Composition Of Human Milk Research Articles

Breastfeeding and Allergic Diseases: What's New?

Asthma and other allergic disorders, such as atopic dermatitis and food allergies, are common chronic health problems in childhood. The rapid rise in the prevalence of these conditions registered over the last few decades has stressed the need to identify the modifiable risk factors associated with the development of these diseases. Breast milk, recognized as the gold standard for healthy growth and development of the newborn, is one of the major factors associated with a lower incidence of allergic and infectious diseases in childhood and young adulthood. Although the underlying mechanisms for these effects are not well understood, breastfeeding leads to immune system maturation. In this narrative review, we summarize existing evidence on breastfeeding and human milk composition in relation to allergic disease prevention or development.

Breast milk: more than just nutrition!

From an evolutionary and nutritional standpoint, exclusive human milk feeding for the first 6 months of life, with continued breastfeeding for 1 to 2 years of life, is recognized as the gold standard nourishment for the infant: it is a species-specific food, with a composition designed by nature to better respond to the biological and psychological needs of the newborn/infant. Human milk contains many hundreds of bioactive molecules that protect newborn against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Compared with formula feeding, breastfeeding has been associated with decreased morbidity and mortality in infants and to lower incidence of gastrointestinal infections and inflammatory, respiratory and allergic disease. Here, we briefly review the nutritional and functional composition of human milk and provide an overview of its varied bioactive factors.

No Evidence for Sex-specificity in Vitamins C, E, and Fatty Acid Content of Human Milk from Healthy Polish Mothers.

Human milk (HM) is a complex fluid that meets the nutritional needs of infants. Its composition is associated with environmental, maternal, and fetal variables. It provides nutrients and bioactive substances, including cytokines, immunoglobulins, and constituents with antioxidative properties. Boys are reportedly more susceptible to oxidative stress. This study aimed to determine the relationship between infant sex and the antioxidants vitamins C and E, and the fatty acid (FA) profile of HM. Results of this investigation may infer sex differences for the composition of infant formulas. Thirty days after delivery, a sample of HM was collected from 152 healthy, non-smoking mothers of full-term new-borns (77 males) born in good clinical condition. After FAs were extracted from the fat component, they were converted into methyl esters and separated using high-performance gas chromatography. Tocopherol content was determined using a method described in a previous study. Vitamin C content was determined using reversed-phase high-performance liquid chromatography with ultraviolet detection, as described in the same study. The study groups (male vs female offspring) did not differ in terms of vitamin and FA content in HM. The only difference found was in gondoic acid 20:1 (n-9), with a higher concentration in the HM of mothers with female offspring (mean 0.63 ± 0.18 vs 0.59 ± 0.15 g/100 g FA; P < 0.047). Despite the acknowledged differences in the composition of HM associated with infant sex and the increased oxidative stress in males, antioxidant content did not appear to differ according to infant sex. These results suggest that there is no need for the antioxidant content of infant formulas to be sex-specific.

Maternal and Infant Factors Influencing Human Milk Oligosaccharide Composition: Beyond Maternal Genetics.

Maternal genetics is a key determinant of human milk oligosaccharide (HMO) composition in human milk. Beyond genetic status, other factors influencing the HMO profile are poorly defined. Thus, we aimed to review the existing evidence on the associations between nongenetic maternal and infant factors and HMO composition. A systematic search was performed on PubMed and Web of Science (without a time restriction) to identify any relevant studies published. In total, 1056 results were obtained, of which 29 articles were selected to be included in this review. The range of factors investigated include lactation stage, maternal pre-pregnancy BMI (ppBMI), maternal age, parity, maternal diet, mode of delivery, infant gestational age, and infant sex. The data suggest that, beyond maternal genetics, HMO composition seems to be influenced by all these factors, but the underlining mechanisms remain speculative. The published evidence is discussed in this review, along with potential implications for infant growth and development. For example, 2'-fucosyllactose, which was reportedly increased in mothers with higher ppBMIs, was also associated with increased infant weight and height. In addition, greater levels of sialylated HMOs after preterm birth may support brain development in these infants.

The Relationship Between Breast Milk Components and the Infant Gut Microbiota.

