MILK LET-DOWN—The Use of Intranasal Oxytocin for Nursing Mothers

A study was carried out to determine whether intranasal spraying with a solution of oxytocin was an effective way to increase flow of milk in mothers who wished to breast-feed their babies.A hundred such women were given the drug intramuscularly for two days before they were to begin nursing. Then administration by that means was discontinued and 50 of the hundred were given oxytocin nasal spray kits for use at home. In general the patients receiving the spray kits were those who were apprehensive about sufficient lactation, those who had had previous difficulty and those who had flat, inverted or tender nipples.Results were not much different between the 50 women who used the spray and the 50 controls, but since the former group included the “difficult” cases, some benefit may be attributed to the aerosol therapy. Ninety per cent of those who used it said they would be willing to use it again.     

Zinc and copper in human milk

Studies of zinc and copper contents of breast milk were performed in 34 mothers during their lactation period until 5 days postpartum. They experienced no problems during pregnancy and delivery. All women had full term healthy infants, 22 were multiparous and 12 primiparous. The highest zinc concentration was found in the colostrum, and subsequently the concentration declined. Copper content was stable during the 5 days of lactation. Significantly lower zinc concentration and higher copper concentration were found in the serum of lactating women 3 days post partum, when compared with non-lactating women. Factors including lactation history, age of lactating women, serum levels of zinc and copper did not affect the contents of these trace minerals in breast milk.     

Breast-feeding and plasma oxytocin concentrations.

The patterns of response of oxytocin to a breast feed were studied in 10 mothers in the first week post partum. The initiation of lactation did not appear to be related to release of oxytocin. In established lactation an oxytocin response did not appear to be essential for adequate milk flow and did not occur always at the time of peak milk flow. The only factor identified that positively correlated with release of oxytocin was multiparity. In those subjects who showed a response the hormone was released in surges, some of which persisted in the circulation for less than one minute. These findings cast some doubt on the conventional view that release of oxytocin is essential for satisfactory milk flow during breast-feeding.     

Variation of the cholesterol content in breast milk during 10 days collection at early stages of lactation

More and more research is done concerning nutritional programming. Human milk nutrients which are consumed by infants can influence their health in later life. High level of cholesterol in human milk paradoxically lowers the cholesterol concentration in blood in adults. During the course of human lactation the cholesterol concentration decreases from 31 mg/100cm(3) (colostrum) to 16 mg/100 cm(3) (mature milk). According to Scopesi et al., 2002, Clin Nutr 21: 379-384, cholesterol concentration in mature milk ranged from 6.5 to 18.4 mg/100 cm(3). The aim of the study was to assess the variations in breast milk cholesterol content during 10 day collection at early lactation. 48 samples of human milk were analyzed. Mean age of women was 31 years. Women were collecting samples during 10 days of an early lactation stage (1-3 months after delivery). An Attenuated Total Reflectance Fourier Transformed Infrared (FTIR-ATR) method for easy and rapid determination of cholesterol in human milk was elaborated. Cholesterol content assessed by the FTIR method ranged from 3.36 to 12.98 mg/100 cm(3). Results indicate that milk cholesterol concentration during 10 consecutive days of early lactation is highly variable. Cholesterol content depends on an individual. Therefore it is suggested that not only the period of lactation but also mother's diet, age, season and place of residence are important factors determining cholesterol content.     

Physiological basis of longitudinal changes in human milk yield and composition

Currently in Western Australia more than 85% of women are breast-feeding after discharge from the hospital. Breast milk is the only fluid consumed by 64% of infants at 6 months of age, and 25% of infants are still breast-fed at 12 months of age. Therefore, many Western Australian mothers have optimized the art of breast-feeding and thereby provide an ideal population for studies of the physiological, pathological, and pharmacological factors affecting lactation. Reports from other countries conclude that the maximum milk yield of well-nourished women is 700-900 ml/24 h. Our studies have found the average milk yield of mothers breast-feeding single infants was in excess of 1100 ml/24 h for the first 6 months of lactation. Furthermore, mothers breast-feeding twins produced in excess of 2100 ml/24 h over this period, which demonstrates that the potential milk yield for mothers is much higher than 700-900 ml/24 h. Substantial alterations in the composition of breast milk occur at the initiation of lactation and after the cessation of suckling. During established lactation it is generally believed that there is only a slight variation in the composition of the milk. However, intensive studies have revealed acute changes in the concentrations of lactose, glucose, sodium, potassium, and chloride 5-6 days before and 6-7 days after ovulation. These findings suggest that unknown hormonal events associated with the reproductive cycle in women also influence breast milk composition.     

