Role of the biological active components of human milk on long-term growth and neurodevelopmental outcome.

Human Milk is the best option for infant feeding; and for this reason, it should be promoted, protected, and supported. HM is an individual-specific-dynamic biofluid, characterized by an extreme variability in its composition. A wealth of literature has investigated how HM is related to healthy development. An association between HM composition, including nutrients and growth-related hormones as well as other bioactive components, and short-term and long-term infant outcomes could support this statement; however, the evidence is limited. In fact, HM composition is difficult to examine as it is dynamic and changes within a single feed, diurnally, according to stage of lactation and between and within populations. The aim of this review is summarizing only the innovative knowledge on the association between HM composition and long-term outcomes: infant growth and neurodevelopment. In this specific contest, macronutrients and historical biological component with well recognized effect were excluded (i.e. LCPUFA, DHA, iodine). Revised articles have been found in MEDLINE using breast milk-related outcomes, neurodevelopment, infant growth, breast milk-related biological factors, biomarkers, biological active components, and constituents as keywords. Moreover, we focus our search on the latest research results.

Microbial colonization programs are structured by breastfeeding and guide healthy respiratory development.

Breastfeeding and microbial colonization during infancy occur within a critical time window for development, and both are thought to influence the risk of respiratory illness. However, the mechanisms underlying the protective effects of breastfeeding and the regulation of microbial colonization are poorly understood. Here, we profiled the nasal and gut microbiomes, breastfeeding characteristics, and maternal milk composition of 2,227 children from the CHILD Cohort Study. We identified robust colonization patterns that, together with milk components, predict preschool asthma and mediate the protective effects of breastfeeding. We found that early cessation of breastfeeding (before 3 months) leads to the premature acquisition of microbial species and functions, including Ruminococcus gnavus and tryptophan biosynthesis, which were previously linked to immune modulation and asthma. Conversely, longer exclusive breastfeeding supports a paced microbial development, protecting against asthma. These findings underscore the importance of extended breastfeeding for respiratory health and highlight potential microbial targets for intervention.

Beliefs About Donating Human Milk to a Milk Bank: A Theory-Based Salient Belief Elicitation.

BACKGROUND: Pasteurized donor human milk provides a safe and desirable alternative when a parent's own milk is insufficient or unavailable. Currently, the demand for donor human milk exceeds the available supply. Little is known about the beliefs breastfeeding individuals have about milk bank donation. RESEARCH AIMS: The aims of this exploratory study were to (a) provide a preliminary estimate of how well intention can be predicted, and to suggest which of the global constructs of the Reasoned Action Approach has the most influence on intention; and (b) identify the salient, top-of-the-mind beliefs underlying the intention to donate some of the milk an individual is currently producing to a milk bank. METHODS: An exploratory, cross-sectional study design, based on the Reasoned Action Approach, was used to measure the theory's global constructs and elicit beliefs underlying the intention to donate milk of lactating individuals (N = 118) living in Indiana, Illinois, Missouri, and Kentucky. Thematic and frequency analyses and multiple regression were performed. RESULTS: Quantitative analyses found that injunctive norm and the autonomy component of perceived behavioral control were independently associated with intention. Qualitative analyses identified the advantages (e.g., help and save babies, won't waste milk), referents who support (e.g., husband, family), and facilitators (e.g., having a convenient, close location, having more knowledge and information) of donating milk. CONCLUSIONS: This research provides insight into how milk banks might recruit and retain donors. Additional quantitative research with a larger sample is necessary to confirm the preliminary findings of this study.

Maternal dietary protein and amino acid intake is not associated with the amino acid composition of human milk in an affluent environment.