The assembly of the newborn's gut microbiota during the first months of life is an orchestrated process resulting in specialized microbial ecosystems in the different gut compartments. This process is highly dependent upon environmental factors, and many evidences suggest that early bacterial gut colonization has long-term consequences on host digestive and immune homeostasis but also metabolism and behavior. The early life period is therefore a “window of opportunity” to program health through microbiota modulation. However, the implementation of this promising strategy requires an in-depth understanding of the mechanisms governing gut microbiota assembly. Breastfeeding has been associated with a healthy microbiota in infants. Human milk is a complex food matrix, with numerous components that potentially influence the infant microbiota composition, either by enhancing specific bacteria growth or by limiting the growth of others. The objective of this review is to describe human milk composition and to discuss the established or purported roles of human milk components upon gut microbiota establishment. Finally, the impact of maternal diet on human milk composition is reviewed to assess how maternal diet could be a simple and efficient approach to shape the infant gut microbiota.

Human milk metabolome is associated with symptoms of maternal psychological distress and milk cortisol

The composition of human milk is subject to considerable variation, but the effects of maternal stress are largely unknown. We studied differences in human milk metabolome between Finnish mothers (n = 120, secretors) with symptoms of prenatal symptoms of psychological distress and milk cortisol concentrations. Human milk samples acquired at 2.5 months postpartum were analyzed using targeted 1H NMR metabolomics. Self-reported scores for depression (EPDS), overall anxiety (SCL-90), and pregnancy-related anxiety (PRAQ) were used to evaluate psychological distress. Prenatal psychological distress was positively associated with concentrations of short-chain fatty acids, caprate, and hypoxanthine (q < 0.0012). Milk cortisol was positively associated with lactate concentration (q < 0.05). Changes in the human milk metabolome were shown to be associated with maternal psychological distress and concentration of milk cortisol in a dissimilarly, suggesting alterations in bacterial and energy metabolism of the mother, respectively.

Human Milk Oligosaccharide Profiles and Associations with Maternal Nutritional Factors: A Scoping Review.

Human milk oligosaccharides (HMOs) are complex unconjugated glycans associated with positive infant health outcomes. This study has examined current knowledge of the effect of maternal diet and nutritional status on the composition of HMOs in breast milk. Using the PRISMA-ScR guidelines, a comprehensive, systematic literature search was conducted using Scopus, Web of Science, Global Health (CABI), and MEDLINE. Titles and abstracts were screened independently by two reviewers against predefined inclusion and exclusion criteria. Fourteen studies met the inclusion criteria and reported on maternal dietary intake (n = 3), maternal body composition indices (n = 9), and dietary supplementation interventions (n = 2). In total, data from 1388 lactating mothers (4011 milk samples) were included. Design methodologies varied substantially across studies, particularly for milk sample collection, HMO analysis, dietary and body composition assessment. Overall, this review has identified potential associations between maternal dietary intake and nutritional status and the HMO composition of human milk, though an abundance and sufficiency of evidence is lacking. Standardised procedures for human milk sample collection and HMO analysis, along with robust and validated nutrition assessment techniques, should be employed to further investigate the impact of maternal nutritional factors on HMO composition.

Antimicrobial Effect of Zn2+ Ions Governs the Microbial Quality of Donor Human Milk.

Donor human milk (HM) obtained at HM banks is exceptionally crucial for the feeding and treatment of preterm infants. Bacterial contaminations of HM in various stages of its handling are very common and can lead to disqualification of donations or severe infections in worse cases. Hence, HM donations are subject to strict bacteriological evaluations pre- and post-pasteurization. The main contaminating species vary between countries, banks and donors and even exhibit inter-individual variation. We initiated an assessment of the bacteriological composition of HM donated by women hospitalized in a neonatal intensive care unit in Israel. The most common bacterium identified was Staphylococcus epidermidis, found in all but one of the HM samples; the presence of several species of coagulase-negative Staphylococci was also noted. Next, we sought to develop a platform towards antibacterial treatment using Zn2+ ions that have recently been found to be potent against contaminants isolated from bovine milk. Zn2+ efficiently inhibited the growth of viable aerobic population and S. epidermidis in HM. Growth was also inhibited in other Gram-positive bacteria such as Bacillus cereus, a well-known food-borne pathogen. S. epidermidis and B. cereus cells grown in the presence of zinc were taken for microscopic evaluation, aiming to demonstrate zinc’s antimicrobial mode of action morphologically. Images obtained using scanning electron microscopy indicated leakage of cellular content and cell lysis in S. epidermidis. Besides, B. cereus cells showed abnormalities in their cell surface and complete loss of flagella upon treatment with zinc. Along with the above findings, it should be noted that this was a pilot study that tested how high doses of Zn2+ affect breast milk as a product. Further research is likely needed on the safety of consumption of Zn2+-treated HM in infants and older children.

