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ABSTRACT Breastmilk has been recently identified as a rich source of miRNA with potential regulatory functions in the infant. We compared the miRNA content of breastmilk with that of circulating blood in lactating women, with the aim to... more
ABSTRACT Breastmilk has been recently identified as a rich source of miRNA with potential regulatory functions in the infant. We compared the miRNA content of breastmilk with that of circulating blood in lactating women, with the aim to shed light into the potential functions of these milk molecules and their origin. Breastmilk and blood samples were collected from 10 mothers in month 2 of lactation. miRNA was analyzed from the cellular and lipid fraction of breastmilk as well as maternal peripheral blood mononucleated cells (PBMCs) and plasma using the TaqMan OpenArray system for 770 different human miRNAs. The total miRNA content of breastmilk and blood was high, particularly in the breastmilk cellular fraction and PBMCs. More than 293 miRNA species were detected in breastmilk cells, 233 in the breastmilk lipids, 169 in blood plasma and 345 in PBMCs. Single correlation analysis showed that within milk cells, milk lipids, and PBMCs, miRNA expression levels were similar among participants. In plasma, marked inter-individual variation in single miRNA species was observed. Cluster analysis indicated that the miRNA profiles of breastmilk cells and lipids grouped together; however, differences were seen between PBMCs and plasma, with the latter showing the most variable miRNA composition. This study confirms the rich miRNA nature of human breastmilk. Our comparisons between blood and milk miRNA suggest that a proportion of milk miRNA may be derived from the maternal bloodstream, whilst some may originate from the breast epithelium. Given the recently identified stability and function of food-derived miRNA in regulating mammalian genes, we propose that breastmilk is a rich source of miRNA, which may contribute to early infant development.
Human milk contains both free and encapsulated RNA and microRNA in its cell, lipid and skim milk fractions. Recently, the microRNA content of human milk has attracted much attention due to its high...
BackgroundPreterm infants' meals typically progress to higher volumes over time. Knowledge of gastric emptying (GE) responses to differing meal volumes may inform enteral feeding management. We examined the effect of meal volume and... more
BackgroundPreterm infants' meals typically progress to higher volumes over time. Knowledge of gastric emptying (GE) responses to differing meal volumes may inform enteral feeding management. We examined the effect of meal volume and composition on preterm GE.MethodsForty infants were studied at 33.3±1.4 (29.7-35.6) weeks postmenstrual age when fully enteral fed (target 150 ml/kg/day). Intraindividual comparisons of GE were made for paired meals of 100% and 75% prescribed volume and identical composition of mother's own milk (n=21) and pasteurized donor human milk (n=19). Serial stomach ultrasound images were used to calculate gastric residual volumes (GRVs) and remaining meal proportions (% meal).ResultsGE was faster in the early postprandial period and slowed over time (P<0.001). Reduced volume meals had slower GE rates and lower GRV (P<0.001). Serial postprandial % meal was similar between reduced and full volume meals (P=0.41). Higher milk casein concentration was a...
This study is a collaborative effort among lactation specialists and fluid dynamic engineers. The paper presents clinical results for suckling pressure pattern in lactating human breast as well as a 3D computational fluid dynamics (CFD)... more
This study is a collaborative effort among lactation specialists and fluid dynamic engineers. The paper presents clinical results for suckling pressure pattern in lactating human breast as well as a 3D computational fluid dynamics (CFD) modeling of milk flow using these clinical inputs. The investigation starts with a careful, statistically representative measurement of suckling vacuum pressure, milk flow rate, and milk intake in a group of infants. The results from clinical data show that suckling action does not occur with constant suckling rate but changes in a rhythmic manner for infants. These pressure profiles are then used as the boundary condition for the CFD study using commercial ansys fluent software. For the geometric model of the ductal system of the human breast, this work takes advantage of a recent advance in the development of a validated phantom that has been produced as a ground truth for the imaging applications for the breast. The geometric model is introduced i...
Preterm nutrition guidelines target nutrient accretion and growth at intrauterine rates, yet at term equivalent age, the phenotype of the preterm infant differs from that of term infants. Monitoring early changes in preterm body... more
Preterm nutrition guidelines target nutrient accretion and growth at intrauterine rates, yet at term equivalent age, the phenotype of the preterm infant differs from that of term infants. Monitoring early changes in preterm body composition (BC) in response to macronutrient intakes may facilitate our understanding of how best to meet preterm nutrition and growth targets. Macronutrient intakes based on milk analysis were calculated from birth for infants born <33 weeks gestation. BC was measured in the PEA POD when infants were thermodynamically stable, free of intravenous lines and independent of respiratory support. Subsequent BC measurements were taken at least fortnightly until term age. Regression analysis was used to assess macronutrient influences on changes in BC. Median (range) gestation and birthweight of preterm infants (n = 27) were 29 (25-32) weeks and 1395 (560-2148) g, respectively. The youngest corrected gestational and postnatal ages that infants qualified for a P...