Amino acids (AA) are essential nutrients in human milk (HM) and critical for infant growth and development. Several maternal lifestyle factors have been suggested to influence HM AA composition, with possible consequences for the breastfed infant. Whether maternal dietary protein and AA intake is associated with AA concentrations in HM is still largely unknown. Therefore, the aim of this study was to investigate the association between maternal dietary AA intake and AA concentrations in HM over the first month postpartum. Data from the observational longitudinal Amsterdam Mother's Milk study were used, consisting of 123 lactating women in their first postpartum month. HM samples were collected three times, on day 10, 17 and 24 postpartum. Maternal dietary protein and AA intake on these collection days was assessed using three 24-h recalls. HM protein-bound and free AA (BAA and FAA, respectively) were analysed by liquid chromatography. Associations between maternal AA intake and AA concentrations in HM were assessed using linear mixed models. Maternal intake was negatively associated with milk concentrations of free arginine (-0·0003; P = 0·01) and free lysine (-0·0004; P = 0·03) and was positively associated with free glutamine (0·002; P = 0·03) and free threonine (0·0008; P = 0·03). However, these associations were attenuated after correction for multiple testing. Both the quality and quantity of dietary protein intake in lactating women do not seem to influence the amino composition of their breast milk when living in an affluent environment.

Factors Associated with Mother's Own Milk Feeding and Direct Breastfeeding at Discharge in Preterm Infants with Feeding Difficulties: Clinical and Research Implications.

Background: Prematurity presents numerous barriers to mother's own milk (MOM) feeding and direct breastfeeding (DBF). Aim: This study aimed to determine factors associated with MOM feeding and DBF at discharge from the neonatal intensive care unit (NICU) in preterm-born infants presenting with feeding difficulties. Methods: A retrospective study of data from 237 preterm-born infants referred for evaluation of feeding difficulties and discharged home on full oral feeds was examined. Maternal and infant characteristics and oral feeding milestones were examined for their association with MOM intake and DBF at discharge using bivariate and multivariate regression analyses. Results: MOM feeding at discharge occurred in 35.4% (n = 84) infants. The odds of any MOM feeding at discharge were higher with higher maternal age, absence of maternal substance use, and fewer days between full per oral (PO) and discharge (all, p < 0.05). Among the 84 MOM-fed infants, 4.76% (n = 4) were exclusively breastfed, whereas 39.3% (n = 33) were partially DBF at discharge. The DBF infants had higher birthweight, no incidence of being small for gestational age, lower incidence of respiratory support at birth and intraventricular hemorrhage, lower postmenstrual age (PMA) at full PO, shorter duration from first PO to full PO, and lower PMA at discharge (all, p < 0.05). Conclusion: We found reduced use of MOM and DBF among preterm-born infants with feeding difficulties at NICU discharge. Clinical management and research advocacy must focus on targeted interventions in this setting by recognizing significant modifiable factors applicable to prepregnancy, pregnancy, NICU, and postdischarge care.

Supporting Breastfeeding Exchange Relations by Building Equitable and Innovative Solutions: An Interview With João Aprigio Guerra de Almeida.

Professor Joao Aprigio Guerra de Almeida graduated in Food Engineering (UFV-1981) with a Master in Microbiology (UFV-1986) and a doctorate in Women's and Children's Health (Fiocruz/IFF, 1998) He is founder and coordinator of the Brazilian Human Milk Banks Network (Ministry of Health-Brasil/Oswaldo Cruz Foundation-Fiocruz, 1987 to 2024); Head of the National Reference Center for Human Milk Banks at the National Institute of Women, Children and Adolescent Health Fernandes Figueira-IFF (Fiocruz/IFF, 1987 to 2024); Executive Secretary of the Ibero-American Human Milk Banks Network Program (Ibero-American General Secretariat-SEGIB/Brazilian Cooperation Agency-ABC/MS-FIOCRUZ, 2008 to 2020); Coordinator of International Technical Cooperation in Human Milk Banks ABC/Fiocruz/MS (2005 to 2024); and Coordinator of the Human Milk Banks Network of the Community of Portuguese Speaking Countries - CPLP (2017 to 2024). He has been recognized with the Sasakawa Health Prize (World Health Organization [WHO], 2001); as Officer of the Order of Rio Branco (Presidency of the Federative Republic of Brazil, 2001); with Global Health Challenges and Responses of the South in Time of Crisis (WHO, 2009); as Commendator of the Order of Rio Branco-Ministry of Foreign Affairs/Presidency of the Federative Republic of Brazil (2018); and Dr LEE Jong-wook Memorial Prize for Public Health (WHO, 2020). His areas of activity include Public Health, breastfeeding, Human Milk Banks, Public Management, and International Technical Cooperation.

Mother's milk microbiota is associated with the developing gut microbial consortia in very-low-birth-weight infants.