Resolving Human Lactation Heterogeneity Using Single Milk-Derived Cells, a Resource at the Ready.

Single cell RNA sequencing (scRNAseq) of human milk-derived cells (HMDCs) makes highly detailed analyses of the biology of human lactation possible. We explore this powerful application as an exciting tool to inspect the cellular composition of human milk. We point out some important challenges unique to this approach and highlight the importance of collaborations between biologists and well-trained bioinformaticians to utilize these data to their maximum potential. We extend this focus by discussing the first two such studies that describe HMDCs via scRNAseq and a variety of important questions in the field that warrant attention through further research. The stage is set to apply scRNAseq in human lactation biology, potentially leading to new insights regarding the molecular and cellular diversity of human secretory mammary epithelial cells.

The implications of routine milk fortification for the short and long-term health of preterm babies

Fortification refers to the practice of enriching human milk feeds for very preterm babies with macronutrients, minerals and vitamins. Though standard of care in some parts of the world, adoption of fortification is not universal. Fortification entered into use on the assumption that human milk macronutrient content, principally protein, is insufficient to support the growth and development of very preterm babies. However, because of the substantial variability in human milk composition, routine fortification risks exposing some babies to very high protein intakes, which may be dangerous. Some clinicians fear fortification with cow-milk derived products will increase the risk of necrotising enterocolitis, leading them to favour commercial fortifiers made from pooled human milk over cow milk based products, a practice that has additional ethical implications. Randomised controlled trials of multi-nutrient fortification to-date are inadequate. No trial has had power to detect important functional effects; the majority are methodologically weak and focus primarily upon short-term growth. Evidence to guide practice is inadequate. There is an urgent need for collaboration to conduct high-quality research to end these long-standing uncertainties.

Maternal Diet and Infant Feeding Practices Are Associated with Variation in the Human Milk Microbiota at 3 Months Postpartum in a Cohort of Women with High Rates of Gestational Glucose Intolerance

Human milk contains a diverse community of bacteria believed to play a role in breast health and inoculation of the infant's gastrointestinal tract. The role of maternal nutrition and infant feeding practices on the human milk microbiota remains poorly understood. Our aim was to explore the associations between maternal diet (delivery to 3 mo postpartum), infant feeding practices, and the microbial composition and predicted function in milk from women with varied metabolic status. This was an exploratory analysis of a previously completed prospective cohort study of women with varying degrees of gestational glucose intolerance (NCT01405547). Milk samples (n=93 mothers) were collected at 3 mo postpartum. Maternal dietary information (validated food-frequency questionnaire) and infant feeding practices (human milk exclusivity, frequency of direct breastfeeding per day) were collected. V4-16S ribosomal RNA gene sequencing (Illumina MiSeq) was conducted to determine microbiota composition. Intake of polyunsaturated fat [β estimate (SE): 0.036 (0.018), P=0.047] and fiber from grains [0.027 (0.013), P=0.048] were positively associated with ɑ-diversity (Shannon index) of human milk. Overall microbial composition of human milk clustered based on human milk exclusivity (weighted UniFrac R2=0.034, P=0.015; Bray-Curtis R2=0.041, P=0.007), frequency of direct breastfeeding per day (Bray-Curtis R2=0.057, P=0.026), and maternal fiber intake from grains (Bray-Curtis R2=0.055, P=0.040). Total fiber, fiber from grains, dietary fat, and infant feeding practices were also associated with a number of differentially abundant taxa. The overall composition of predicted microbial functions was associated with total fiber consumption (Bray-Curtis R2=0.067, P=0.036) and human milk exclusivity (Bray-Curtis R2=0.041, P=0.013). Maternal consumption of fiber and fat, as well as mother's infant feeding practices, are important determinants of the human milk microbiota. Understanding whether these microbial changes impact an infant's overall health and development requires future study.

Preterm human milk composition and dietary intake of breastfeeding mothers in the Indonesian population

Background Human milk consumption is a protective factor against infection. However, the high variability of human milk composition makes it difficult for clinicians and researchers to assess the adequacy of nutritional intake.&#x0D; Objective To identify the nutritional profiles and composition of premature human milk and dietary intake of breastfeeding mother.&#x0D; Methods Human milk specimens were collected from mothers who gave birth to very premature and/or very low birth weight infants. Infants had been admitted to the Neonatology Unit of Dr. Cipto Mangunkusumo Hospital, Jakarta. The milk specimens were analyzed with a mid-infrared milk analyzerTM (MIRIS) for four weeks, and maternal dietary macronutrient intake was determined with food record questionnaires on food consumption frequency and food recall.&#x0D; Results Significant changes in nutritional composition of human milk were observed, with the fat concentration and calories increasing with time, and protein concentration decreasing with time. There were no significant differences observed in carbohydrate concentration of milk over the four weeks (P=0.447). Maternal intake of protein, carbohydrates, fat and calories was lower than the recommended values for breastfeeding women.&#x0D; Conclusion The macronutrient (protein and fat) and energy contents of human milk change weekly. Dietary intake of breastfeeding women are lower than recommended values.

