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: 9295540
• 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/9295540
• 关键词: 5 year old; Affect; Age; Anti-Inflammatory Agents; Anti-inflammatory; Area; Bangladesh; Bangladeshi; Behavior; Biological Response Modifiers; Birth; Birth History; Brain; Brain Injuries; Child; Child Development; 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，50万年龄以下的2亿儿童未能达到其全部认知发展， 低收入国家（LIC）的绝大多数案件。全球残疾人负担的百分之十 来自围产期侮辱引起的神经发育障碍。孕产妇的营养不足和感染是 两种流行且可修改的妊娠风险与不良神经发育结果有关。在此K23中 提案，李博士将检验以下假设，即围产期营养不良和感染使胎儿更大 炎症的风险，反过来，白质损伤，大脑生长不良和长期发育的风险。 目标：在300名孟加拉国母亲和婴儿的队列中，李博士将：1）确定协会 妊娠不足和胎儿炎症反应的感染，2）检查胎儿的关联 2年时的炎症和神经发育结局，3）探索炎症在婴儿中的作用 大脑结构和功能在3个月时。她将进一步探索高风险之间的这些关联 中度的早产，胎龄（SGA）婴儿小。 设计：在持续的纵向怀孕群体和标本生物叛逆者中，李博士将测试 用于促炎性介体的脐带血并进行次要数据分析。她将评估 孕产妇营养状况，潜在免疫调节营养素的饮食摄入量之间的关系， 两年后的产前感染，胎儿炎症和神经发育结局。多元模型将 创建以确定暴露与结果调整其他相关结果之间的关联 决定因素。在婴儿的一部分中，李博士还将探讨炎症和 使用MRI和视觉诱发电位上的大脑结构和功能早产。 创新：孕产妇营养对胎儿炎症的影响以及营养与营养与 感染，在怀孕中的特征很差。炎症在预测中的作用 神经发育结果在中等局部早产和SGA婴儿中未充分描述， 在LIC中非常普遍。 Lee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奖将使Lee博士能够将调查扩展到神经上 开发和建立一个新的独立的多学科研究计划。提出了指导的培训 在四个关键领域：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，Co-Encormor：Nelson），2）炎症（Fichorova），3）营养（Fawzi，Oken）和4）和4） 儿童结局的纵向统计建模（Rosner，Baqui）。专业知识，知识和试点数据 从K23计划中获得的将使Lee博士获得R01资金来进行随机对照试验 针对胎儿炎症的围产期干预措施，以优化LIC中的婴儿神经发育。