Determining the Neurodevelopmental Effects of Transition from Breastfeeding to Infant Formula using a Novel Biomarker

项目摘要 我是一名分析化学家，致力于开发新的方法来研究婴儿营养如何影响 早期生活的健康轨迹。在与我的导师协商后，我制定了一个培训计划， 额外的技能，使我能够成为一个独立的跨学科研究营养 流行病学。拟议的研究项目将促进必要的培训和开发一种新的生物标志物 可以量化母乳与配方奶粉的摄入量和成分，从而克服了 研究婴儿营养的长期影响，并为未来的赠款申请奠定基础。 我已经召集了一个专家小组的导师互补的专业知识，涵盖儿科，儿童 发展、流行病学、营养学、接触生物学和高级统计学。通过指导，正式 课程和教学研讨会我将获得儿童的健康和营养知识和技能， 生物学和高级统计学。有了这些新技能，我可以实现我的长期职业目标， 一项有竞争力的、独立资助的研究计划，旨在研究婴儿营养及其相关的长期影响。 关于健康。虽然这项研究的重点是儿童的神经发育，但重要的是要注意， 获得的技能将适用于可能与营养有关的多种儿童健康成果（例如， 肥胖，免疫功能，过敏和糖尿病），并奠定了基础，后来包括产前 营养作为生物标志物可以捕获产前时期。具体来说，我将1）获得全面的培训， 应用生物标志物研究化学和饮食因素与健康结果的关联; 2） 学习用于评估儿童神经发育的措施; 3）学习营养在婴儿健康中的作用; 4）学习和获得分析复杂多维数据所需的统计工具的经验。 越来越多的证据表明，一些成人疾病是通过婴儿饮食编程的，但研究表明， 由于缺乏可靠、客观的标记物，无法准确重建婴儿的饮食结构。拟议 研究项目将开发第一个客观的，婴儿营养的时间生物标志物，并将证明其 应用于研究婴儿营养对儿童神经发育的影响。这种生物标志物将 客观定量地重建过去的饮食习惯。我们将使用最先进的分析技术， 确定儿童牙齿中多种元素的分布。像树一样，牙齿也有年轮， 每个环的元素含量反映了当时的膳食摄入量。我们的初步 结果表明，特定的元素签名可以用来确定饮食从排他性的转变， 从母乳喂养到婴儿配方奶粉。我们将扩大这项工作，以开发一个更强大的指数， 用于确定母乳或配方奶摄入的持续时间、剂量和成分。我们将应用 生物标志物来研究婴儿饮食对神经发育的影响。这项研究极具成本效益，因为我们会 利用现有的纵向出生队列的资源，其中收集了所有支持数据。

PROJECT SUMMARY I am an analytical chemist committed to developing new methods to study how infant nutrition influences health trajectories in early life. In consultation with my mentors, I have developed a training plan to gain additional skills that will enable me to become an independent transdisciplinary researcher in Nutritional Epidemiology. The proposed research project will facilitate necessary training and develop a new biomarker that can quantify breast milk vs formula intake and composition, thereby overcoming a major limitation to the study of long term impacts of infant nutrition and lay the foundation for future grant applications. I have assembled an expert panel of mentors with complementary expertise, covering pediatrics, child development, epidemiology, nutrition, exposure biology and advanced statistics. Through mentorship, formal coursework and didactic seminars I will gain knowledge of children's health and nutrition and skills in exposure biology and advanced statistics. With these new skills, I can follow my long-term career goal of establishing a competitive, independently funded research program to study infant nutrition and associated long term impacts on health. While this study focuses on children's neurodevelopment, it is important to note that the knowledge and skills obtained will be applicable to multiple child health outcomes that may be linked to nutrition (e.g. obesity, immunological function, allergies and diabetes) and lays the foundation to later include prenatal nutrition as the biomarker can capture the prenatal period. Specifically, I will 1) gain comprehensive training in the application of biomarkers to study the association of chemical and dietary factors and health outcomes; 2) learn the measures used to assess neurodevelopment in children; 3) learn the role of nutrition in infant health; and 4) learn and gain experience with the statistical tools required to analyze complex multidimensional data. There is growing evidence that some adult diseases are programmed through infant diets but studies are hampered by the lack of a reliable, objective marker that can accurately reconstruct infant diet. The proposed research project will develop the first objective, temporal biomarker of infant nutrition and will demonstrate its application to study the effect of infant nutrition on children's neurodevelopment. This biomarker will reconstruct past diet objectively and quantitatively. We will use state-of-the-art analytical techniques to determine the distribution of multiple elements in children's teeth. Like trees, teeth contain growth rings that can be aged and the elemental content of each ring reflects the dietary intake at that time. Our preliminary results show that specific element signatures can be used to determine diet transitions from exclusive breastfeeding to infant formula. We will expand upon this work to develop a more robust index that can be used to determine the duration, dose and composition of breast milk or formula intake. We will apply the biomarker to study the effect of infant diet on neurodevelopment. This study is highly cost-effective as we will leverage the resources of an existing longitudinal birth cohort where all supporting data has been collected.