Assessing the relationship between environmental enteric dysfunction and poor growth via a newly developed 11-plex assay

通过新开发的 11 重检测评估环境肠道功能障碍与生长不良之间的关系

• 批准号: 10021657
• 负责人: CHRISTOPHER P DUGGAN
• 金额: $ 18.52万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-21 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021657
• 关键词: 5 year old; Adult; Affect; Age; Age-Months; Assessment tool; Biological Assay; Biological Markers; Biological Sciences; Birth; Birth Weight; Birth length; Blood; C-reactive protein; CD14 gene; Caregivers; Child; Child Mortality; Childhood; Cholecalciferol; Chronic; Clinic Visits; Cognitive; Data; Development; Economics; Enrollment; Enteral; Environment; Environmental Epidemiology; Exposure to; Failure; Ferritin; Flagellin; Functional disorder; Growth; Growth and Development function; HIV; Health; Height; Histologic; Human Development; Hygiene; Hypertension; Immunoglobulins; Individual; Infant; Inflammation; Insulin-Like Growth Factor I; Intestinal permeability; Intestines; Knowledge; Language; Length; Life; Link; Lipopolysaccharides; Longitudinal cohort study; Malnutrition; Measures; Methods; Micronutrients; Morbidity - disease rate; Mothers; Motor; Mucositis; Orosomucoid; Outcome; Permeability; Personal Satisfaction; Plasmodium falciparum; Population; Postpartum Period; Pregnancy; Pregnant Women; Productivity; RBP4 gene; Randomized; Reporting; Research; Risk; Role; Sampling; Serum; Severities; Small Intestines; Somatotropin; Standardization; Supplementation; Surrogate Mothers; TFRC gene; Tanzania; Thyroglobulin; Time; Villous; Vitamins; absorption; adverse birth outcomes; base; burden of illness; cholecalciferol supplementation; cognitive development; double-blind placebo controlled trial; enteric pathogen; fibroblast growth factor 21; gastrointestinal; hormone resistance; improved; in utero; indexing; infancy; inflammatory disease of the intestine; innovation; intestinal fatty acid binding protein; low and middle-income countries; microbial; mortality; neurodevelopment; nutrition; screening; work-study

Project Summary: Undernutrition remains one of the greatest human development challenges of our time. In 2017, an estimated 151 million children < 5 years of age (i.e., 22.2% of the global population) were stunted, increasing their risk for morbidity and mortality in childhood, suboptimal cognitive development, poorer educational outcomes, and lower economic productivity and earnings in adulthood. It has been increasingly appreciated that growth failure can begin in utero and worsen during early infancy; recently, environmental enteric dysfunction (EED) has been hypothesized as an important causal factor. EED is an acquired, subclinical condition of the small intestine associated with chronic exposure to an unhygienic environment where enteric pathogens persist. Histologic features include mucosal inflammation, villous blunting, altered barrier integrity, and reduced intestinal absorptive capacity. Despite EED’s purported link to poor health and nutrition outcomes in young children in low- and middle- income countries (LMICs), our knowledge of EED is relatively limited. Research gaps include the role of infant EED on subsequent poor growth and development and the possible role of maternal EED on adverse birth outcomes. The Trial of Vitamins-5 (ToV5) is an individually randomized, double-blind, placebo-controlled trial (R01 HD83113; ClinicalTrials.gov: NCT02305927) of maternal vitamin D3 (cholecalciferol) supplementation conducted among 2,300 HIV-infected pregnant women in Dar es Salaam, Tanzania. Following enrollment into the trial, mothers were followed-up at monthly clinic visits during pregnancy, at delivery, and then with their child at monthly postpartum clinic visits. Using data and serum samples collected in the ToV5 study, the main objectives of the current proposal are to assess 1) the relationship between infant EED and linear growth, i.e., length-for-age Z-score (LAZ) at 12 months of age; 2) the relationship between infant EED and development, measured by the Caregiver-Reported Early Development Index (CREDI) at 12 months of age; and 3) the relationship between maternal EED during pregnancy and birth outcomes, primarily infant birth weight and duration of gestation. We also aim to 4) examine relationships between the EED, systemic inflammation, and micronutrient biomarkers from a newly developed 11-plex multi-micronutrient and EED assessment tool (MEEDAT); consisting of intestinal fatty acid–binding protein (I-FABP), soluble CD14 (sCD14), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 21 (FGF21), alpha-1-acid glycoprotein (AGP), C-reactive protein (CRP), ferritin, soluble transferrin receptor (sTfR), retinol binding protein 4 (RBP4), thyroglobulin (Tg), and Plasmodium falciparum exposure (HRP2); and anti-flagellin/anti-LPS Igs. Overall, this proposed research will contribute to our understanding of the consequences of EED in LMICs, specifically related to poor growth and adverse birth outcomes, using two innovative methods for assessing EED, namely anti-flagellin/anti-LPS Igs and MEEDAT.

项目摘要： 营养不良仍然是我们这个时代最大的人类发展挑战之一。在2017年，一个 估计有1.51亿儿童<5岁（即22.2％的全球人口）发育不良，增加 他们在童年时期发病和死亡率，次优认知发展，教育较差的风险 成果，降低成年后的经济生产率和收入。它越来越感谢 在开始时期的子宫内，这种生长失败可以开始。最近，环境输入 功能障碍（EED）已被认为是重要的因果因素。 EED是一个获得的亚临床 与长期暴露于不卫生环境有关的小肠的状况 病原体持续存在。组织学特征包括粘膜注射，绒毛钝，屏障完整性改变， 并降低了肠吸收能力。尽管EED据称与健康和营养成果不佳有关 在低收入和中等收入国家（LMIC）的幼儿中，我们对EED的了解相对有限。 研究差距包括婴儿EED在随后的不良生长和发展中的作用以及可能的 物物eed在不良出生结果中的作用。 维生素5（TOV5）的试验是一项单独的随机，双盲，安慰剂对照试验（R01） HD83113; Clinicaltrials.gov：NCT02305927）的母体维生素D3（胆固醇）补充 在坦桑尼亚达累斯萨拉姆的2300名HIV感染孕妇中进行。入学后 试验，在怀孕期间，分娩时，在每月诊所就诊时进行了对母亲的随访 儿童在产后诊所就诊。使用TOV5研究中收集的数据和血清样品，主要是 当前建议的目标是评估1）婴儿EED与线性增长之间的关系，即 12个月大时长的Z分数（LAZ）； 2）婴儿EED与发育之间的关系， 由12个月大的护理人员报告的早期发展指数（Credi）衡量； 3） 怀孕期间和出生结果，初级婴儿的出生体重和 妊娠持续时间。我们还旨在4）检查EED，系统注射和 来自新开发的11个PLEX多微量营养素和EED评估工具的微量营养素生物标志物 （Meedat）;由肠道脂肪酸结合蛋白（I-FABP），可溶性CD14（SCD14），胰岛素样组成 生长因子1（IGF-1），成纤维细胞生长因子21（FGF21），α-1-酸糖蛋白（AGP），C反应性 蛋白质（CRP），铁蛋白，固体转铁蛋白受体（STFR），视黄醇结合蛋白4（RBP4），甲状腺球蛋白（TG）， 和恶性疟原虫暴露（HRP2）；和抗鞭毛蛋白/抗LPS IG。总体而言，这项拟议的研究 将有助于我们理解EED在LMIC中的后果，特别与增长差有关 和不良的出生结果，使用两种创新方法来评估EED，即抗氟lagellin/anti-LPS IGS和MEEDAT。