Lactation and Breastfeeding

Stages of Lactogenesis

Full alveolar development and maturation of the breast must await the hormones of pregnancy—progesterone, estrogen, prolactin, human growth hormone, thyroxine, and hPL—for completion of the developmental process at delivery. This is termed secretory differentiation , or lactogenesis stage I. By mid-pregnancy, the gland is competent to secrete milk (colostrum), although full function is not attained until the tissues are released from the inhibition of high levels of circulating progesterone. In very preterm births, most breasts have the capacity to produce enough milk to support the growth and development of these tiny babies.

The hypertrophy of the alveolar cells, lactiferous ducts, and support tissues results in a dramatic increase in the size of breasts through pregnancy and lactation , with the average size of each breast growing threefold (1 to 2 cup sizes in bra fitting) from prepregnancy to full lactation.

Currently, there is no imaging technique that has proved more accurate in determining “adequate” glandular tissue than a physical examination. Once standardized methodology and validation studies are performed, i.e., ultrasound using 3-D, volume measurements, or mammography may allow more precise measurement of glandular volume.

Primary lactation failure is defined as a neonatal who fails to gain weight without supplementation, despite documented expert support, a normal latch, adequate stimulation (>10 to 12 nursing episodes in 24 hours), and the failure to demonstrate milk ejection. Primary lactation failure is very rare (<0.01%) and may be associated with low third trimester and 2-week postpartum maternal serum prolactin levels (<15 ng/mL). More common is glandular insufficiency, perhaps with an incidence of 1% to 16% depending on the definition of poor weight gain. Glandular insufficiency is defined as a neonate who fails to gain appropriate weight in spite of documented expert support, a normal latch, adequate stimulation (>10 to 12 nursing episodes a day), and demonstrated milk ejection, In a prospective cohort study, Neifert et al. found that 23% of women with minimal breast size increase during pregnancy had an insufficient milk supply, defined as infant growth of less than 28.5 g/day, compared with 16% of women with greater than 1 bra cup size of growth during pregnancy. Any concerns about breast size, shape, or growth during pregnancy should be shared with the infant's provider to assure early follow-up.

Secretory activation, or lactogenesis stage II, occurs as progesterone levels fall during the subsequent 7 days after delivery of the placenta. During the first 2 to 4 days after delivery, incremental secretion of colostrum occurs (50 to 400 mL/day). Until lactogenesis stage II has fully developed, the breasts secrete colostrum, which differs from mature milk in volume and constituents. Colostrum has more protein, especially secretory immunoglobulins, and more lactose; it also has a lower fat content than mature milk. Prolactin and glucocorticoids play important promoter roles in this stage of development.

At 2 to 6 days postpartum, a dramatic increase occurs in mammary blood flow and oxygen/glucose uptake by the breast. The secretion of milk is copious, with 500 to 900 mL/day when “the milk comes in.” This is the most common time for engorgement if the breasts are not drained by efficient, frequent nursing.

After lactogenesis stage II, which occurs from 2 to 6 days postpartum, lactation enters an indefinite period of milk production formerly called galactopoiesis but now termed lactogenesis stage III . The duration of this stage is dependent on the continued production of breast milk and the efficient removal of milk via transfer to the infant or, if mother and infant are separated, by hand expression or use of a breast pump. Prolactin appears to be the single most important galactopoietic hormone because selective inhibition of prolactin secretion by bromocriptine disrupts lactogenesis; oxytocin appears to be the major galactokinetic hormone. Stimulation of the nipple and areola and infant behavioral cues cause a reflex contraction of the myoepithelial cells that surround the alveoli and trigger ejection of milk from the breast.

