Maternal Obesity, Breast Milk Composition, and Infant Growth

描述（由申请人提供）：今天，美国大多数孕妇在受孕时超重或肥胖，其后代在出生时具有更大的肥胖症，以后肥胖的风险增加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，全母乳喂养被推荐为前六个月的理想婴儿喂养策略。长期以来，人们一直认为母乳的成分在女性中是相当均匀的，经过进化时间的优化，无论环境如何，都能为成长中的婴儿提供足够的营养。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 浓度的普遍性母体肥胖是人类物种的一种进化上的新病症，但很少有人系统地研究这种新病症如何与母乳脂肪组织来源的激素和细胞因子（脂肪细胞因子）变异相关，或者这种变异是否与婴儿代谢状态相关。我们的目标是全面评估“哺乳期编程”假说，即，是否最近记录的变化，母乳成分与产妇肥胖和婴儿的代谢状态。中心假设是，一个分级的，剂量反应关系之间的母亲肥胖和脂肪细胞因子浓度在母乳中存在，牛奶脂肪细胞因子浓度与改变的身体组成，在他们的纯母乳喂养的后代。在令人信服的初步数据的指导下，并考虑到潜在的混杂因素，将通过以下三个具体目标来检验这一假设：1）确定围产期的暴露窗口（妊娠前、妊娠、产后）当母体体重和体重增加与乳汁脂肪细胞因子浓度相关时; 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;和3）进一步描述母亲肥胖与乳汁变化和婴儿结果的关系，以使用最先进的母亲和婴儿身体组成方法来增强目标1和2，全面的母乳取样技术和代谢组学分析。这项拟议中的研究意义重大，因为它解决了一个研究不足，但潜在的重要途径，解释了当今流行的母婴肥胖传播的恶性循环。研究结果将用于设计干预措施，以减少怀孕和哺乳期间的产妇体重，并增加哺乳教育材料，重点关注肥胖母乳喂养妇女的需求。最终目标是在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.