Maternal Obesity, Milk Composition, and Infant Growth

项目摘要 在纯母乳喂养的美国，代际肥胖和糖尿病已达到流行病的程度 被认为可以减少肥胖和糖尿病从母亲传染给孩子的风险。然而，人乳 在非营养性生物活性化合物中表现出很高的个体差异性，我们现在意识到， 差异跟踪母亲的营养状况。关键是要提供一个更完善的证据基础， 母乳变化的原因和后果，特别是对未来肥胖风险高的婴儿， 糖尿病在我们目前的资助期内，我们正在推进母乳研究领域，以证明母乳 激素和细胞因子浓度，以及新的牛奶代谢组学特征， 研究表明，母乳中的“生物活性物质”可以预测婴儿早期生长的改变。的 成功的第一个5年的牛奶队列（母亲和婴儿的健康成长联系），包括 360只纯母乳喂养，非糖尿病母婴配对，是极少数研究之一， 配备了全面表征牛奶变化的大样本的深度表型 妇女，并检查其子女的未来协会。的主要目标 建议的更新申请是：1）扩大我们对原因和后果的理解 从出生到5岁的妇女和儿童的母乳变化。具体目标是：（1）识别 母乳生物活性物质因孕妇怀孕代谢和体重状态而异; 2）识别人类 与婴儿和幼儿生长和代谢结果相关的乳生物活性物质;以及3） 检测GDM和非GDM女性在哺乳期间母乳代谢组学特征的变化。 这些目标将通过利用现有MILK研究队列和乳汁样本的资源来实现， 并通过扩大招生，以额外的妇女与GDM，特别强调招生， 留住有色人种女性这项研究使用了最先进的婴儿身体成分方法， 采用全面母乳采样时后代的能量消耗和燃料氧化 技术和代谢组学分析。这项拟议中的研究意义重大，因为它解决了一个未被充分研究的问题， 但可能是解释母婴肥胖/糖尿病传播恶性循环的重要途径 今天流行。这项研究的结果将有助于设计干预措施，以优化牛奶成分， 为肥胖和糖尿病妇女提供量身定制的哺乳支持。最终目标是支持 在婴儿出生后的前1000天内哺乳的妇女及其婴儿。

PROJECT SUMMARY Intergenerational obesity and diabetes are at epidemic proportions in the US, with exclusive breastfeeding thought to lessen the risk of obesity and diabetes transmission from mother to child. However, human milk exhibits high individual variability in non-nutritive bioactive compounds and we are now realizing that this variation tracks maternal nutritional status. It is critical to provide a more refined evidence base on the causes and consequences of breast milk variation, especially for infants at high risk of future obesity and diabetes. In our current grant period we are advancing the field of human milk research to show that milk hormone and cytokine concentrations, as well as novel milk metabolomic signatures, significantly vary with maternal body weight and adiposity, and that these milk “bioactives” predict altered early infant growth. The successful first 5 years of the MILk cohort (Mothers and Infants Linked for Healthy Growth), composed of 360 exclusively breastfeeding, non-diabetic mother-infant dyads, is one of very few studies that are equipped to both comprehensively characterize milk variation in a large sample of deeply phenotyped women, and also to examine prospective associations in their children. The primary objectives of the proposed renewal application are: 1) to expand our understanding of the causes and consequences of breast milk variation for women and children from birth to age 5 years. The Specific Aims are 1) To identify human milk bioactives that differ by maternal pregnancy metabolic and weight status; 2) To identify human milk bioactives that are associated with infant and early childhood growth and metabolic outcomes; and 3) To test changes during lactation in the metabolomic profile of human milk in women with and without GDM. These aims will be achieved by leveraging the resources of the existing MILk Study cohort and milk specimens, and by expanding enrollment to additional women with GDM, with a particular emphasis on enrolling and retaining women of color. The study uses state-of-the-science infant body composition methods, evaluating energy expenditure and fuel oxidation in the offspring while employing comprehensive breast-milk sampling techniques and metabolomic analysis. The proposed research is significant because it tackles an understudied, but potentially important pathway explaining the vicious cycle of maternal-child obesity/diabetes transmission prevalent today. The results of the study will help to design interventions to optimize milk composition in, and provide tailored lactation support for, women with obesity and diabetes. The ultimate goal is to support breastfeeding women and their infants during the first 1000 days of the child’s life.