Maternal Obesity, Breast Milk Composition, and Infant Growth

描述(申请人提供)：如今，美国大多数孕妇在受孕时要么超重，要么肥胖，她们的后代出生时肥胖程度更高，日后肥胖的风险增加2倍，以及新生儿胰岛素抵抗。母乳喂养有许多明显的好处，可能包括防止肥胖及其后遗症，建议将纯母乳喂养作为前六个月婴儿的理想喂养策略。长期以来，人们一直认为，母乳成分在女性中相当一致，经过进化时间的优化，无论环境情况如何，都能为成长中的婴儿提供充足的唯一营养。然而，最近的证据表明，母乳是一种高度复杂的液体，在激素和细胞因子方面存在显著的个体差异。 浓度。对于人类来说，普遍存在的母体肥胖是一种进化上的新疾病，但目前还没有人系统地研究这种新疾病与母乳脂肪组织衍生激素和细胞因子(脂肪细胞因子)变异的关系，或者这种变异是否与婴儿的代谢状态有关。我们的目标是全面评估“哺乳程序”假说，即最近记录的母乳成分变化是否与母亲肥胖和婴儿新陈代谢状态有关。中心假设是，母亲肥胖和母乳中脂肪细胞因子浓度之间存在分级的剂量-反应关系，母乳中脂肪细胞因子浓度与其纯母乳喂养的后代的身体成分变化有关。在令人信服的初步数据指导下，并考虑到潜在的混杂因素，将通过追求三个具体目标来检验这一假说：1)确定围产期(孕前、怀孕、产后)当母亲体重和体重增加与乳汁脂肪细胞因子浓度相关时的暴露窗口；2)测试母乳脂肪细胞因子浓度与婴儿身体组成和胰岛素分泌之间的新关系；以及3)进一步表征母亲肥胖与乳汁变化和婴儿结局的关系，以利用最先进的母婴身体成分方法、全面的母乳采样技术和代谢分析来增强目标1和2。这项拟议的研究意义重大，因为它解决了一条未被充分研究但可能很重要的途径，解释了当今流行的母婴肥胖传播的恶性循环。这项研究的结果将被用于设计干预措施，以减轻怀孕和哺乳期间的母亲体重，并增加哺乳期教育材料，重点关注肥胖哺乳妇女的需求。最终目标是在这一发育可塑性的关键时期为妇女和婴儿提供支持，以预防肥胖、糖尿病和心血管疾病。

DESCRIPTION (provided by applicant): Today the majority of pregnant women in the United States are either overweight or obese at conception with their offspring having greater adiposity at birth, a 2-fold greater risk of later obesity, and neonatal insulin resistance. Breastfeeding ha many clear benefits that may include protection against obesity and its sequelae, and exclusive breast milk feeding is recommended as the ideal infant feeding strategy for the first six months. It was long thought that breast milk composition was fairly uniform among women, having been optimized through evolutionary time to provide adequate sole nutrition for the growing infant regardless of the environmental circumstances. However, recent evidence shows that breast milk is a highly complex fluid with significant inter-individual variation in hormonal and cytokine concentrations. Pervasive maternal obesity is an evolutionarily novel condition for the human species but little effort has yet been made to systematically examine how this novel condition is associated with breast milk adipose-tissue derived hormone and cytokine (adipocytokine) variation, or whether that variation relates to infant metabolic status. Our objective is to comprehensively assess the "lactational programming" hypothesis, that is, whether or not recently documented variation in breast-milk composition is related to both maternal adiposity and to infant metabolic status. The central hypothesis is that a graded, dose-response relationship between maternal adiposity and adipocytokine concentrations in breast milk exists and that milk adipocytokine concentrations are associated with altered body composition in their exclusively breast-fed offspring. Guided by compelling preliminary data, and with consideration of potential confounders, this hypothesis will be tested by pursuing three Specific Aims: 1) Identify windows of exposure during the perinatal period (pre-pregnancy, pregnancy, post-partum) when elevated maternal weight and weight gain are associated with milk adipocytokine concentrations; 2) Test novel relationships between breast-milk adipocytokine concentrations and infant body composition and insulin secretion; and 3) Further characterize the relationship of maternal adiposity to milk variation and infant outcomes, to augment Aims 1 and 2 using state-of-the-science maternal and infant body composition methods, 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 transmission prevalent today. The results of the study will be used to design interventions to reduce maternal weight during pregnancy and lactation and to augment lactation education materials to focus on the needs of obese breast-feeding women. The ultimate goal is to support women and infants during this crucial period of developmental plasticity, for the prevention of obesity, diabetes and cardiovascular disease.