The final stage of lactation, lactogenesis stage IV, is cessation of breastfeeding and involution of glandular tissue. As the frequency of breastfeeding is reduced to less than six episodes in 24 hours, and the produced milk volume is less than 400 mL in 24 hours, prolactin levels fall in proportion to the frequency of nipple stimulation, ultimately leading to a total cessation of milk production. After 24 to 48 hours of no transfer of breast milk to the infant, increasing intraductal pressure and production of inhibitory proteins from the alveolar epithelium appear to initiate apoptosis of the secretory epithelial cells and proteolytic degradation of the basement membrane . Recent work in fur seals suggests that α-lactalbumin (LALBA) may be the inhibitory protein that causes involution during milk stasis. It is thought that this increase in concentration of inhibitory proteins in the absence of milk drainage decreases milk production by the alveolar cells. This negative feedback system allows for the day-to-day adjustment in infant demands.

Endocrinology of Lactogenesis

Prolactin is the major hormone that promotes milk production, and thyroid hormones selectively enhance the secretion of lactalbumin. Cortisol, insulin, parathyroid hormone, and growth hormone are supportive metabolic hormones in the production of carbohydrates and lipids in breast milk. Ovarian hormones, i.e., estrogen and progesterone, are not required for the maintenance of established milk production, and the hypothalamic-pituitary-ovarian axis is suppressed by high levels of prolactin.

The alveolar cell is the principal site to produce milk. Neville describes five pathways for milk synthesis and secretion in the mammary alveolus, including four major transcellular and one paracellular pathway: (1) exocytosis (merocrine secretion) of milk protein and lactose in Golgi-derived secretory vesicles; (2) milk fat secretion via milk fat globules (apocrine secretion); (3) secretion of ions and water across the apical membrane; (4) pinocytosis-exocytosis of immunoglobulins; and (5) a paracellular pathway for plasma components and leukocytes. During lactation, very few of the constituents of breast milk are transferred directly from maternal blood. The junctions between cells, also known as tight junctions, are closed. As weaning occurs, the tight junctions are released and sodium and other minerals easily cross to the milk, which changes the taste of the milk. The change in taste during involution may affect the interest of the infant in continuing to breastfeed.

Most milk components are produced de novo by the breast rather than by direct absorption from the maternal gut or maternal organs such as the liver, kidneys, and so on. The substrates for milk production are primarily absorbed from the maternal gut or are produced in elemental form by the maternal liver. Glucose is the major substrate for milk production, serves as the main source of energy for other reactions, and is a critical source of carbon. The synthesis of fat from carbohydrates plays a predominant role in fat production in human milk, whereas proteins are built from free amino acids derived from plasma.

While there is controversy, a sizable proportion of breast milk is produced during the nursing phase, perhaps the fluid component. To supply the substrates for milk production, blood flow increases to the mammary glands (20% to 40%), gastrointestinal (GI) tract, and liver. Cardiac output is increased by 10% to 20% during a nursing episode. The vasodilation of the regional vascular beds is under the control of the autonomic nervous system via the 4th lateral and cutaneous nerves, and oxytocin may play a critical role in directing the regional distribution of maternal cardiac output through an autonomic, parasympathetic action. Given that milk is produced during the nursing episode, variation in content during a feed is expected. During a feeding episode, the lipid content of milk rises by more than twofold to threefold (1% to 5%), with a corresponding 5% fall in lactose concentration. The protein content remains relatively constant. At the extreme, there can be a 30% to 40% difference in the volume obtained from each breast. Likewise, intra-individual variations have been observed in lipid and lactose concentrations.

The volume and concentration of constituents also vary during the day. The volume and fat per feed increases by 10% to 15% at night and in the morning ; nitrogen content peaks in the late afternoon and falls to a nadir at 5:00 am ; fat concentrations peak in the early morning and reach a nadir at 9:00 pm ; and lactose levels stay relatively stable throughout the day. The variation in milk volume and content in working women who nurse only when at home has not been studied. The variation in volume and content is preserved if the woman pumps breast milk adequately (every 2 to 3 hours) during the day.

