Inflammatory Mediators of Stress Exposure and Neurodevelopment in Very Preterm Infants

项目总结/文摘

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.