DISCLOSURES

1. DISCLOSURES

2. Accreditation and Educational Credit The University of South Carolina School of Medicine-Palmetto Health Continuing Medical Education Organization designates this enduring material for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This CME Activity is planned and presented in accordance with all ACCME Essential Areas and Elements (including the Standards for Commercial Support) and Accreditation Policies. Relevant financial relationships and acknowledgements of commercial support will be disclosed to participants. Faculties are required to disclose off-label/investigative uses of commercial products/devices.

3. Breastfeeding Educationfor Physicians: The Road to Baby Friendly Designation Jennifer Amrol, MD Assistant Professor of Clinical Pediatrics University of South Carolina School of Medicine

4. Objectives Review the anatomy and physiology of breastfeeding. Examine the composition of human milk and the significance of individual components.

5. Breast Anatomy

6. Breast • Mammary tissue • Alveoli • Ducts • Nipple and Areola • Supporting connective tissue and fat, blood and lymphatic vessels, nerves • Adipose tissue distribution greatly differs among women and is not related to milk production

7. Breast Anatomy • Mammary tissue • Alveoli • Small sacs of milk secreting and storing cells clustered into lobules • Surrounded by myoepithelial cells which contract in response to oxytocin for milk ejection • Ducts • Connect lobules to form distinct mammary lobe • Then connect lobes to end at the galactophore • Ducts beneath areola become fuller due to oxytocin during a feed • Number is not related to milk production

8. Breast Anatomy • Nipple • Has an average of 9 milk ducts passing to outside • Has smooth muscle fibers and sensory nerves • Shape and size vary between women

9. Inverted Nipples Women with inverted nipples can breastfed but they many need more help postpartum. She should request assistance with breastfeeding as soon as possible after her baby is born. After delivery, a breast pump might be useful to help evert the nipples. If a pump is not available, a 20ml syringe with the adaptor end cut off and the plunger inserted backwards is used to help draw out a nipple. Avoid bottle and pacifier use so the baby does not become accustomed to the longer artificial nipple which feels and flows differently. When all else fails, an ultra-think silicone nipple shield can be tried temporarily. Nipple preparation during pregnancy is not recommended.

10. Breast Anatomy • Areola • Circular and pigmented • Contains Montgomery glands • Secrete a bacteriostatic, oily fluid to protect the areola and nipple during lactation • Produces the mother’s scent that attracts the baby • Shape and size vary between women

11. Stages of Lactation • Mammogenesis • Growth of the breasts • In utero, prepubertal, pubertal • Lactogenesis • Functional change of the breasts so that they can secrete milk • Occurs during pregnancy and initial postpartum period • Galactopoiesis • Maintaining the production of milk • Begins 9 days postpartum • Involution • Termination of milk production • With weaning

12. Mammogenesis • In utero • Mammary bulb is seen at 18-19 weeks gestation • Fat pad precursor develops • Rudimentary ductal system is present at birth • After birth/before puberty • Small set of branching ducts grows with child • Remains inactive

13. Mammogenesis • Puberty -Thelarche • Takes 3 to 3 ½ years • Occurs 2 ½ to 3 years prior to menarche • Initial stages • Increase in size and pigmentation of areola • Development of breast bud

14. Mammogenesis • Puberty -Thelarche • Estrogen • Breast tissue enlarges • Stimulates growth of mammary ducts into preexisting fat pad • Progesterone • Effect begins with onset of menses and ovulation • Secreted by ovary during luteal phase (second half of menstrual cycle) • Stimulates lobulo-alveolar development • Alveolar clusters grow with each luteal phase and regress with onset of menses and loss of hormones

15. Lactogenesis • Mammary gland develops capacity to secrete milk • Includes all steps needed to transform undifferentiated breast tissue in early pregnancy to fully differentiated state after pregnancy • Two stages • Beginning at the twelfth week of pregnancy • Beginning shortly after delivery

16. Lactogenesis Stage 1 • Occurs by mid pregnancy • Pregnancy hormones • Progesterone • Lactogenic hormones • Prolactin and Human placental hormone • Stimulate nipple and areolar growth • Breast changes • Double in weight • Increased blood flow • Growth in lobules and alveoli (progesterone effect) • Increased secretory activity • Mammary gland becomes competent to secrete milk • Alveoli accumulate colostrum • Colostrum is secreted immediately postpartum when the newborn feeds • Milk secretion is prevented by elevated levels of estrogen and progesterone

