Recognizing and Treating Delayed or Failed Lactogenesis II

Nancy M. Hurst, RN, DSN, IBCLC


J Midwifery Womens Health. 2007;52(6):588-594. 

In This Article

Physiology of Lactogenesis

In simplistic terms, lactation is the process of milk secretion, and it occurs as long as milk is removed from the breast on a frequent basis. However, the process of lactation and the act of breastfeeding is quite complex, because a range of factors in the mother's external and internal environment determines her breastfeeding efficacy. Her internal environment includes her physical and mental health, past experiences and intentions related to breastfeeding, and body image, all of which impact her breastfeeding experience. Her external environment, such as socioeconomic factors, her general physical environment, and spousal, family, and hospital staff support also influence breastfeeding success. And most importantly, the quality and quantity of maternal-infant interaction during the early postpartum period, sometimes described as the fourth trimester, sets the stage for a successful breastfeeding experience.

There are five distinct stages of human mammary gland development: embryogenesis, puberty, pregnancy, lactation, and involution.[3] The first two stages lay the groundwork for glandular growth; full development and maturation of the mammary epithelium await the hormones of pregnancy. By mid-pregnancy, the mammary glands have developed extensively and small amounts of secretion product are formed; however, the glands continue to develop until parturition, with the secretory process being held in check by the high circulating plasma concentrations of progesterone. The change that occurs between pregnancy and lactation is called lactogenesis.

Lactogenesis is a two-stage event. Lactogenesis I occurs during pregnancy and is the initiation of the synthetic capacity of the mammary glands. Lactogenesis II commences after delivery and is the initiation of plentiful milk secretion.[4] Concurrent with the increase in milk secretion associated with lactogenesis II are significant changes in several milk constituents, termed "biomarkers of lactation," as the transition from colostrum (high concentration of total protein, immunoglobulins, sodium, and chloride; low concentrations of lactose, potassium, glucose, and citrate) to mature milk (a reversal in concentration of these factors) takes place.[5] These changes in milk composition -- coupled with a sudden feeling of breast fullness -- identify the onset of lactogenesis II, which usually occurs between 30 and 40 hours following the birth of full-term infants.[3]

Lactation is influenced by a complex hormonal milieu including reproductive hormones (estrogen, progesterone, placental lactogen, prolactin, and oxytocin) and metabolic hormones (glucocorticoids, insulin, growth, and thyroid). The reproductive hormones act directly on the mammary gland, whereas the metabolic hormones act indirectly by altering endocrine response and nutrient flux to the mammary gland.[6] Ductal growth is primarily regulated by estrogen and growth hormone, and alveolar development requires progesterone, prolactin, and possibly placental lactogen.[7] During pregnancy, the high levels of circulating progesterone inhibit the secretory process of the mammary gland. Once the placenta is expelled after birth, progesterone levels decline rapidly, and increasing prolactin levels trigger the beginning of lactogenesis II, which is the onset of copious milk secretion. Oxytocin is essential for milk removal from the mammary gland.[8] In response to infant suckling, afferent impulses from sensory stimulation of nerve terminals in the areola travel to the central nervous system triggering the release of oxytocin from the posterior pituitary. In turn, oxytocin is carried through the bloodstream to the mammary gland where it interacts with specific receptors on the myoepithelial cells located on milk-secreting cells (alveoli) and ducts, initiating contraction of the cells, which results in expulsion of milk from the gland.[9]

The main role of insulin appears to be in regulating nutrient fluctuation to the mammary gland by shunting nutrients away from traditional storage depositories, thereby making them more readily available for milk synthesis.[10] Thyroid hormones are essential for efficient milk production and, in animals, appear to be necessary for mammary responsiveness to growth hormone and prolactin during lactation.[11] One study in women with insufficient lactation found that the nasal administration of thyrotrophin-releasing factor (TRH) increased prolactin and daily milk volume.[12] In this randomized, double-blinded study, 19 women with insufficient lactation (< 50% of normal milk yield) were allocated to receive TRH or a placebo nasal spray. At the end of 10 days of treatment, milk yield increased significantly (P = .014) in the TRH group from a mean of 142 ± 33.9 g/d to 253 ± 105.3 g/d compared to no change in the placebo group. Additionally, prolactin levels increased in the TRH group from a mean of 117 ± 45.2 µg to 173 ± 55.5 µg (P < .001), whereas in the placebo group prolactin levels decreased from 137 ± 69.5 µg to 82 ± 37.7 µg.

The early influence of these reproductive and metabolic hormones sets the stage for a transition to the autocrine function of the mammary gland. Autocrine control, also known as local control, refers to a mechanism whereby the gland regulates its own function through the local production of hormones and growth factors.[13] Evidence that the rate of milk secretion within individuals (and between breasts in the same mother) is directly correlated with the frequency of milk removal strengthens the theory of local control.[13,14] The mechanisms that regulate local control are not fully understood, but may include factors such as intramammary pressure,[15] milk removal,[4] bioactive factors in the milk that interact with milk cell membranes,[13,16] or a combination of these factors.

In addition to these anatomical and physiologic processes, breastfeeding is a process that also involves psychological and emotional responses in the mother. Many areas within the maternal brain, such as the amygdala, the striatum, the vagal motor and sensory nuclei, and preganglionic sympathetic neurons of the intermediolateral column of the spinal cord[17] undergo profound morphologic and secretory changes during lactation. Although prolactin and oxytocin are primarily secreted by the pituitary gland, both hormones are also secreted in these higher brain regions and have been implicated in promoting maternal behavior.[18] Furthermore, these lactogenic hormones can be released in the brain not only by suckling, but also by close physical contact such as that experienced during breastfeeding, thereby maximizing the neurohormonal response.[9]


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