Obesogenic Programming Effects during Lactation: A Narrative Review and Conceptual Model Focusing on Underlying Mechanisms and Promising Future Research Avenues.

Animal studies have consistently demonstrated that maternal obesity and a high-fat diet during lactation enhances obesity risk in the offspring. However, less is known about these potential obesogenic programming effects in obese humans. We propose three important pathways that may explain obesogenic programming effects of human breastmilk. First, human milk components and hormones may directly affect child eating and satiety characteristics. Second, human milk constituents can affect child microbiota that, in turn, may influence child eating and weight outcomes. Third, human milk composition may affect child eating and weight outcomes through flavor exposure. We reviewed a few very recent findings from well-powered longitudinal or experimental human research with regard to these three pathways. Moreover, we provide a research agenda for future intervention research with the overarching aim to prevent excessive pediatric weight gain during lactation and beyond. The ideas presented in this paper may represent important “black box” constructs that explain obesogenic programming effects during lactation. It should be noted, however, that given the scarcity of studies, findings should be seen as working hypotheses to further test in future research.

Tandem Breastfeeding: A Descriptive Analysis of the Nutritional Value of Milk When Feeding a Younger and Older Child.

Breastfeeding is a gold standard of feeding of newborns and infants. Tandem breastfeeding (TBF) is feeding two children of different ages at the same time. The knowledge about the composition of human milk in prolonged lactation is still scarce. Milk from tandem breastfeeding women and after weaning was examined. Milk samples were collected from 13 TBF mothers. A 24-h milk collection was done. Analyses of fat, protein, carbohydrate and energy content were performed using MIRIS. Sociodemographic characteristics of TBF mothers was done. Higher fat content, energy value and total protein concentration was found in TBFM milk during tandem breastfeeding, than in milk after weaning the older child. The carbohydrate content remained stable. The composition of breastmilk, in terms of macronutrients, changes after weaning, taking into account the nutritional requirements of the younger child. The milk of nursing mothers in tandem did not show diurnal variability in individual components. These findings suggest an adaptive role of human milk to nutrient requirements of newborn and older children. The results may support the promotion of long breastfeeding, including tandem breastfeeding.

Comparative Lipidomics Analysis of Human Milk and Infant Formulas Using UHPLC-Q-TOF-MS.

The lipidome and fatty acid composition of human milk and different infant formulas with animal- and/or plant-based fat sources are analyzed and compared in this study. The results obtained using positive and negative ionization modes indicate that there are 48 and 71 lipid species, respectively, that are common between the human milk and infant formulas. Moreover, the fatty acid composition in infant formulas varies significantly, depending on the fat source. Human milk is rich in triacylglycerols that contain linoleic acid, α-linolenic acid, arachidonic acid, and docosahexaenoic acid. Meanwhile, the triacylglycerols in IFB comprise long-chain fatty acids at the sn-1,3 position. Compared to human milk, IFC has the same level of sphingomyelin species. Based on univariate and multivariate analyses, there are 37, 34, 31, and 36 lipid species that can be used to distinguish between human milk and infant formulas. Overall, the results reported herein are useful in designing new milk formulas that better mimic human milk.

Medium- and long-chain triacylglycerols composition in preterm and full-term human milk across different lactation stages

Human milk is a natural source of medium-chain fatty acids (MCFAs). It is generally acknowledged that MCFAs exist in medium-chain triacylglycerols (MCTs). However, a previous study revealed that human milk is naturally rich in medium- and long-chain triacylglycerols (MLCTs). Few data are available on the MLCT composition of preterm milk. This study compared the MCFA and MLCT profiles in human milk from mothers after preterm (28–37 weeks) and term (>37 weeks) delivery during three lactational stages. The results showed that almost half of the triacylglycerol species in human milk are MLCT, accounting for approximately 30% of the total TAGs, mainly composed of one MCFA and two long-chain fatty acids, that is, MLL-type MLCT. In addition, MCFAs and MLCTs showed an increase from colostrum to transitional milk, while they were comparable between preterm and full-term milk. This research could help to develop infant formula, which is of great significance for infants.

