Human Breast Milk Enhances Cellular Proliferation in Cornea Wound Healing.

PURPOSE: Corneal epithelial defects from trauma or surgery heal as new epithelial cells grow centripetally from the limbus and replenish the epithelium. Corneal wound healing requires cell signalling molecules. However, a topical treatment with these components is not available. Human breast milk (HBM) offers a potential, novel treatment as it contains bioactive molecules important in epithelial cell healing. This study seeks to investigate the potential of HBM in cornea wound healing. METHODS: Balb/c mice, 8-12 weeks old, were anesthetized prior to creating a 2 mm central cornea epithelial defect. Mice were randomly assigned to a treatment group: HBM, ophthalmic ointment containing neomycin, polymyxin B, dexamethasone (RxTx), or saline and treated 4x/day for 2 days. Wound area was quantified by fluorescein and ImageJ at 0, 8, 24, and 48 h post wounding and eyes used for histology, RT-qPCR, and ELISA. RESULTS: Wounded corneas treated with HBM demonstrated increased re-epithelialization at 8 h post injury compared to saline treatments. ELISA showed significantly higher Ki67 in HBM treated eyes vs. saline control at 8 h (p = 0.0278). Additionally, immunohistology revealed more Ki67 positive cells in the HBM group compared to saline at 8 h and 24 h (p = 0.0063 8 h; p = 0.0007 24 h). For inflammatory analysis, HBM group IL-1ß levels were similar to the saline group, and higher than RxTx treated eyes (p < 0.05). Immunohistochemical staining for CD11b (macrophage marker) revealed HBM-treated eyes had significantly more positive cells vs. saline. RT-qPCR of limbal stem cell markers (LESCs) revealed upregulation of Integrin αV at 8 h with HBM vs. saline. CONCLUSIONS: HBM treatment on corneas with debridement of epithelium demonstrated improved healing, cellular proliferation, and upregulation of the LESC gene transcript, integrin αV, after wounding. Future studies could investigate LESC response to different signalling molecules in HBM to better understand the efficacy of this potential therapy.

Breast milk-transmitted acquired cytomegalovirus infection in an extremely low birth weight infant.

We encountered an extremely low birth weight infant with breast milk-transmitted cytomegalovirus (CMV) infection. To determine the transmission route, we conducted direct sequence analysis of two variable CMV genes, UL139, and UL146. When utilizing breast milk, the possibility of acquired CMV infection should be considered and tested for prompt diagnosis and treatment.

Mother's Milk Donation to a Human Milk Bank During Bereavement: Circumstances Associated with Completing the Donation Process.

Background: Bereaved mothers describe positive experiences donating breast milk and negative experiences when not informed of opportunities to donate. Predictors of whether mothers donate milk are unknown, impairing efforts to optimize support in completing donation. Objective: To define circumstances associated with completing mother's milk (MM) donation during bereavement. Methods: A retrospective cohort study included dyads of bereaved mothers and their deceased children if a child's death occurred on-site at a quaternary care children's hospital during 2016-2020, the child had documentation of MM availability, and age at death <24 months. The primary outcome was the completion of MM donation to the milk bank. Multivariate logistic regression measured associations between clinical variables and odds of completion. Results: Of 124 deceased children with documented MM exposure, 34 mothers (28%) of 35 of those children completed MM donation, donating a mean of 13.7 liters (SD 16.8). The child's race/ethnicity documented in the medical record was White for 25 (71%), Black/African American (AA) for 1 (3%), Asian for 1 (3%), and Hispanic/Latino for 8 (23%). Referenced to mothers of White children, being a mother of an AA [OR 0.05 (95% CI: 0.01-0.43)] or Asian [0.08 (0.01-0.75)] child was associated with lower odds of donation. Referenced to mothers delivering full term (≥37 weeks'), mothers delivering <34 weeks showed higher odds [5.0 (1.5-17.5)] of donation. Conclusion: Relatively few bereaved mothers of children with indicators of MM exposure completed donation. The results suggest an opportunity to ensure bereaved mothers are uniformly informed and supported in donating.

