Search

Human milk provides all of the elements necessary for infant growth and development. Previous studies have reported associations between breastfeeding and a reduced risk of developing obesity and late-onset metabolic disorders; however, the underlying mechanisms are poorly understood. Recently, intakes of human milk components have been associated with infant body composition, which is likely partially implicated in the reduced risk of developing childhood obesity among breastfed infants. In this systematic review, we searched electronic bibliographic databases for studies that explored relationships between the 24 h intakes of human milk macronutrients and bioactive components and infant body composition and/or growth parameters. Of 13 eligible studies, 10 assessed relationships of infant body composition and growth outcomes with human milk macronutrients, while 8 studies assessed relationships with human milk bioactive components. Significant time-dependent relationships with infant anthropometrics and body composition were found for intakes and no relationships for concentrations of several human milk components, such as lactose, total protein, and human milk oligosaccharides, suggesting that measuring concentrations of human milk components without quantifying the intake by the infant may provide a limited understanding. Future studies investigating the effect of human milk components on infant growth and body composition outcomes should consider measuring the actual intake of components and employ standardised methods for measuring milk intake.

Temporal development of maternal and infant microbiomes during early life impacts short- and long-term infant health. This study aimed to characterize bacterial dynamics within maternal faecal, human milk (HM), infant oral, and infant faecal samples during the exclusive breastfeeding period and to document associations between human milk oligosaccharide (HMO) intakes and infant oral and faecal bacterial profiles. Maternal and infant samples (n = 10) were collected at 2–5, 30, 60, 90 and 120 days postpartum and the full-length 16S ribosomal RNA (rRNA) gene was sequenced. Nineteen HMOs were quantitated using high-performance liquid chromatography. Bacterial profiles were unique to each sample type and changed significantly over time, with a large degree of intra- and inter-individual variation in all sample types. Beta diversity was stable over time within infant faecal, maternal faecal and HM samples, however, the infant oral microbiota at day 2–5 significantly differed from all other time points (all p < 0.02). HMO concentrations and intakes significantly differed over time, and HMO intakes showed differential associations with taxa observed in infant oral and faecal samples. The direct clinical relevance of this, however, is unknown. Regardless, future studies should account for intakes of HMOs when modelling the impact of HM on infant growth, as it may have implications for infant microbiota development.

Human milk (HM) components may influence infant growth and development. This study aimed to investigate relationships between infant body composition (BC) and HM lactose, insulin, and glucose (concentrations and calculated daily intakes (CDI)) as well as 24-h milk intake and maternal BC at 3 months postpartum. HM samples were collected at 2 months postpartum. Infant and maternal BC was assessed with bioimpedance spectroscopy. Statistical analysis used linear regression accounting for infant birth weight. 24-h milk intake and CDI of lactose were positively associated with infant anthropometry, lean body mass and adiposity. Higher maternal BC measures were associated with lower infant anthropometry, z-scores, lean body mass, and adiposity. Maternal characteristics including BC and age were associated with concentrations and CDI of HM components, and 24-h milk intake. In conclusion, 24-h intake of HM and lactose as well as maternal adiposity are related to development of infant BC.

Researchers have recently called for human lactation research to be conceptualized as a biological framework where maternal and infant factors impacting human milk, in terms of composition, volume and energy content are studied along with relationships to infant growth, development and health. This approach allows for the development of evidence-based interventions that are more likely to support breastfeeding and lactation in pursuit of global breastfeeding goals. Here we summarize the seminal findings of our research programme using a biological systems approach traversing breast anatomy, milk secretion, physiology of milk removal with respect to breastfeeding and expression, milk composition and infant intake, and infant gastric emptying, culminating in the exploration of relationships with infant growth, development of body composition, and health. This approach has allowed the translation of the findings with respect to education, and clinical practice. It also sets a foundation for improved study design for future investigations in human lactation.

Human milk (HM) contains a wide array of peptide hormones including leptin and adiponectin, which are involved in the regulation of infant growth and development. These essential hormones might play an important role in the regulation of metabolic reprogramming of the new-born infant. However, HM hormone studies are sparse and heterogeneous in regard to the study design, sample collection, preparation and analysis methods. This review discussed the limitations of HM hormone analysis highlighting the gaps in pre-analytical and analytical stages. The methods used to quantify HM metabolic hormones (leptin, adiponectin, ghrelin, insulin, obestatin, resistin and apelin) can be classified as immunoassay, immunosensor and chromatography. Immunoassay methods (ELISA and RIA) have been predominantly used in the measurement of these HM hormones. The relative validity parameters of HM hormones analysis are often overlooked in publications, despite the complexity and differences of HM matrix when compared to that of plasma and urine. Therefore, appropriate reports of validation parameters of methodology and instrumentation are crucial for accurate measurements and therefore better understanding of the HM metabolic hormones and their influences on infant outcomes.