This work studies a simple model for milk transport through lactating human breast ducts, and describes mathematically the mass transfer from alveolar sacs through the mammary ducts to the nipple. In this model both the phenomena of... more
This work studies a simple model for milk transport through lactating human breast ducts, and describes mathematically the mass transfer from alveolar sacs through the mammary ducts to the nipple. In this model both the phenomena of diffusion in the sacs and conventional flow in ducts have been considered. The ensuing analysis reveals that there is an optimal range of bifurcation numbers leading to the easiest milk flow based on the minimum flow resistance. This model formulates certain difficult-to-measure values like diameter of the alveolar sacs, and the total length of the milk path as a function of easy-to-measure properties such as milk fluid properties and macroscopic measurements of the breast. Alveolar dimensions from breast tissues of six lactating women are measured and reported in this paper. The theoretically calculated alveoli diameters for optimum milk flow (as a function of bifurcation numbers) show excellent match with our biological data on alveolar dimensions. Als...
The aim of the present study was to determine whether serial gastric volumes and intragastric curding are repeatable within individual preterm infants when given sequential feeds of the same volume and composition. Infant and feeding... more
The aim of the present study was to determine whether serial gastric volumes and intragastric curding are repeatable within individual preterm infants when given sequential feeds of the same volume and composition. Infant and feeding characteristics that may influence differences in measured gastric volumes, echogenicity, and intragastric curding were also explored. Ultrasound images were used to calculate gastric volumes and to rate echogenicity and intragastric curding for 20 infants. A total of 29 paired feeds of the same volume and composition were monitored prefeed and postfeed and at 30-minute intervals thereafter. Statistical comparisons of paired gastric volume measurements and agreement between echogenicity and curding ratings were made for each time point. Analyses of factors that influence discrepancies between volume measurements and between curding ratings were performed. Paired gastric volume measurements were repeatable (intraclass correlation coefficient [ICC] = 0.971, 0.938 < ICC < 0.987). Most (75%) discrepancies were <2 mL and increased over time, although volume differences were small. Overall moderate levels of consistency were observed for ratings of echogenicity (κ = 0.44), and curd presence (κ ≤ 0.65), density (κ = 0.41), and volume (κ = 0.47). Gastric emptying during feed delivery is influenced with infant positioning, fortification of breast milk, and feeding frequency. For preterm infants serial gastric volumes are repeatable and ratings of intragastric echogenicity and curding are moderately consistent when fed milk of the same volume and composition. Ultrasound has the potential to further explore factors that influence gastric emptying in the preterm infant.
To assess ultrasound as a method for (i) measuring body composition (BC) of preterm infants and for (ii) assessing the influence of macronutrient intakes on tissue accretion rates. Preterm ultrasound studies of four anatomical sites were... more
To assess ultrasound as a method for (i) measuring body composition (BC) of preterm infants and for (ii) assessing the influence of macronutrient intakes on tissue accretion rates. Preterm ultrasound studies of four anatomical sites were performed approximately every three weeks from birth to corrected-term age. Preterm measurements were compared to foetal reference data. Duplicate scans at each site were taken on a subset of infants to test the reproducibility of the method, assessed as the coefficient of variation (CV). The influence of measured macronutrient intakes on preterm BC was assessed by regression analysis. Median (range) gestation and birth weight of 40 preterm infants were 27 (23-29) weeks and 1022 (480-1475) g, respectively. Accretion rates of adipose and muscle tissues were not uniform across the four sites. Relative to the foetus, preterm adipose tissue thickness was reduced at an equivalent (corrected) gestation, but towards term, a faster accretion rate of subcutaneous abdominal adipose and limb muscle tissue was evident. Timing of fortification (p=0.012), enteral carbohydrate intake (p=0.008) and the protein energy ratio of intakes (p=0.038) moderated the ratio of adipose to muscle tissue accretion over the four sites by -0.004, -0.048 and -0.042, respectively. Ultrasound provides a non-invasive, portable method of assessing changes in subcutaneous adipose tissue and muscle accretion and appears sufficiently sensitive to detect influences of macronutrient intakes on accretion rates from birth. The method warrants further investigation as a bedside tool for measuring BC of preterm infants.