Maternal-infant transfer of SARS-CoV-2 antibodies following vaccination in pregnancy: A prospective cohort study.

OBJECTIVES: To measure and evaluate the impact of receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in pregnancy on immunoglobulin G (IgG) and immunoglobulin A (IgA) titres in maternal and infant samples. DESIGN: Prospective cohort study. SETTING: Tertiary obstetric centre. POPULATION OR SAMPLE: 52 pregnant women who received one or more SARS-CoV-2 vaccine doses during pregnancy and their neonates. METHODS: IgG and IgA concentrations against SARS-CoV-2 antigens were measured from samples collected at delivery and 4-6 weeks postpartum and compared using Spearman correlations. MAIN OUTCOME MEASURES: Maternal and infant IgG and IgA titres in response to vaccination and infection in pregnancy. RESULTS: In maternal serum collected at delivery, participants without evidence of prior infection who received 3 + doses of a SARS-CoV-2 vaccine had higher Anti-Spike (S) IgG geometric mean concentrations (log10 AU/mL)(GMC) than those who received 2 doses (3 + Doses = 5.00, 2 Doses = 4.60, p = 0.08). The differences in IgG Anti-S GMC were statistically significant in cord serum, and in postpartum samples of maternal serum, infant serum and breast milk (Cord GMCs: 3 + Doses = 5.32, 2 Doses = 4.98, p < 0.05; Postpartum maternal serum GMCs: 3 + Doses = 5.25, 2 Doses = 4.57, p < 0.001; Postpartum infant serum GMCs: 3 + Doses = 5.10, 2 Doses = 4.72, p = 0.03; Postpartum breast milk GMCs: 3 + Doses = 2.61, 2 Doses = 1.94, p < 0.0001). Among participants with 3 + Doses, those with evidence of SARS-CoV-2 infection had statistically significant higher anti-S IgG GMCs than those without prior infection (Maternal serum at delivery: SARS-CoV-2+=5.65, SARS-CoV-2-=5.00, p = 0.004; Cord: SARS-CoV-2+=5.68, SARS-CoV-2-=5.32, p = 0.02; Postpartum maternal serum: SARS-CoV-2+=5.66, SARS-CoV-2-=5.25, p < 0.001; postpartum infant serum: SARS-CoV-2+=5.50, SARS-CoV-2-=5.10, p = 0.003; Postpartum breast milk: SARS-COV-2+=3.25, SARS-COV-2-=2.61, p = 0.009). Significant positive correlations were found for anti-S IgG titres between paired maternal and infant samples at delivery and postpartum (Delivery: R = 0.91, p < 0.001; postpartum: R = 0.86, p < 0.001). CONCLUSIONS: Receipt of a SARS-CoV-2 vaccine and SARS-CoV-2 infection elicit strong IgG and IgA antibody responses in pregnant women with evidence of transplacental transfer to the fetus.

From frozen to feeding: storage characteristics of banked donor human milk used in a single level IV academic neonatal intensive care unit.

Background: The storage time of banked donor human milk (DHM) administered in an academic hospital to critically ill preterm neonates was previously unknown. Objective: This study was designed to determine the storage time of banked DHM by measurements obtained at the hospital level (by lot finish date) and individual patient level (by feeding date) over 2-year observation period. Results: Both methods of measuring storage time (hospital-level and patient-level) showed that DHM was stored on average 8 ±1 months before use. Variations in storage time fluctuated across months with a minimum and maximum storage duration of 119 to 317 days. Most infants received a median of 3 [2-5 IQR] unique lots of DHM. Conclusion: The storage time of DHM was successfully measured. Over 95% of DHM received was stored longer than 6 months. Storage times varied widely, uncovering a potential area of future research.

Streptococcus raffinosi sp. nov., isolated from human breast milk samples.