Release of oxytocin and prolactin in response to suckling.

The oxytocin and prolactin responses to suckling were measured in 10 women in early (n = 5) and established lactation (n = 5). Oxytocin was released in a pulsatile manner during suckling in all women, but the response was not related to milk volume, prolactin response, or parity of the mother. In all 10 women plasma oxytocin concentrations increased three to 10 minutes before suckling began. In five women this occurred in response to the baby crying, in three it coincided with the baby becoming restless in expectation of the feed, while in two it corresponded with the mother preparing for the feed. There was no prolactin response to stimuli other than stimulation of the nipple associated with suckling. These results clearly indicate that the milk ejection reflex, with release of oxytocin, occurs in most women before the tactile stimulus of suckling. A second release of oxytocin follows in response to the suckling stimulus itself. Thus it is important that care is taken to protect breast feeding mothers from stress not only during suckling but also immediately before nursing, when conditioned releases of oxytocin will occur.     

Changes in breast sensitivity at puberty,during the menstrual cycle,and at parturition.

Sensitivity to pain and touch was measured in the nipple, areola, and cutaneous breast tissue of prepubertal boys and girls, postpubertal men and nuliparous women before and after delivery. Before puberty there were no differences between the sexes, but after puberty the tactile sensitivity of all areas of the women''s breast was significantly greater than the men''s. Tactil sensitivity of all areas also varied during the menstrual cycle, with maximal sensitivity at midcycle and at menstruation; the mid-cycle peak was absent when the women were taking oral contraceptives. But the most dramatic changes occured within 24 hours of parturition, when there was a great increase in breast sensitivity. This may be the key event for activating the suckling-induced discharge of oxytocin and prolactin and inhibiting ovulation during lactation.     

Changing characteristics of the milk-ejection reflex during pregnancy, lactation and after weaning in the rat

The pattern of reflex milk ejection during suckling was investigated in anaesthetized Wistar rats at various stages of pregnancy, lactation and after weaning. Milk-ejection responses were measured using intramammary pressure recordings, and the amount of oxytocin released was estimated from log dose-response lines compiled from the mammary responses to exogenous oxytocin. The number of rats showing intramammary pressure responses to oxytocin increased on Day 22 of pregnancy (the day of parturition) and decreased at 8 days after weaning. The dose-response lines from pregnant animals were shallow, but steepened and shifted to the left during lactation and after weaning. Reflex milk-ejection responses during suckling were detectable in primigravid animals, indicating that birth of the litter and previous suckling experience are unnecessary for the immediate functioning of the reflex. Reflex milk-ejection responses improved during early lactation (such that the frequency and the amount of oxytocin released at each response were maximal at Day 10 of lactation), and subsequently declined in late lactation. Although the frequency of responses in animals 2 and 4 days after weaning was similar to that in late lactating animals, the amount of oxytocin released at each response had risen again to mid-lactation values. In animals undergoing a second pregnancy and lactation the pattern of change in the milk-ejection responses was similar to that of primiparous animals.     

Detection of Human Cytomegalovirus DNA in Breast Milk by Means of Polymerase Chain Reaction

Three hundred and twenty-five breast milk samples were examined for the occurrence of human cytomegalovirus (HCMV) by cell culture method. Virus was isolated from the milk in 1 of 177 samples collected within 6 days after delivery, 2 of 115 samples collected during the period of 7 days to 1 month after delivery, 10 of 33 samples collected over 1 month after delivery. Next, we tried to amplify HCMV DNA from the breast milk samples from HCMV seropositive mothers and seronegative mothers at 1 month after delivery by polymerase chain reaction. HCMV DNA was detected in 12 of 13 samples from seropositive mothers and in none of 7 samples from seronegative mothers. It was thought that all women seropositive for HCMV principally shed the virus into their breast milk at 1 month after delivery.     

Effects of far-infrared radiation on lactation

Massage and warm compresses to the breast have been commonly used for stimulating and/or increasing blood flow to the breasts, and for enhancing lactation consequently. However, more effective and easier remedies seem to be necessary. The vasodilating and warming effects of ceramics far-infrared radiation were studied. Based on the results obtained, the effect of a ceramic disc on lactation, attached to the breast skin, was evaluated in 27 puerperal women who had had poor lactation previously and in 36 with currently poor lactation monthly until weaning. Approximately 3/4 of these puerperal women enhanced lactation significantly one month after attachment and 1/2 of the women were able to breast-feed until weaning. Thus, we found that ceramics far-infrared radiation may be an effective remedy for enhancing lactation.     