Background: Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes. Objective: We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children. Methods: Electronic bibliographic databases (MEDLINE, EMBASE and Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. Results: A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema; 14, allergic sensitization; nine, wheezing/asthma; six, food allergy; three, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. Conclusion and Clinical Relevance: In contrast with previous findings, we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on diverse populations employing standardized methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required.

Human milk is a complex and variable ecosystem fundamental to the development of newborns. This study aimed to investigate relationships between human milk oligosaccharides (HMO) and human milk bacterial profiles and infant body composition. Human milk samples (n = 60) were collected at two months postpartum. Infant and maternal body composition was measured with bioimpedance spectroscopy. Human milk bacterial profiles were assessed using full-length 16S rRNA gene sequencing and 19 HMOs were quantitated using high-performance liquid chromatography. Relative abundance of human milk bacterial taxa were significantly associated with concentrations of several fucosylated and sialylated HMOs. Individual human milk bacteria and HMO intakes and concentrations were also significantly associated with infant anthropometry, fat-free mass, and adiposity. Furthermore, when data were stratified based on maternal secretor status, some of these relationships differed significantly among infants born to secretor vs non-secretor mothers. In conclusion, in this pilot study the human milk bacterial profile and HMO intakes and concentrations were significantly associated with infant body composition, with associations modified by secretor status. Future research designed to increase the understanding of the mechanisms by which HMO and human milk bacteria modulate infant body composition should include intakes in addition to concentrations.

This study aimed to investigate relationships between infant abdominal visceral and subcutaneous adiposity and human milk (HM) components and maternal body composition (BC) during first year of lactation. Subcutaneous-abdominal depth (SAD), subcutaneous-abdominal fat area (SFA), visceral depth (VD) and preperitoneal fat area of 20 breastfed infants were assessed at 2, 5, 9 and 12 months using ultrasound. Maternal BC was determined with bioimpedance spectroscopy. HM macronutrients and bioactive components concentrations and infant 24-h milk intake were measured and calculated daily intakes (CDI) determined. Maternal adiposity associated with infant SFA (negatively at 2, 5, 12, positively at 9 months, all overall p &lt, 0.05). 24-h milk intake positively associated with infant SAD (p = 0.007) and VD (p = 0.013). CDI of total protein (p = 0.013), total carbohydrates (p = 0.004) and lactose (p = 0.013) positively associated with SFA. Lactoferrin concentration associated with infant VD (negatively at 2, 12, positively at 5, 9 months, overall p = 0.003). CDI of HM components and maternal adiposity have differential effects on development of infant visceral and subcutaneous abdominal adiposity. Maintaining healthy maternal BC and continuing breastfeeding to 12 months and beyond may facilitate favourable BC development reducing risk of obesity.

BackgroundInfants breastfed on demand exhibit a variety of feeding patterns and self-regulate their nutrient intake, but factors influencing their gastric emptying (GE) are poorly understood. Despite research into appetite regulation properties of leptin, there is limited information about relationships between human milk leptin and infant GE.MethodsGastric volumes were calculated from ultrasound scans of infants' stomachs (n=20) taken before and after breastfeeding, and then every 12.5 min (median; range: 3-45 min) until the next feed. Skim milk leptin and macronutrient concentrations were measured and doses were calculated.ResultsThe leptin concentration was (mean±SD) 0.51±0.16 ng/ml; the leptin dose was 45.5±20.5 ng per feed. No relationships between both concentration and dose of leptin and time between the feeds (P=0.57; P=1, respectively) or residual stomach volumes before the subsequent feed (P=0.20; P=0.050) were found. Post-feed stomach volumes (GE rate) were not associated with leptin concentration (P=0.77) or dose (P=0.85).ConclusionGE in term breastfed infants was not associated with either skim milk leptin concentration or dose. Further investigation with inclusion of whole-milk leptin and other hormones that affect gastrointestinal activity is warranted.

