New Paradigms of Cerebral Palsy Etiology: A Comprehensive Case Control Study

脑瘫病因学的新范式：综合病例对照研究

• 批准号: 7473511
• 负责人: NIGEL SEFTON PANETH
• 金额: $ 96.26万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7473511
• 关键词: Acidosis; Apgar Score; Archives; Asphyxia; Bacterial Vaginosis; Biological; Biological Assay; Birth; Birth Certificates; Blood; Case-Control Studies; Cerebral Palsy; Child; Childhood; Clinical; Coagulation Process; Collaborations; Cytokine Gene; DNA; Data; Enrollment; Environment; Etiology; Event; Family; Family history of; Fetal Heart Rate; Future; Gene Expression; Genes; Genetic Materials; Genetic Screening; Genomics; Hemiplegia; Hormonal; Hypoxia; Infection; Inflammation; Inflammatory; Inflammatory Response; Interview; Laboratories; Link; Maternal Exposure; Messenger RNA; Michigan; Minnesota; Molecular; Molecular Profiling; Mothers; Neonatal; Neurologic; Newborn Infant; Parents; Pathway interactions; Patient Self-Report; Pediatric Hospitals; Perinatal; Pregnancy; Production; Proteins; Quadriplegia; Recording of previous events; Reporting; Research Institute; Risk Factors; Role; Sampling; Screening Result; Screening procedure; Source; Specimen; Spottings; Stroke; Thrombosis; Thyroid Diseases; Thyroid Gland; Thyroid Hormones; Thyroxine; Triad Acrylic Resin; Universities; Urinary tract; Vagina; Viral; Virus; Virus Diseases; base; case control; disability; fetal; fetal infection; mRNA Expression; maternal serum; prevent; programs; salivary assay; therapy design

This proposal is a revised version of an R01 application for a comprehensive five-year case-control study of CP (New Paradigms of CP Etiology 1R01NS055101). We now propose to perform a two year case-control study that focuses centrally on one rich source of exposure information, the newborn blood spot, which is available on all MI births since 1986, supplemented with a maternal interview about pregnancy exposures, birth certificate data, newborn thyroid hormone screening data, and, when available, maternal serum assays. We will collect and store (but not assay) salivary-based genetic material from enrolled subjects and their parents. The overall aim of the project is to assess the extent to which children with CP and matched controls differ in newborn expression of genes relating to inflammation, hypoxia, coagulation and thyroid hormone production, as well as presence of viruses in blood at birth. Through collaborations with the University of Michigan and the DeVos Children’s Hospital, we will expand our enrollment from Central Michigan to West and Southeast Michigan, enrolling the same number of cases and controls (440) in two years as we had originally planned in five years. The blood spot material will be assessed in three laboratories: mRNA expression will be assessed in triplicate at the Van Andel Research Institute (Grand Rapids, MI); key mRNA species will be further assessed by qPCR at MSU; viral genomic markers will be examined at the University of Minnesota. Maternal antenatal specimens will be assessed at MSU. We will extend these hypotheses to include maternal exposures in pregnancy in the fraction of subjects for whom maternal serum can be retrieved. Maternal interviews and birth certificates will inform the above analyses by linking molecular information to self-reported and recorded clinical events and conditions. 

该提案是针对 CP 的全面五年病例对照研究的 R01 申请的修订版（CP 病因学新范式 1R01NS055101），我们现在建议进行一项集中于一个丰富来源的两年病例对照研究。暴露信息、新生儿血斑（自 1986 年以来所有 MI 出生均可获得），并辅以有关妊娠暴露的产妇访谈、出生证明数据、新生儿甲状腺激素筛查数据，如果有的话，我们将收集和储存（但不分析）来自登记受试者及其父母的基于唾液的遗传物质。该项目的总体目标是评估儿童患有 CP 和匹配对照的程度。新生儿与炎症、缺氧、凝血和甲状腺激素产生以及出生时血液中病毒存在相关的基因表达存在差异，通过与密歇根大学和德沃斯儿童医院的合作，我们将扩大密歇根中部的招生范围。向西和东南密歇根州，两年内招募的病例和对照人数 (440) 与我们最初计划的五年内相同。 血斑材料将在三个实验室进行评估：mRNA 表达将在范安德尔研究所 (Van Andel Research Institute) 进行三次评估。密西根州大急流城）；密歇根州立大学将通过 qPCR 进一步评估病毒基因组标记；我们将在密歇根州立大学对母体产前样本进行评估。可以检索母体血清的部分受试者的怀孕情况通过将分子信息与自我报告和记录的临床事件和状况联系起来，母亲访谈和出生证明将为上述分析提供信息。 