Metergoline in the inhibition of puerperal lactation.

Seventy-eight mothers who did not want to breast-feed their newborn infants took part in a trial to assess whether metergoline could effectively suppress puerperal lactation. Metergoline 8 mg/day was given to 69 women within 24 hours after delivery and continued for five days to prevent lactation. The remaining nine women were given a course of metergoline once lactation had started. The drug was effective in both preventing and suppressing lactation. Milk secretion, engorgement, and pain were significantly reduced in women taking metergoline. Metergoline has a similar effect to bromocriptine in suppressing lactation, but its mechanism of action remains unknown.     

Single dose cabergoline versus bromocriptine in inhibition of puerperal lactation: randomised,double blind,multicentre study. European Multicentre Study Group for Cabergoline in Lactation Inhibition.

OBJECTIVE--To compare the efficacy and safety of a single dose of 1 mg of cabergoline with that of bromocriptine 2.5 mg twice daily for 14 days in the inhibition of puerperal lactation. DESIGN--Prospective, randomised, double blind, parallel group, multicentre study. SETTING--University of hospital departments of obstetrics and gynaecology in different European countries. SUBJECTS--272 puerperal women not wishing to lactate (136 randomised to each drug). INTERVENTIONS--Women randomised to cabergoline received two 0.5 mg tablets of cabergoline and one placebo tablet within 27 hours after delivery and then placebo twice daily for 14 days. Those randomised to bromocriptine received 2.5 mg of bromocriptine and two placebo tablets within 27 hours and then 2.5 mg of bromocriptine twice daily for 14 days. MAIN OUTCOME MEASURES--Success of treatment (complete or partial) according to milk secretion, breast engorgement, and breast pain; rebound symptomatology; serum prolactin concentrations; and number of adverse events. RESULTS--Complete success was achieved in 106 of 136 women randomised to cabergoline and in 94 of 136 randomised to bromocriptine and partial success in 21 and 33 women respectively. Rebound breast symptomatology occurred respectively in five and 23 women with complete success up to day 15 (p less than 0.0001). Serum prolactin concentrations dropped considerably with both drugs from day 2 to day 15; a prolactin secretion rebound effect was observed in women treated with bromocriptine. cabergoline and 36 receiving bromocriptine (p = 0.054), occurring most during the first treatment day. CONCLUSION--A single 1 mg dose of cabergoline is at least as effective as bromocriptine 2.5 mg twice daily for 14 days in preventing puerperal lactation. Because of the considerably lower rate of rebound breast activity and adverse events and the simpler administration schedule cabergoline should be the drug of choice for lactation inhibition.     

Breast milk donation after neonatal death in Australia: a report

Lactation and breast milk can hold great value and meaning for grieving mothers who have experienced a recent death of an infant. Donation to a human milk bank (HMB) as an alternative to discarding breast milk is one means of respecting the value of breast milk. There is little research, national policy discussion, or organizational representation in Australia on the subject of breast milk donation after infant death. On 29 November 2013 the Mercy Hospital for Women in Melbourne, Australia hosted Australia’s first National Stakeholder Meeting (NSM) on the topic of milk donation after neonatal death. The NSM drew together representatives from Australian HMBs, neonatal intensive care units (NICUs) currently using donor human milk, and Australia’s chief NICU parent support organization. The NSM was video-recorded and transcribed, and analyzed thematically by researchers. This article reports the seven dominant themes discussed by stakeholders during the NSM: the spectrum of women’s lactation and donation experiences after infant death; the roles of the HMB and NICU in meeting the needs of the bereaved donor; how bereaved mothers’ lactation autonomy may interface with a HMB’s donation guidelines; how milk donation may be discussed with bereaved mothers; the variation between four categories of milk donation after neonatal death; the impact of limited resources and few HMBs on providing donation programs for bereaved mothers in Australia. This article provides evidence from researchers and practitioners that can assist HMB staff in refining their bank’s policy on milk donation after infant death, and provides national policy makers with key considerations to support lactation, human milk banking, and bereavement services nation-wide.     

Plasma oxytocin during third stage of labour: comparison of natural and active management.