Novel Gram-positive, catalase-negative, α-haemolytic cocci were isolated from breast milk samples of healthy mothers living in Hanoi, Vietnam. The 16S rRNA gene sequences of these strains varied by 0-2 nucleotide polymorphisms. The 16S rRNA gene sequence of one strain, designated as BME SL 6.1T, showed the highest similarity to those of Streptococcus salivarius NCTC 8618T (99.4 %), Streptococcus vestibularis ATCC 49124T (99.4 %), and Streptococcus thermophilus ATCC 19258T (99.3 %) in the salivarius group. Whole genome sequencing was performed on three selected strains. Phylogeny based on 631 core genes clustered the three strains into the salivarius group, and the strains were clearly distinct from the other species in this group. The average nucleotide identity (ANI) value of strain BME SL 6.1T exhibited the highest identity with S. salivarius NCTC 8618T (88.4 %), followed by S. vestibularis ATCC 49124T (88.3 %) and S. thermophilus ATCC 19258T (87.4 %). The ANI and digital DNA-DNA hybridization values between strain BME SL 6.1T and other species were below the cut-off value (95 and 70 %, respectively), indicating that it represents a novel species of the genus Streptococcus. The strains were able to produce α-galactosidase and acid from raffinose and melibiose. Therefore, we propose to assign the strains to a new species of the genus Streptococcus as Streptococcus raffinosi sp. nov. The type strain is BME SL 6.1T (=VTCC 12812T=NBRC 116368T).

Personalized Nutrition with Banked Human Milk for Early Gut Microbiota Development: In Pursuit of the Perfect Match.

The correct initial colonization and establishment of the gut microbiota during the early stages of life is a key step, with long-lasting consequences throughout the entire lifespan of the individual. This process is affected by several perinatal factors; among them, feeding mode is known to have a critical role. Breastfeeding is the optimal nutrition for neonates; however, it is not always possible, especially in cases of prematurity or early pathology. In such cases, most commonly babies are fed with infant formulas in spite of the official nutritional and health international organizations' recommendation on the use of donated human milk through milk banks for these cases. However, donated human milk still does not totally match maternal milk in terms of infant growth and gut microbiota development. The present review summarizes the practices of milk banks and hospitals regarding donated human milk, its safety and quality, and the health outcomes in infants fed with donated human milk. Additionally, we explore different alternatives to customize pasteurized donated human milk with the aim of finding the perfect match between each baby and banked milk for promoting the establishment of a beneficial gut microbiota from the early stages of life.

Human Milk Protein-Derived Bioactive Peptides from In Vitro-Digested Colostrum Exert Antimicrobial Activities against Common Neonatal Pathogens.

Human milk reduces risk for necrotizing enterocolitis in preterm infants. Necrotizing enterocolitis occurs in the ileocecal region where thousands of milk protein-derived peptides have been released from digestion. Digestion-released peptides may exert bioactivity, such as antimicrobial and immunomodulatory activities, in the gut. In this study, we applied mass spectrometry-based peptidomics to characterize peptides present in colostrum before and after in vitro digestion. Sequence-based computational modeling was applied to predict peptides with antimicrobial activity. We identified more peptides in undigested samples, yet the abundances were much higher in the digested samples. Heatmapping demonstrated highly different peptide profiles between undigested and digested samples. Four peptides (αS1-casein [157-163], αS1-casein [157-165], ß-casein [153-159] and plasminogen [591-597]) were selected, synthesized and tested against common pathogenic bacteria associated with necrotizing enterocolitis. All four exhibited bacteriostatic, though not bactericidal, activities against Klebsiella aerogenes, Citrobacter freundii and Serratia marcescens, but not Escherichia coli.

Physiology of Human Lactation and Strategies to Support Milk Supply for Breastfeeding.

Despite advances across the globe in breastfeeding initiation rates, many families continue to report they are not meeting their breastfeeding goals. Concerns about milk supply, infant nutritional intake, and infant weight gain are among the most commonly cited reasons for early breastfeeding cessation. Nurses working with individuals during the perinatal period are uniquely positioned to educate families and offer evidence-based interventions to promote optimal milk supply, infant growth, and maternal mental and physical health. Such interventions include early and frequent skin-to-skin care, emptying of the breast, and professional lactation support. By implementing such evidence-based practices in the first hours after birth and connecting families to lactation support in the first 14 days, nurses can begin to help families achieve their breastfeeding goals.

