth. (Czank C, Henderson JJ, et al. Hormonal control of nancy. (Czank C, Henderson JJ, et al. Hormonal control of the lactation cycle. In: Hale TW, Hartmann P. Textbook of the lactation cycle. In: Hale TW, Hartmann P. Textbook of human lactation, New York: Springer; 2007) human lactation, New York: Springer; 2007) 4.4 Physiology 59 tory differentiation could be one of the factors lim- medical follow-up of lactation occurs after admin- iting successful development of lactation in pre- istration of pain relief to the mother. Analgesia can term mothers. prevent the mother sensing when her baby is in- correctly attached during a breastfeed and thus predispose her to nipple trauma. 4.4.3 Secretory Activation Oestrogen withdrawal was once favoured as the Secretory activation (previously termed lactogene- stimulus for secretory activation because pharma- sis II) is the second stage in the initiation of lacta- cological doses of estrogenic hormones inhibited tion and occurs during the first 3 days after birth milk synthesis. These findings encouraged [16]. Secretory activation is characterised by the Gunther to recommend graded doses of diethyl- initiation of copious milk production and is argu- stilbestrol as a method of suppressing postpartum ably the most important phase of the lactation breast engorgement [18]. This practice has since Setting the Scene cycle. Unlike secretory differentiation, secretory been abandoned due to long-term unfavourable activation has to be tightly coupled to the time of outcomes. The classic findings of Kuhn in birth, so that the newborn can make a seamless 1969 clearly demonstrated that progesterone transition from the protective environment of the withdrawal was the lactogenic trigger in rats, but uterus and continuous nourishment from the um- progesterone withdrawal has since been shown to bilical vein to the intermittent provision of protec- be the universal trigger for secretory activation in tion and nourishment from the mother’s milk. Ap- all Eutherian mammals including women [19]. In- propriate management of secretory activation is deed, Neifert, et al. found that secretory activation crucial for the successful development of optimal was inhibited after birth in a woman with retained milk production. Only one study has investigated placental fragments [20]. Milk secretion (secretory the sensitivity of the breast during pregnancy and activation) rapidly increased from about 10 mL/24 lactation. This study showed that areola and nip- h to about 350 mL/24 h on day 28 after curettage ple sensitivity increased markedly within 24 hours (▶ Fig. 4.20) [20]. In this context it should be noted postpartum and then declined in the following that progesterone synthesis occurs in the placenta days [17]. Presumably sensitivity of the nipple at in women but that oestrogen synthesis requires this time provides a signal to the mother (pain) if the presence of both placenta and foetus. her infant is not appropriately attached to her While precipitous progesterone withdrawal oc- breast when feeding. It is of concern that little curs just before birth in most mammals, this

Retained Placental Fragments Birth % max Lactose 400 Secretory activation

80

200 Rat Human 40 D & C

Progesterone 0 0 0 714 21 28 35 42 –8 –4 02 46

Volume of Breast Secretion (ml/24h) of Breast Secretion Volume Postpartum (days) Postpartum (days)

▶ Fig. 4.20 Milk production (mL/24h) in a woman with ▶ Fig. 4.21 Concentration of progesterone (% of maxi- placental retention from 20 to 44 days postpartum. Dilata- mum values) in blood and lactose (% of maximum values) tion and curettage was carried out at day 23 to remove pla- in mammary secretion from –6 days prepartum to 5 days cental fragments. postpartum in women and rats. (Reproduced from Hart- mann, P.E. 1990. Unpublished data.) 4 – How Breastfeeding Works 60

abrupt withdrawal occurs after birth in women to influence milk production, perhaps due to following placental delivery. As a result, secretory down-regulation of progesterone receptors in the activation occurs 30–40 hours after birth breast. Once lactation is established, milk produc- (▶ Fig. 4.21). This seems counterintuitive to the tion is not coupled to progesterone levels during high-energy requirements of the newborn infant. the menstrual cycle and progesterone-containing However, unlike the newborn of most other mam- low dose contraceptives do not appear to inhibit mals, the human newborn has high levels of body lactation. Thus, the important role for progester- fat (10–15%) to draw on for its energy require- one centres on the early postpartum period. In ments. This feature has facilitated the survival of view of the universality of the progesterone with- newborn infants for days without nourishment, drawal mechanism, it is puzzling that more atten- such as after earthquakes. It is likely that the pro- tion has not been given to the potential effects that tective role of human milk (innate immunity) and, subtle changes in progesterone withdrawal could in particular colostrum, is as important as its nu- have on the immediate and long-term synthesis tritional role. Therefore, the small volume of colos- of breastmilk, particularly as there are potential trum secreted after birth (~30 mL/24h) [21] with therapeutic options in relation to regulating pro- its high concentration of protective glycoproteins, gesterone receptors in the breast at this time. oligosaccharides, and fatty acids facilitates protec- The administration of Bromocriptine (to sup- tion of the surfaces of the respiratory and gastro- press prolactin secretion) inhibits secretory activa- intestinal tracts against pathogenic microorgan- tion in women suggesting that prolactin is re- isms. quired for this stage of gland development [22]. The withdrawal of progesterone from the ma- Furthermore, a number of studies have con- ternal blood is rapid, declining by more than 10- cluded that milk production can be increased by fold within 3 days postpartum, and the literature the administration of galactogogues (e.g., domper- is quite consistent on the nature of this fall idone and metoclopramide) that increase blood (▶ Fig. 4.22). Due to this rapid decline, accurate prolactin. Indeed, these medications are often pre- timing between the delivery of the placenta and scribed when women present with either low milk blood sampling would likely improve the precision supply or perceived low milk supply. Unfortu- of these values. In contrast to parturition, changes nately, measurements of blood prolactin and milk in the concentration of progesterone in maternal production are rarely made prior to medication blood during established lactation do not appear administration to justify their use.

