In Utero Infection: Child Health and Neurodevelopment

子宫内感染：儿童健康和神经发育

• 批准号: 6739702
• 负责人: WILLIAM Walton ANDREWS
• 金额: $ 57.05万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-17 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6739702
• 关键词: academic achievement; biomarker; child (0-11); child physical development; clinical research; cognition; cord blood; developmental neurobiology; disease /disorder proneness /risk; human subject; interpersonal relations; language development; longitudinal human study; nerve /myelin protein; nervous system disorder; neuropsychological tests; pregnancy infection; premature infant human; psychological adaptation; psychomotor function; respiratory disorder

DESCRIPTION (provided by applicant): Preterm birth is the highest risk factor for cerebral palsy, other adverse neurological outcomes (such as blindness deafness, and mental retardation), and long-term adverse child health outcomes accounting for up to 50% of these adverse sequelae. Most of this morbidity is concentrated among the subset of preterm births that deliver at less than 32 weeks' gestation. Because of the increasing rate of preterm birth in the United States and the increased survival of infants delivered at the earlier gestational ages, the incidence of adverse long-term sequelae is rising. It is now well established that clinically silent upper genital tract intrauterine bacterial infection is strongly associated with a majority of preterm births that occur prior to 32 weeks' gestation. Additionally, emerging data implicate fetal in utero exposure to bacterial infection/inflammation as an independent risk factor for development of cerebral palsy and other adverse health outcomes, it is speculated that proinflammatory cytokine exposure may represent the link to these adverse outcomes. Most of the studies linking infection to adverse neurological outcomes have been limited to short-term neonatal outcomes including markers for subsequent development of cerebral palsy such as periventricular leukomalacia. Long-term follow-up studies in this area are sparse, are largely limited to cerebral palsy as the primary outcome, and provide limited information regarding the maternal/neonatal clinical course. The current literature lacks a longitudinal study with extensive maternal and neonatal clinical, laboratory, microbiological, and histological data on a cohort of maternal-infant pairs on whom long-term outcome evaluation is available including not only cerebral palsy but also other important neurodevelopmental and health outcomes. We hypothesize that in utero exposure to infection/inflammation is associated with increased risk of adverse neurodevelopmental and child health outcomes at age 4-7 years. We propose to test this hypothesis in a cohort of 424 maternal-infant pairs that delivered at our institution between 24 weeks 0 days and 31 weeks 6 days gestation. This cohort has already been studied resulting in an extensive database that includes almost every detail of antepartum, intrapartum, and neonatal clinical data. Also already available from this cohort are histological, microbiological, and biochemical data including umbilical cord blood and neonatal cultures, umbilical cord blood cytokine data, placental histology, and placental cultures. We propose a longitudinal follow-up study of this preterm cohort in order to systematically evaluate the relationship between maternal/fetal infection, fetal exposure to inflammation, neonatal short-term outcomes and ultimate neurodevelopmental outcomes at age 4 to 7 years (Aims 1 and 2) including the potential influence of effect modifiers such as environmental factors and caregiver characteristics (Aim 3). We will also determine if umbilical cord blood markers of neuronal damage are associated with short-term or long-term outcomes (Aim 4) and the strength of association between in utero infection/inflammation, bronchopulmonary dysplasia and long-term indicators of pulmonary dysfunction (Aim 5).

描述（由申请人提供）：早产是脑瘫，其他不良神经系统结局（例如失明聋和智力低下）的最高危险因素，以及长期不良儿童健康结果，最多占这些不良反射的50％。这种发病率的大部分集中在不到32周妊娠的早产子集中。由于美国早产率的增加以及在妊娠年龄较早的婴儿的存活率增加，因此不良的长期后遗症的发生率正在上升。现在已经很好地确定，临床上静音的上层生殖道细菌感染与在妊娠32周之前发生的大多数早产相关。此外，新兴的数据暗示胎儿暴露于细菌感染/炎症是发展脑瘫和其他不良健康结果的独立危险因素，据推测，促炎细胞因子的暴露可能代表与这些不良局势的联系。将感染与不良神经系统结合的大多数研究仅限于短期新生儿结局，包括随后发展大脑麻痹（如脑室性白细胞室）的标志物。该领域的长期随访研究很少，很大程度上仅限于脑瘫作为主要结果，并提供有关母亲/新生儿临床过程的有限信息。目前的文献缺乏一项纵向研究，对一系列产妇对孕产妇和新生儿临床，实验室，微生物学和组织学数据缺乏一项纵向研究，其中长期结局评估不仅包括大脑瘫痪，而且还包括其他重要的神经性发育和健康的结果。我们假设在子宫内暴露于感染/炎症中，与4-7岁的不良神经发育和儿童健康结局的风险增加有关。我们建议在424对孕产妇对妊娠的424对组成的队列中检验这一假设。该队列已经进行了研究，导致了一个广泛的数据库，该数据库几乎包含了动作，内部和新生儿临床数据的每个细节。该队列也已经获得了组织学，微生物学和生化数据，包括脐带血和新生儿培养物，脐带血细胞因子数据，胎盘组织学和胎盘培养物。我们提出了一项对该早产队列的纵向后续研究，以系统地评估孕产妇/胎儿感染，胎儿暴露于炎症，新生儿短期结局以及4至7岁时的最终神经发育结果（目标1和2）（目标1和2）（目标1和2），包括效应效应的潜在影响，例如环境因素和Caregiver sartiviver and Caregiver and Caregiver and Caregiver and Caregiver特征的影响。我们还将确定神经元损伤的脐带血标志物是否与短期或长期结局有关（AIM 4）以及子宫感染/炎症，支气管肺发育不良和肺部功能障碍的长期指标（AIM 5）之间的关联强度。