The variable content of human breast milk suggests that its routine fortification may result in sub-optimal nutritional intakes and growth. In a pragmatic trial, we randomised infants born below 30 weeks of gestation to either the... more
The variable content of human breast milk suggests that its routine fortification may result in sub-optimal nutritional intakes and growth. In a pragmatic trial, we randomised infants born below 30 weeks of gestation to either the intervention (Igp) of fortifying milk on measured composition according to birth weight criteria and postmenstrual age (PMA) or our routine practice (RPgp) of fortifying on assumed milk composition to target 3·8-4·4 g protein/kg per d and 545-629 kJ/kg per d. Milk composition was measured using the MIRIS® Human Milk Analyser. Percentage fat mass (%FM) was measured using PEA POD (COSMED). The effects of macronutrient intakes and clinical variables on growth were assessed using mixed model analysis. Mean measured protein content (1·6 g/100 ml) was higher than the assumed value (1·4 g/100 ml), often leading to lower amounts of fortifier added to the milk of intervention infants. At discharge (Igp v. RPgp), total protein (3·2 (sd 0·3) v. 3·4 (sd 0·4) g; P=0·06...
Breastfeeding has been regarded first and foremost as a means of nutrition for infants, providing essential components for their unique growth and developmental requirements. However, breast milk is also rich in immunologic factors,... more
Breastfeeding has been regarded first and foremost as a means of nutrition for infants, providing essential components for their unique growth and developmental requirements. However, breast milk is also rich in immunologic factors, highlighting its importance as a mediator of protection. In accordance with its evolutionary origin, the mammary gland offers via the breastfeeding route continuation of the maternal to infant immunologic support established in utero. At birth, the infant's immune system is immature, and although it was exposed to the maternal microbial flora during pregnancy, it experiences an abrupt change in its microbial environment during and after birth, which is challenging and renders the infant highly susceptible to infection. Active and passive immunity protects the infant via breast milk, which is rich in immunoglobulins, lactoferrin, lysozyme, cytokines, and numerous other immunologic factors, including maternal leukocytes. Breast milk leukocytes provide ...
Despite the importance of the suck-swallow-breathe reflex during breastfeeding, a large proportion of our understanding is derived from bottle-feeding studies. Given the differences in the delivery of milk during breast and bottle... more
Despite the importance of the suck-swallow-breathe reflex during breastfeeding, a large proportion of our understanding is derived from bottle-feeding studies. Given the differences in the delivery of milk during breast and bottle feeding, it is imperative that a more general view of the suck-swallow-breathe and milk removal process during breastfeeding is available. This systematic review aimed to assess the evidence for the mechanism of milk removal during breastfeeding; evaluate how the term infant coordinates sucking, swallowing, breathing (SSwB) and cardiorespiratory patterns; and how these patterns change with maturation during breastfeeding. A literature search of PubMed and MEDLINE was performed to assess the mechanism of milk removal and patterns of sucking, swallowing, breathing, and cardiorespiratory control during breastfeeding in healthy term infants. Seventeen studies were selected and a narrative synthesis was performed. Nine studies assessing the infant sucking mecha...
High infant weight gain is associated with subsequent overweight and obesity and so may contribute to related comorbidities such as metabolic syndrome and cardiovascular disease. The growth acceleration hypothesis proposes that early and... more
High infant weight gain is associated with subsequent overweight and obesity and so may contribute to related comorbidities such as metabolic syndrome and cardiovascular disease. The growth acceleration hypothesis proposes that early and rapid growth in infancy can shape the metabolic profile to increase susceptibility to obesity. Although breastfeeding reduces the infant's risk of subsequent overweight and obesity, high infant weight gains are observed in this population. We report the case of an infant with excessive weight gains that persisted throughout 6 months of exclusive breastfeeding. The mother chose to continue breastfeeding despite medical advice to wean, and high weight gains continued for a further 8 months of breastfeeding and complementary foods. This is the first reported case of an exclusively breastfed infant with excessive weight gains (> 97th percentile) with contemporaneous measures of 24-hour breast milk intake and doses and concentrations of protein, f...