μg/l 300 50 Lunch Dinner Sleep 250 Prolactin 200

150 30 100

50 Prolactin (μg/ml) Progesterone 0 021 34 5678 0 Postpartum (days) 08:0016:00 24:00 08:00 Clock time

▶ Fig. 4.22 Concentration of progesterone (μg/L) and pro- ▶ lactin (μg/L) in blood of women from birth to 8 days post- Fig. 4.23 Circadian changes in the concentration of pro- μ partum. (Boss M, Gardner H and Hartmann P. Normal Hu- lactin ( g/L) in the blood plasma of 8 normal women. (Re- ff man Lactation: closing the gap [version 1; referees: 4 ap- produced from Yen, S., Ja e, R. 1999. Prolactin in Human th proved]. F1000Research 2018, 7(F1000FacultyRev):801 Reproduction. In: Reproductive Endocrinology. 4 ed. Phil- (doi: 10.12688/f1000research.114452.1)) adelphia: WB Saunders Co.) 4.4 Physiology 61

▶ Fig. 4.24 Concentration of pro- lactin (μg/L) in the blood plasma of Nursing breastfeeding women from 60 mi- 300 nutes before to 180 minutes after the commencement of breastfeeds. 250 Play 200 with infant 150

100 Milk Prolactin (μg/ml) letdown 50 Setting the Scene

0 –60–30 0 30 60 90 120 150 180 Minutes

While the literature on progesterone with- drawal is quite consistent, the literature for prolac- ▶ Before breastfeed tin is not ( Fig. 4.23). Prolactin concentrations re- 300 ported for mothers in the immediate postpartum 45 min. after start period vary greatly and averages don’t make much 250 of breastfeed sense. The reason for much of this variation is 200 probably due to sample collection. It has been 150 shown that the concentration of prolactin has a circadian rhythm, with the lowest concentrations 100 Prolactin (μg/ml) during the day and high concentrations during 50 sleep (▶ Fig. 4.24). In addition, prolactin concen- tration increases at mealtimes and doubles when 0 measured before a breastfeed to about 30–45 mi- 12 46 Postpartum (months) nutes after the commencement of the breastfeed. This response decreases from one to six months of ▶ lactation ( Fig. 4.25). Much of the large variation ▶ Fig. 4.25 Concentration of prolactin (μg/L) in the blood between samples might be removed if care was plasma of 11 lactating women at 1, 2, 4, and 6 months of taken to standardise blood-sampling procedures lactation. Blood samples were taken immediately before in relation to infant’s breastfeeds, time of day, and and 45 minutes after the commencement of the breast- meal times. Obviously, with the wide use of dom- feed. (Reproduced from Cox, D.B. 1996. The morphological and functional development of the human breast during peridone and metoclopramide, it is very important pregnancy and lactation. PhD Thesis: The University of to establish reference values for postpartum pro- Western Australia; p3-6 3-7.) lactin concentration in maternal blood. Although it is clear that prolactin is required for secretory activation, it probably does not play a rate-limiting transcription factors to enable the synthesis of role during normal secretory activation and in es- milk proteins. While progesterone binds to the tablished lactation. glucocorticoid receptor, it does not translocate to Glucocorticoid receptors are present in the cyto- the nucleus and deactivate the milk synthesis sol of lactocytes. When bound with glucocorti- genes. coids, these receptors translocate to the nucleus Despite the obvious association between preg- and act synergistically with prolactin-activated nancy and secretory differentiation and activation, 4 – How Breastfeeding Works 62