Changes in macronutrients of human milk after bolus feeding: a simulation study.

Enteral nutrition supply to preterm infants requires feeding through a feeding tube. The aim of this study was to evaluate changes in macronutrient composition of human milk (HM) while passing through a gastric feeding tube. Simulated real-life practice tube feeding was performed by using an infusion pump connected to a feeding tube. A human milk analyzer was used to compare the pre infusion and post infusion macronutrient contents of HM. There was a significant decrease in fat (from 4.06 ± 0.6 g/100 ml to 3.95 ± 0.6 g/100 ml), carbohydrates (from 7.51 ± 0.4 g/100 ml to 7.33 ± 0.5 g/100 ml), and energy content (from 70.77 ± 5.4 kcal/100 ml to 69.72 ± 0.5 kcal/100 ml) after passing through the feeding tube (P < 0.001). A simulated real-life bolus tube feeding model demonstrated small but significant decreases in fat, carbohydrate, and energy content. The biological significance of our results to the very low birth weight infants should be further studied.

Human milk composition promotes optimal infant growth, development and health

Human milk is a living dynamic fluid that promotes optimal nutrition and development of the infant and impacts health across the lifespan. This review reports on the diverse range of nutrients, immune protection factors, hormones, microbes and metabolites in human milk and their impacts on infant nutrition and health. While many of these components are stable across lactation and similar between women, some vary over time, and in response to maternal and infant health status, maternal diet and geographic location. Human milk may be considered as personalized nutrition, with many components working synergistically to stimulate and support the infant's immature immune system, while enhancing appropriate development, growth and body composition.

Centering human milk composition as normal human biological variation

AbstractObjectivesHuman biological variation in the phenotype is the cornerstone of modern human biology, evolutionary anthropology, and related studies of human evolution. Minimal dialogue, however, has considered human milk to be part of this phenotypic variation. This may reflect researcher bias‐mental models oriented around commercial infant formula and homogenized cow's milk, both of which present milk composition as static. A general lack of research outside primarily Western, well‐nourished populations has also contributed to this underestimation of biological variation.MethodsThis review analyzes published research on breast milk composition, developmental metabolic programming, and maternal body composition to articulate the ways in which population‐based studies of human milk outside the United Sates are necessary to better understanding biological variation in human milk phenotypes.ResultsThis review discusses some of the common issues in current research on the biological variation in human milk composition and argues that anthropological inquiries that frame milk as part of an adaptive phenotype are necessary to better understand the biological significance of human milk composition in the production of human biological variation.ConclusionsBiological anthropology is uniquely positioned to investigate biological variation in human milk, using evolutionary theory, cutting edge biology, and anthropologically informed perspectives that challenge the biomedical framing of lactation and often act to privilege well nourished, primarily western populations and formula feeding as normatives for infant feeding research.

MACRONUTRIENTS OF MOTHERS' MILK OF VERY LOW BIRTH WEIGHT INFANTS: ANALYSIS ACCORDING TO GESTATIONAL AGE AND MATERNAL VARIABLES.

ABSTRACTObjective: To analyze the composition of macronutrients present in the milk of mothers of preterm newborn infants (PTNB) - protein, fat, carbohydrate, and calories - by gestational age (GA), chronological age (CA) and maternal variables.Methods: Longitudinal study that analyzed 215 milk samples from the 51 mothers of PTNB admitted in three Neonatal Intensive Care Units of Rio de Janeiro from May/2013-January/2014. Milk collection was performed by pickup pump, on a fixed day of each week until discharge. The spectrophotometric technique with Infrared Analysis (MilkoScan Minor 104) was used for the quantitative analysis. A sample of 7 mL of human milk was taken from the total volume of milk extracted by the mother. The data was grouped by GA (25-27, 28-31, 32-36, 37-40 weeks) and by CA (zero to 4, 5-8, 9-12, 13-16 weeks).Results: Protein, carbohydrate, fat and calories did not show any pattern of change, with no difference among groups of GA. When the macronutrients were analyzed by groups of CA, protein decreased, with significant difference between the first two groups of CA. Carbohydrates, fat and calories presented increasing values in all groups, without significant differences. Weight gain during pregnancy, maternal hypertension and maternal age were associated with changes in fat and calories in the first moment of the analysis of milk.Conclusions: There was a significant decrease in the levels of protein during the first eight weeks after birth. CA may be an important factor in the composition of human milk.