In Utero Infection: Child Health and Neurodevelopment

子宫内感染：儿童健康和神经发育

• 批准号: 6882702
• 负责人: WILLIAM Walton ANDREWS
• 金额: $ 37.51万
• 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/6882702
• 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、其他不良神经系统后果（如失明、耳聋和智力低下）的最高风险因素，而长期不良儿童健康后果占这些不良后果的 50%后遗症。大多数发病率集中在妊娠 32 周以下的早产儿中。由于美国早产率不断上升以及早产儿存活率的提高，不良长期后遗症的发生率不断上升。现已明确，临床上无症状的上生殖道宫内细菌感染与大多数妊娠 32 周之前发生的早产密切相关。此外，新出现的数据表明，胎儿在子宫内接触细菌感染/炎症是发生脑瘫和其他不良健康结果的独立危险因素，推测促炎细胞因子暴露可能与这些不良结果有关。大多数将感染与不良神经系统结局联系起来的研究仅限于短期新生儿结局，包括随后发展为脑瘫的标志物，例如脑室周围白质软化症。该领域的长期随访研究很少，主要限于脑瘫作为主要结局，并且提供的有关孕产妇/新生儿临床病程的信息有限。目前的文献缺乏对一组母婴对进行广泛的孕产妇和新生儿临床、实验室、微生物学和组织学数据的纵向研究，对这些母婴对进行长期结果评估不仅包括脑瘫，还包括其他重要的神经发育和健康结果。我们假设，在子宫内接触感染/炎症与 4-7 岁时不良神经发育和儿童健康结果的风险增加相关。我们建议在 424 对母婴队列中检验这一假设，这些母婴是在我们机构妊娠 24 周 0 天到 31 周 6 天期间分娩的。该队列已经经过研究，形成了一个广泛的数据库，其中包括产前、产时和新生儿临床数据的几乎所有细节。该队列还已经提供了组织学、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。我们建议对这个早产儿队列进行一项纵向随访研究，以便系统地评估母婴感染、胎儿炎症暴露、新生儿短期结局和 4 至 7 岁时最终神经发育结局之间的关系（目标 1 和 2） ）包括环境因素和护理人员特征等效果调节剂的潜在影响（目标 3）。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果相关（目标 4），以及子宫内感染/炎症、支气管肺发育不良和肺功能障碍长期指标之间的关联强度（目标 5)。

项目成果

Predicting long-term neurodevelopmental outcomes in very preterm neonates by umbilical cord gas parameters.

通过脐带气体参数预测极早产新生儿的长期神经发育结果。

• 发表时间: 2021
• 作者: Baalbaki, Sima H;Wood, S Lindsay;Tita, Alan T;Szychowski, Jeff M;Andrews, William W;Subramaniam, Akila
• 通讯作者: Subramaniam, Akila