Infants of breastfeeding mothers with persistent nipple pain have been shown to apply stronger vacuums to the breast and transfer less milk during one monitored feed. This may be associated with differences in the movement of the tongue.... more
Infants of breastfeeding mothers with persistent nipple pain have been shown to apply stronger vacuums to the breast and transfer less milk during one monitored feed. This may be associated with differences in the movement of the tongue. The aim was to analyse the intra-oral nipple shape and movement of the tongue of infants of mothers with and without nipple pain. Breastfeeding infants of mothers with or without nipple pain were monitored using ultrasound and intra-oral vacuum during one breastfeed. From cine clips of the ultrasound scans measurements were made of the depth of the intra-oral space between the hard-soft palate junction (HSPJ) and the mid-tongue; the distance of the tip of the nipple to the HSPJ; and nipple diameters from the tip to the base. During nutritive sucking, tongue movements of infants of mothers with nipple pain resulted in a smaller intra-oral space (p = 0.040) and restricted nipple expansion compared to controls (p < 0.012). Stronger baseline and peak vacuums compared to controls were confirmed (p = 0.002). In these mothers, nipple pain was associated with restricted infant tongue movement. Ultrasound may complement measurement of intra-oral vacuum in monitoring treatment strategies in breastfeeding women experiencing nipple pain.
Persistent nipple pain is one of the most common reasons given by mothers for ceasing exclusive breastfeeding. We aimed to determine the frequency of nipple pain as a reason for consultation, the most common attributed aetiologies, and... more
Persistent nipple pain is one of the most common reasons given by mothers for ceasing exclusive breastfeeding. We aimed to determine the frequency of nipple pain as a reason for consultation, the most common attributed aetiologies, and the effectiveness of the advice and treatment given. All consultations at the Breast Feeding Centre of Western Australia (WA) were audited over two six-month periods in 2011 (n = 469) and 2014 (n = 708). Attributed cause(s) of nipple pain, microbiology results, treatment(s) advised, and resolution of pain were recorded. Nipple pain was one of the reasons for consultation in 36% of cases. The most common attributed cause of nipple pain was incorrect positioning and attachment, followed by tongue tie, infection, palatal anomaly, flat or inverted nipples, mastitis, and vasospasm. Advice included correction of positioning and attachment, use of a nipple shield, resting the nipples and expressing breastmilk, frenotomy, oral antibiotics, topical treatments, and cold or warm compresses. Pain was resolving or resolved in 57% of cases after 18 days (range 2-110). The multiple attributed causes of nipple pain, possibly as a result of a cascade of events, suggests that effective early lactation management for prevention of nipple pain and early diagnosis and effective treatment are crucial to avoid early weaning.
Breastmilk is a rich source of cells with a heterogeneous composition comprising early-stage stem cells, progenitors and more differentiated cells. The gene expression profiles of these cells and their associations with characteristics of... more
Breastmilk is a rich source of cells with a heterogeneous composition comprising early-stage stem cells, progenitors and more differentiated cells. The gene expression profiles of these cells and their associations with characteristics of the breastfeeding mother and infant are poorly understood. This study investigated factors associated with the cellular dynamics of breastmilk and explored variations amongst women. Genes representing different breastmilk cell populations including mammary epithelial and myoepithelial cells, progenitors, and multi-lineage stem cells showed great variation in expression. Stem cell markers ESRRB and CK5, myoepithelial marker CK14, and lactocyte marker α-lactalbumin were amongst the genes most highly expressed across all samples tested. Genes exerting similar functions, such as either stem cell regulation or milk production, were found to be closely associated. Infant gestational age at delivery and changes in maternal bra cup size between pre-pregnan...
Preterm nutrition guidelines target nutrient accretion and growth at intrauterine rates, yet at term equivalent age, the phenotype of the preterm infant differs from that of term infants. Monitoring early changes in preterm body... more
Preterm nutrition guidelines target nutrient accretion and growth at intrauterine rates, yet at term equivalent age, the phenotype of the preterm infant differs from that of term infants. Monitoring early changes in preterm body composition (BC) in response to macronutrient intakes may facilitate our understanding of how best to meet preterm nutrition and growth targets. Macronutrient intakes based on milk analysis were calculated from birth for infants born <33 weeks gestation. BC was measured in the PEA POD when infants were thermodynamically stable, free of intravenous lines and independent of respiratory support. Subsequent BC measurements were taken at least fortnightly until term age. Regression analysis was used to assess macronutrient influences on changes in BC. Median (range) gestation and birthweight of preterm infants (n = 27) were 29 (25-32) weeks and 1395 (560-2148) g, respectively. The youngest corrected gestational and postnatal ages that infants qualified for a P...