pregnancy is not an essential prerequisite for lac- ment of secretory activation. The metabolic tation. There are numerous reports of the induc- changes that occur in the breast offer more precise tion of mammary growth and lactation arising objective assessments. The withdrawal of proges- from repeated application of stimulation by either terone triggers the closure of tight junctions be- suckling or massage in non-pregnant women. tween lactocytes. Synthesis and secretion of lac- Although responses are highly variable, there are tose rapidly increases, drawing water with it to reports of infertile women establishing exclusive maintain osmotic equilibrium. As a result of these breastfeeding by the application of suckling and metabolic changes, the concentrations of sodium, massage for just a few weeks. chlorine, and total protein decrease. Conversely, By definition, the ideal method for determining lactose and citrate concentrations, and milk pro- secretory activation is to measure milk produc- duction increase as mammary secretion transi- tion. However, this is quite difficult to do in the tions from colostrum to milk over the first 5 days immediate postpartum period. Furthermore, milk postpartum. Thus, analysis of mammary secretion synthesis at this time is greatly influenced by the for sodium, chloride, citrate, and total protein over ability of the infant to remove all of the available this early postpartum period can be used to assess colostrum. In many women the onset of lactation the progress of secretory activation (▶ Fig. 4.26). is accompanied by a sudden feeling of breast full- Unfortunately, there is not sufficient appropriate ness and leakage. If this is not managed properly it research available to enable the establishment of can lead to extremely engorged and painful reference values for these milk constituents during breasts. Nevertheless, this is a subjective assess- this crucial period in the lactation cycle.

200 70 Lactose Total Protein 400 60 160 Milk production 50 300 120 40

200 30 80

Lactose (mM) Lactose 20 100 (g/l) Protein Total 40

Milk production (ml/24h) 10

0 0 0 12345 12345

6 90 Citrate Sodium 5

4 60

3 Citrate (mM) Citrate 2 Sodium (mM) 30

1

0 0 12345 12345 Postpartum (days) Postpartum (days)

▶ Fig. 4.26 Milk production (mL/24h) and the concentrations of lactose (mM), total protein (g/L), citrate (mM) and so- dium (mM) in mammary secretion from day 1 to day 5 of lactation, that is, during secretory activation. 4.4 Physiology 63

▶ Tab. 4.1 Prevalence of exclusive breastfeeding postpartum (%). 6 weeks 14 weeks 6 months

Group 1: Standard care 51 34 14 Group 2: Steps 1–9 alone 90 76 45 Group 3: Steps 1–10 81 47 14

The importance of secretory activation is clearly cant long-term effects presumably associated with demonstrated from three recent rather subtle in- a critical learning period. tervention studies that focused on the first 3 days Morton, et al. showed that combining hand postpartum. Yotebieng and colleagues randomly massage techniques with electric pumping in- Setting the Scene assigned clinics to three groups to investigate opti- creased milk production in preterm mothers at 2 misation of the Baby Friendly Hospital Initiative weeks and beyond [24]. The treatment was only (BFHI) ten steps to successful breastfeeding [23]. applied in the immediate postpartum period and Steps 1–9 focus on promotion and establishment again emphasises the importance of the secretory of breastfeeding in the clinical setting after birth. activation period. Similarly, in another study of Step 10 promotes the establishment of breastfeed- preterm mothers, Meier, et al. used an experimen- ing support groups and referral of mothers to tal suction pattern that was designed to resemble these on discharge from either hospital or clinic. the suckling patterns of neonatal infants [25]. The The primary outcomes were initiation of lactation pattern was applied until the onset of secretory (commencing breastfeeding within 1 hour of activation (approximately for the first 80 hours birth) and exclusive breastfeeding. Exclusive postpartum). Mothers were then changed to the breastfeeding was higher in groups 2 and 3 at 14 commercial pattern for the electric breast pump. weeks but surprisingly was only significantly high- Interestingly, this intervention in the first 80 hours er in Group 2 at 6 months (▶ Table 4.1). Leaving after birth increased milk production significantly aside the unexpected finding that the results for at 1 week postpartum and by 2 weeks postpartum. the 1–9 steps group (Group 2) were significantly The experimental group were producing approxi- better than those for the controls and the 1–10 mately 60% more milk than the standard electric steps group (Group 3), these findings clearly show breast pump group (▶ Fig. 4.27). that interventions at birth can have very signifi- Although there is compelling evidence that hu- man lactation is “hard-wired” and essential for the

▶ Fig. 4.27 Milk production (mL/ 900 24h) in three groups of mothers 33 EXP-EXP (n = 33) 800 * to 38 preterm from birth to 14 days EXP-STD (n = 34) * * * * postpartum. One group used an ex- 700 STD-STD (n = 38) * * perimental suction pattern that was 600 * designed to simulate the baby suck- ing, another group received the ex- 500 perimental pattern until secretory 400 activation (~80h postpartum) and then the standard pattern and the 300 final group only received the stand- 200 ard pattern. (Reproduced from Mean daily Milk Output (ml) Mean daily Milk Output Meier, P. P., et al. 2012. Breast pump 100 *p < 0,05 suction patterns that mimic the hu- 0 man infant during breastfeeding: 1234567891011121314 Greater milk output in less time Postpartum (days) spent pumping for breast pump-de- pendent mothers with premature in- fants. J Perinatol, 32, 103–110.) 4 – How Breastfeeding Works 64

