Inflammatory Mediators of Stress Exposure and Neurodevelopment in Very Preterm Infants

项目摘要/摘要 早产儿(月经后28-31周)患损伤的风险增加。 早产和延长新生儿重症监护病房住院时间对神经发育的影响 (NICU)。与早产儿相比，早产儿的认知、运动、行为和社会情绪功能较差 对于足月出生的健康婴儿，这种情况可能会持续到儿童后期和成年早期。早产儿暴露在 许多经验(例如痛苦的程序)、环境(例如感官刺激)和生理(例如败血症， 重病)住院期间可能影响其长期神经发育的压力源。研究人员 提出了炎症与早产儿脑损伤和神经发育受损之间的直接因果关系 婴儿。确定将压力和神经发育联系在一起的潜在可修改的介质对改善压力至关重要 早产儿的长期结局。本研究的目的是评估应激之间的关系。 早产儿暴露、炎症和神经发育。这项研究将完成以下具体工作 目的：(1)确定早产儿应激暴露、炎症和神经发育之间的关系 婴儿，(2)确定压力暴露对炎症和抗炎细胞因子每周变化的影响 从一周龄到35周PMA，以及(3)检验已发表的NICU应激量表之间的相关性 通过毛发皮质醇浓度测量极早产儿的暴露和慢性应激反应。累积和 每周的压力暴露分数将使用新生儿应激源量表(NISS)计算。炎症将会是 用一组促炎和抗炎细胞因子测定，用多重分析进行量化。 神经发育将使用早产儿神经行为评估(NAPI)进行评估。这项研究 包括一个探索性的目标，以衡量NISS评分和头发皮质醇浓度之间的相关性，这是一个创新的 住院早产儿慢性应激反应测量方法的探讨这项研究与 国家护理研究所的使命是促进终身健康，是 开发有针对性的干预措施以优化早产儿的神经发育结果。培训计划 将为申请者提供大量正式和非正式的职业发展机会，同时允许 申请者需要为独立研究人员的成功职业生涯奠定坚实的基础。这项研究建立在 应聘者作为NICU护士和研究助理的经验，并结合她的生物学，护理和 分子生物学实验室技术。

PROJECT SUMMARY/ABSTRACT Infants born very preterm (28-31 weeks post-menstrual age (PMA)) are at an increased risk for impaired neurodevelopment as a result of their preterm birth and extended hospitalization in the neonatal intensive care unit (NICU). Very preterm infants experience poorer cognitive, motor, behavioral, and socioemotional functioning compared to healthy infants born at term, which may persist into late childhood and early adulthood. Preterm infants are exposed to numerous experiential (e.g. painful procedures), environmental (e.g. sensory stimulation), and physiologic (e.g. sepsis, critical illness) stressors during their hospitalization which may affect their long-term neurodevelopment. Researchers have suggested a direct causal pathway linking inflammation with brain injury and impaired neurodevelopment in preterm infants. Determining the potentially modifiable mediators linking stress and neurodevelopment is paramount to improve the long-term outcomes of very preterm infants. The purpose of this study is to evaluate the relationships among stress exposure, inflammation, and neurodevelopment in very preterm infants. This study will accomplish the following specific aims: (1) determine the relationships among stress exposure, inflammation, and neurodevelopment in very preterm infants, (2) determine the effect of stress exposure on weekly changes in inflammatory and anti-inflammatory cytokines from one week of age until 35 weeks PMA, and (3) examine the correlation between a published scale of NICU stress exposure and chronic stress response measured by hair cortisol concentration in very preterm infants. Cumulative and weekly stress exposure scores will be calculated using the Neonatal Infant Stressor Scale (NISS). Inflammation will be measured with a panel of pro-inflammatory and anti-inflammatory cytokines, quantified by multi-plex assay. Neurodevelopment will be assessed using the Neurobehavioral Assessment of the Preterm Infant (NAPI). The study includes an exploratory aim to measure the correlation between NISS scores and hair cortisol concentration, an innovative approach to the measurement of a chronic stress response in hospitalized preterm infants. This study aligns with the National Institute of Nursing Research’s mission to promote life-long wellness and is an important step in the development of targeted interventions to optimize neurodevelopmental outcomes for preterm infants. The training plan will provide the applicant with numerous formal and informal opportunities for professional development while allowing the applicant to build a solid foundation for a successful career as an independent researcher. This study builds on the applicant’s experiences as a NICU nurse and research assistant and integrates her knowledge of biology, nursing, and molecular biology lab techniques.