A transient laminar Newtonian three-dimensional CFD simulation has been studied for milk flow in a phantom model of the 6-generations human lactating breast branching system. Milk is extracted by the cyclic pattern of suction from the... more
A transient laminar Newtonian three-dimensional CFD simulation has been studied for milk flow in a phantom model of the 6-generations human lactating breast branching system. Milk is extracted by the cyclic pattern of suction from the alveoli through the duct and to the nipple. The real negative (suction) pressure data are applied as an outlet boundary condition in nipple. In this study, the commercial CFD code (Fluent Inc., 2004) is employed for the numerical solution of the milk flow. The milk intake flow rate from simulation is compared to the real clinical data from published paper. The results are in good agreement. It is believed that the methodology of the lactating human breast branching modeling proposed here can provide potential guidelines for further clinical and research application.
Currently, the methods for assessing milk ejection in women include serial sampling of plasma oxytocin and measurement of intraductal pressure, both of which are invasive and may induce stress. We hypothesized that milk ejection would... more
Currently, the methods for assessing milk ejection in women include serial sampling of plasma oxytocin and measurement of intraductal pressure, both of which are invasive and may induce stress. We hypothesized that milk ejection would cause an increase in milk-duct diameter that could be observed noninvasively with ultrasound, and this could be used to investigate the physiology of milk ejection in women. One milk duct was scanned in the unsuckled breast in 2 groups of mothers: group BB (n = 21) for the beginning of a breastfeed and group EB (n = 24) for the entire breastfeed. A duct also was monitored for a 5-minute period on 2 separate days in the absence of factors that may induce milk ejection in group EB to provide a baseline duct diameter. Milk intake at a breastfeed was measured by test weighing. A significant increase in milk-duct diameter was observed when milk ejection was sensed and/or the infant changed its swallowing pattern in both groups. Multiple increases and decrea...
This work studies a model for milk transport through lactating human breast ducts, and describes mathematically the mass transfer from alveolar sacs through the mammary ducts to the nipple. In this model both the phenomena of diffusion in... more
This work studies a model for milk transport through lactating human breast ducts, and describes mathematically the mass transfer from alveolar sacs through the mammary ducts to the nipple. In this model both the phenomena of diffusion in the sacs and conventional flow in ducts have been considered. The ensuing analysis reveals that there is an optimal range of bifurcation numbers leading to the easiest milk flow based on the minimum flow resistance. This model formulates certain difficult-to-measure values like diameter of the alveolar sacs, and the total length of the milk path as a function of easy-to-measure properties such as milk fluid properties and macroscopic measurements of the breast. Alveolar dimensions from breast tissues of six lactating women are measured and reported in this paper. The theoretically calculated alveoli diameters for optimum milk flow (as a function of bifurcation numbers) show excellent match with our biological data on alveolar dimensions. Also, the mathematical model indicates that for minimum milk flow resistance the glandular tissue must be within a short distance from the base of the nipple, an observation that matches well with the latest anatomical and physiological research.
... 2. Armstrong ML,; Caliendo C,; Roberts AE. . Pregnancy, lactation and nipple piercings. AWHONN Lifelines . 2006;10(3):212–217, pmid:16792708. Medline. 3. Meltzer DI. . Complications of body piercing. Am Fam Physician .... more
... 2. Armstrong ML,; Caliendo C,; Roberts AE. . Pregnancy, lactation and nipple piercings. AWHONN Lifelines . 2006;10(3):212–217, pmid:16792708. Medline. 3. Meltzer DI. . Complications of body piercing. Am Fam Physician . 2005;72(10):2029–2034, pmid:16342832. ...
Coordination of... more
Coordination of infants' suck-swallow-breathing patterns is integral to safe and efficient feeding. However, assessment of these patterns is difficult and often invasive, particularly in breast-fed infants less than 4 months of age. The aims of this study were to develop an ultrasound approach to visualize swallowing in term breast-feeding infants and to determine the accuracy of ultrasound imaging of swallowing compared to respiratory inductive plethysmography (RIP). On ultrasound, the breast milk bolus was observed as a predominantly echogenic area moving inferiorly. Of the 388 swallows detected with ultrasound, 379 correlated with the swallow apneas detected by RIP (R(2) = 0.98). The mean duration of the swallow was 0.63 +/- 0.06 s. Ultrasound imaging is a noninvasive accurate method for detection of swallowing by visualization of movement of the milk bolus through the pharyngeal area of a breast-feeding infant. These techniques may potentially provide useful information for infants experiencing breast-feeding difficulties.