healthy growth and development of infants, these the milk is thus, in some degree, prepared for the studies show that even subtle intervention in the child. By the occasional, is to be understood that first 3 days after birth can have major influences secretion which is called by mothers and nurses, on the success of lactation. It is likely that, as in the draught of the breast, by which is meant a other mammals, the period from just before partu- sudden rush of blood to the gland, during which rition to the immediate postpartum period is vi- the milk is so abundantly secreted, that if the nip- tally important for both birth and lactation. Per- ple be not immediately caught by the child, the haps Michel Odent’s non-intervention approach in milk escapes from it, and the child when it re- relation to childbirth may also apply to successful ceives the nipple is almost choked by the rapid secretory activation and the establishment of and abundant flow of fluid; if it lets go its hold, breastfeeding [26]. Nevertheless, it is indisputable the milk spurts into the infant’s eyes.’ [10]. that removal of colostrum and then mature milk from the breast is essential for the continuation of More than 100 years later it was still claimed that milk production. Thus, milk removal is essential milk secretion was mostly confined to the periods for secretory activation as well as established lac- of sucking. Finally, in 1941 Ely & Petersen carried tation. Two physiological processes, maternal milk out studies in cows and correctly concluded, ejection and infant breastfeeding, are required for the removal of milk from the lactating breast and ‘The letting down of milk is a conditioned reflex normal lactation. operated by sensory stimuli associated with milk- ing. Afferent impulses reach the central nervous system and release oxytocin from the posterior 4.4.4 Milk Ejection pituitary, which in time causes a rise in milk pres- The history of the understanding of the milk ejec- sure probably because of the contraction of mus- tion reflex is important because it illustrates how cular tissue which is believed to surround the al- a simple misunderstanding of a physiological veoli and small ducts’ [27]. process can impact on the understanding of a whole physiological process — in this case, the It is now known that myoepithelial cell processers physiology of lactation. In the 19th century it was surround the alveoli (▶ Fig. 4.28) and contract generally accepted that milk was synthesised in when stimulated by oxytocin, forcing the milk the breast from components carried to it in the along the milk ducts towards the nipple. 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 synthe- sis of some components occurred in the breast. Then a stalemate existed for more than a century in the understanding of milk synthesis and secre- tion. This arose because of the erroneous conclu- sion 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 res- ▶ Fig. 4.28 Myoepithelial cells surrounding contracted al- ervoirs are constantly supplied by means of a veoli from the mammary gland of a lactating goat. (Cowie, A. T., Forsyth, I. A., Hart, I. C. 1980. Lactation. Hormonal slow and continuous production of fluid, so that control of lactation. Springer. p194.) 4.4 Physiology 65 Setting the Scene

▶ 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 Milk ejections accumulated weight of milk in left L L R R and right breasts during breast ex- 70 0.5 pression. The peaks in milk flow re- Left and Right Breasts 60 Mother 1 late to the number of milk ejections 0.4 that occurred during the expression 50 period. (Reproduced from Prime, D. 40 0.3 K., et al. Using milk flow rate to in- vestigate milk ejection in the left 30 0.2 and right breasts during simultane-

20 (g/s) Rate Flow ous breast expression in women. Int 0.1 Breastfeed J. 4, 10.) Cumulative Weight (g) Weight Cumulative 10

0 0.0 0 264810 12 14 Time (Minutes)

Milk ejection can be measured either by the in- Although 88% of mothers sense the first milk ejec- crease in milk duct diameter viewed by ultrasound tion, almost all mothers fail to sense subsequent imaging (▶ Fig. 4.29) or by the change in milk flow milk ejections. rate when milk is expressed using an electric Maternal sensation of milk ejection varies. breast pump. Mothers have several milk ejections Mothers have reported sensations such as a pleas- during a breastfeed (▶ Fig. 4.30). Each mother has ant tingling, pins and needles, sharp nipple pain, a particular pattern of milk ejections during a warmth, thirst, sleepiness, and mild nausea before breastfeed, and this pattern holds throughout the milk flow increases. In addition, as noted by Coop- lactation and for subsequent lactations. Thus, the er, milk can spurt from the breast for a distance of initial sucking of the infant is important in initiat- a meter or more in some women. These sensations ing the first milk ejection but subsequent milk are more common in early lactation. Milk ejection ejections are intrinsic to the mother. Failure to re- usually occurs within one minute of putting the lease oxytocin is rare for breastfeeding mothers. baby to the breast but can occur at other times (for Milk ejection may be identified by changes in the example when the mother thinks about her baby) infant’s sucking pattern (from rapid initial sucking because milk ejection is a conditioned reflex. Like to a slower suck and swallowing pattern). other conditioned reflexes it can be inhibited by 4 – How Breastfeeding Works 66