Indications for extensively hydrolyzed cow's milk protein in the neonatal period.

A large proportion of prescriptions for extensively hydrolyzed cow's milk protein (CMP) in newborns are not based on any scientific data justifying the indication. Many of these prescriptions are old habits or are based on incomplete data. The aim of this article is to analyze these practices and propose recommendations. The following points are covered: (a) indications for extensively hydrolyzed formula based on studies demonstrating their benefits in these situations-newborns with a proven allergy to CMP and occasional prescription of supplements to breastfeeding; (b) possible indications not based on a high level of evidence-re-initiation of feeding due to necrotizing enterocolitis, short bowel syndrome, re-initiation of feeding of newborns following intestinal surgery, and laparoschisis if neither the mother's own milk nor milk from a lactarium is available; (c) unjustified indications-newborns at risk of atopy, prematurity, severe neurological pathologies, newborns who are hemodynamically unstable and/or have congenital cardiopathy, neonatal hypoxic-ischemic encephalopathy treated with hypothermia, and newborns with esophageal atresia or diaphragmatic hernia. By following this classification, the prescriber will be guided to use the milk best suited to the pathology, bearing in mind that each situation must be adapted individually and the tolerance and effectiveness of the food reassessed from a nutritional and functional point of view.

A rapid review of motives and barriers for living substance of human origin donation and an extended typology.

Our objective is to review motives and barriers for non-reproductive, living substance of human origin (SoHO) donation, and to extend existing typologies beyond blood. The expansion of SoHO collection is currently unmatched by increased living donors. Thus, there is a critical need to understand how to effectively recruit and retain donors to ensure a sustainable supply of SoHO. We undertook a rapid review and narrative synthesis of published, peer-reviewed literature reporting on motives and/or barriers for living SoHO donation (whole-blood, blood products [2009-2023], bone marrow/stem cells, cord blood, organ, human breast milk, intestinal microbiota [2000-2023]). Results were interpreted through directed qualitative content analysis using an extended typology of motives/barriers largely drawn from blood donation research, and subsequently refined based on results to be inclusive of other SoHO. 234 articles with 237 studies met review criteria. Most were quantitative (74.3%), conducted in Western countries (63.8%), focused on blood donation (64.2%), reported motives and barriers (51.9%) and did not examine differences by donor characteristics or history (74%). We present a revised typology inclusive of motives/barriers for donation of substances beyond blood. This shows while broader motives and barriers are shared across substances donated, there are critical differences at the subcategory level that may account for heterogeneity in results of prior interventions. The nuances in how broad categories of motives and barriers manifest across different SoHO are critical for blood collection agencies to consider as they attempt to expand collection of products beyond whole-blood, plasma, and platelets. WHAT IS KNOWN ABOUT THE TOPIC?: Blood collection agencies (BCAs) continue to expand SoHO product collection beyond whole-blood, plasma, and platelets. The demand for SoHO is currently unmatched by increased living donors. The need to understand how to recruit new and retain existing living donors to ensure a sustainable supply of SoHO remains critical. However, there is no available synthesis of the factors, such as motives/facilitators and barriers/deterrents, to inform our understanding. WHAT IS NEW?: Comprehensively reviewed evidence for motives and barriers of willing/actual donors and nondonors across all types of non-reproductive living SoHO donation. Explored variations in motives and barriers based on substance, donor history and demographic differences (gender, age, ethnicity or culture). Extended typology of motives and barriers inclusive of all non-reproductive living SoHO, beyond solely whole-blood and blood products. Identified that while there are commonalities in the overarching motive and barrier categories across substances (e.g., prosocial motivation, low self-efficacy), within these broader constructs there are differences at the subcategory level (e.g., low-self efficacy was about eligibility, lifestyle barriers, or lack/loss of financial or material resources depending on the substance donated) that are crucial for development of future interventions and for BCAs to consider as they expand SoHO product collection. Highlighted the continued focus on motives and barriers for whole-blood and blood product donation to the exclusion of other, particularly newer, SoHO; lack of qualitative work for newer SoHO; and lack of consideration of differences based on donor characteristics (especially ethnicity/culture) and donor history, which limits our understanding. WHAT ARE THE KEY QUESTIONS FOR FUTURE WORK ON THE TOPIC?: What are the motives and barriers (in both qualitative and quantitative studies) for donation of newer SoHO such as stem cells, cord blood, human milk, and intestinal microbiota? Are there differences in motives and barriers within and across SoHO that are informed by individual and contextual-level factors? How can we develop interventions that respond to the nuances of motives and barriers present across different forms of SoHO that are effective in encouraging new and maintaining continuing donors?