Human milk (HM) influences infant feeding patterns and body composition (BC). This small proof-of concept longitudinal study investigated relationships between infant/maternal BC and HM casein, whey and total protein during the first 12 months of lactation. BC of breastfeeding dyads (n = 20) was measured at 2 (n = 15), 5 (n = 20), 9 (n = 19), and/or 12 (n = 18) months postpartum with ultrasound skinfolds (infants) and bioimpedance spectroscopy (infants/mothers). Proteins concentrations and 24-h milk intake were measured and calculated daily intakes (CDI) determined. Higher maternal weight, body mass index, fat-free mass, fat-free mass index, and fat mass index were associated with higher concentration of whey protein (p ≤ 0.034, n = 20). There were no associations between infant BC and concentrations of all proteins, and CDI of whey and total protein. Higher CDI of casein were associated with lower infant fat-free mass (p = 0.003, n = 18) and higher fat mass (p &lt, 0.001), fat mass index (p = 0.001, n = 18), and % fat mass (p &lt, 0.001, n = 18) measured with ultrasound skinfolds. These results show a differential effect of HM casein on development of infant BC during the first year of life, suggesting that there is a potential to improve outcome for the infant through interventions, such as continuation of breastfeeding during the first 12 months of life and beyond, which may facilitate favourable developmental programming that could reduce risk of non-communicable diseases later in life.

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 (P0.001). Reduced volume meals had slower GE rates and lower GRV (P0.001). Serial postprandial % meal was similar between reduced and full volume meals (P=0.41). Higher milk casein concentration was associated with slower GE (P=0.04). Complete gastric emptying (GRV=0 ml) was more common in infants fed at 3 h intervals compared with those fed every 2 h (P=0.002).ConclusionEarly postprandial GE is more rapid for larger meal volumes. Stable preterm infants may tolerate feeding of a 3 h meal volume at shorter intervals.

Human milk (HM) carbohydrates may affect infant appetite regulation, breastfeeding patterns, and body composition (BC). We investigated relationships between concentrations/calculated daily intakes (CDI) of HM carbohydrates in first year postpartum and maternal/term infant BC, as well as breastfeeding parameters. BC of dyads (n = 20) was determined at 2, 5, 9, and/or 12 months postpartum using ultrasound skinfolds (infants) and bioelectrical impedance spectroscopy (infants/mothers). Breastfeeding frequency, 24-h milk intake and total carbohydrates (TCH) and lactose were measured to calculate HM oligosaccharides (HMO) concentration and CDI of carbohydrates. Statistical analysis used linear regression/mixed effects models, results were adjusted for multiple comparisons. Higher TCH concentrations were associated with greater infant length, weight, fat-free mass (FFM), and FFM index (FFMI), and decreased fat mass (FM), FM index (FMI), %FM and FM/FFM ratio. Higher HMO concentrations were associated with greater infant FFM and FFMI, and decreased FMI, %FM, and FM/FFM ratio. Higher TCH CDI were associated with greater FM, FMI, %FM, and FM/FFM ratio, and decreased infant FFMI. Higher lactose CDI were associated with greater FM, FMI, %FM, and FM/FFM, ratio and decreased FFMI. Concentrations and intakes of HM carbohydrates differentially influence development of infant BC in the first 12 months postpartum, and may potentially influence risk of later obesity via modulation of BC.

Human milk (HM) contains a plethora of metabolic hormones, including leptin, which is thought to participate in the regulation of the appetite of the developing infant. Leptin in HM is derived from a combination of de novo mammary synthesis and transfer from the maternal serum. Moreover, leptin is partially lipophilic and is also present in HM cells. However, leptin has predominately been measured in skim HM, which contains neither fat nor cells. We optimised an enzyme-linked immunosorbent assay for leptin measurement in both whole and skim HM and compared leptin levels between both HM preparations collected from 61 lactating mothers. Whole HM leptin ranged from 0.2 to 1.47 ng/mL, whilst skim HM leptin ranged from 0.19 to 0.9 ng/mL. Whole HM contained, on average, 0.24 ± 0.01 ng/mL more leptin than skim HM (p < 0.0001, n = 287). No association was found between whole HM leptin and fat content (p = 0.17, n = 287), supporting a cellular contribution to HM leptin. No difference was found between pre- and post-feed samples (whole HM: p = 0.29, skim HM: p = 0.89). These findings highlight the importance of optimising HM leptin measurement and assaying it in whole HM to accurately examine the amount of leptin received by the infant during breastfeeding.