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 ad- equacy 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 Fig. 4.31 Sagittal mid-line images of an infant s oral cavity during breastfeeding showing stylised overlay of ul- is important to ensure that only breastfeeding in- trasound images showing the soft palate, hard palate, nip- fants are considered because the dynamics of ple and tongue, (a) tongue up (baseline vacuum), (b) suckling are different in bottle-fed infants. Breast- tongue down (peak vacuum). (Geddes, D., Sakalidis V. feeding is a very complicated process in that it re- 2015. Breastfeeding: How do they do it? Infant sucking, – quires the coordination of sucking, swallowing, swallowing and breathing. Infant, 11; 146 150.) and breathing. This is reflected by the attention that clinicians give to positioning and attachment of the baby at the breast. However, this interven- nutritive sucking bursts were shorter with a ten- tion is very subjective, and advice has changed dency to occur towards the end of a breastfeed with time without support from evidence-based compared with nutritive sucking. research. For the development of an evidence- Nutritive sucking is achieved by an intraoral based assessment of breastfeeding, it was impor- vacuum (negative pressure), which is generated by tant to develop synchronized continuous meas- the downward movement of the infant’s tongue urements to describe this complex behaviour. In- during feeding and intermittent positive pressure formation was gathered from synchronised ultra- generated within the milk ducts at milk ejection. sound imaging of tongue movement and milk Infants attach to the breast and generate a baseline flow, the intraoral vacuum generated by the vacuum that stretches the nipple to within 5– downward movement of the tongue, and respira- 7 mm of the junction between the hard and soft tory-inductive plethysmography to identify suck- palates. Under the influence of this vacuum, milk ing, breathing, and swallowing (▶ Fig. 4.31). ducts in the nipple expand and milk flows into the First, it was important to define nutritive and oral cavity space bounded by the tip of the tongue, non-nutritive sucking. Nutritive sucking showed the hard-soft palate junction, and the oral epithe- milk flow coupled with frequent swallowing. In lial lining of the cheeks. The vacuum is released as non-nutritive sucking, little milk was removed the tongue rises, and compression of the nipple al- from the breast and swallowing occurred only oc- lows the milk to be cleared from the oral space to casionally due to the accumulation of saliva. Non- the pharyngeal area at each suck. The milk bolus 4.4 Physiology 67

Baseline vacuum

Pause

Peak vacuum Intra-oral vacuum Intra-oral

Expiration

I-S-I Setting the Scene E-S-I Inspiration Respiration

142 144 146 148 150 152 154 Swallow Swallow

▶ 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 (suck- ing 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, inspira- tion-suck-inspiration).

may remain in this area for a number of sucks be- 4.4.6 Established Lactation ▶ fore it is swallowed ( Fig. 4.32). In the 1970’s, the slowing of infant growth at 2–3 Sakalidis and Geddes found that infants were months of age in low and middle-income coun- able to simultaneously suck and swallow, and suck tries was of great concern. Maternal diets in these and breathe, but not breathe and swallow [28]. countries were very poor compared to interna- Breastfeeding infants did not have a consistent tional recommendations. As such, it was con- suck-swallow-breathe pattern. Respective ratios cluded that poor infant growth was due to infants can range from 1:1:1 to 12:1:4 during nutritive receiving insufficient breastmilk from their moth- sucking to from 2:0:1 to 23:1:23 for non-nutritive ers. This conclusion was consistent with research sucking. This range for nutritive sucking is not sur- on dairy cows, dairy goats, and sows that showed prising as the rate of milk flow rapidly increases that increased food intake was required to support and decreases at each milk ejection, particularly milk production. The summation of these factors during the first few minutes of a breastfeed. In ad- resulted in the slogan, ‘Feed the nursing mother dition, there is large variation in the pattern of re- and thereby feed the child’ [29]. This slogan was lease of oxytocin between mothers. readily accepted at the time because it was logical In summary, these studies clearly show that the and consistent with contemporary nutritional application of vacuum by the infant is critical for knowledge. Nevertheless, Ann Prentice and her successful milk removal. Sucking dynamics with colleagues studied poorly-nourished lactating good coordination of the suck-swallow-breathe women in The Gambia and well-nourished lactat- reflex are evident in the early postnatal period for ing women in the UK [30]. They concluded that term babies. However, changes in oxygen satura- tion, heart rate, feed duration, and the applied vac- ‘the processes controlling lactation performance uum change in relation to neurological maturation are remarkably similar and that the same control and conditioning as lactation proceeds. mechanisms will be revealed in most other com- munities’. 4 – How Breastfeeding Works 68

They also concluded that times per day consistently produced more milk. This effect was clearly shown in women by the ‘there is a strong drive towards milk production finding that when the breast was drained of milk, in lactating women, often to the detriment of ma- the rate of milk synthesis was high and when the ternal tissues, and that even low dietary intakes breast was filled with milk the rate of milk synthe- observed in most countries in the developing sis was low (▶ Fig. 4.34). Conclusions drawn from world do not fall below the threshold at which these studies were that the regulation of milk syn- lactation performance is compromised’. thesis was local within each breast (autocrine), and that the hour-to-hour regulation of milk syn- This was surely a seminal finding as it not only thesis was relatively independent of endocrine in- supported the concept that human lactation is fluences. “hard-wired” but totally reversed the mindset of However, a compensatory response was also scientists investigating the control of the synthesis found in dairy animals. That being, if the rate of of human milk. The question then became “How milk removal was reduced in one udder-half, a does the mother regulate her milk synthesis to compensatory increase in milk production oc- meet the unpredictable appetite of her baby?” curred in the other udder-half without a change in Many studies have shown that the infant only the frequency of milk removal. These findings have consumes enough milk to satisfy its appetite and important implications for human lactation. If a that variable milk volumes are taken at each mother can store a lot of milk in her breasts then breastfeed regardless of whether the feeds are un- she could breastfeed at less frequent intervals. On paired or paired (▶ Fig. 4.33). Studies in dairy ani- the other hand, if she has a small storage capacity mals have also found that goats milked three times the breast will fill with milk more quickly and per day produced more milk than if milked twice down-regulate milk synthesis sooner. This means daily. Furthermore, if half the udder was milked that more frequent breastfeeds are required to three times per day while the other half was maintain milk production in mothers with low milked twice per day, the udder-half milked three storage capacity. It has been proposed that the

