A Population-based Study of SLE Pregnancy: Risks and Outcomes in Mother and Child

描述（由申请人提供）：这是斯坦福大学医学院流行病学家Julia Simard博士的K 01奖的新申请，她计划开展一项研究计划，重点关注系统性红斑狼疮（SLE）女性的不良生殖和出生结局。虽然Simard博士在流行病学和登记研究方面有很强的背景，但她需要在三个其他领域的技能来实现她的长期目标：（1）深入了解免疫系统和受系统性自身免疫疾病影响的其他器官系统的基础和临床科学;（2）生殖和围产期流行病学方面的高级培训;以及（3）熟练掌握荟萃分析、使用贝叶斯方法进行研究综合和多变量建模的高级统计技术。为了建立这个基础，Simard博士和她的导师们制定了一个多学科的职业发展计划，其中包括以下内容：（1）临床医学、免疫学、病理学和母胎医学的高级课程，乌茨博士和萨尔蒙博士在基础和临床免疫学方面提供额外的个人指导;（2）通过Druzin博士和Salmon博士的一对一辅导和研究监督，直接培训生殖和围产期流行病学;以及（3）研究综合、贝叶斯方法和多变量分析的高级课程，辅以古德曼和纳尔逊博士指导的指导性阅读。在斯坦福大学的正式课程和指导将补充短期课程和参加有关生殖和围产期流行病学，风湿病学和免疫学的国家会议。将这种实质性和方法学知识与她的指导研究项目相结合，将大大增强Simard博士的研究能力，并使她能够领导一个独立的多学科研究项目。 对于她的K 01指导研究项目，Simard博士将进行瑞典人口为基础的登记数据的链接，以创建世界上最大的SLE患者队列之一，与普通人群中的个体相匹配，作为对照组。这些数据将用于评估母亲和后代的风险和结局，并调查SLE发病机制中驱动这些风险的方面。在目标1中，Simard博士将使用从一般人群中抽样的至少1000例SLE妊娠和超过40，000例妊娠女性中前瞻性收集的相关国家数据进行队列研究，以评估孕产妇妊娠风险，包括早产、晚期妊娠流产、先兆子痫、中风和死亡。将研究与SLE相关的不良结局，以确定潜在的预测因子和临床可改变的因素。在目标2中，Simard博士将使用相同的基于人群的数据库来识别与SLE妊娠相关的不良胎儿和儿童结局。除了确定妇女的子集，以密切监测有针对性的干预措施，Simard博士的指导研究项目预计将产生信息，使临床医生能够更好地咨询SLE妇女关于妊娠风险，并可能导致有关SLE的病理生理学的重要新见解。

DESCRIPTION (provided by applicant): This is a new application for a K01 award for Dr. Julia Simard, an epidemiologist at Stanford University School of Medicine, who plans a research program focusing on adverse reproductive and birth outcomes of women with systemic lupus erythematosus (SLE). Although Dr. Simard has a strong background in epidemiology and registry research, she requires skills in three additional areas to achieve her long-term goals: (1 in-depth knowledge of basic and clinic science of the immune system and the other organ systems affected by systemic autoimmune diseases; (2) advanced training in reproductive and perinatal epidemiology; and (3) proficiency in advanced statistical techniques for meta-analysis, research synthesis using Bayesian methods, and multivariate modeling. To build this foundation, Dr. Simard and her mentors have created a multi-disciplinary career development plan that includes the following elements: (1) advanced coursework in clinical medicine, immunology, pathology and maternal-fetal medicine, with additional individual mentoring in basic and clinical immunology by Drs. Utz and Salmon; (2) direct training in reproductive and perinatal epidemiology through one-on-one tutorials and research supervision by Drs. Druzin and Salmon; and (3) advanced coursework in research synthesis, Bayesian methods and multivariate analyses, complemented by mentored directed readings with Drs. Goodman and Nelson. Formal coursework and mentoring at Stanford University will be supplemented with short courses and attendance at national conferences related to reproductive and perinatal epidemiology, rheumatology, and immunology. Integrating this substantive and methodological knowledge with her mentored research project will substantially augment Dr. Simard's research capabilities and enable her to lead an independent multidisciplinary research program. For her K01 mentored research project, Dr. Simard will carry out a linkage of Swedish population-based register data to create one of the world's largest cohorts of patients with SLE matched to individuals from the general population as a comparator group. These data will then be used to assess risks and outcomes in mothers and offspring, and to investigate the aspects of SLE pathogenesis that drive these risks. In Aim 1, Dr. Simard will conduct a cohort study using prospectively collected linked national data from at least 1000 SLE pregnancies and over 40,000 pregnancies among women sampled from the general population to assess maternal risks of pregnancy including preterm labor, late-term pregnancy loss, pre-eclampsia, stroke, and death. Adverse outcomes associated with SLE will be investigated to identify potential predictors and clinically modifiable factors. In Aim 2, Dr. Simard will use the same population-based database to identify adverse fetal and childhood outcomes associated with SLE pregnancy. In addition to identifying subsets of women to monitor closely for targeted interventions, Dr. Simard's mentored research project is expected to yield information that will enable clinicians to better counsel women with SLE regarding pregnancy risks, and could lead to important new insights about the pathophysiology of SLE.