Prevalence and concentration of aflatoxin M1 in breast milk in Africa: a meta-analysis and implication for the interface of agriculture and health.

Breast milk is one of the many distinct forms of food that can be contaminated with aflatoxin M1 (AFM1). They may be consumed by eating contaminated foods, such as contaminated meat and crops, which would then be present in breast milk and cause health problems, including nervous system disorders and cancers of the lungs, liver, kidneys, and urinary tract. However, the prevalently inconsistent explanation of prevalence and concentration remains a big challenge. Thus, this meta-analysis was conducted to determine the prevalence and concentration of harmful chemicals in breast milk in an African context. The databases MEDLINE, PubMed, Embase, SCOPUS, Web of Science, and Google Scholar were searched for both published and unpublished research. To conduct the analysis, the collected data were exported to Stata version 18. The results were shown using a forest plot and a prevalence with a 95% confidence interval (CI) using the random-effects model. The Cochrane chi-square (I2) statistics were used to measure the studies' heterogeneity, and Egger's intercept was used to measure publication bias. This review included twenty-eight studies with 4016 breast milk samples and newborns. The analysis showed the overall prevalence and concentration of aflatoxin M1 in breast milk were 53% (95% CI 40, 65; i2 = 98.26%; P = 0.001). The pooled mean aflatoxin M1 concentration in breast milk was 93.02 ng/l. According to this study, the eastern region of Africa was 62% (95% CI 39-82) profoundly affected as compared to other regions of the continent. In subgroup analysis by publication year, the highest level of exposure to aflatoxins (68%; 95% CI 47-85) was observed among studies published from 2010 to 2019. This finding confirmed that more than half of lactating women's breast milk was contaminated with aflatoxin M1 in Africa. The pooled mean aflatoxin M1 concentration in breast milk was 93.02 ng/l. According to this study, the eastern region of Africa was profoundly affected compared with other regions. Thus, the government and all stakeholders must instigate policies that mitigate the toxicity of aflatoxins in lactating women, fetuses, and newborns.

The relationship between mothers' body composition and anthropometric characteristics of baby and breast milk nutrient content: A cross-sectional study.

BACKGROUND: The composition and amount of breast milk is affected by factors such as the duration and frequency of breastfeeding, the time between two breastfeeding sessions, the effectiveness of breastfeeding, breastfeeding technique, genetic characteristics of the mother and diet. Breast milk macronutrients are provided by milk synthesized in lactocytes, mother's diet and maternal stores. RESEARCH AIM: This study was conducted to investigate the relationship between the body composition of mothers and the anthropometric characteristics of the baby and the nutritional content of breast milk. METHOD: The descriptive study was conducted between March and November 2023 in a hospital in a low socioeconomic neighbourhood in Turkey. The study sample consisted of 96 mothers and ibabies. Anthropometric measurements of mothers and babies and the nutrient content of breast milk were evaluated on the first postpartum day, Days 5 and 15. Breast milk macronutrient content was analyzed by Miris milk analyzer and body composition of mothers was analyzed by TANITA BC 730. RESULTS: From the weight and body composition of the mothers in the study group; a positive correlation was found between body fat, muscle and water ratio, and breast milk carnonhydrate and protein (p < 0.05). There was no correlation between the gestational age of the baby and the content of breast milk (p > 0.05). A positive correlation was found between the weight and height of the babies and the macronutrients of breast milk (p < 0.05). CONCLUSION: As the weight of mothers increases, breast milk protein and carbohydrate levels increase. As breast milk macronutrients increase, babies' weight and height increase.