Mother's milk contains diverse bacterial communities, although their impact on microbial colonization in very-low-birth-weight (VLBW, <1,500 g) infants remains unknown. Here, we examine relationships between the microbiota in preterm mother's milk and the VLBW infant gut across initial hospitalization (n = 94 mother-infant dyads, 422 milk-stool pairs). Shared zero-radius operational taxonomic units (zOTUs) between milk-stool pairs account for ∼30%-40% of zOTUs in the VLBW infant's gut. We show dose-response relationships between intakes of several genera from milk and their concentrations in the infant's gut. These relationships and those related to microbial sharing change temporally and are modified by in-hospital feeding practices (especially direct breastfeeding) and maternal-infant antibiotic use. Correlations also exist between milk and stool microbial consortia, suggesting that multiple milk microbes may influence overall gut communities together. These results highlight that the mother's milk microbiota may shape the gut colonization of VLBW infants by delivering specific bacteria and through intricate microbial interactions.

Infant nutrition at risk: a global systematic review of ochratoxin A in human breast milk-human health risk assessment.

Human breast milk is the optimal source of nutrition for newborns, but the potential transfer of contaminants like mycotoxins, particularly ochratoxin A (OTA), from maternal blood to milk remains a concern. This systematic review aims to provide a comprehensive analysis of global OTA levels in human breast milk and assess the associated health risks. We conducted a thorough search of scientific databases, including Web of Science, ScienceDirect, Scopus, Google Scholar and PubMed, using keywords related to OTA in human breast milk. A total of 39 studies met the inclusion criteria for this review. OTA levels compared to limits, estimated infant intake at various ages and health risks assessed using Margin of Exposures (MOEs) and Hazard quotient (HQ). Our findings reveal the widespread presence of OTA in breast milk across different regions, with notably higher levels detected in Africa compared to Asia, South America and Europe. The higher concentrations observed in warmer, humid climates suggest that environmental factors significantly influence OTA contamination. Mature breast milk samples generally exhibited greater OTA exposure. The neoplastic and non-neoplastic effects demonstrate generally low risks globally. The regional differences in OTA levels and associated health risk assessments underscore the need for continued research into the health impacts of OTA exposure in infants. This includes further investigation into multiple sources of exposure, such as infant formula, within the broader context of the exposome framework.

Maternal Breast Growth and Body Mass Index Are Associated with Low Milk Production in Women.

BACKGROUND: Maternal breast volume is determined by the quantity of glandular and adipose tissue, and it undergoes significant changes during pregnancy. These changes are intricately linked to the development of glandular tissue, which most likely reflects lactation capacity. Evidence indicates that women with overweight or obesity exhibit larger breast volume compared to those with a normal body mass index (BMI), emphasizing the close relationship between breast volume and maternal adiposity. Hence, we aim to investigate breast volume growth and maternal BMI as potential risk factors for low milk production. METHODS: Lactating women (n = 609) from the Perth metropolitan area in Western Australia between 2011 and 2023 were included in the analysis. Twenty-four-hour milk production measurements were conducted using the test weighing method, and milk removal frequencies were recorded. Mothers completed questionnaires regarding demographic, obstetric and infant details. Linear and logistic regression models were used to determine maternal and infant factors associated with milk production. RESULTS: Here we show that increasing maternal age and BMI are associated with low milk production. Moreover, larger pre-pregnancy breast volume and breast growth are associated with both higher BMI and milk production. CONCLUSIONS: Women who are older, have an obese BMI and who have minimal pre-pregnancy breast volume and breast growth should be provided with antenatal screening and breastfeeding support as they are more likely to experience low milk production.

Human Milk Oligosaccharides in Combination with Galacto- and Long-Chain Fructo-Oligosaccharides Enhance Vaccination Efficacy in a Murine Influenza Vaccination Model.