17. Lactogenesis Stage 2 • Occurs whether or not the newborn breastfeeds • Day 2 or 3 to day 8 after birth • Average of 40 hours postpartum • Earlier in multiparous women • Tight junction in alveolar cell closes • Onset of copious milk secretion • Drop in levels of estrogen and progesterone • Relative increase in prolactin levels • Breasts are full and warm • Switch from endocrine to autocrine control • Continued milk production depends on regular milk removal

18. Lactogenesis Stage 2 • Blood flow, oxygen, and glucose uptake increase • Progesterone • Removal of placenta with its progesterone is required for milk secretion • Progesterone receptors appear to be lost in lactating tissues so that the inhibitory effect of circulating progesterone is decreased once lactation is established • So progesterone only birth control can be used once lactation is going well • Insulin, GH, cortisol, and PTH • Maternal secretion allows for mobilization of nutrients and minerals required for lactation

19. Galactopoesis • Begins 9 days after birth and continues until weaning • Established milk secretion/production is maintained • Continued autocrine system of control • Prolactin • Required to maintain milk secretion • Oxytocin • Required to produce let-down to allow milk extraction

20. Involution • Begins at weaning • Regular milk extraction ceases • Prolactin is withdrawn • Is completed ~40 days after last breastfeeding • Milk secretion decreases due to the buildup of inhibitory peptides • Mammary gland returns nearly to pre-pregnancy state

21. Lactation • The cyclical process of milk synthesis and secretion • Occurs with the help of prolactin and oxytocin • Regulation of milk synthesis • Quite efficient • Average of ~800 ml/day but volume secreted may vary depending on infant’s requirement • Milk production • Improves with relaxation • Decreases with maternal stress and fatigue • Increased dopamine and/or norepinephrine inhibit prolactin synthesis • Stress and fatigue inhibit oxytocin release • Effect of Alcohol • Lower levels may enhance milk letdown due to decreased stress but higher doses inhibit oxytocin release thereby inhibiting letdown

22. Physiology of Lactation

23. Physiology of Lactation • Prolactin • Polypeptide hormone synthesized in the anterior pituitary • Positive regulation of secretion • Released from anterior pituitary with the peak determined by the intensity of suckling by the infant • Negative regulation of secretion • Main control is from hypothalamic inhibitory factors (dopamine acts through the D2 receptors in lactotrophs) • Stimulates mammary gland ductal growth and epithelial cell proliferation • Stimulates milk synthesis in mammary gland epithelial cells • Suppresses ovulation

24. Physiology of Lactation • Prolactin • Levels increase from 10 ng/ml in prepregnant state to ~200 ng/ml at term • Secretion occurs 7 to 20 times per day with peaks of up to 75 minutes • Peaks are superimposed on continuous background level of secretion • Levels quickly rise with suckling and peaks ~30 minutes after start of a feed • Effect on milk production is most pronounced in first few weeks after birth • Levels are not proportional to milk secretion and do not directly regulate milk synthesis or secretion • More is produced at night so nocturnal feeds are helpful in keeping up supply • Makes mother feels relaxed and sleepy

25. Physiology of Lactation

26. Physiology of Lactation • Oxytocin • Synthesized in hypothalamus and stored in the posterior pituitary • Release is stimulated by suckling • Neuroendocrine reflex has a significant psychological component • Oxytocin release may be stimulated by thought, sight, or sound of infant • Stimulates myoepithelial cells in alveoli to contract and expel milk • Forcible milk removal is called milk ejection or let-down • Variation in perception of let-down • Aids in uterine involution after delivery • Uterine contractions may be associated with “after pains” that indicate oxytocin release

27. Physiology of Lactation • Signs of Oxytocin Release • Tingling sensation in breast before or during a feed • Milk flowing when mother thinks of baby or hears crying baby • Milk flowing from other breast during feeding • Milk streaming from breast if latch is interrupted • Slow deep sucks and swallows by the baby during feed • Uterine pain during feed • Thirst during a feed