Biological clock and circadian rhythm of breast milk composition.

Breast milk provides numerous benefits for both the baby and the mother, making it a unique and valuable food. The World Health Organization and the United Nations International Children's Emergency Found (UNICEF) state that exclusive breastfeeding in the first six months of life is an important strategy for reducing mortality and morbidity in infants. The circadian rhythm formation, which starts in the mother's womb, continues after the baby is born. Breast milk plays an active role in regulating the baby's circadian rhythm through the hormones, basic immune factors and bioactive components it contains, as well as meeting almost all nutritional elements for babies. Since the neural control mechanisms in the newborn are not yet fully developed, breast milk undertakes the task of helping the biological rhythms in the regulation of the infant's sleep-wake cycles, thanks to the circadian rhythm of some elements in its composition. There are studies showing that breast milk contains high levels of cortisol and amino acids that promote activity during the day, while night milk has high levels of melatonin and tryptophan, and micronutrients vary throughout the day. A better understanding of the circadian rhythm displayed by the elements in the composition of breast milk is important for improving maternal and infant health. Since there are many factors affecting the composition of breast milk, it is recommended that breast milk studies should be done on a country or regional basis, and breastfeeding policies can be developed as a result of the results to be obtained.

Stakeholders' views of the Baby Friendly Initiative implementation and impact: a mixed methods study.

BACKGROUND: The Baby Friendly Hospital Initiative (BFHI) was launched in 1991 as an intervention to support healthy infant feeding practices, but its global coverage remains around 10%. This study aimed to explore stakeholders' views of the Baby Friendly Initiative (BFI) programme, the barriers and facilitators to accreditation and its perceived impact. METHODS: A mixed methods approach was used. An online survey was distributed through numerous professional networks from September 2020 to November 2020. Quantitative data were analyzed using descriptive statistics, with simple content analysis undertaken on open-ended responses. Individual semi-structured interviews were also undertaken and analyzed using inductive thematic analysis. RESULTS: A total of 322 respondents completed the survey in part or in full, mainly from the United Kingdom. Fifteen key stakeholders and two maternity service users undertook interviews. Respondents were from various professional backgrounds and currently worked in different roles including direct care of women and their families, public health, education and those responsible for purchasing health services. Survey respondents viewed the BFI to have the greatest impact on breastfeeding initiation, duration, and infant health outcomes. Three overall themes were identified. The first was "BFI as an agent for change". Most participants perceived the need to implement the whole package, but views were mixed regarding its impact and the accreditation process. Secondly, BFI was regarded as only "one part of a jigsaw", with no single intervention viewed as adequate to address the complex cultural context and social and health inequities that impact breastfeeding. Finally, "cultural change and education" around breastfeeding were viewed as essential for women, staff and society. CONCLUSIONS: The BFI is not a magic bullet intervention. To create a more supportive breastfeeding environment within society a holistic approach is required. This includes social and cultural changes, increased education ideally starting at school age, and advancing positive messaging around breastfeeding within the media, as well as fully banning breastmilk substitute advertising. Although the BFI comprises a whole package, few survey respondents rated all aspects as equally important. Additional evidence for the effectiveness of each element and the importance of the whole package need to be established and communicated.

Protection from environmental enteric dysfunction and growth improvement in malnourished newborns by amplification of secretory IgA.