Early-life nutrition significantly impacts vaccination efficacy in infants, whose immune response to vaccines is weaker compared to adults. This study investigated vaccination efficacy in female C57Bl/6JOlaHsd mice (6 weeks old) fed diets with 0.7% galacto-oligosaccharides (GOS)/long-chain fructo-oligosaccharides (lcFOS) (9:1), 0.3% human milk oligosaccharides (HMOS), or a combination (GFH) for 14 days prior to and during vaccination. Delayed-type hypersensitivity (DTH) was measured by assessing ear swelling following an intradermal challenge. Influvac-specific IgG1 and IgG2a levels were assessed using ELISAs, while splenic T and B lymphocytes were analyzed for frequency and activation via flow cytometry. Additionally, cytokine production was evaluated using murine splenocytes co-cultured with influenza-loaded dendritic cells. Mice on the GFH diet showed a significantly enhanced DTH response (p < 0.05), increased serological IgG1 levels, and a significant rise in memory B lymphocytes (CD27+ B220+ CD19+). GFH-fed mice also exhibited more activated splenic Th1 cells (CD69+ CXCR3+ CD4+) and higher IFN-γ production after ex vivo restimulation (p < 0.05). These findings suggest that GOS/lcFOS and HMOS, particularly in combination, enhance vaccine responses by improving memory B cells, IgG production, and Th1 cell activation, supporting the potential use of these prebiotics in infant formula for better early-life immune development.

Modifiable and Non-Modifiable Factors That Affect Human Milk Oligosaccharides Composition.

Human milk, the gold standard in infant nutrition, is a unique fluid that provides essential nutrients such as lactose, lipids, proteins, and free oligosaccharides. While its primary role is nutritional, it also protects against pathogens. This protection mainly comes from immunoglobulins, with human milk oligosaccharides (HMOs) providing additional support by inhibiting pathogen binding to host cell ligands. The prebiotic and immune-modulatory activity of HMOs strongly depends on their structure. Over 200 individual structures have been identified so far, with the composition varying significantly among women. The structure and composition of HMOs are influenced by factors such as the Lewis blood group, secretor status, and the duration of nursing. HMO profiles are heavily influenced by maternal phenotypes, which are defined based on the expression of two specific fucosyltransferases. However, recent data have shown that HMO content can be modified by various factors, both changeable and unchangeable, including diet, maternal age, gestational age, mode of delivery, breastfeeding frequency, and race. The first part of this overview presents the historical background of these sugars and the efforts by scientists to extract them using the latest chromatography methods. The second part is divided into subchapters that examine modifiable and non-modifiable factors, reviewing the most recent articles on HMO composition variations due to specific reasons and summarizing potential future challenges in conducting these types of studies.

Investigation of Human Milk as a Biological System in a Multicenter Mother-Infant Cohort: Protocol Design and Cohort Profile of the Phoenix Study.

Breastfeeding and human milk are the gold standard for infant feeding. Studying human milk with a systems biology approach in a large longitudinal cohort is needed to understand its complexity and health implications. The Phoenix study is a multicenter cohort study focusing on the interactions of maternal characteristics, human milk composition, infant feeding practices, and health outcomes of Chinese mothers and infants. A total of 779 mother-infant dyads were recruited from November 2021 to September 2022, and 769 mother-infant dyads were enrolled in the study. Scheduled home visits took place at 1, 4, 6, and 12 months postpartum, and 696 dyads (90.5% participants) completed the 12-month visit. At each visit, maternal and infant anthropometry was assessed. Questionnaires were administered to collect longitudinal information on maternal characteristics and lifestyle, infant feeding, and health. Digital diaries were used to record maternal dietary intake, infant feeding, and stool character. Human milk, maternal feces, infant feces, and infant saliva were collected. An external pharmaceutical-level quality assurance approach was implied to ensure the trial quality. Multi-omics techniques (including glycomics, lipidomics, proteomics, and microbiomics) and machine learning algorithms were integrated into the sample and data analysis. The protocol design of the Phoenix study provides a framework for prospective cohort studies of mother-infant dyads and will provide insights into the complex dynamics of human milk and its interplay with maternal and infant health outcomes in the Chinese population.

Adjusted versus Targeted Fortification in Extremely Low Birth Weight Preterm Infants: Fortin Study-A Randomized Clinical Trial.

