Physiologic Stress During Pregnancy on Maternal and Infant Outcomes

应聘者：我的生物学、心理学和护理学本科学位和护理学博士学位为我成为一名生物行为护士科学家提供了教育基础。我在新生儿重症监护病房(NICU)的床边护理和运送护理的经验为新生儿人群的研究提供了临床基础。我的长期职业目标是降低新生儿并发症的严重程度，最终改善那些出生时面临长期、令人衰弱的结局的婴儿的健康状况，并为整个生命周期的健康奠定基础。我的长期研究目标是：1)参与将病理生理学机制和生物学措施从实验室科学转化为临床研究和实践，以应对有不良后果风险的婴儿；以及2)开发一个基于证据的筛查计划，用于产前，以便在孕妇中实施健康促进和疾病预防干预措施，以改善其新生儿的结局。K01应用程序的目标是为实现这些长期研究目标提供必要的知识和技能的关键发展：从氧化应激专家那里获得氧化应激机制和测量技术的培训，以便将其转化为临床新生儿研究；从产前研究方面的资深护士科学家那里获得关于孕妇的行为、应激和免疫机制及测量的培训；从从事新生儿研究的资深护士科学家那里获得关于新生儿的行为、应激和免疫机制和测量的培训；以及加强学术和专业技能，以成为一名独立的护士科学家。环境：内布拉斯加大学医学中心(UNMC)是一个学术医学中心，在校园内设有医院附属机构，鼓励跨学科研究和教育合作。UNMC在氧化还原生物学方面有一个强大的研究计划，有几位专家科学家和可用的资源。作为UNMC氧化还原生物学的一名专家，Matthew Zimmerman博士将担任主要导师，以增强我在与氧化应激相关的生理学和测量技术方面的知识。我将参加几个教育和实验室的机会，以获得必要的技能，与一个多学科团队进行翻译研究。Ann Berger博士将担任共同导师、现场资深护士科学家和关键导师，以协调和跟踪朝着我的目标和目标的进展。我的论文研究为检验产前对新生儿结局的影响提供了数据。因此，珍妮·鲁伊斯博士，一位产前生物行为研究的专家护士科学家，将担任共同导师，在我的研究计划中提供产前研究的教育和应用。由于我的主要研究兴趣是新生儿群体，丽塔·皮克勒博士还将担任共同导师，因为她在新生儿研究和早产儿神经行为发展方面的专业知识。皮克勒博士和鲁伊斯博士都有来自美国国立卫生研究院资助的研究的大型数据库，这将有助于与我的研究相关的分析。研究：该职业发展奖的主要目标是调查高危孕妇及其新生儿的异位负荷(慢性应激对身体系统影响的生物-心理-社会模型)与围产期结局之间的潜在关系。从概念和操作上讲，稳态负荷是指免疫系统对炎症和氧化应激等参数的生理性失调。高危孕妇在胎龄18-21周和分娩前采集的血液、出生时采集的脐带血和新生儿出生后24-48小时内采集的血液中的AL参数将被测量，包括来自免疫系统的特定自由基(例如超氧化物、羟基自由基、一氧化氮)、抗氧化剂(例如胆红素、谷胱甘肽、超氧化物歧化酶)和炎性细胞因子(例如IL-6、IL-8和IL-10)。高危母胎医学实践小组看到的60名妇女和她们的新生儿没有已知的先天性异常将被招募。这项研究的目的是：1)调查高危孕妇AL参数与脐带血及其新生儿AL参数之间的关系；2)确定有产前并发症的高危孕妇AL参数之间的关系；3)检查新生儿结局与高危孕妇AL参数、出生时采集的脐血AL参数及其新生儿AL参数之间的关系。这项研究的成功完成将为与产前和新生儿并发症相关的生物因素提供新的见解。这项研究将促进我们对氧化应激和炎症机制在推动产前和新生儿人群发生这些并发症中可能发挥的作用的理解。这项研究的意义在于，它将增强知识，以改善有不良结局风险的婴儿的结局。培训计划将把申请者培养成一名独立的护士科学家，专注于产妇和新生儿群体的生物行为研究，并利用多学科团队进行转化性研究。

DESCRIPTION (provided by applicant): Candidate: My undergraduate degrees in Biology, Psychology, and Nursing and the PhD in Nursing have provided the educational foundation to become a biobehavioral nurse scientist. My experiences in bedside and transport nursing in the newborn intensive care unit (NICU) have provided the clinical foundation for research in the neonatal population. My long-term career goal is to reduce the severity of neonatal complications and ultimately improve the health of infants who are born at risk for long-term, debilitating outcomes and build the foundation of health across the lifespan. My long-term research goals are to: 1) participate in the translation of pathophysiologic mechanisms and biological measures from bench science to clinical research and practice for infants at risk for adverse outcomes; and 2) develop an evidenced-based screening program for use during the prenatal period to allow for the implementation of health promotion and disease prevention interventions in pregnant women to improve outcomes their newborn infants. The objectives for this K01 application provide the critical development of knowledge and skills necessary to achieve these long-term research goals: obtain training on oxidative stress mechanisms and measurement techniques from an expert bench scientist in oxidative stress for translation to clinical neonatal research; obtain training on behavioral, stress, and immunological mechanisms and measurements in pregnant women from a senior nurse scientist in prenatal research; obtain training on behavioral, stress, and immunological mechanisms and measurements in neonates from a senior nurse scientist in neonatal research; and strengthen academic and professional skills to be an independent nurse scientist. Environment: The University of Nebraska Medical Center (UNMC) is an academic medical center with a hospital affiliate on campus that encourages collaboration across disciplines for