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: 10202673
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10202673
• 关键词: 5 year old; Affect; Age; Anti-Inflammatory Agents; Area; Bangladesh; Bangladeshi; Behavior; Biological Response Modifiers; Birth; Birth History; Body mass index; 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; 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; 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; neonatal health; neurobehavior; neurodevelopment; neuroimaging; nutrition; perinatal intervention; premature; prenatal; programs; systemic inflammatory response; 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.

摘要 理由：每年有2亿5岁以下儿童未能达到全面认知发展， 绝大多数病例发生在低收入国家（LIC）。全球残疾负担的10% 由围产期损伤引起的神经发育障碍。产妇营养不良和感染是 两种普遍存在且可改变的妊娠风险与不良神经发育结果相关。在K23 李博士将测试这一假设，即围产期营养不良和感染使胎儿处于更高的水平。 炎症的风险，进而白色物质损伤的风险，不良的脑生长和长期发育。 目的：在一个由300名孟加拉国母亲和婴儿组成的队列中，Lee博士将：1）确定 妊娠期营养不良和感染对胎儿炎症反应的影响，2）检查胎儿炎症反应与妊娠期营养不良和感染的关系。 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。她将进一步探讨这些关联之间的高风险 中晚期早产儿和小于胎龄（SGA）婴儿。 设计：在正在进行的纵向妊娠-出生队列和标本生物储存库中，Lee博士将进行测试 脐带血促炎介质和执行二次数据分析。她将评估 母体营养状况、潜在免疫调节营养素的饮食摄入量 产前感染、胎儿炎症和2年时的神经发育结果。多变量模型将 以确定风险暴露与结果之间的关联，并针对其他相关因素进行调整 决定因素在婴儿的一个子集中，李博士还将探索炎症的潜在影响， 早产儿脑结构和功能的MRI和视觉诱发电位。 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，在怀孕期间表现不佳。炎症在预测中的作用 中晚期早产儿和SGA婴儿的神经发育结果描述不充分， 这在低收入国家非常普遍。李博士将使用神经成像和电生理学来研究 这些过程的基本机制。 职业发展：K23奖将使李博士能够扩大她对神经系统的研究， 发展和建立一个新的，独立的多学科研究计划。建议进行辅导培训 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，共同导师：纳尔逊），2）炎症（Fichorova），3）营养（Fawzi，Oken）和4） 儿童结局的纵向统计模型（Rosner，Baqui）。专业知识和试点数据 从K23项目中获得的资金将使Lee博士能够获得R 01资金进行随机对照试验 针对胎儿炎症的围产期干预措施，以优化LIC婴儿的神经发育。

项目成果

Maternal short stature and under-weight status are independent risk factors for preterm birth and small for gestational age in rural Bangladesh.

• DOI: 10.1038/s41430-018-0237-4
• 发表时间: 2019-05
• 期刊: European journal of clinical nutrition
• 影响因子: 4.7
• 作者: Khanam R;Lee AC;Mitra DK;Ram M;Das Gupta S;Quaiyum A;Choudhury A;Christian P;Mullany LC;Baqui AH
• 通讯作者: Baqui AH

Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses - finding and creating similarities in variables and data collection.

• DOI: 10.1186/s12884-023-05366-2
• 发表时间: 2023-02-11
• 期刊: BMC pregnancy and childbirth
• 影响因子: 3.1

Dietary Perspectives and Practices during Pregnancy in Rural Amhara Region of Ethiopia: An Exploratory Qualitative Study.

• DOI: 10.1016/j.cdnut.2023.100079
• 发表时间: 2023-06
• 期刊: CURRENT DEVELOPMENTS IN NUTRITION
• 影响因子: 4.8
• 作者: Workneh, Firehiwot;Tsegaye, Sitota;Amanuel, Hanna;Eglovitch, Michelle;Shifraw, Tigest;Shiferie, Fisseha;Tadesse, Amare W;Worku, Alemayehu;Isanaka, Sheila;Lee, Anne Cc;Berhane, Yemane
• 通讯作者: Berhane, Yemane

Establishing a conceptual framework of the impact of placental malaria on infant neurodevelopment.

建立胎盘疟疾对婴儿神经发育影响的概念框架。

• DOI: 10.1016/j.ijid.2019.04.019
• 发表时间: 2019
• 期刊: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
• 作者: Lawford,HarrietLS;Lee,AnneCc;Kumar,Sailesh;Liley,HelenG;Bora,Samudragupta
• 通讯作者: Bora,Samudragupta

Effect of birthweight measurement quality improvement on low birthweight prevalence in rural Ethiopia.

• DOI: 10.1186/s12963-021-00265-0
• 发表时间: 2021-09-22
• 期刊: Population health metrics
• 影响因子: 3.3
• 作者: Baye E;Abate FW;Eglovitch M;Shiferie F;Olson IE;Shifraw T;Kidane WT;Yibeltal K;Tsegaye S;Derebe MM;Isanaka S;Wylie BJ;Molina RL;Chan GJ;Worku A;Mullany LC;Worku A;Berhane Y;Lee ACC
• 通讯作者: Lee ACC