Environmental enteric dysfunction (EED) is a condition associated with malnutrition that can progress to malabsorption and villous atrophy. Severe EED results in linear growth stunting, slowed neurocognitive development, and unresponsiveness to oral vaccines. Prenatal exposure to malnutrition and breast feeding by malnourished mothers replicates EED. Pups are characterized by deprivation of secretory IgA (SIgA) and altered development of the gut immune system and microbiota. Extracellular ATP (eATP) released by microbiota limits T follicular helper (Tfh) cell activity and SIgA generation in Peyer's patches (PPs). Administration of a live biotherapeutic releasing the ATP-degrading enzyme apyrase to malnourished pups restores SIgA levels and ameliorates stunted growth. SIgA is instrumental in improving the growth and intestinal immune competence of mice while they are continuously fed a malnourished diet. The analysis of microbiota composition suggests that amplification of endogenous SIgA may exert a dominant function in correcting malnourishment dysbiosis and its consequences on host organisms, irrespective of the actual microbial ecology.

The association between maternal factors and milk hormone concentrations: a systematic review.

Background: Breast milk is the gold standard for infant feeding. It is a dynamic biological fluid rich in numerous bioactive components. Emerging research suggests that these components, including hormones, may serve as signals between mother and offspring. From an evolutionary perspective, maternal hormonal signals could allow co-adaptation of maternal and offspring phenotype, with implications for their Darwinian fitness. However, a series of steps need to be considered to establish the role of a component as a signal and this systematic review focuses on one step: 'Do maternal factors influence the concentration of milk hormones?' Objective: To systematically review human studies which analyze the association between maternal factors and the concentration of hormones in breast milk. Methods: Three databases were searched for studies reporting the association of maternal factors including body mass index (BMI), weight, fat mass, age, ethnicity, smoking with hormones such as adiponectin, leptin, insulin, ghrelin, and cortisol in breast milk. Results: Thirty-three studies were eligible for inclusion. Maternal BMI was positively associated with milk leptin (20/21 studies) and with milk insulin (4/6 studies). Maternal weight also displayed a positive correlation with milk leptin levels, and maternal diabetes status was positively associated with milk insulin concentrations. Conversely, evidence for associations between maternal fat mass, smoking, ethnicity and other maternal factors and hormone levels in breast milk was inconclusive or lacking. Conclusion: Current evidence is consistent with a signaling role for leptin and insulin in breast milk, however other steps need to be investigated to understand the role of these components as definitive signals. This review represents a first step in establishing the role of signaling components in human milk and highlights other issues that need to be considered going forward.

Transfer of celiac disease-associated immunogenic gluten peptides in breast milk: variability in kinetics of secretion.

Background: Exposure to antigens is crucial for child immune system development, aiding disease prevention and promoting infant health. Some common food antigen proteins are found in human breast milk. However, it is unclear whether gluten antigens linked to celiac disease (CD) are transmitted through breast milk, potentially impacting the development of the infant's immune system. Objective: This study aimed to analyze the passage of gluten immunogenic peptides (GIP) into human breast milk. We evaluated the dynamics of GIP secretion after lactating mothers adopted a controlled gluten-rich diet. Methods: We prospectively enrolled 96 non-CD and 23 CD lactating mothers, assessing total proteins and casein in breast milk, and GIP levels in breast milk and urine. Subsequently, a longitudinal study was conducted in a subgroup of 12 non-CD lactating mothers who adopted a controlled gluten-rich diet. GIP levels in breast milk and urine samples were assayed by multiple sample collections over 96 hours. Results: Analysis of a single sample revealed that 24% of non-CD lactating mothers on a regular unrestricted diet tested positive for GIP in breast milk, and 90% tested positive in urine, with significantly lower concentrations in breast milk. Nevertheless, on a controlled gluten-rich diet and the collection of multiple samples, GIP were detected in 75% and 100% of non-CD participants in breast milk and urine, respectively. The transfer dynamics in breast milk samples were long-enduring and GIP secretion persisted from 0 to 72 h. In contrast, GIP secretion in urine samples was limited to the first 24 h, with inter-individual variations. In the cohort of CD mothers, 82.6% and 87% tested negative for GIP in breast milk and urine, respectively. Conclusions: This study definitively established the presence of GIP in breast milk, with substantial inter-individual variations in secretion dynamics. Our findings provide insights into distinct GIP kinetics observed in sequentially collected breast milk and urine samples, suggesting differential gluten metabolism patterns depending on the organ or system involved. Future research is essential to understand whether GIP functions as sensitizing or tolerogenic agents in the immune system of breastfed infants.