research and education. UNMC has a strong research program in Redox Biology with several expert scientists and resources available. As an expert bench scientist in Redox Biology at UNMC, Dr. Matthew Zimmerman will serve as primary mentor to enhance my knowledge on the physiology and measurement techniques associated with oxidative stress. I will participate in several educational and laboratory opportunities to acquire the necessary skills to conduct translational research with a multidisciplinary team. Dr. Ann Berger will serve as a Co-mentor and on-site senior nurse scientist and key mentor to coordinate and track progress towards my goals and objectives. My dissertation research provided data to examine prenatal influences on neonatal outcomes. Therefore, Dr. Jeanne Ruiz, an expert nurse scientist in prenatal biobehavioral research, will serve as a co-mentor to provide education and application of prenatal research into my research program. Since my primary research interest is in the neonatal population, Dr. Rita Pickler also will serve as a Co-mentor because of her expertise in neonatal research and neurobehavioral development in preterm infants. Both Dr. Pickler and Dr. Ruiz have large databases from NIH-funded research and will facilitate analyses related to my research. Research: The primary goal of this career development award is to investigate potential relationships between allostatic load (a bio-psycho-social model of the effects of chronic stress on body systems) in high-risk pregnant women, their newborn infants, and perinatal outcomes. Allostatic load (AL) is conceptually and operationally defined as physiologic dysregulation of AL parameters of inflammation and oxidative stress from the immune system. AL parameters will be measured in the blood of high-risk pregnant women collected between 18-21 weeks gestational age and prior to delivery, in the cord blood collected at birth, and in the blood collected between 24-48 hours after birth in the newborn infant and include specific free radicals (e.g. superoxide, hydroxyl radical, nitric oxide), antioxidants (e.g., bilirubin, glutathione, superoxide dismutase), and inflammatory cytokines (e.g., IL-6, IL-8, IL-10) from the immune system. Sixty women seen by the high-risk maternal-fetal-medicine practice group and their newborn infants with no known congenital anomalies will be recruited. The aims of the research study are: 1) investigate associations between AL parameters in high-risk pregnant women with AL parameters in the cord blood and in their newborn infants; 2) determine relationships among AL parameters in high-risk pregnant women with prenatal complications; and 3) examine associations among neonatal outcomes and AL parameters in high-risk pregnant women, AL parameters in the cord blood collected at birth, and AL parameters in their newborn infants. Successful completion of this study will provide new insight into biological factors associated with prenatal and neonatal complications. This study will advance our understanding of the role that oxidative stress and inflammatory mechanisms may be playing in driving these complications in prenatal and neonatal populations. The significance of this study is that it will enhance knowledge to improve outcomes for infants at risk for adverse outcomes. The training program will develop the applicant to become an independent nurse scientist with a focus on biobehavioral research in maternal and neonatal populations and to conduct translational research using multidisciplinary teams.