Maternal Obesity, Milk Composition, and Infant Growth

项目总结 在美国，代际肥胖和糖尿病的流行比例很高，纯母乳喂养 被认为可以降低肥胖和糖尿病从母亲传给孩子的风险。然而，人类乳汁 在非营养性生物活性化合物中表现出高度的个体变异性，我们现在意识到这一点 变异跟踪母亲的营养状况。提供更完善的证据基础是至关重要的 母乳变异的原因和后果，特别是对未来肥胖和 糖尿病。在我们目前的赠款期间，我们正在推进母乳研究领域，以表明母乳 激素和细胞因子浓度，以及新的牛奶代谢特征，显著不同 孕妇体重和肥胖之间的关系，以及这些乳汁“生物活性物质”可以预测婴儿早期发育的改变。这个 成功的前5年母乳队列(母亲和婴儿健康成长)，由以下组成 360纯母乳喂养，非糖尿病的母婴二人组，是为数不多的研究之一 配备了在大样本中全面表征牛奶变化的深度表型 调查对象是妇女，也要研究她们子女之间的潜在联系。该计划的主要目标 建议的续期申请是：1)扩大我们对以下原因和后果的了解 妇女和儿童从出生到5岁的母乳变化。具体目标是：1)确定 母乳生物活性因母亲怀孕、代谢和体重状况不同而不同；2)识别人类 与婴幼儿生长发育和代谢结果有关的乳制品生物活性物质； 测试患有和不患有妊娠期糖尿病的妇女在哺乳期母乳代谢谱的变化。 这些目标将通过利用现有牛奶研究队列和牛奶样本的资源来实现。 并扩大对更多患有妊娠期糖尿病的妇女的招生，特别强调招生和 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，评估 采用全面母乳采样时子代的能量消耗和燃料氧化 技术和代谢组学分析。这项拟议的研究具有重要意义，因为它解决了一个研究不足的问题， 但可能是解释母婴肥胖/糖尿病传播恶性循环的重要途径 在今天很流行。这项研究的结果将有助于设计干预措施，以优化牛奶成分，并 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 在婴儿出生后的头1000天内哺乳妇女及其婴儿。

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.