Persistent organic pollutants in human milk (HM) at high levels are considered to be detrimental to the breastfed infant. To determine the pesticide concentration in HM, a pilot cross-sectional study of 40 Western Australian (WA) women was carried out. Gas chromatography-tandem mass spectrometry (GC-MS/MS) with a validated QuEChERS was used for the analysis of 88 pesticides in HM. p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) with a mean concentration of 62.8 ± 54.5 ng/g fat was found, whereas other organochlorines, organophosphates, carbamates and pyrethroids were not detected in HM. Overall, no association was observed between HM p,p'-DDE concentrations and maternal age, parity, body mass index and percentage fat mass. Furthermore, for the first time no significant association was found between p,p'-DDE concentrations in HM and infant growth outcomes such as weight, length, head circumference and percentage fat mass. The calculated daily intake was significantly different to the estimated daily intake of total DDTs and was well below the guideline proposed by WHO. The DDTs levels in WA have also significantly decreased by 42 - fold since the 1970s and are currently the lowest in Australia.

Accurate, noninvasive, and inexpensive methods are required to measure infant body composition. Ultrasound (US) and bioimpedance spectroscopy (BIS) have been validated in adults and introduced in pediatric populations. The aim of this study was to evaluate the performance of both methods in determining percentage fat mass (%FM) in breastfed infants. %FM of 2, 5, 9, and 12 mo-old healthy, breastfed term infants (n = 58) was calculated using BIS-derived total body water equations and skinfold equations then compared with reference models. Skinfolds were measured with US at two and four sites (biceps, suprailiac and/or triceps, and subscapular). %FM differed widely within and between methods, with the degree of variation affected by infant age/sex. Not a single method/equation was consistent with the distributions of appropriate reference values for all age/sex groups. Moderate number of matches with references values (13–24 out of 36) was seen for both types of equations. High number of matches (25–36) was seen for US skinfold-based equations. %FM values calculated from US and BIS were not significantly different (P = 0.35). Both BIS and US are practical for predicting %FM in infants. BIS calculations are highly dependent upon an appropriate set of validated age-matched equations.

Human milk (HM) adipokines may influence infant feeding patterns, appetite regulation, and body composition (BC). The associations between concentrations/calculated daily intakes (CDI) of HM adipokines in the first 12 months postpartum and maternal/term infant BC, and infant breastfeeding parameters were investigated. BC of breastfeeding dyads (n = 20) was measured at 2, 5, 9, and/or 12 months postpartum with ultrasound skinfolds (infants) and bioimpedance spectroscopy (infants/mothers). 24-h milk intake and feeding frequency were measured along with whole milk adiponectin and skim and whole milk leptin (SML and WML) and CDI were calculated. Statistical analysis used linear regression/mixed effects models, results were adjusted for multiple comparisons. Adipokine concentrations did not associate with infant BC. Higher CDI of adiponectin were associated with lower infant fat-free mass (FFM, p = 0.005) and FFM index (FFMI, p = 0.009) and higher fat mass (FM, p &lt, 0.001), FM index (FMI, 0.001), and %FM (p &lt, 0.001). Higher CDI of SML were associated with higher infant FM (p &lt, 0.001), FMI (p &lt, 0.001), and %FM (p = 0.002). At 12 months, higher CDI of WML were associated with larger increases in infant adiposity (2&ndash, 12 month: FM, p = 0.0006, %FM, p = 0.0004), higher CDI of SML were associated with a larger decrease in FFMI (5&ndash, 12 months: p = 0.0004). Intakes of HM adipokines differentially influence development of infant BC in the first year of life, which is a critical window of infant programming and may potentially influence risk of later disease via modulation of BC.

Breastfeeding has been implicated in the establishment of infant appetite regulation, feeding patterns and body composition (BC). A holistic approach is required to elucidate relationships between infant and maternal BC and contributing factors, such as breastfeeding parameters. Associations between maternal and breastfed term infant BC (n = 20) and feeding parameters during first 12 months of lactation were investigated. BC was measured at 2, 5, 9 and/or 12 months postpartum with ultrasound skinfolds (US; infants only) and bioimpedance spectroscopy (infants and mothers). 24-h milk intake (MI) and feeding frequency (FFQ) were measured. Higher FFQ was associated with larger 24-h MI (p ≤ 0.003). Higher 24-h MI was associated with larger infant fat mass (FM) (US: p ≤ 0.002), greater percentage FM (US: p ≤ 0.008), greater FM index (FMI) (US: p ≤ 0.001) and lower fat-free mass index (FFMI) (US: p = 0.015). Lower FFQ was associated with both larger FFM (US: p ≤ 0.001) and FFMI (US: p < 0.001). Greater maternal adiposity was associated with smaller infant FFM measured with US (BMI: p < 0.010; %FM: p = 0.004; FMI: p < 0.011). Maternal BC was not associated with FFQ or 24-h MI. These results reinforce that early life is a critical window for infant programming and that breastfeeding may influence risk of later disease via modulation of BC.

