A bench to population epidemiologic approach to investigating the effects of antenatal stress and inflammation on child gut inflammation, growth, and development

研究产前应激和炎症对儿童肠道炎症、生长和发育影响的人群流行病学方法

• 批准号: 10447791
• 负责人: Audrie Lin
• 金额: $ 4.49万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-06 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10447791
• 关键词: 5 year old; Adopted; Adult; Affect; Age; Area; Bangladesh; Biological; Biological Markers; Biometry; C-reactive protein; California; Child; Child Development; Child Health; Cluster randomized trial; Country; Critical Pathways; Data; Development; Dietary Intervention; Disease; Doctor of Philosophy; Environment; Epidemiology; Evaluation; F2-Isoprostanes; Functional disorder; Funding; Future; Goals; Grant; Growth; Growth and Development function; Handwashing; Health; Hydrocortisone; Hygiene; Immunology; Impairment; Infant; Infection; Infectious Diseases Research; Inflammation; Insulin-Like Growth Factor I; International; Intervention; Intestinal permeability; Lactulose; Lead; Length; Life; Machine Learning; Malnutrition; Mannitol; Maternal Exposure; Measurement; Measures; Mentors; Mentorship; Methods; Microbiology; Modeling; Modernization; Molecular; Molecular Biology; Mucous Membrane; Neopterin; Nutritional; Observational Study; Orosomucoid; Outcome; Pathogenesis; Pathway interactions; Peroxidases; Physiology; Population; Predisposition; Pregnancy; Prognostic Marker; Public Health; Randomized; Recording of previous events; Research; Research Personnel; Research Project Grants; Research Training; Risk; Risk Factors; Rural; Sampling; Sanitation; Scientist; Small Intestines; Stress; Structural Models; Surface; Surveys; Testing; Training; Treatment Efficacy; Universities; Villous Atrophy; Water; Work; absorption; alpha 1-Antitrypsin; antenatal; base; biomarker discovery; career; cytokine; efficacy evaluation; efficacy trial; experience; fetal programming; global health; gut inflammation; improved; innovation; low income country; maternal stress; neurodevelopment; oral vaccine; prevent; professor; prospective; repository; socioeconomics; theories; therapy development; vaccine failure

PROJECT SUMMARY / ABSTRACT Candidate: Dr. Lin is a research scientist at the University of California, Berkeley in Professor John (Jack) Colford's group. She completed her PhD in Microbiology and Immunology at Stanford University in 2012. Since 2010, she has worked as the coordinating microbiologist for the WASH Benefits study, a large-scale, multi- country cluster randomized trial evaluating the impact of water, sanitation, hygiene, and nutritional interventions on child health, with a focus on gut inflammation. This research and training plan builds on her strong interdisciplinary background at the nexus of microbiology, immunology, and global health. Gaining experience in epidemiology and biostatistics will facilitate her transition to a `bench to population' independent investigator at UC Berkeley and will ultimately enable her to achieve her long-term career goal to become a global health leader in the evaluation of antenatal and early life interventions to improve child health. Environment: UC Berkeley has a long history of conducting innovative and groundbreaking research advancing epidemiological and biostatistical theory and application in international health. To achieve her career goal, Dr. Lin seeks training in (1) epidemiology, with a focus on causal inference methods (in particular, marginal structural models for direct and indirect effects and targeted maximum likelihood estimation) (2) biostatistics and (3) child stress and development. To achieve these goals, Dr. Lin has assembled a unique interdisciplinary training and mentoring team based at UC Berkeley. Jack Colford (primary mentor) will guide her training in epidemiological theory and application. Alan Hubbard (co-mentor) will guide her training in biostatistics and causal inference methods including models for direct and indirect effects and targeted maximum likelihood estimation. Lia Fernald (co-mentor) will guide her training in child development and stress. Research Project: Early life linear growth faltering is associated with impaired development, but its underlying pathogenesis is poorly understood. Subclinical intestinal inflammation and damage affects children living in low-income countries and is increasingly recognized as a potential main contributor to the vicious cycle of early life malnutrition and oral vaccine failure. Little is known about the pregnancy risk factors associated with gut inflammation and the impact of these antenatal factors on linear growth and neurodevelopment. In Aim 1, Dr. Lin will determine the association between maternal stress and inflammation during pregnancy and subsequent measures of child gut inflammation and permeability. In Aim 2, she will evaluate the relationship between antenatal stress and inflammation and future child linear growth and development. She proposes to use modern causal inference methods to elucidate the potential pathways from antenatal stress and inflammation to child gut inflammation, linear growth faltering, and poor development. Ultimately, this mentored research will prepare Dr. Lin for a successful R01-level application to investigate potential downstream effects of antenatal stress and inflammation on child stress, inflammation, and susceptibility to infections.

项目概要/摘要 候选人：林博士是加州大学伯克利分校约翰（Jack）教授的研究科学家 科尔福德的小组。她于 2012 年在斯坦福大学获得微生物学和免疫学博士学位。 2010 年，她担任 WASH 效益研究的协调微生物学家，这是一项大规模、多方面的研究 评估水、环境卫生、个人卫生和营养影响的国家集群随机试验 对儿童健康的干预措施，重点是肠道炎症。这项研究和培训计划建立在她的基础上 在微生物学、免疫学和全球健康方面具有强大的跨学科背景。获得 流行病学和生物统计学方面的经验将有助于她过渡到独立的“替补人口” 加州大学伯克利分校的研究员，最终将使她实现长期职业目标，成为一名 评估产前和早期生命干预措施以改善儿童健康的全球健康领导者。 环境：加州大学伯克利分校在开展创新和突破性研究方面拥有悠久的历史 推进流行病学和生物统计学理论及其在国际卫生中的应用。去成就她 为了实现职业目标，林博士寻求 (1) 流行病学方面的培训，重点是因果推理方法（特别是， 直接和间接影响和目标最大似然估计的边际结构模型）(2) 生物统计学和（3）儿童压力和发展。为了实现这些目标，林博士组建了独特的 加州大学伯克利分校的跨学科培训和指导团队。 Jack Colford（主要导师）将指导 她接受过流行病学理论和应用方面的培训。艾伦·哈伯德（联合导师）将指导她的培训 生物统计学和因果推理方法，包括直接和间接影响模型以及目标模型 最大似然估计。 Lia Fernald（共同导师）将指导她在儿童发展和压力方面的培训。 研究项目：生命早期线性生长迟缓与发育受损有关，但其根本原因 发病机制尚不清楚。亚临床肠道炎症和损伤影响生活在 低收入国家，并日益被认为是早期恶性循环的潜在主要推动者。 生活营养不良和口服疫苗失败。关于与肠道相关的妊娠危险因素知之甚少 炎症以及这些产前因素对线性生长和神经发育的影响。在目标 1 中，Dr. 林将确定怀孕期间母亲压力和炎症之间的关联 儿童肠道炎症和渗透性的后续测量。在目标 2 中，她将评估这段关系 产前应激和炎症与未来儿童线性生长发育之间的关系。她提议 使用现代因果推理方法来阐明产前应激和产前应激的潜在途径 炎症导致儿童肠道炎症、线性生长迟缓和发育不良。最终，这位辅导员 研究将为林博士成功的 R01 级应用做好准备，以调查潜在的下游影响 产前应激和炎症对儿童应激、炎症和感染易感性的影响。