28. Physiology of Lactation • Milk production • Positive local regulation by demand • Increased suckling • Increased emptying • Increased milk secretion/production • Skin to Skin (SSC) supports successful breastfeeding • Partial milk removal sets a new, lower rate of milk production • Negative local regulation of milk production • Feedback Inhibitor of Lactation • Accumulates in milk between feeds so without removal of milk, secretion/production is inhibited • Explains why an empty breast makes milk faster than a fuller one • Distention or stretch of the alveoli • Local effect to inhibit milk secretion/production • Once milk removal stops, involution begins

29. Physiology of Lactation • Feedback Inhibitor of Lactation • Inhibitory whey protein present in breast milk • Builds up as milk accumulates in the mammary gland • Without milk removal, the inhibitor stops epithelial cells from secreting/producing more milk • Protects breast from harmful effects of overfilling • Once milk is removed, secretion restarts • Allows production of milk to be determined by infant’s needs • Especially important regulatory mechanism once lactation is established since prolactin does not control milk volume produced

30. Maternal Diet and Milk Supply Mothers make nourishing milk for their infants from all kinds of food. There are no foods that must be avoided, unless mother or baby develops an allergic reaction. Breastfeeding mothers have an increased thirst that usually maintains an adequate fluid intake; no data support the assumption that increasing fluid intake will increase milk volume. Mothers do not need to drink milk to make milk; thirst can be satisfied from a variety of nourishing beverages, including water. Calcium is available not only in milk and milk products but in many other foods, such as broccoli, spinach, kale, bok choy, collards, mustard and turnip greens, almonds, and canned fish. Poor maternal nutrition is not a contraindication to breastfeeding. Mothers following a vegan diet should take a B12 supplement

31. Galactagogues Metoclopramide — most commonly used Domperidone — not approved in USA. Similar to metoclopramide but less side effects as little crosses blood brain barrier Fenugreek and other herbal medicines — no scientific data except anecdotal reports Goat’s rue, milk thistle, anise, basil, blessed thistle, fennel seeds and marshmallow

32. Metoclopramide • Effect is to increase prolactin level • Benefit shown in small placebo controlled crossover study with increase of 50 cc per feed with dose of at least 30 mg per day • Side effects • gastrointestinal, anxiety, sedation, and rare dystonic reactions • No documented neonatal reactions • Short term: 1–3 weeks is common. • No evidence supporting long-term use. • Usually wean after 10–14 days • Common dosing regimen • 10 mg poqd first day • Then 10 mg po bid • Then 10 mg po TID

33. Fenugreek • Most commonly recommended herbal galactogogue • Usual dose is 1-4 capsules (580-610mg) tid to qid • No standard dosing • May also be taken as one cup of strained tea tid • ¼ tsp seeds steeped in 8oz water for 10 minutes • Increases supply within 24 to 72 hours • Side effects in mother • Maple like odor to sweat, milk, and urine • Diarrhea • Increased asthmatic symptoms • Lower blood sugar • Contraindicated during pregnancy due to uterine stimulant effects

34. Human Milk Composition

35. Human Milk Composition • Colostrum • Denser milk provided for the first 2-3 days after birth • Facilitates the passage of meconium to decrease enterohepatic circulation and thus encourage elimination of bilirubin • Aids in establishment of Lactobacillus bifidus flora in infant’s gut • Milk Volumes • Day 1 40-50 ml (range of 7-123ml) • Day 3 300-400 ml • Day 5 500-800 ml • Low volumes encourage frequent feeds to stimulate milk synthesis • Colostrum Energy Value • 67 kcal/100ml • Colostrum components • Higher concentrations of Na, K, and Cl than mature milk • Higher percentage of protein, minerals and fat soluble vitamins than mature milk

36. Human Milk Composition • Colostrum • Denser milk with higher concentration of proteins • White cells and antibodies (especially sIgA) • Important immune protection from exposures to environmental micro-organisms • 40-60% of cells are macrophages • Epidermal growth factor • Prepares gut lining to receive nutrients in milk • Lactose • Prevents hypoglycemia and facilitates meconium passage and therefore bilirubin excretion • Vitamin A • Protects the eyes and epithelial surfaces • Beta carotene, its precursor, provides yellowish color of colostrum

37. Human Milk Composition Immunoglobulins in Human Milk (levels decrease over time) Output - mg/24 hours Day PostpartumIgGIgMIgA 1 80 120 11,000 3 50 40 2,000 7 25 10 1,000 8 – 50 10 10 1,000

38. Human Milk Composition Note the increases in calories, lactose, and fat while the protein decreases from colostrum to mature milk.