Unpaired Feeds (30% of babies) Paired Feeds (13% of babies) 140 140 left 120 120 right 100 100

80 80

60 60

40 40 Feed Volume (ml) Volume Feed (ml) Volume Feed 20 20

0 0 06:0012:00 18:00 00:00 06:00 12:0018:00 00:00 06:00 12:00 18:00 Time of Day Time of Day

24h Production 24h Production Left Breast 253 ml Left Breast 353 ml Right Breast 534 ml Right Breast 397 ml a Total 787 ml b Total 750 ml

▶ 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). 4.4 Physiology 69

▶ Fig. 4.34 (a) Changes in breast a volume for each breast at each 2000 breastfeed over a 24h period. (b) Right Breast The rate of milk synthesis between Storage capacity each breastfeed for each breast over 600 ml 1800 a 24h period.

Mother A 1600 Right plus left Breast – 930 ml/24h

1400 Breast Volume (ml) Volume Breast Left Breast Setting the Scene Storage capacity 1200 180 ml

1000

b 40

20 (ml/h) Milk Synthesis Milk Synthesis 0 06:00 18:00 06:00 06:00 18:00 06:00 Time of Day

▶ 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.)

down-regulation of milk synthesis is controlled by sition from full to drained gland (▶ Fig. 4.35). This a feedback inhibitor of lactation [31]. However, change could expose or mask receptors in the lac- identification of such a compound remains elusive. tocytes to either up regulation or down regulation Alternatively, it is possible the down-regulation of depending on whether the alveoli were distended milk synthesis is related to major morphologic or drained of milk, thereby regulating the lacto- changes in the secretory parenchyma during tran- cytes’ response to lactocrine hormones. 4 – How Breastfeeding Works 70

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. Additional- ly, 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 prob- lem 100 years ago. For this reason, early last cen- tury, 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 ▶ Fig. 4.36 Death of babies in summer from diarrhoea full complement of minerals and vitamins. Some 1895–1904. Deaths of babies in summer from diarrhoea and high incidence of tuberculosis in army recruits of these components (e.g., milk fat) vary from be- prompted the Government to establish Child Health Nurses ginning to end of both a breastfeed and breast ex- who were trained by free immigrants who, in turn, learnt pression (▶ Fig. 4.37), over the day, with diet, and hygiene on sailing boats coming to Australia. (Muslett, P. during the lactation period. Unfortunately, with 1903. Australian Medical Guide, Sydney, William Brooks the notable exception of breastfed infant growth and Co.) (▶ 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 Healthy exclusively breastfed infants have a milk composition. Thus, values currently given for mean daily intake of 750–800 mL/24 h from one to milk production and concentrations of breastmilk six months of lactation; however, the range is components are flawed. wide (from 500 to 1200 mL/24 h) [32]. There is a Standardised experimental inclusion and exclu- relationship between infant growth and milk pro- sion criteria are required for development of pro- duction but, unexpectedly, no relationship be- tocols to define normal ranges carefully for human tween infant growth and total energy, protein, fat, lactation in the mother and her infant. This is an or lactose intake from breastmilk. The relatively important prerequisite for establishing an objec- constant milk production from one to six months tive evidence-base for the diagnosis of problems of lactation is most likely explained by the rela- associated with human lactation. tively slow growth of the human infant. The en- Measurement of 24-hour milk production pro- ergy saving from the decrease in the ratio of sur- vides an objective measure of breast function and face area to body mass is probably sufficient to has been shown to be useful to both mother [33] and clinician (Kent, personal communication 4.4 Physiology 71

▶ 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.) Setting the Scene

▶ 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.)

2016). Conversely, the measurement of milk in- mother-infant dyads would likely reduce the cur- take at a single breastfeed is of less value because rent wide range for normal milk production. Simi- milk intake is controlled by the infant’s appetite lar concerns are valid for maternal and infant en- and can vary greatly from one breastfeed to the docrine and metabolic parameters. This highlights next. The measurement of 24-hour milk produc- the urgent need to establish reference ranges for tion is useful in tracking changes within the moth- objective diagnosis and treatment of problems as- er-infant dyad but is not useful in determining sociated with human lactation. whether the level of milk production is normal. More stringent assessment of the recruitment of 4 – How Breastfeeding Works 72

▶ 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.)

