The Roles of Perinatal Nutrition, Infection and Inflammation in the Neurodevelopment of Bangladeshi Infants

围产期营养、感染和炎症在孟加拉国婴儿神经发育中的作用

• 批准号: 9547476
• 负责人: Anne Shee CC Lee
• 金额: $ 17.28万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-21 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9547476
• 关键词: 5 year old; Affect; Age; Anti-inflammatory; Area; Bangladesh; Bangladeshi; Behavior; Biological Response Modifiers; Birth; Birth History; Brain; Brain Injuries; Child; Child Development; Child Welfare; Childhood; Clinical; Clinical Investigator; Cognitive; Country; Data; Data Analyses; Development; Dietary intake; Electrophysiology (science); Exposure to; Fetus; Folic Acid; Follow-Up Studies; Foundations; Funding; Gestational Age; Goals; Growth; Head circumference; Health; Hemoglobin; IL8 gene; Image; Infant; Infection; Infectious Pregnancy Complications; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Interdisciplinary Study; Interleukin-1 beta; Interleukin-6; Investigation; Joints; Knowledge; Language; Life; Link; Magnetic Resonance Imaging; Malnutrition; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Modeling; Mothers; Motor; National Institute of Child Health and Human Development; Neonatal; Neurodevelopmental Impairment; Neurologist; Newborn Infant; Nutrient; Nutritional status; Outcome; Oxidants; Perinatal; Perinatal Epidemiology; Polyunsaturated Fatty Acids; Pregnancy; Pregnancy Histories; Premature Infant; Prenatal Nutrition; Process; Protein-Energy Malnutrition; Randomized Controlled Trials; Recording of previous events; Research; Research Priority; Risk; Risk Factors; Role; Rural; Small for Gestational Age Infant; Specimen; Statistical Models; Structure; Sustainable Development; TNF gene; Testing; Training; Umbilical Cord Blood; United Nations; Visual evoked cortical potential; biobank; brain volume; career development; cognitive development; cohort; critical period; design; disability burden; disability-adjusted life years; effective intervention; experience; fetal; global health; high risk; immunoregulation; improved; indexing; innovation; intrapartum; low income country; mother nutrition; multidisciplinary; myelination; neurobehavior; neurodevelopment; neuroimaging; nutrition; perinatal intervention; premature; prenatal; programs; white matter; white matter injury

ABSTRACT Rationale: Every year, 200 million children under 5 years of age fail to reach their full cognitive development, the vast majority of cases in low-income countries (LIC). Ten percent of the global burden of disability results from neurodevelopmental impairment arising from perinatal insults. Maternal undernutrition and infections are two prevalent and modifiable pregnancy risks linked with adverse neurodevelopmental outcomes. In this K23 proposal, Dr. Lee will test the hypothesis that perinatal undernutrition and infections place the fetus at greater risk of inflammation, and in turn, risk of white matter injury, poor brain growth and long-term development. Objectives: In a cohort of 300 Bangladeshi mothers and infants, Dr. Lee will: 1) determine the associations of pregnancy undernutrition and infections on fetal inflammatory responses, 2) examine the associations of fetal inflammation and neurodevelopmental outcomes at 2 years, and 3) explore the role of inflammation in infant brain structure and function at 3 months. She will further explore these associations among higher-risk moderate-late preterm and small for gestational age (SGA) infants. Design: In an ongoing longitudinal pregnancy-birth cohort and specimen bio-repository, Dr. Lee will test umbilical cord blood for pro-inflammatory mediators and perform secondary data analysis. She will assess the relationships between maternal nutritional status, dietary intake of potentially immuno-modulatory nutrients, prenatal infections, fetal inflammation, and neurodevelopmental outcomes at 2 years. Multivariate models will be created to determine associations between exposures and outcomes adjusting for other relevant determinants. In a subset of infants, Dr. Lee will also explore the potential effects of inflammation and prematurity on brain structure and function using MRI and visual evoked potentials. Innovation: The effects of maternal nutrition on fetal inflammation, and the interactions between nutrition and infection, have been poorly characterized in pregnancy. The role of inflammation in predicting neurodevelopmental outcomes has been inadequately described in moderate-late preterm and SGA infants, which are highly prevalent in LIC. Dr. Lee will use neuroimaging and electrophysiology in order to study the underlying mechanisms of these processes. Career Development: The K23 award would enable Dr. Lee to expand her investigation into neuro- development and build a new, independent multi-disciplinary research program. Mentored training is proposed in four key areas: 1) neurodevelopmental assessment, including neurobehavior, electrophysiology and imaging (Primary mentor: Inder, co-mentor: Nelson), 2) inflammation (Fichorova), 3) nutrition (Fawzi, Oken), and 4) longitudinal statistical modeling of child outcomes (Rosner, Baqui). The expertise, knowledge, and pilot data gained from the K23 program will enable Dr. Lee to obtain R01 funding to conduct a randomized controlled trial of perinatal interventions targeting fetal inflammation to optimize infant neurodevelopment in LIC.

抽象的 理由：每年有 2 亿 5 岁以下儿童未能达到充分的认知发展， 绝大多数病例发生在低收入国家（LIC）。全球残疾负担的百分之十是由残疾造成的 围产期损伤引起的神经发育障碍。产妇营养不良和感染 两种普遍且可改变的妊娠风险与不良神经发育结果相关。在这个K23 根据该提案，李博士将检验以下假设：围产期营养不良和感染会使胎儿处于更严重的状态。 炎症的风险，进而导致白质损伤、大脑生长和长期发育不良的风险。 目标：在 300 名孟加拉国母亲和婴儿的队列中，Lee 博士将：1) 确定 妊娠营养不良和感染对胎儿炎症反应的影响，2）检查胎儿炎症反应的关联 2 岁时的炎症和神经发育结果，以及 3) 探索炎症在婴儿中的作用 3个月时的大脑结构和功能。她将进一步探讨高风险人群之间的这些关联 中晚期早产儿和小于胎龄 (SGA) 婴儿。 设计：在一个持续的纵向妊娠-出生队列和样本生物存储库中，李博士将测试 脐带血中的促炎介质并进行二次数据分析。她将评估 母亲营养状况、潜在免疫调节营养素的膳食摄入量之间的关系， 产前感染、胎儿炎症和 2 岁时的神经发育结果。多元模型将 创建以确定暴露和结果之间的关联，并根据其他相关因素进行调整 决定因素。在一部分婴儿中，李博士还将探索炎症和炎症的潜在影响。 使用 MRI 和视觉诱发电位来评估早产儿的大脑结构和功能。 创新：母体营养对胎儿炎症的影响，以及营养与炎症之间的相互作用 感染，在怀孕期间的特征很少。炎症在预测中的作用 中晚期早产儿和 SGA 婴儿的神经发育结局尚未得到充分描述， 这在低收入国家非常普遍。李博士将使用神经影像学和电生理学来研究 这些过程的基本机制。 职业发展：K23 奖项将使李博士能够扩大她对神经系统的研究 开发和建立一个新的、独立的多学科研究项目。建议进行辅导培训 四个关键领域：1）神经发育评估，包括神经行为、电生理学和成像 （主要导师：Inder，共同导师：Nelson），2）炎症（Fichorova），3）营养（Fawzi，Oken），以及 4） 儿童结局的纵向统计模型（Rosner，Baqui）。专业知识、知识和试点数据 从K23计划中获得的收益将使李博士能够获得R01资金来进行随机对照试验 针对胎儿炎症以优化 LIC 婴儿神经发育的围产期干预措施。