Relationship between Receipt of the Samples of Breast Milk Substitutes in Hospitals and Breastfeeding Practice in Japan.

Objective: This study estimated the percentage of mothers who received samples of breast milk substitutes at medical facilities and examined the relationship between receipt of the samples and breastfeeding practices in Japan. Methods: We used the data from the "The Japan COVID-19 and Society Internet Survey (JACSIS)" conducted in 2021. Two groups of mothers were analyzed: mothers 0-5 months postpartum (n = 1,412) and mothers 5-12 months postpartum (n = 2,045). Logistic regression analysis was conducted with the practice of exclusive breastfeeding as the dependent variable and the receipt of the sample as the explanatory variable. Exclusive breastfeeding was defined in different ways for each group: "exclusive breastfeeding under five months" as measured by 24-hour recall for mothers 0-5 months postpartum, and "exclusive breastfeeding for the first five months" as defined by asking mothers 5-12 months postpartum when they first fed infant formula or baby food and when they finished breastfeeding. Results: The proportion of mothers who received the samples was 82.4%. We found that mothers who received the samples were found to be less likely to continue "exclusive breastfeeding under five months" (odds ratio: 0.71, 95% confidence interval [CI]: 0.51-0.98). In addition, a similar trend was found in a subsample analysis restricted to mothers who intended to breastfeed during pregnancy (odds ratio: 0.62, 95% CI: 0.40-0.94). Conclusions: This study showed that more than 80% of mothers had received the samples of breast milk substitutes, and that receipt of the samples decreased the probability of their practicing exclusive breastfeeding. Regulating distribution of the samples at medical facilities is necessary to prevent interruptions of exclusive breastfeeding.

Smoking-induced suppression of ß-casein in milk is associated with an increase in miR-210-5p expression in mammary epithelia.

Smoking during lactation harmfully affects the amount and constituents of breast milk. Infants who consume breast milk containing miR-210-5p may have a higher risk of brain-related diseases. We investigated whether smoking during lactation decreases ß-casein concentrations in milk and whether miR-210-5p expression is involved in smoking-induced ß-casein suppression. During lactation, maternal CD1 mice were exposed to cigarette smoke (1.7 mg of tar and 14 mg of nicotine) in a smoke chamber for 1 h twice/day for five consecutive days. Control mice were placed in an air-filled chamber equivalent in size to the smoke chamber, with maternal separation times identical to those of the smoked mice. Maternal exposure to smoke during lactation significantly decreased ß-casein expression in the mammary epithelia of smoked mice compared to that of the control mice. Signal transducer and activator transcription 5 (STAT5) and phosphorylated STAT5 (pSTAT5) are transcription factors involved in ß-casein expression. In the mammary epithelia of smoked mice, the pSTAT5 and STAT5 levels were significantly lower, and miR-210-5p expression was significantly higher than that of the control mice. The ß-casein, pSTAT5, and STAT5 protein levels of miR-210-5p mimic-transfected human mammary epithelial MCF-12A cells were significantly lower than those of control siRNA-transfected cells. These results indicate that smoke exposure led to an increase in miR-210-5p expression in mammary epithelium and a decrease in pSTAT5 and ß-casein protein levels through the inhibition of STAT5 expression. Moreover, nicotine treatment decreased ß-casein protein levels and increased miR-210-5p expression in non-malignant human mammary epithelial MCF-12A cells in a concentration-dependent manner, demonstrating that nicotine significantly affects the ß-casein and miR-210-5p levels of breast milk. These results highlight the adverse effects of smoking on breast milk, providing essential information for healthcare professionals and general citizens.