Impact of diet composition during infancy on energy balance, satiety and growth

描述（由申请人提供）：配方奶喂养经常导致体重迅速增加，是儿童和成人肥胖的危险因素。在生命的第一年，婴儿的快速生长也增加了后期代谢综合征和心血管疾病死亡率的风险，这导致一些人认为，应该把重点放在生命早期，进行终身预防干预和进一步的科学探究。我们最近发现，一种婴儿配方奶粉使配方奶粉喂养的婴儿在出生后第一年相对于母乳喂养的婴儿体重增加正常化，因此我们不能认为配方奶粉喂养的婴儿在配方奶粉的成分、生长和随后的健康结果方面是一个同质群体。在一项随机对照试验中，喂养由广泛水解蛋白（ePHF）组成的配方奶，婴儿的年龄比体重和身高比体重z分数符合世卫组织生长标准（以健康母乳喂养的婴儿为基础），而喂养等热量完整蛋白牛奶配方奶（CMF）的婴儿的相同指标则加快了。我们面临的挑战是了解配方奶粉成分对能量平衡和生长影响的潜在机制，这是提供可用于减少配方奶粉喂养婴儿肥胖和相关晚年风险的实际替代方案的第一步。我们建议在24个月的窗口期内对婴儿及其母亲进行随机试验，操纵婴儿饮食的组成。当婴儿满1周龄时，当母亲明确决定不母乳喂养时，婴儿将被随机分为不同类型的配方奶粉组（ePHF， CMF），母亲将在婴儿出生后的第一年给他们喂食配方奶粉。在生命的头2年里，每隔一段固定的时间，将对儿童进行称重和测量，以确定其生长（能量沉积/储存）。当他们0.5、3和12月龄时，能量平衡将通过测量其组成部分来确定：总能量和静息能量消耗（初级目标1）、能量摄入（初级目标2）和粪便能量损失（初级目标3）。当孩子3个月、12个月和24个月大时，在孩子主导的喂养过程中，他们在喂食指定的配方食品或固体食物时被录像，之后将评估饱腹感和饱腹感的生物标志物（分别是活性GLP-1和胃饥饿素）以及各种接受度和饥饿感的测量（次要目标1）。将获得人体测量测量和食物偏好，以探索基于早期配方奶粉成分的后期生长（次要目标2）和后期饮食和食物偏好（次要目标3）是否以及如何在儿童断奶后持续存在。由于早期生活对规划晚年健康结果和预防性干预的重要性，本研究调查了与早期生活饮食有关的能量平衡和饱腹感周围高度普遍但未被调查的现象，与许多其他试图将饮食组成和能量平衡联系起来的研究形成对比的研究在大龄儿童和成人中。从这项研究中获得的知识将有助于提供实际的替代方案，以减少肥胖风险，改善美国婴儿的健康喂养配方。

DESCRIPTION (provided by applicant): Formula feeding often results in rapid weight gain and is a risk factor for pediatric and adult obesity. Rapid rates of growth during the first year of lie also increase risks for later metabolic syndrome and mortality from cardiovascular disease, leading some to argue that the focus should be on early life for both lifelong preventive interventions and further scientific inquiry. We recently discovered that one type of infant formula normalized weight gain of formula-fed infants relative to that of breastfed infants during the first year of life so we cannot consider formula-fed infants as a homogeneous group regarding the composition of the formula they feed, growth and consequent health outcomes. In a randomized, controlled trial, feeding a formula that consisted of extensively hydrolyzed protein (ePHF) resulted in weight-for-age and weight-for-length z-scores that followed the WHO growth standards (which are based on healthy breastfed infants), whereas the same measures in infants fed an isocaloric intact protein cow milk formula (CMF) were accelerated. The challenge is to understand the mechanisms underlying the effects of formula composition on energy balance and growth as a first step in providing practical alternatives that could be used to reduce obesity and related later-life risks in formula-fed infants. We propose to conduct a randomized trial of infants and their mothers during a 24-month window, manipulating the composition of the diet fed to infants. When the infants are 1 week of age and when the mothers' decision not to breastfeed is firmly established, infants will be randomized into groups that differ in the type of formula (ePHF, CMF) that the mothers will feed their infants during the first year of life. At fixed intervals during first 2 years of life, children will be weighed and measured to determine growth (energy deposition/storage). When they are 0.5, 3, and 12 months of age, energy balance will be determined by measuring its components: total and resting energy expenditure (Primary Aim 1), energy intake (Primary Aim 2), and energy loss in stool (Primary Aim 3). When the children are 3, 12, and 24 months, they will be videotaped while feeding their assigned formula, or solid foods, to satiation during child-led feeding sessions, after which biomarkers of satiation and satiety (active GLP-1 and ghrelin, respectively) and various measures of acceptance and hunger will be assessed (Secondary Aim 1). Anthropometric measures and food preferences will be obtained to explore whether and how later growth (Secondary Aim 2) and later diet and food preferences (Secondary Aim 3) based on early formula composition persists after children are weaned from formula. Because of the importance of early life for programming later-life health outcomes and for preventive intervention, this research examines highly pervasive and under-investigated phenomena surrounding energy balance and satiation related to diet in early life, in contrast to many other studies that attempt to relate diet composition and energy balance in older children and adults. The knowledge gained from this research will help provide practical alternatives to reduce obesity risk and improve the health of American infants who feed formula.