4.5 – Optimal neurological development Changes to Physiology – Prebiotic components that promote favorable in Mother and Infant microbiota in the infant – Probiotic transfer of a favourable microbiome Physiologically, there are two very important as- to infant pects to human lactation. First, lactation is impor- ● Importance of lactation for the mother: tant for the mother and her baby and secondly, – Recovery from childbirth the importance of lactation in relation to breast- – Cholesterol clearance feeding behaviour and breastmilk composition – Suppression of maternal fertility must be considered. This is a very large topic and – Glucose control in diabetic mothers therefore only some pertinent points can be dis- – Improved bone mineralisation cussed here. Much of the importance of lactation – Reduced obesity – has focused on the infant (Table 2a) but the impor- Reduced risk of breast and ovarian cancer tance to the mother (Table 2b) must also be con- – Reduced risk of cardio-vascular disease sidered. – Increased self esteem ● Importance of lactation for the infant: – Improved IQ – Immunological protection (both innate and acquired) A good illustration of the complexity of human – Optimal nutrition lactation in relation to the mother can be illus- – Optimal metabolic development trated by examining calcium metabolism during 4.5 Changes to Physiology in Mother and Infant 73 pregnancy and lactation. In the past, nutritionists to release of growth hormones, and from appetite were aware of the high levels of calcium in breast- to the intensity of activity. Hofer says: milk and thus it was concluded that breastfeeding was an impost on calcium metabolism. To empha- ‘The mere presence of the mother not only ensures sise this, textbooks claimed “for every child a the infant’s well being, but also creates a kind of tooth” and high calcium diets were recommended invisible hot house in which the infant’s develop- for pregnant and lactating women. Research from ment can unfold. Mother and offspring live in a Ann Prentice’s group challenged this orthodoxy by biological state that has much in common with showing that increasing calcium supply to inter- addiction. When they are parted, the infant does national recommendations in the diet of mothers not just miss its mother, it experiences a physical in populations with low calcium intake was nei- and psychological withdrawal from a host of her ther beneficial for mothers during pregnancy and sensory stimuli, not unlike the plight of a heroin Setting the Scene lactation nor for their children [34]. She showed addict who goes cold turkey. For a baby, the envi- that intuitive thinking is not always supported by ronment is the mother,’ research. Thus, studies in The Gambia showed that breastfeeding Gambian mothers who received cal- Furthermore, it was known that a mother must cium supplements during pregnancy had accentu- keep her infant warm for its body and brain to ma- ated bone mobilisation during lactation, and that ture; however, Hofer discovered that thermal con- their lower bone mineral density persisted long tact with the mother regulated the infant’sbehav- term. These unexpected findings raise mechanistic iour and activity as well. Conversely, it has also questions about the underlying physiology of cal- been shown that the infant influences the moth- cium metabolism during pregnancy and lactation, er’s metabolism and cycle of activity primarily and illustrate the importance of a complete basic through the act of breastfeeding. These findings understanding of calcium metabolism before clini- provide a basis for understanding the beneficial ef- cal intervention. Presently, the nutritional advice fects of skin-to-skin contact. In addition, recent re- offered by James in 1912 seems appropriate. search has shown that breastfeeding and vaginal birth are physiologically important because they ‘There is no special food for the production of facilitate optimal passage (inoculation?) of mater- milk: That which is best for the general health of nal symbiotic microorganisms to the infant. the mother is the best for the child.’ [35] This is of particular importance when consider- ing the composition of human milk and function The importance of the intimate but fragile meta- of the components in the infant. Transfer of nu- bolic relationship between mother and infant is trient and bioactive components from mother to clearly illustrated in Hofer’s studies [36]. Breast- infant occurs though colostrum and milk after feeding is related to complex signals that pass birth. The substitution of infant formula for hu- from mother to infant and from infant to mother. man milk deprives the infant of the nutrients in There are significant subtle interchanges that oc- human milk (e.g., essential amino acids and hu- cur during human lactation. Hofer determined man casein) and of the many bioactive and immu- that the mother-infant relationship is built on noprotective factors (e.g., oligosaccharides, lacto- many layers of sensory complexity. What seems to ferrin, and lysozyme) directed specifically against be a single physical function, such as either pathogens in the infant’s environment. Human grooming or nursing, is actually a kind of umbrella milk components also compensate for the imma- that covers stimuli of touch, balance, smell, hear- ture functioning of infant metabolism, in which ing, and vision, each with specific effects on the in- endogenous digestive enzymes, secretory immu- fant. He identified a ‘private realm of sensory noglobulin A, taurine, choline, nucleotides, and stimulation constructed by the mother and infant long-chain polyunsaturated fatty acids are insuffi- from numberless exchanges of subtle cues’. Hofer cient. The importance of these nutritive and bioac- discovered that a mother precisely controls every tive components makes human milk superior to element of her infant’s physiology, from heart rate even the best infant formula. 4 – How Breastfeeding Works 74