The incidences of postpartum haemorrhage and retained placenta have decreased with the use of synthetic oxytocin and controlled cord traction. Whether such treatment is valuable is open to question because of the lack of clinical and physiological studies. The physiological effects of synthetic oxytocin on plasma concentrations of oxytocin and events during delivery were assessed. Plasma oxytocin concentration was determined in serial samples during the late second stage and throughout the third stage of labour in 25 women. Ten women received combined ergotamine and synthetic oxytocin intramuscularly and 15 were not treated. The geometric mean plasma oxytocin concentration significantly increased in the women given oxytocin when measured before and after delivery of the fetal anterior shoulder (3.1 (SD 2.0) pmol/l before and 15.9 (2.7) pmol/l after). Six of the women who did not receive treatment showed a significant increase in geometric mean plasma oxytocin concentration before and after delivery of the fetal shoulder (3.2 (2.0) pmol/l before and 6.4 (2.0) pmol/l after) and nine did not show an increase (geometric mean 2.4 (3.1) pmol/l before and 2.2 (2.2) pmol/l after). Of these nine women, two had an abnormal third stage of delivery; one woman had a postpartum haemorrhage and one required manual removal of the placenta. As it is impossible to predict which women will show a rise in the plasma concentration of endogenous oxytocin, intramuscular oxytocin should be given routinely.     

Oxytocin facilitates behavioural, metabolic and physiological adaptations during lactation

The aim of this article is to propose that oxytocin not only stimulates milk let down, but also adapts behaviour and physiology to facilitate lactation in mammals including dairy cattle. Circulating oxytocin as well as neurogenic oxytocin participates in these regulatory processes. In short, oxytocin stimulates maternal interaction and attachment between mother and young. It also participates in the metabolic prerequisites for milk production by e.g. stimulating glucagon release and thereby, mobilisation of glucose. Digestive and anabolic aspects of metabolism are also stimulated, e.g. by increased vagal nerve activity. Adaptations consistent with an antistress like pattern are also induced. Cortisol levels are decreased as well as blood pressure, and behaviours characterised by calm, reduced levels of anxiety and more social activity are promoted. These effects seem to be present in monogastric animals as well as in ruminants. The expression of various aspects of these adaptations vary according to the special needs and living environmental circumstances of different species. The mechanisms behind the effect spectrum of oxytocin are being explored in other experimental models. A second aim of this paper is to suggest that efficiency of lactation can be promoted by facilitating oxytocin release in connection with milking by enhancing the amount of sensory stimulation.     

Choline status in newborns, infants, children, breast-feeding women, breast-fed infants and human breast milk

This study assessed the choline status in newborns, infants, children, breast-feeding women, breast milk, infant formula, breast-fed and formula-fed infants. The serum free choline level was 35.1+/-1.1 micromol/L at birth and decreased to 24.2+/-1.6, 18.1+/-0.8, 16.3+/-0.9, 14.3+/-0.8, 12.9+/-0.6 or 10.9+/-0.6 micromol/L at 22-28, 151-180, 331-365, 571-730, 731-1095 or 4016-4380 days after birth, respectively. The serum phospholipid-bound choline level was 1997+/-75 micromol/L at birth and increased gradually to 2315+/-190 or 2572 +/-100 micromol/L at 571-730 or 4016-4380 days after birth, respectively. In breast-feeding women, serum free and phospholipid-bound choline levels were doubled at 12-28 days after birth, they decreased toward the control values with time. Free choline, phosphocholine and glycerophosphocholine were major choline compounds in breast milk. Their concentrations in mature milk were much greater than in colostrum and serum. Choline contents of breast milk varied greatly between mothers, and milk free choline levels were correlated with serum free choline (r=.541; P<.001), phospholipid-bound choline (r=.527; P<.001) and glycerophosphocholine (r=.299; P<.01) concentrations and lactating days (r=.520; P<.001). In breast-fed infants, serum free choline concentrations were correlated with free choline (r=.47; P<.001), phosphocholine (r=.345; P<.002), glycerophosphocholine (r=.311; P<.01) and total choline (r=.306; P<.01) contents of breast milk. Serum free choline concentration in formula-fed infants was lower than breast-fed infants. These data show that (a) circulating choline status is elevated during infancy and lactation, (b) choline contents of breast milk vary between mothers and milk free choline contents are influenced by maternal circulating choline status, and (c) the choline contents of breast milk can influence infants' circulating choline status.     

Longitudinal study of the dietary selenium intake of exclusively breast-fed infants during early lactation in Korea and Japan.

