Mammary Epithelium Permeability, Lactation Outcomes, and Infant Health

乳腺上皮渗透性、哺乳结果和婴儿健康

• 批准号: 10753649
• 负责人: Kathleen Frances Arcaro
• 金额: $ 70.07万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-11 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753649
• 关键词: 37 weeks gestation; Academy; Address; Affect; Allergic Disease; American; Anti-Inflammatory Agents; Antibodies; Antibody-mediated protection; Autoimmune Diseases; Bacteria; Behavioral; Bilateral; Birth; Black race; Breast; Breast Feeding; Carbohydrates; Cohort Studies; Counseling; Data; Dietary Intervention; Elements; Enrollment; Fatty acid glycerol esters; Geography; Goals; Growth; Growth Factor; Growth and Development function; Health; Health Benefit; Hispanic; Human; Human Milk; Immune; Immune system; Indigenous; Infant; Infant Health; Inflammation; Inflammatory; Intervention; Intestines; Knowledge; Lactation; Life; Link; Literature; Longitudinal Studies; Maintenance; Massachusetts; Measures; Milk; Mothers; New Mexico; Nutrient; Nutritional; Outcome; Parents; Participant; Pathway interactions; Pattern; Pediatrics; Perception; Periodicals; Permeability; Pharmaceutical Preparations; Physiological; Physiology; Population; Postpartum Period; Pregnant Women; Prevalence; Probiotics; Proteins; Public Hospitals; Questionnaires; Recommendation; Reporting; Research; Risk Factors; Role; Sampling; Severities; Sodium; Supplementation; Systems Development; Testing; Third Pregnancy Trimester; Tissues; United States; Weaning; Woman; Work; clinical practice; clinically relevant; cohort; cytokine; dietary; dysbiosis; ethnic diversity; gastrointestinal epithelium; gut microbiome; improved; improved outcome; infection risk; mammary; mammary epithelium; mastitis; microbial; microbiome; microbiome composition; milk microbiome; milk removal; milk secretion; milk supply; novel; obesity in children; prevent; racial diversity; recruit

Project Summary/Abstract Human milk provides significant health benefits for infants. Beyond nutrients, breastmilk contains antibodies for immunity, growth factors associated with gut epithelial maturation, bacteria for establishment of the gut microbiome, and metabolites that modulate inflammation. These important elements of human milk support strong immune system development within the infant gut and better infant health. Unfortunately, many parents aiming to breastfeed will supplement or wean earlier than planned and frequently report perceived low milk supply as the reason. Increased mammary epithelium permeability (IMEP), as indicated by elevated milk sodium, is a physiologic condition that could have significant implications for milk secretion, composition and infant health. Lactation physiology studies have established that closed paracellular pathways, i.e., low permeability, are essential for the establishment and maintenance of adequate milk secretion. Human studies on permeability have focused on the period of secretory activation and persistent mammary epithelium permeability at day 7 postpartum has been associated with perceived low milk supply. However, little is known about IMEP during established lactation. We recently reported that IMEP among US women is more common across lactation than previously recognized. Longitudinal US studies are needed to quantify mammary epithelium permeability during established lactation and to investigate the extent to which increased permeability influences lactation insufficiency. Our overall goal is to establish a clinically relevant robust IMEP threshold, based on our analysis of sodium as a continuous variable, and determine the extent to which IMEP is associated with suboptimal lactation outcomes and reduced infant health. We propose that IMEP is associated with low milk supply and earlier than desired weaning. We also posit that IMEP results in altered milk nutrient content, shifted inflammatory profiles and milk microbiome composition impacting the infant gut immune profile and microbiome. We will enroll a diverse cohort of 400 mother-infant dyads from New Mexico and Massachusetts. Participants will provide bilateral milk and infant fecal samples at four timepoints spanning transitional, early and mature milk. Understanding the extent of IMEP linkage to suboptimal lactation outcomes and infant intestinal health is of major importance because IMEP can be measured, treated and prevented. Interventions to limit IMEP could include behavioral and dietary changes, as well as medications or supplements. This will be the first study to determine the prevalence of IMEP and associated changes in milk throughout the first five months postpartum, and the only large US cohort study of IMEP. Results from this study could lead to a major change in clinical practice. Assessment of IMEP in milk could become routine, especially among women seeking lactation counseling, and this may lead to improved outcomes. We expect that our geographically and ethnically diverse cohorts will provide novel data on differences in risk factors for IMEP with implications for lactation outcomes.

项目总结/文摘