Does diet affect the volume and constitution of breast milk? For the average American woman with the range of diets from teenagers to mature, health-conscious adults, the answer is no . There is no convincing evidence suggesting that the macronutrients in breast milk—protein, fats, and carbohydrates—vary across the usual range of American diets, although volume may vary in the extremes. In developing countries where starvation is widespread and daily calorie intake is less than 1600 kcal/day during prepregnancy and pregnancy, the mother's milk volume and its caloric density are only minimally decreased (5% to 10%) in underweight breastfeeding women. In a controlled experiment, well-nourished European women reduced their calorie intake by 33% for 1 week. Milk volume was not reduced when the diet was maintained at more than 1500 kcal/day; but if the daily energy intake was less than 1500 kcal, milk volume was reduced by 15%. Moderate dieting and weight loss postpartum (4.5 lb/month) are not associated with changes in milk volume, nor does aerobic exercise have any adverse effect.

In the first year of life, infants undergo tremendous growth, doubling their birthweight in 180 days. Infants exclusively fed artificial breast milk (formula) lose up to 5% of their birthweight during the first week of life, and those exclusively fed breast milk lose approximately 7% of their birthweight. The timing and extent of the weight loss varies with the mode of delivery, as demonstrated by nomograms derived from more than 100,000 exclusively breastfed infants; thus, infant weight loss should be interpreted within a broader clinical context. Clinicians can determine percentile for infant weight loss using the Newborn Weight Tool (NEWT; www.newbornweight.org ). Weight loss of more than 10%, or greater than the 75th percentile for gestational age and mode of delivery using the NEWT nomograms should prompt careful evaluation of the mother-infant dyad by a trained health care provider. Although supplementation with donor breast milk or artificial breast milk may be necessary, the key focus of intervention is establishing good breast milk transfer by ensuring adequate production, correct nursing behavior, correct latch-on, and adequate frequency. Once lactogenesis stage III occurs, “the milk has come in” and recent evidence suggests that the term infant will gain a median of 40 g/day. By 14 days, the breast-fed infant should have returned to its birthweight.

Food intake and energy needs are not constant. The infant's need for energy and fluids can vary daily or weekly because of growth spurts, greater activity, immunologic challenges such as when fighting an illness, or with greater fluid losses during hot weather . Mammals have developed an extremely efficient mechanism to adjust milk supply within 24 to 48 hours, depending on demand, via oxytocin and the let-down reflex ( Fig. 25.3 ) and prolactin production. The prolactin and oxytocin travel to their target cells: prolactin goes to the alveolar epithelium in the breast and oxytocin goes to the myoepithelial cells that surround the alveolar epithelium. In lactating women, baseline prolactin levels are 200 ng/mL at delivery, 75 ng/mL between 10 and 90 days postpartum, 50 ng/mL between 90 and 180 days postpartum, and 35 ng/mL after 180 days postpartum. Maternal serum prolactin levels rise by 80% to 150% of baseline levels within seconds of nipple stimulation. As long as nursing frequency is maintained at more than 8 episodes a day for 10 to 20 minutes per episode, the serum prolactin levels will suppress the luteinizing hormone (LH) surges and ovarian function . Serum oxytocin levels also rise with nipple stimulation; however, the oxytocin response is much more affected by operant conditioning, and its response may precede the rise in prolactin levels. The maternal cerebrum is influenced by exposure to nursing cues and to the influences of nipple stimulation. Cerebral influences have a lesser effect on the release of prolactin. Positive sights, sounds, or smells related to nursing often stimulate the production of oxytocin, which, in turn, causes the myoepithelial cells to contract and allows milk to leak from the breasts. This observation is a good clinical clue to indicate an uninhibited let-down reflex.

In a classic series of experiments in 1948, Newton and Newton demonstrated the power of noxious influences to inhibit the release of oxytocin and reduce milk transfer to the infant. The baseline milk production per feed was measured in controlled situations at approximately 160 g per feed. During a consecutive feed, a noxious event (i.e., saline injection) was administered and the amount of milk produced was cut in half, to 80 to 100 g per feed. Subsequently, the milk production was measured in a trial in which a noxious event was administered and bucchal or intranasal oxytocin was given concomitantly. The milk production was restored to almost 90% of baseline production, at 130 to 140 g. A wide variety of noxious events elicited the same decrease in milk production. More recently, less noxious events, i.e., math calculations or loud noise, reduced hypothalmamic oxytocin pulsitility. Pain, anxiety, and insecurity may disrupt breastfeeding through inhibition of the let-down reflex. In contrast, the playing of a soothing motivational/educational audio tape to women who were pumping milk for their premature infants has improved milk yields.