Fortified human milk is the first choice for preterm infants. Although individualized fortification is recommended, the optimal method for this population remains uncertain. We conducted a comparative study assessing the growth effects of adjusted (AF) and targeted fortification (TF) in extremely low birth weight (ELBW) infants. This single-center, randomized, controlled clinical trial was conducted at a tertiary neonatal unit in Spain. Eligible participants were premature infants with a birthweight of <1000 g exclusively fed with human milk. A total of 38 patients were enrolled, 15 of them randomized to AF group and 23 to TF group. AF was based on blood urea nitrogen (BUN) concentration and TF on human milk analysis. The primary outcome was weight gain velocity (g/kg/day). No significant differences were found in weight gain velocity at 28 days, at 36 weeks of postmenstrual age, at discharge, nor during the intervention. Protein intake was significantly higher in the AF group (5.02 g/kg/day vs. 4.48 g/kg/day, p = 0.001). No differences were found in the lipid, carbohydrate, and energy intake; in the weight z score change between the different time points; nor in the length and head circumference growth. Both AF and TF are comparable methods of fortification and provide the appropriate growth rate in ELBW infants.

Human Milk Oligosaccharides and Their Pivotal Role in Gut-Brain Axis Modulation and Neurologic Development: A Narrative Review to Decipher the Multifaceted Interplay.

BACKGROUND: Human milk oligosaccharides (HMOs), which are unique bioactive components in human milk, are increasingly recognized for their multifaceted roles in infant health. A deeper understanding of the nexus between HMOs and the gut-brain axis can revolutionize neonatal nutrition and neurodevelopmental strategies. METHODS: We performed a narrative review using PubMed, Embase, and Google Scholar to source relevant articles. The focus was on studies detailing the influence of HMOs on the gut and brain systems, especially in neonates. Articles were subsequently synthesized based on their exploration into the effects and mechanisms of HMOs on these interconnected systems. RESULTS: HMOs significantly influence the neonatal gut-brain axis. Specific concentrations of HMO, measured 1 and 6 months after birth, would seem to agree with this hypothesis. HMOs are shown to influence gut microbiota composition and enhance neurotransmitter production, which are crucial for brain development. For instance, 2'-fucosyllactose has been demonstrated to support cognitive development by fostering beneficial gut bacteria that produce essential short-chain fatty acids. CONCLUSIONS: HMOs serve as crucial modulators of the neonatal gut-brain axis, underscoring their importance in infant nutrition and neurodevelopment. Their dual role in shaping the infant gut while influencing brain function presents them as potential game-changers in neonatal health strategies.

Comprehensive lipidomic profiling of human milk from lactating women across varying lactation stages and gestational ages.

An untargeted lipidomic analysis was conducted to investigate the lipid composition of human milk across different lactation stages and gestational ages systematically. A total of 25 lipid subclasses and 934 lipid species as well as 90 free fatty acids were identified. Dynamic changes of the lipids throughout lactation and gestational phases were highlighted. In general, lactation stages introduced more variations in the lipid composition of human milk than gestational ages. Most lipids decreased as the milk progressed from the colostral stage to the mature stage, with some reaching a peak at the transitional stage. Significant variations in lipid composition across gestational ages were predominantly evident during early lactation period. In mature milks, most of the lipids exhibited no discernible statistical differences among gestational ages. This elucidation offers valuable insights and guidance for tailoring precise nutritional strategies for infants with diverse health needs.

The Association Between Maternal Psychological Health and Human Milk Oligosaccharide Composition.

Background and Objective: Human milk oligosaccharides (HMOs) are carbohydrates abundant in human breast milk. Their composition varies widely among women, and prior research has identified numerous factors contributing to this variation. However, the relationship between maternal psychological health and HMO levels is currently unknown. Thus, our objective was to identify whether maternal stress, anxiety, or depressive symptoms are associated with HMOs. Methods: Data originated from 926 lactating individuals from the UC San Diego Human Milk Biorepository. Nineteen prevalent HMOs were assayed using high-performance liquid chromatography. Participants self-reported measures of the Edinburgh Postnatal Depression Scale (n = 495), State-Trait Anxiety Inventory S-Scale (n = 486), and/or Perceived Stress Scale (n = 493) within 60 days of their milk collection; their results were categorized using standard screening cutoffs. HMOs were assessed individually and grouped by principal component analysis (PCA), and associations with maternal psychological symptoms were analyzed using multivariable linear regression adjusted for covariates. Results: After Bonferroni correction (p < 0.002), the following HMOs significantly varied with maternal psychological distress in multivariate analysis: lacto-N-fucopentaose III (LNFP III) and lacto-N-hexaose (LNH) among Secretors with depressive symptoms and difucosyllactose (DFLac), LNFP III, and disialyl-LNH (DSLNH) among Secretors with stress. In PCA, depressive symptoms and stress were associated with one principal component among Secretors. No HMOs varied with anxiety symptoms. Conclusions: Several HMOs varied with maternal depressive symptoms and stress, suggesting a relationship between maternal psychological health and breast milk composition. Additional studies are needed to determine the impact of this variation on infant health.

