Neonatal Stress in Very Preterm Infants: Longitudinal Effects on Epigenetics and Neurodevelopment

项目总结/文摘

PROJECT SUMMARY/ABSTRACT Preterm birth affects 1 in 10 infants born in the United States, resulting in significant morbidity and economic cost. Children who are born very preterm (VPT; gestational age<32 weeks) have increased risk for impaired neurodevelopment. VPT infants experience increased physiologic stress while their caregivers experience increased psychological distress—both are associated with impaired neurodevelopment. Epigenetic modifications are proposed as a possible mechanism linking physiologic stress and neurodevelopment in VPT infants. The main objective of the proposed research is to identify the mechanisms by which neonatal physiologic stress induces epigenetic modifications that contribute to impaired neurodevelopment, as well as how caregiver distress moderates the relationship between longitudinal neonatal physiologic stress and neurodevelopmental outcomes. Specifically, the proposed research aims to (1) create and validate novel indices of neonatal physiologic stress in VPT infants; (2) identify the effects of neonatal physiologic stress on epigenetic modifications and later neurodevelopment in VPT infants; and (3) determine the effects of caregiver distress on neurodevelopment in VPT infants. This aligns with the NICHD Strategic Plan 2020 scientific priority—to reduce the incidence of neurodevelopmental disorders by improving the understanding of their origins in the developmental process and identifying potential targets and optimal timing for intervention. The training plan includes several components necessary to reach the PI’s goal of becoming an independent clinical scientist, studying early life risk factors and etiological mechanisms in neurodevelopmental disorders. Specifically, the proposed training aims to enhance the PI’s molecular genetic expertise by adding training in epigenetic analyses via intensive workshops and laboratory experiences with an expert mentor and to expand the PI’s quantitative expertise to include complex longitudinal analyses. The new education and training on neonatal physiological stress will provide the PI with unique expertise that will lead to new avenues of investigation. Finally, the PI will develop professional development skills that will be critical for success as a tenure track assistant professor and independent clinical scientist. The academic environment at the University of Iowa is well-suited for the proposed research and training. Faculty members with expertise in advanced quantitative methods, epigenetics, and neonatal physiology are willing to provide expert mentorship to the PI. The Division of Neonatology conducts numerous research studies on preterm birth each year and has the infrastructure, including an outstanding team of clinical research nurses and a high-risk infant follow-up clinic, to support the proposed research. The Iowa Institute of Human Genetics provides researchers with a state-of-the-art, high-throughput genetic analysis facility and supports research focused on human genetics. Numerous institutional organizations provide a variety of opportunities to develop the skills necessary for success as an independent clinical scientist.