The positive and negative influences of the cerebrum are further highlighted by the observation of maternal and family attitudes. Seventy-five percent of women who had a positive attitude during pregnancy were likely to be successful at breastfeeding, whereas 75% of women who had a negative attitude during pregnancy had an unsuccessful breastfeeding experience. In a similar study 53 years later, when the mother's attitude was good or very good and the family was present and supportive, the exclusive breastfeeding rate was 20% at 6 months, whereas if the mother's attitude was fair, the breastfeeding rate was 5% at 6 months. The important takeaway for the obstetrician is to engage the mother's family and friends to support the breastfeeding dyad.

Oxytocin has additional target cells in the mother (see Fig. 25.3 ), and the effect of oxytocin on uterine activity is well known. Uterine involution is enhanced with breastfeeding. Animal and human research suggests that oxytocin is a neurohormone associated with an anti–fight/flight response in the autonomic nervous system, better toleration of stress by the mother, and improved maternal-infant bonding. The causal direction of this association is unclear. Lower oxytocin levels have been observed during feeding among women with anxiety and depression symptoms. Moreover, researchers have found that genetic polymorphisms in the oxytocin gene modify association between adverse childhood experiences and both postpartum depression and breastfeeding duration. In clinical practice, breastfeeding difficulties and postpartum depression symptoms often present together, and clinicians should be prepared to assess and manage these issues simultaneously.

In addition, surges in oxytocin levels are associated with the release of GI hormones and increased GI motility. In the mother, these actions enhance the absorption of substrates necessary for lactogenesis, and a growing body of knowledge indicates similar associations with oxytocin surges in infants. Skin-to-skin (STS) contact and the oral stimulation of nursing stimulate a parasympathetic, anti-fight/flight response in the infant. So-called kangaroo care of premature newborns, with STS contact, is associated with a physiologically stable state, improved stress responses, and improved weight gain. Oxytocin appears to mediate this response. Breastfeeding is associated with far more STS contact than bottle feeding.

Imprinting immediately after birth is an important predictor of breastfeeding success. Several trials with random assignment of subjects to early nursing (delivery room) or late nursing (2 hours after birth) demonstrated a 50% to 100% higher number of breastfeeding mothers at 2 to 4 months postpartum among those who had nursed in the delivery room. One of the keys to obstetric management is to have the mother give STS contact and nurse her newborn in the delivery room within 30 to 60 minutes of birth.

Recent research suggests that early STS contact in the delivery room is at least as important as early breastfeeding. The 2016 Cochrane Review of the effects of early STS found that STS care improves initiation, exclusiveness, effective latch-on, and duration of breastfeeding. Early STS contact has a powerful vagal, anti-stress response in the mother and neonate that appears to persist. Regardless of feeding method, mothers and infants benefit from frequent, sustained STS contact.

Milk Transfer

Milk transfer to the infant is a key physiologic principle in lactation. The initial step of milk transfer is a good latch-on. With light tactile stimulation of the infant's cheek and lateral angle of the mouth, the infant reflexively turns its head and opens its mouth, as in a yawn ( Fig. 25.4 ). The nipple is tilted slightly downward using a “C-hold” or palmar grasp. In this hand position, the fingers support the breast from underneath and the thumb lightly grasps the upper surface 1 to 2 cm above the areola-breast line. The infant is brought firmly to the breast by the supporting arm, being careful not to push the back of the baby's head ( Fig. 25.5 ). The nipple and areola are drawn into the mouth as far as the areola-breast line. The posterior areola may be less visible than the anterior areola, and the lower lip of the infant is often curled out. The infant's lower gum lightly fixes over the NAC at the circumareolar line.