Bioimpedance spectroscopy is an accurate non-invasive method for measuring body composition in adults, but in infants it requires further testing and validation. Of the few studies of bioimpedance conducted in infants, none have comprehensively investigated the effect of milk intake volume. This study assessed the effect of the milk intake, feed duration and the volume of the infant's stomach and bladder on the resistance values pre-/post-feed to establish the feasibility of using these values interchangeably during data collection.Forty-eight breastfeeding infants were measured at 2, 5, 9 and/or 12 months (n=62 sessions) within 1-2 min before the start and after the end of breastfeed. Median (IQR) time between measurements was 24 (20.0-30.0) min. Resistance measurements at 0 and 50 kHz, and infinite frequency (R0, R50 and Rinf) and resistance of intracellular water (Ricw) were analysed with customised infant settings. Milk intake was measured by test weights. Free-water volumes and free-water change were determined from stomach and bladder volumes calculated from ultrasound images.Small pre-to-post-feed changes (median (IQR): R0 -3.7 (-14.8, 14.3); R50 0.3 (-10.4, 15.0); Rinf 2.8 (-13.3, 35.5); Ricw 20.8 (-98.1, 290.9)) were not significantly different from zero (R0: P=0.92; R50: P=0.48; Rinf: P=0.32; Ricw: P=0.097). No significant effect of milk intake or free-water change was detected.The lack of consistent change in resistance across a breastfeed provides flexibility in the timing of measurements of infants in the research setting, such that typically pre- and post-feed measures of resistance can be used interchangeably.

Higher breastmilk casein concentration increases gastric emptying in preterm infants, however there are limited information regarding whether casein or other components of breastmilk affect gastric...

The crystallization patterns of calcium phosphate precipitated on a acrylic hydrogels in abiogenic conditions are studied. The poly(2-hydroxyethyl methacrylate) (PHEMA) contains three polarizable oxygen atoms to which calcium ions have great tendency to chelate. Changing the oxygen content or the chemical environment around the oxygen results in changes in both crystallization patterns and the amount of calcium deposited. One disk of each polymers were immersed in vial containing 3 ml of the calcifying medium and incubated at 37°C in a shaker at 150 cycles/min for 2 weeks.

The calcification of acrylic hydrogels in abiotic calcifying media was analyzed. The calcification in hydrogels was independent of the physiological microenvironment and biological factors. In all the experiments high purity, sterile and nonpyrogenic water was used for injections with osmolality zero. The results show that all ionic species involved in the calcification of PHEMA hydogels in a metastable solution of CaCl and NaPO induced salting-out effects.

Human milk (HM) components influence infant feeding patterns and nutrient intake, yet it is unclear how they influence gastric emptying (GE), a key component of appetite regulation. This study analyzed GE of a single breastfeed, HM appetite hormones/macronutrients and demographics/anthropometrics/body composition of term fully breastfed infants (n = 41, 2 and/or 5 mo). Stomach volumes (SV) were calculated from pre-/post-feed ultrasound scans, then repeatedly until the next feed. Feed volume (FV) was measured by the test-weigh method. HM samples were analyzed for adiponectin, leptin, fat, lactose, total carbohydrate, lysozyme, and total/whey/casein protein. Linear regression/mixed effect models were used to determine associations between GE/feed variables and HM components/infant anthropometrics/adiposity. Higher FVs were associated with faster (−0.07 [−0.10, −0.03], p < 0.001) GE rate, higher post-feed SVs (0.82 [0.53, 1.12], p < 0.001), and longer GE times (0.24 [0.03, 0.46], p = 0.033). Higher whey protein concentration was associated with higher post-feed SVs (4.99 [0.84, 9.13], p = 0.023). Longer GE time was associated with higher adiponectin concentration (2.29 [0.92, 3.66], p = 0.002) and dose (0.02 [0.01, 0.03], p = 0.005), and lower casein:whey ratio (−65.89 [−107.13, −2.66], p = 0.003). FV and HM composition influence GE and breastfeeding patterns in term breastfed infants.