Achievements and Challenges in Breastfeeding During Two Years of War in Ukraine.

Background: This article informs about the state of breastfeeding in Ukraine after more than 2 years of war. The article presents important information on breastfeeding data, the widespread implementation of the baby-friendly hospital initiative, human milk banks working in difficult situations, the first overestimation of breast milk substitute needs, the International Code, and the presence of donations reaching an overburdened health system. It covers the training of health care professionals as well as counseling in wartime. Conclusion: It is a testimony of important work done on different levels of the Ukrainian population as well as among the aid agencies present and the health system to protect and support breastfeeding for infants and mothers' health in a war situation. The acquired breastfeeding knowledge through BFHI training of health care professionals and the whole package of BFHI measures is important for ensuring the health and survival of children.

Exploring the Potential Probiotic Properties of Bifidobacterium breve DSM 32583-A Novel Strain Isolated from Human Milk.

Human milk is the best nutrition for infants, providing optimal support for the developing immune system and gut microbiota. Hence, it has been used as source for probiotic strain isolation, including members of the genus Bifidobacterium, in an effort to provide beneficial effects to infants who cannot be exclusively breastfed. However, not all supplemented bifidobacteria can effectively colonise the infant gut, nor confer health benefits to the individual infant host; therefore, new isolates are needed to develop a range of dietary products for this specific age group. Here, we investigated the beneficial potential of Bifidobacterium breve DSM 32583 isolated from human milk. We show that in vitro B. breve DSM 32583 exhibited several characteristics considered fundamental for beneficial bacteria, including survival in conditions simulating those present in the digestive tract, adherence to human epithelial cell lines, and inhibition of growth of potentially pathogenic microorganisms. Its antibiotic resistance patterns were comparable to those of known beneficial bifidobacterial strains, and its genome did not contain plasmids nor virulence-associated genes. These results suggest that B. breve DSM 32583 is a potential probiotic candidate.

Shifting the Paradigm for Establishing and Maintaining Milk Production in the Setting of Mother/Infant Separation.

Establishing lactation when mother and infant are separated, such as when the neonate is admitted to the neonatal intensive care unit (NICU), is challenging. The most common clinical advice is to express milk eight or more times per day, every 3 hours, around the clock. Sometimes, the first time that parents hear this is after the birth of their baby. This can be overwhelming and sometimes unachievable. A five-step paradigm shift is proposed that refocuses lactation care on providing evidence-based assistance and ongoing clinical education, and assessment beginning prenatally and extending past maternal discharge, to improve outcomes through curated support. Simple guidelines can begin with expressing milk at least five times a day by Day 5 of life (5 × 5), and expressing milk at least once between 0100 and 0500 (overnight pumping). With these measures, neonatal care in the NICU setting can provide personalized and achievable guidance on pumping schedules.

Armond S. Goldman (1930-2023) and the development of the immunobiology of human milk.

The understanding of the immunobiology of human milk is primarily a 20th-century phenomenon, but, even with our contemporary understanding, it remains a bit of a mystery. Breastfeeding of human milk, although the most obvious and natural form of nutrition for human infants, has been hindered by cultural and societal norms since ancient times. Thus, not all infants have experienced the advantages this form of nutrition may offer. Although these advantages have been anecdotally suggested since ancient times, it was only in the late 19th and early 20th centuries that the superiority of human milk was scientifically documented. The underlying immunobiological properties of human milk underpinning its observed superiority only became appreciated with advances in immunology that occurred in the mid to late 20th century. Armond S. Goldman (1930-2023) was in the vanguard of those promoting and developing an understanding of the immunobiology of human milk and its superiority in promoting the health of human infants.