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

描述(由申请人提供)：配方奶喂养通常会导致体重迅速增加，是儿童和成人肥胖的危险因素。出生后第一年的快速增长也会增加后来的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，无论是终身预防干预还是进一步的科学研究，都应该把重点放在早期生活上。我们最近发现，一种类型的婴儿配方奶粉使配方奶粉喂养的婴儿在出生第一年相对于母乳喂养婴儿的体重增加正常化，因此我们不能认为配方奶粉喂养的婴儿在他们喂养的配方奶粉的组成、生长和随后的健康结果方面是一个同质的群体。在一项随机对照试验中，喂养含有广泛水解蛋白(EPHF)的配方奶粉后，婴儿的年龄体重和身长体重z分数符合世卫组织的生长标准(基于健康的母乳喂养婴儿)，而喂食等卡路里完整蛋白牛奶配方奶粉(CMF)的婴儿的相同措施则加快了。挑战是了解配方奶粉成分对能量平衡和生长的影响的潜在机制，作为提供实用替代品的第一步，这些替代品可用于减少配方奶喂养婴儿的肥胖和相关的晚年风险。我们建议在24个月的时间内对婴儿和他们的母亲进行一项随机试验，控制婴儿饮食的组成。当婴儿1周大时，当母亲决定不母乳喂养时，婴儿将被随机分成不同的组，这些组的母亲在婴儿出生第一年将喂养婴儿的配方奶粉类型(ePHF，CMF)。在儿童出生的头两年，每隔一段固定的时间就会对儿童进行称重和测量，以确定其生长发育情况(能量储存/储存)。当它们0.5个月、3个月和12个月时，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)、能量摄入量(主要目标2)和粪便能量损失(主要目标3)。当儿童3个月、12个月和24个月时，将对他们在由儿童引导的喂养过程中喂食他们指定的配方或固体食物的过程进行录像，之后将评估饱足感和饱腹感的生物标记物(分别为活性GLP-1和Ghrelin)以及接受和饥饿的各种衡量标准(次级目标1)。将获得人体测量和食物偏好，以探索儿童在断奶后是否以及如何保持基于早期配方奶粉成分的后期生长(次级目标2)和后来的饮食和食物偏好(次级目标3)。由于早期生活对于规划晚年健康结果和预防干预的重要性，本研究调查了与早期饮食有关的高度普遍和未被充分研究的现象，这与许多其他试图将儿童和成年人的饮食构成和能量平衡联系起来的研究形成了鲜明对比。从这项研究中获得的知识将有助于提供实用的替代方案，以降低肥胖风险，并改善美国婴儿喂养配方奶粉的健康。

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.