The microbiome as a potential mediator of socio-economic disparities in preterm infant neurodevelopmental trajectories from NICU discharge to school age

项目总结/摘要 新生儿重症监护室（NICU）的目标不仅是早产儿的生存，而且是完整的 神经系统的发育。许多因素影响神经发育。鉴定 在足够早的时间点可以改变的因素，以改善个体的发展轨迹 婴儿需要。虽然早产儿从NICU出院时具有一定的发育潜力 根据其胎龄和临床病程，家庭环境的社会经济地位（SES）可以 这将极大地改变发展轨迹。贫困会增加神经发育恶化的风险， 造成了巨大的健康差距。贫穷改变神经发育的方式尚不清楚。 微生物组受环境影响，反过来又影响大脑发育。我们假设 微生物组是SES和环境对神经发育影响的生物效应器。这 该提案将重点关注微生物组暴露于重要环境的两个关键时间点， 改变-在NICU中的前2周和在家庭环境中的6-12个月。纵向 临床数据、患者微生物样本、环境数据和SES数据将在建立的 来自美国五个机构的早产儿队列已经在研究肠道 早产儿的微生物组。将进行神经发育检查以评估功能结局 学校准备。该提案的目标是证明微生物组的发育影响 神经发育此外，我们将确定与SES相关的环境因素，这些因素会影响 微生物组和神经发育结果。该提案的优势包括以下方面的独特专长： 新生儿护理，神经发育，微生物组分析， 生物信息学、经济学和家庭环境特征分析。先进 排序技术、环境因素的空间分析（地理制图）和经济建模将 用于研究SES、环境、微生物组和神经发育之间的关系 结果，以确定一个时间点和可能的环境或微生物组的修改，以改善结果。 除了增加社会策略，扩大有效的学习模式，并减轻医疗需求， 风险婴儿，了解和促进微生物组的变化可能会导致更好的理解， 健康差距，并使干预措施能够以创新的方式改变婴儿的神经发育轨迹。

Project Summary/Abstract The goal of neonatal intensive care unit (NICU) care is not just survival of preterm infants, but also intact neurodevelopment for these vulnerable patients. Many factors affect neurodevelopment. Identification of factors that are modifiable at a time point early enough to improve the developmental trajectory of an individual infant is needed. While preterm infants are discharged from the NICU with a certain developmental potential based on their gestational age and clinical course, socioeconomic status (SES) of the home environment can significantly alter the developmental trajectory. Poverty increases risk for neurodevelopmental deterioration, resulting in significant health disparities. The means by which poverty alters neurodevelopment are unknown. The microbiome is influenced by environment and in turn influences brain development. We hypothesize that that the microbiome is a biologic effector of the influence of SES and environment on neurodevelopment. This proposal will focus on two key time points at which the microbiome is exposed to significant environmental alteration – first 2 weeks of life in the NICU and 6-12 months of life in the home environment. Longitudinal clinical data, patient microbial samples, environmental data, and SES data will be collected on established cohorts of preterm infants from five institutions across the United States already investigating the intestinal microbiome of preterm infants. Neurodevelopmental exams will be performed to assess the functional outcome of school readiness. The goal of this proposal is to demonstrate that microbiome development influences neurodevelopment. Furthermore we will identify environmental factors associated with SES that influence the microbiome and thus neurodevelopmental outcomes. Strengths of this proposal include distinctive expertise of the interdisciplinary investigative team in neonatal care, neurodevelopment, microbiome analysis, bioinformatics, economics, and analysis of environmental features of the home environment. Advanced sequencing techniques, spatial analysis of environmental factors (geomapping), and economic modeling will be used to investigate the relationships among SES, environment, microbiome, and neurodevelopmental outcome to identify a time point and possible environmental or microbiome modification to improve outcomes. Beyond increasing social strategies, expanding effective learning models, and mitigating medical needs of at risk infants, understanding and promoting shifts in the microbiome could lead to improved understanding of health disparities and enable interventions to alter infant neurodevelopmental-trajectories in innovative ways.