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是整个达特茅斯儿童环境和疾病预防研究中心的核心。越来越多的数据表明，在胎儿发育和幼儿期的脆弱窗口期接触砷可能会产生各种不良影响。在实验研究和高度接触人群中，免疫改变是确定受砷影响的关键途径之一。然而，在与我们的人口相关的水平上，美国没有这样的研究。感染是美国儿童最常见的疾病原因，也是全球儿童死亡的主要原因。此外，近年来，过敏和特应性反应已成为儿童发病率的一个更广泛的来源，原因尚不清楚。