Secondary Analyses of RCT Data on Infant Formula and Nutritional Programming

项目摘要 Precis：我们的目标是对来自随机数据集的综合数据进行二次数据分析 旨在确定早期差异的能量平衡机制的对照试验(RCT) 喂食蛋白质形式不同的等卡路里婴儿配方奶粉的婴儿体重增加。 除了实现主要目标外，我们还收集了母亲的多种表型- RCT期间的婴儿二胎，从产后2周持续到婴儿12.5个月，有一个 随访评价时间为1.5年。因此，我们有一个独特的机会，超越了 评估早期饮食对高度普遍的糖尿病现象的直接和间接影响的原始随机对照试验 营养节目。 这项试验随机选择了一组不同的健康婴儿(60%是美国黑人)，分别喂养两种奶粉中的一种 (CMF)或生命第一年的等卡路里广泛水解式(EHF)。随机化到CMF， 与流行性出血热相比，显著增加了早期快速体重增加的可能性，这是后来肥胖的一个风险因素， 通过能量流入和流出的差异。在整个过程中收集的其他表型(次要结果) RCT包括对发育里程碑、饮食、母亲喂养方式、食物偏好和 味觉基因。这些数据将进行二次分析，并根据假设， 与人体测量的主要结果相比，早期体重增加、肥胖和体力活动。 该提案的核心是五个目标，完成后将产生至少六份出版物。目标1将 测试已提出的风险因素(早期体重快速增加、体力活动减少、运动发育延迟)和 生物标志物(乳牙萌出的时间)独立或联合预测肥胖和Z评分 12.5个月零1.5年。目标2将从每月的饮食记录中确定配方奶喂养的模式和 从母亲的喂养行为问卷中，检验奶瓶中配方奶粉类型的假设 与母亲的喂养做法相比，这是导致早期体重增加轨迹和儿童肥胖的更大因素。 由于流行性出血热的味道比CMF更苦，因此AIM 3将检验流行性出血热喂养的婴儿将更多 接受CMF喂养的婴儿食用西兰花口味的食物；已知苦味感受器的遗传变异 被西兰花中的硫代葡萄糖苷激活将在分析中被考虑在内。目标4将描述模式， 随着时间的推移，母亲饮食的质量、营养含量和与其孩子的饮食相一致。目标5 每月将提供与(A)配方与非配方的能量贡献相关的描述性数据 和(B)确定用于估计婴儿的经验方程的准确性 基础代谢和总能量消耗，通过与实际能量消耗测量进行比较。 这些分析将增加关于早期方案拟订的知识库，目的是改善 配方奶粉喂养的下一代婴儿。

PROJECT ABSTRACT Précis: Our goal is to conduct secondary data analyses on a comprehensive data set from a randomized controlled trial (RCT) designed to determine the energy balance mechanisms underlying the differential early weight gain experienced by infants who were fed isocaloric infant formulas that differed in the form of protein. In addition to accomplishing the primary aims, we collected multiple and diverse phenotypes from mother- infant dyads during the RCT, which lasted from 2 weeks postpartum until infants were 12.5 months, with a follow-up evaluation at 1.5 years. Therefore, we have a unique opportunity that go beyond the goals of the original RCT to assess direct and indirect effects of early diet on the highly pervasive phenomenon of nutritional programming. The trial randomized a diverse group of healthy infants (60% black Americans) to feed either cow milk formula (CMF) or an isocaloric extensively hydrolyzed formula (EHF) for the first year of life. Randomization to CMF, compared to EHF, significantly increased the likelihood of early rapid weight gain, a risk factor for later obesity, via differences in energy in and out. Additional phenotypes (secondary outcomes) collected throughout the RCT included measures of developmental milestones, diet, maternal feeding styles, food preferences, and taste genotype. These data will be subjected to secondary analyses and, depending on the hypothesis, compared with primary outcomes of anthropometry, early weight gain, adiposity, and physical activity. At the heart of the proposal are five aims, which upon completion will yield at least six publications. AIM 1 will test how proposed risk factors (early rapid weight gain, low physical activity, delayed motor development) and biomarkers (timing of primary teeth eruption), independently or in combination, predict adiposity and Z scores at 12.5 months and 1.5 years. AIM 2 will determine from monthly diet records the formula-feeding patterns and from questionnaires the feeding practices of mothers, to test the hypothesis that type of formula in the bottle is a bigger contributor to early weight gain trajectories and childhood obesity than are maternal feeding practices. Because EHF tastes more bitter than CMF, AIM 3 will test the hypothesis that EHF-fed infants will be more accepting than CMF-fed infants of broccoli-flavored food; genetic variation in a known bitter taste receptor activated by glucosinolates in broccoli will be factored in the analyses. AIM 4 will characterize the pattern, quality, and nutrient content of the diet of mothers over time and concordance with their children’s diets. AIM 5 will provide descriptive data related to (a) contribution of energy from formula versus non-formula each month during the first year of life and (b) determination of the accuracy of empiric equations used to estimate infant basal metabolic and total energy expenditure, by comparisons with actual measures of energy expenditure. These analyses will add to the knowledge base on early programming, with the goal of improving the health of the next generation of infants who are formula fed.