Recent studies have used ultrasound imaging of breastfeeding mothers to determine how infants remove milk from the lactating breast. Current work suggests that during initial latch, the infant elongates the nipple and areola to form a teat, with the tip of the nipple approaching the junction of the hard and soft palate. Closure of the lower jaw compresses the nipple, expressing milk, and then the opening of the lower jaw enlarges the oral cavity, creating negative pressure that withdraws milk from the breast. This process is dependent on the infant being able to create suction by closing nasal passages and tightening lips around the breast. While the anterior tongue remains relatively rigid during breastfeeding, the posterior tongue peristalses, initiating the swallowing reflex.

Coordinated suction and expression are necessary to remove milk from the breast. In addition, the infant must coordinate swallowing and breathing . In healthy breastfeeding infants, evidence suggests that swallowing occurs at the peak of intraoral sucking pressure; infants time their swallows between breaths to avoid aspirating milk. This coordination appears to be easier during breastfeeding than bottle-feeding: breastfeeding infants have more coordinated swallowing patterns and higher oxygen levels during feeding than bottle-fed infants.

The movement of the infant's tongue is most frequent in the first 3 minutes of a nursing episode; the mean latency from latch-on to milk ejection is 2.2 minutes. After milk flow is established, the frequency of sucking falls to a much slower rate. The change in cadence is recognizable as suck-suck-swallow-breath. Audible swallowing of milk is a good sign of milk transfer. At the start of a feeding, the infant obtains 0.10 to 0.20 mL per suck and as infants learn how to suck, they become more efficient at obtaining more milk in a shorter duration. In the first 5 minutes the infant nurses on each breast, 80% to 90% of the milk is obtained, but the fat-rich and calorie-dense hind milk is obtained during the remainder of the time sucking at each breast, usually less than 20 minutes total. A bottle-fed infant sucks steadily in a linear fashion and receives approximately 80% of the artificial breast milk substitute in the first 10 minutes.

Milk transfer is made more efficient by proper positioning of the infant to the breast , which places the infant and mother chest-to-chest (see Fig. 25.5 ). The infant's ear, shoulder, and hip are in line. The most common maternal positions are the cradle hold (see Fig. 25.5 ), side-lying ( Fig. 25.6 ), or the football hold ( Fig. 25.7 ). Each has its advantages. Rotating positions for nursing allows improved drainage of different lobules, which is important in the management of a “plugged” duct or mastitis. Maternal comfort and convenience are the major reasons for changing nursing positions; the football hold and side-lying positions are more comfortable when the mother has an abdominal incision.

Recently, the traditional positions of breastfeeding have been challenged by videophotography. Research by Colson et al. using videography and standardized observer judgement scoring demonstrated that of 40 healthy term neonates and mothers in the first month postpartum displayed a repertoire of 14 innate/primitive nursing reflexes to facilitate efficient and effective nursing. They identified the final “best” position for nursing. The neonate who is laid on the maternal abdomen will localize the mother's breast and crawl to the breast to latch. The mother appears to instinctually assume an efficient and effective nursing position and hand support to allow the neonate to display the 14 primitive nursing reflexes. The best position appeared to be a semireclined one where the neonate is abdomen to abdomen and latch-on is supported by gravity rather than by maternal hand pressure. The instinctual dance between the neonate and mother is termed biological nursing. These findings need validation and confirmation of improved milk transfer prior to major changes in the education of “proper” breastfeeding behaviors.

The neonate should be fed at least 8 to 12 times a day in response to the infant's cues ( Box 25.1 ). One of the important educational keys is for the mother to recognize the signs of a hungry baby before the baby is crying, angry, or stressed.