213 samples of human breast milk were collected from 51 healthy Korean women. Selenium content of the samples was determined by atomic absorption spectrometry with hydride generation. The selenium content of Korean milk decreased with increase of days after birth: The arithmetic mean of selenium content was higher in colostrum (< 4 days) 34 micrograms/kg (SD +/- 11, n = 44) than in transitional milk 21 micrograms/kg (SD +/- 8, n = 78) or in mature milk (> 10 days) 13 micrograms/kg (SD +/- 6, n = 91). The daily dietary selenium intake of 0-1 month aged Korean infants fed on breast milk is estimated to be around 10 micrograms per day (3 micrograms/kg body weight) regardless of days postpartum, resulting from the calculation of our selenium data and daily milk intake during early lactation. The same result on selenium intake for Japanese newborns, as well as Korean infants, is also estimated to be around 10 micrograms per day (3 micrograms/kg body weight) regardless of days postpartum.     

Comparison of the fatty acid profile of Spanish infant formulas and Galician women breast milk

The importance of dietary lipids during childhood is evident, as they are necessary for correct growth and development of the newborn. When breastfeeding is not possible, infant formulas are designed to mimic human milk as much as possible to fulfill infant’s requirements. However, the composition of these dairy products is relatively constant, while human milk is not a uniform bio-fluid and changes according to the requirements of the baby. In this study, breast milk samples were donated by 24 Spanish mothers in different lactation stages and different infant formulas were purchased in supermarkets and pharmacies. Gas chromatography coupled to flame ionization detection was used for the fatty acid determination. Compared to breast milk, first-stage formulas are apparently very similar in composition; however, no major differences were observed in the fatty acid profiles between formulas of different lactation stages. The Galician women breast milk has a fatty acid profile rich in oleic acid, linoleic acid, arachidonic acid, and docosahexaenoic acid. When comparing human milk with formulas, it becomes evident that the manufacturers tend to enrich the formulas with essential fatty acids (especially with α-linolenic acid), but arachidonic and docosahexaenoic acid levels are lower than in breast milk. Additionally, the obtained results demonstrated that after 1 year of lactation, human milk is still a good source of energy, essential fatty acids, and long-chain polyunsaturated fatty acids for the baby.     

Changes in element concentration and distribution in breast-milk fractions of a healthy lactating mother

Daily changes in components of breast milk with number of days of lactation after delivery were demonstrated by determining concentrations and distributions of several elements simultaneously. Concentrations of calcium, copper, magnesium, phosphorus, sulfur, and zinc were determined simultaneously by inductively coupled argon plasma-atomic-emission spectrometry (ICP) for whole milk and milk fractions (skimmed milk and whey) collected from 2 to 196 d postpartum from a healthy lactating mother. Calcium and phosphorus concentrations increased in transitional milk. With days postpartum, the other elements decreased from the highest concentrations in colostrum milk, the modes of decrease being characteristic for each element. Distributions of copper, iron, phosphorus, sulfur, and zinc in whey were determined on a gel-filtration column by HPLC with ICP detection (HPLC-ICP method). Distributions of the five elements and absorbance peaks at 254 and 280 nm changed dramatically day by day at the beginning (colostrum milk), resulting in constant distributions after 30 d (mature milk). These results suggest the important roles of daily changing constituents in breast milk, especially in colostrum milk, in the nutrition of the newborn. Several element peaks on a gelfiltration column were identified by comparison with standard samples.     

Myoepithelial cell contraction and milk ejection are impaired in mammary glands of mice lacking smooth muscle alpha-actin

Mammary myoepithelial cells are specialized smooth musclelike epithelial cells that express the smooth muscle actin isoform: smooth muscle alpha-actin (ACTA2). These cells contract in response to oxytocin to generate the contractile force required for milk ejection during lactation. It is believed that ACTA2 contributes to myoepithelial contractile force generation; however, this hypothesis has not been directly tested. To evaluate the contribution of ACTA2 to mammary myoepithelial cell contraction, Acta2 null mice were utilized and milk ejection and myoepithelial cell contractile force generation were evaluated. Pups suckling on Acta2 null dams had a significant reduction in weight gain starting immediately postbirth. Cross-fostering demonstrated the lactation defect is with the Acta2 null dams. Carmine alum whole mounts and conventional histology revealed no underlying structural defects in Acta2 null mammary glands that could account for the lactation defect. In addition, myoepithelial cell formation and organization appeared normal in Acta2 null lactating mammary glands as evaluated using an Acta2 promoter-GFP transgene or phalloidin staining to visualize myoepithelial cells. However, mammary myoepithelial cell contraction in response to oxytocin was significantly reduced in isolated Acta2 null lactating mammary glands and in in vivo studies using Acta2 null lactating dams. These results demonstrate that lack of ACTA2 expression impairs mammary myoepithelial cell contraction and milk ejection and suggests that ACTA2 expression in mammary myoepithelial cells has the functional consequence of enhancing contractile force generation required for milk ejection.