39. Human Milk Composition • Transitional Milk • Milk produced from days 5-12 • Intermediate composition between colostrum and mature milk • Volume continues to increase • Macrophage as percentage of WBCs increases to 80-90% • Concentration is 104 to 105 per ml of milk

40. Human Milk Composition • Mature Milk • Milk produced after ~14 days • Contains all the nutrients an infant needs for the first 6 months of life and is uniquely specific for humans • Fat (3.8%), protein (0.9%), carbohydrates (7.2%), vitamins, minerals, and water (87%) • Is easily digested and efficiently used • Composition varies through lactation: over a day, within a feed, and between women • Calories • 20 calories per ounce (65-75 kcal/100ml)

41. Formula Breast Milk Milk Note the substantial structure of human milk under a microscope; this is due to the compartmentation of the various components such as the nutrients and bioactive substances. This image demonstrates that milk is a living tissue containing about 4000 cells/cubic mm including neutrophils, macrophages, and lymphocytes.

42. Human Milk Composition • Water • Human milk is 87% water • Provides sufficient fluid to maintain hydration even in hot climates

43. Human Milk CompositionFat • Fat content • 3.5-3.8g/100ml provides 50% of energy/calories in milk • Most variable component of human milk • Separates on standing • Contains cholesterol, triglycerides, short-chain fatty acids, and long-chain polyunsaturated fatty acids • Foremilk • Milk that accumulates in breast since previous feed • Lower fat content (1.5 to 2%) and looks bluish-gray • Hindmilk • Milk that is secreted during a feed • Higher fat content (2-3x more than hindmilk- 5 to 6%) and looks creamy white

44. Human Milk Composition Fat content increases from the start of a feed (~1.7%)to the end of a feed (~5.5%). Protein content decreases from the start (0.9%) of a feed to the end (0.7%). Foremilk has less fat but more protein than hindmilk.

45. Human Milk CompositionFat • Lipid Component • Milk fat globule • Forms with lipid secretion from apical mammary epithelial cell and envelopment in its plasma membrane • Also contains proteins, growth factors, and vitamins • Mucins on the globule membrane adhere to viruses and bacteria to aid in elimination from body

46. Human Milk CompositionFat • Lipid Component • Bile salt-stimulated lipase • Acts on triglycerides to produce free fatty acids and 2-monoglycerides • Prevents fatty acids from forming soaps with minerals • Results in superior absorption of fat and minerals • Not present in formula

47. Human Milk CompositionFat • Lipid Component • Abundance of essential fatty acids (linoleic and linolenic acids) • Most exist as triacylglycerols and phospholipids • 167 fatty acids have been identified in human milk • Unique long chain polyunsaturated fatty acids (including omega-3 fatty acids DHA and ARA) • Term infants are able to convert long chain polyunsaturated fatty acids to DHA and ARA so the addition of these to term formulas may be unnecessary but is likely useful for preterm infants who cannot convert them. • Cholesterol is also present in significant quantities

48. Human Milk CompositionProtein • Human milk contains 9g protein/L (whey and casein) • Less than in other animal milks • Whey proteins consist primarily of α-lactalbumin without β-lactalbumin • Cow milk whey contains β-lactalbumin to which infants can become intolerant • Contains less casein than other milks • Provides 80% of milk’s nitrogen • Protein content declines over 2-4 weeks but then is constant until weaning

49. Human Milk CompositionProtein • Colostrum • 90/10 ratio of whey/casein • Mature Milk • 70/30 ratio of whey/casein • Late Lactation • 50/50 ratio of whey/casein • Cow Milk • 18/82 ratio of whey/casein

50. Human Milk CompositionProtein • Whey (70%) • Contains water, electrolytes, and proteins • α-lactalbumin, albumin, lactoferrin, immunoglobulins, enzymes (e.g., lysozyme), growth factors, and hormones • Remains in solution after acidification • Lactoferrin, lysozyme, and sIgA resist proteolytic digestion and line the GI tract to provide host defense • Present only in human milk • Generally more easily digested and associated with more rapid gastric emptying