4.5.1 Menstrual Cycle pounds. Once milk removal has completely Postpartum amenorrhoea lasts for approximately stopped, mammary secretion takes more than 4 55–60 days in non-breastfeeding women. How- weeks to stabilise in women compared with about ▶ ever, this period is much more variable in breast- a week in most other mammals ( Fig. 4.40). feeding women and can extend up to 2 years and In some mothers, breastfeeding may continue beyond. The long period of lactation in traditional into the next pregnancy and even to the next lac- societies increases the duration of amenorrhoea tation (tandem feeding). It is unlikely that breast- and child spacing, with associated benefits to the feeding into a new pregnancy has any undesirable ff mother and child. While lactational amenorrhoea e ect on either the infant or the mother, as two is evident on a population basis, variation between thirds of all cows milk that we drink is from preg- mothers in the timing of the return of menstrua- nant cows. tion indicates that lactational amenorrhoea does Complete weaning of the infant marks the end not alone provide a reliable method of birth con- of the lactation cycle and the breast returns to its trol. non-lactating (resting) state. Studies have moni- tored the changes in breast volume over the entire lactation cycle (▶ Fig. 4.41). The first significant re- 4.5.2 Weaning and Involution duction in breast volume occurs after six months Weaning after six months of lactation is normally of lactation and precedes the first significant de- a gradual process, commencing with the baby hav- crease in milk production. After milk production ing fewer breastfeeds while consuming additional has ceased, there is no significant difference be- foods. This is coupled with the gradual involution tween breast volume prior to conception and that of the secretory and ductal tissue in the breast by measured after complete weaning. apoptosis (programmed cell death), an increase in prominence of fatty tissue, and mammary paren- chyma slowly returning to ducts and terminal end buds containing a colostrum-like fluid with very high concentrations of innate protective com-

▶ Fig. 4.40 Concentration of lac- tose (% of day zero value) in the 100 mammary secretion of (a) women, (b) cow, (c) sows, and (d) rats from 80 0 to 30 days after removal of milk had ceased. (By permission of Ox- ford University Press. Reproduced 60 from Hartmann, PE et al. 1985. Var- iation in the yield and composition of human milk. Oxford Reviews Re- 40 a productive Biology, 7, 118–167.)

20 Lactose concentration) (% day d c b 0 0 612182430 Time (days) 4.6 Conclusion 75

▶ Fig. 4.41 Relative change in Birth breast volume (mL) from pre-con- 250 ception (relative volume, zero), through pregnancy, lactation and 200 weaning. (Reproduced from Czank C, Henderson JJ et al. Hormonal con- 150 trol of the lactation cycle. In: Hale TW, Hartmann P. Textbook of hu- 100 man lactaion, New York: Springer; 2007) 50 Breast volume (ml) volume Breast

0 Setting the Scene

–50 0 3 6 9 3 6 9 12 15 18 21 24 W W + 3 Pregnancy Lactation (months) Weaning

4.6 : Key Points Conclusion ● Astley Cooper in 1840 was the first person to focus on the physiology of the lactating breast but it was Finally, it is appropriate to conclude this chapter not until a 150 years later that modern ultra sound with another quote from Cooper: technology provided a new insight into the work- ings of this amazing organ “If a woman be healthy and she has milk in her ● Today it is understood that lactation occurs in sev- breasts, there can be no question of the propriety eral stages. Beginning with alveolar development of her giving suck. If such a question be put, the and secretory differentiation during pregnancy, fol- answer should be, that all animals, even those of lowed by secretory activation during the first 3 the most ferocious character, show affection to days after birth and ending with involution during their young, do not forsake them, but yield them weaning their milk, do not neglect, but nurse and watch ● Lactation is intricately controlled by endocrine and over them; and shall woman, the loveliest of na- autocrine processes requiring the removal of milk ture’s creatures, possessed of reason as well as in- to sustain it stinct, refuse that nourishment to her offspring ● Complex signals pass between mother and infant which no other animal withholds, and hesitate to during breastfeeding which have subtle influences perform that duty which all animals of the Mam- on the infants’ physiological well-being malia class invariably discharge? Besides it may be truly said that nursing the in- fant 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]. 4 – How Breastfeeding Works 76

Ms Melinda Boss, MPS, B.Pharm, is the team Emeritus Professor Peter E. Hartmann, E/Prof, leader of a multidisciplinary group developing PhD, BRurSc is a Senior Honorary Research Fellow evidence-based protocols for the medical assess- at The University of Western Australia. He has ment and management of lactation dysfunction. published more than 200 research papers and She graduated from Curtin University and be- numerous reviews and book chapters on lacta- came a registered pharmacist in 1993. She has tion in dairy animals and women. He has re- gained experience in both community pharmacy ceived numerous awards including the Macy- and research, most recently publishing, “Normal Gyorgy award, La Leche League International human lactation: closing the gap”. Interrupting Award of Excellence for contribution to support- her career to have her family, she returned to ing breastfeeding, and the Rank Prize for Nutri- work part-time in 2011 as a senior research fel- tion. He is a Fellow of Nutrition Society of Aus- low at The University of Western Australia. tralia, co-editor of a Hale & Hartmann’s Textbook of Human Lactation, and a Member of the Order of Australia.

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