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

描述（由申请人提供）：配方奶粉喂养通常导致体重快速增加，是儿童和成人肥胖的风险因素。出生后第一年的快速增长也增加了后期代谢综合征和心血管疾病死亡率的风险，这使得一些人认为，终身预防干预和进一步科学研究的重点应该放在早期生活上。我们最近发现，在出生后的第一年，一种类型的婴儿配方奶粉使配方奶粉喂养的婴儿相对于母乳喂养的婴儿的体重增加正常化，因此我们不能将配方奶粉喂养的婴儿视为一个同质组，因为他们喂养的配方奶粉的成分，生长和随后的健康结果。在一项随机对照试验中，喂养由广泛水解蛋白（ePHF）组成的配方奶粉导致年龄别体重和身长别体重z评分符合WHO生长标准（基于健康母乳喂养的婴儿），而喂养等热量完整蛋白牛奶配方奶粉（CMF）的婴儿的相同测量结果加速。目前的挑战是了解配方奶粉成分对能量平衡和生长的影响的机制，作为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用替代品的第一步。我们建议在24个月的窗口期内对婴儿及其母亲进行一项随机试验，操纵喂养婴儿的饮食组成。当婴儿满1周龄且母亲明确决定不进行母乳喂养时，婴儿将被随机分配到不同配方奶粉类型（ePHF、CMF）的组中，母亲将在婴儿出生后第一年喂养婴儿。在出生后的前2年内，每隔一段时间，将对儿童进行称重和测量，以确定生长情况（能量沉积/储存）。当它们为0.5、3和12月龄时，将通过测量其组成部分来确定能量平衡：总能量消耗和静息能量消耗（主要目标1）、能量摄入（主要目标2）和粪便中的能量损失（主要目标3）。当儿童为3、12和24个月时，在儿童主导的喂养过程中，在喂食指定的配方奶粉或固体食物至饱腹时对其进行录像，之后将评估饱腹和饱腹感的生物标志物（分别为活性GLP-1和ghrelin）以及接受和饥饿的各种指标（次要目标1）。将获得人体测量指标和食物偏好，以探索在儿童断奶后，基于早期配方食品组成的后期生长（次要目标2）和后期饮食和食物偏好（次要目标3）是否以及如何持续。由于规划晚年的健康结果和预防性干预的重要性，本研究探讨了高度普遍和调查不足的现象，周围的能量平衡和饱腹感与饮食有关的早期生活，在许多其他研究，试图在年龄较大的儿童和成人的饮食组成和能量平衡。从这项研究中获得的知识将有助于提供实用的替代方案，以减少肥胖风险，改善美国婴儿喂养配方奶粉的健康状况。

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.