Baseline prolactin levels appear to be the major determinant of the maternal hormonal state during lactation, a state of high prolactin and low estrogen and progesterone levels. As the frequency of nursing decreases below eight times in 24 hours, the baseline prolactin levels drop below a level at which ovulation is suppressed (35 to 50 ng/mL), LH levels rise, and menstrual cycling is initiated. The intensity (adjusted odds ratio [OR]) of factors that initiate the onset of menses are the duration of sucking episodes less than 7 minutes (OR, 2.4), night feedings less than 4 per 24 hours (OR, 2.3), maternal age 15 to 24 years (OR, 2.1), maternal age 25 to 34 years (OR, 1.7), and day feedings less than 7 per 24 hours (OR, 1.6). In women who feed their infants exclusively artificial breast milk, serum prolactin levels drop to pre-pregnant levels (8 to 14 ng/mL) within days. In summary, the total number of nursing episodes per day (more than 8 per 24 hours) and night nursing are critical to the successful management of breastfeeding.

One of the major determinants of nursing frequency is the introduction of substitute nutriment sources for the infant, artificial breast milk, or solids. Breast milk has the nutritional content to satisfy the growth needs of the infant for at least 6 months postpartum, except for those with glandular insufficiency (infant's failure to gain adequate weight despite professional support and “correct” techniques). In the first 6 months, feeding with artificial breast milk (i.e., formula) affects the physiology of successful lactation in at least two ways: (1) it reduces proportionally the nutriment requirements from breast milk and (2) it increases the gastric emptying time (digestion is slower than with breast milk), with a subsequent decrease in frequency of nursing episodes. If the mother is expressing breast milk, that is, pumping, many episodes of milk expression do not have the same hormonal responses as actual nursing. If the mother identifies a let-down, this is good practical evidence of adequate stimulation.

Like feeding formula, starting the infant on solid foods has a similar impact on the hormonal milieu of the lactating woman. One of the errors in Western child care is the early (<4 months), forced introduction of solids. In most cases, the infant's gut is filled with slowly digesting food with less nutritional value than breast milk and the long-term result of this may be childhood and adolescent obesity. Recent articles underline the uncertainties of associating childhood obesity on early introduction of solid foods . The most logical time to start solid food substitution is when the infant has reached the neurologic maturity to grasp and bring food to its mouth from its mother's plate, which usually occurs at about 6 months. As the infant matures, his or her ability to feed improves and the proportion of the diet supplied by solid food gradually increases.

The failure to develop good milk transfer is the major cause of lactation failure and breast pain, especially in the neonatal period. Inhibition of the let-down reflex and failure to empty the breasts completely lead to ductal distension and parenchymal swelling from extravascular fluid. This is termed engorgement , and it compromises the mechanics of nursing ( Fig. 25.8 ); alveolar distension reduces secretion of milk by the alveolar cells. Without adequate transfer of milk to the infant, disrupted lactation is more likely to occur. Distension of the alveoli by retained milk causes a rapid (6 to 12 hours) decrease in milk secretion and enzyme activity by the alveolar epithelium. The decreased production of milk is explained by pressure inhibition and by an inhibitor secreted in breast milk.

Transfer of Medications and Drugs to the Breastfeeding Child

One of the most common questions obstetricians receive from other healthcare providers, the lactating mother, her family, or pharmacist is, “Will this new medication hurt the baby?” Table 25.3 lists many resources to help answer this common question, especially www.toxnet.nlm.nih.gov/newtoxnet/lactmed.htm and InfantRisk.com . The strongest determinant of the concentration of a medication in breast milk is the maternal plasma (nonprotein bound) concentration of the drug. The actual milk concentration is determined by how the drug characteristics interact with alveolar cells and the chemical characteristics of breast milk stored in the alveolar sacs and lactifereous ducts. As soon as the free drug concentrations in the maternal plasma drop, equilibrium forces rapidly drive the unbound drug in breast milk back into maternal plasma (see Chapter 7 ).

Most medications taken by the mother appear in the milk, but the calculated doses consumed by the nursing infant range from 0.001% to 5% of the standard therapeutic doses for infants and are tolerated by infants without toxicity (see C hapter 8 ). Table 25.3 provides additional guidelines for the use of maternal drugs in breastfeeding women.