Project 1 Childhood Immune Function and Exposure (Karagas)

项目 1 儿童免疫功能和暴露（卡拉加斯）

• 批准号: 8890326
• 负责人: MARGARET Rita KARAGAS
• 金额: $ 2万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-21 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8890326
• 关键词: 5 year old; Adverse effects; Affect; Age; Age-Months; Animals; Antibody Formation; Arsenic; Bacterial DNA; Biological Markers; Birth; Cause of Death; Cessation of life; Child; Child health care; Childhood; Clinical; Clinical Markers; Cohort Studies; Collaborations; Communicable Diseases; Data; Development; Diphtheria; Enrollment; Environment; Environmental Exposure; Environmental Health; Epidemiologic Studies; Epigenetic Process; Exposure to; Feces; Fetal Development; Food; Gene Expression; Gene Family; Health; Household; Hypersensitivity; Immune; Immune response; Immune system; Immunity; Infant; Infant Development; Infection; Interview; Intestines; Life; Measurement; Metabolic Biotransformation; Metabolic Pathway; Metals; Molecular; Molecular Profiling; Morbidity - disease rate; Mothers; Nail plate; Neonatal; New Hampshire; Only Child; Outcome; Pathway interactions; Pertussis; Play; Policy Maker; Poliomyelitis; Population; Pregnancy; Prevention Research; Public Health Practice; Records; Relative (related person); Respiratory Tract Infections; Risk; Role; Route; Sampling; Severities; Source; Streptococcus pneumoniae; Structure of nail of toe; Testing; Tetanus; Translating; United States; Universities; Urine; Vaccines; Venous blood sampling; Visit; Water; animal data; atopy; base; clinical effect; clinical phenotype; cohort; design; disorder prevention; early childhood; early life exposure; environmental agent; epidemiologic data; immune function; in utero; indexing; insight; interdisciplinary approach; microbial; microbiome; mortality; multidisciplinary; new technology; prospective; research study; response; screening

Project 1 is central to the overall Children's Environment and Disease Prevention Research Center at Dartmouth. Accumulating data suggest a variety of adverse effects that may result from arsenic exposure during the vulnerable window of fetal development and early childhood. Altered immunity is among the key pathways identified as affected by arsenic in experimental studies and in highly exposed populations. However, such studies do not exist for the US at levels relevant to our population. Infections are the most common causes of illnesses in children in US, and are the leading causes of deaths in children worldwide. Additionally, allergy and atopy have become a more widespread source of childhood morbidity in recent years for reasons as yet unknown. Our preliminary data from animal and epidemiologic studies provide both mechanistic and clinical evidence of aberrant immune function related to arsenic exposure in infants. Recent studies also suggest a significant impact of certain environmental exposures on vaccine response in children, but the effects of arsenic on vaccine response have not been investigated. Further, new technologies are just beginning to uncover the fundamental role of the establishment of the intestinal microbiome early in life on immune system maturation and competency as well as in metal biotransformation. We propose to build on a prospective cohort study to determine whether prevalent exposure levels of arsenic influence children's immune response including risk of infection, allergy/atopy, vaccine response and intestinal microbial acquisition. The longitudinal birth cohort study comprises 1,000 mother-child dyads who are residents of New Hampshire and obtain household water from private wells, a potential source of arsenic exposure in the region. We will actively follow infants enrolled in the cohort through: (1) interval interviews with the mothers every four months and (2) screening pediatric records up to age 5 years. We will request a venous blood sample from infants during their one-year.well-child visits to test for antibody response to diphtheria/tetanus/pertussis, pneumococcus and polio vaccines in collaboration with Dr. Kari Nadeau at Stanford University. As an exploratory aim, we will sequence bacterial DNA from repeated stool samples (collected at six weeks and 12 months of age) to assess the relation between in utero and early life exposure to arsenic on the developing microbiome. To our knowledge, this is among the first prospective molecular epidemiologic studies of arsenic and children's health in the US, and among the few cohorts in the US with detailed early childhood infection information along with other immune-related variables.

项目1是达特茅斯（Dartmouth）整体儿童环境和疾病预防研究中心的核心。累积数据表明，胎儿发育和幼儿时期的砷暴露可能导致各种不良影响。在实验研究和高度暴露的人群中，免疫力改变是受砷影响的关键途径之一。但是，美国在与我们的人群相关的水平上不存在此类研究。感染是我们儿童中最常见的疾病原因，并且是全球儿童死亡的主要原因。此外，由于尚不清楚的原因，近年来，过敏和特纳在近年来已成为更广泛的儿童发病率来源。 我们来自动物和流行病学研究的初步数据提供了与婴儿砷暴露有关的异常免疫功能的机械和临床证据。最近的研究还表明，某些环境暴露对儿童疫苗反应的重大影响，但尚未研究砷对疫苗反应的影响。此外，新技术刚刚开始揭示生命早期在免疫系统成熟和能力以及金属生物转化中建立肠道微生物组的基本作用。 我们建议在一项前瞻性队列研究的基础上建立，以确定砷普遍的暴露水平是否影响儿童的免疫反应，包括感染风险，过敏/特纳科，疫苗反应和肠道微生物的获取。纵向出生队列研究包括1,000名母子二元组，他们是新罕布什尔州的居民，并从私人井中获取家用水，私人井是该地区砷暴露的潜在来源。我们将积极关注参加队列的婴儿：（1）每四个月与母亲进行一次间隔访谈，以及（2）筛查最高5岁的儿科记录。我们将在一年的时间内要求婴儿的静脉血液样本。以与斯坦福大学的Kari Nadeau博士合作，以测试对白喉/破伤风，pneumococcus和Polio疫苗的抗体反应。作为探索性目的，我们将从重复的粪便样品（在六周和12个月大时收集）中对细菌DNA进行序列，以评估子宫内与早期寿命之间在发育中的微生物组中的砷之间的关系。据我们所知，这是美国砷和儿童健康的首次前瞻性分子流行病学研究，以及美国少数具有详细儿童感染信息以及其他与免疫相关的变量的人群之一。