Late Preterm Birth, Ureaplasma Species and Childhood Lung Disease

已知胎儿暴露会影响儿童期和以后生活中的肺功能。虽然约7%的 所有分娩都被归类为晚期早产（妊娠32 -366周的分娩）， 儿童期肺部相关问题的风险，这一人群的肺部结局研究最少。 胎儿暴露于绒毛膜炎（炎症/感染）可对肺发育产生不利影响， 调节胎儿免疫功能。与胎儿炎症/慢性相关的最常见微生物 人的绒毛膜炎是脲原体属（Ureaplasma spp.）我们假设胎儿暴露于脲原体 调节免疫反应并增加晚期早产儿童早期肺部疾病的风险 婴儿。我们将通过一项临床研究和与美国的平行实验研究来验证这一假设。parvum 胎羊绒毛膜炎。临床研究将根据培养物选择晚期早产儿队列 脲原体属和绒毛膜炎的组织病理学检查。将评价胎儿炎症反应 通过脐带血中的细胞因子/趋化因子谱、分子表型和脐带血的免疫调节 单核细胞和树突细胞将表征胎儿免疫状态。暴露和未暴露的脲原体 晚期早产儿将在9个月和2岁时进行肺健康评估，并在9个月和2岁时进行肺功能测试。 mos以评价肺部结局。在平行实验中，我们将描述炎症和免疫 羊胎对羊膜腔内注射U.小的 我们将探讨体内炎症/免疫反应的多带抗原（MBA）的变异性，因为 MBA在体外已被鉴定为U.小的我们将描述妊娠期 年龄和从暴露到分娩的间隔调节胎儿对U. 小的我们将允许你。parvum暴露胎儿分娩和测量免疫状态肺功能， 2周龄和2月龄时的结构。实验是创新的，因为我们将重点放在晚早产儿上。 婴儿，一个庞大的未充分研究的人群，以确定出生时的免疫状态。我们将胎儿支原体 暴露和绒毛膜炎与肺部结果和免疫学测量。我们将使用一个 临床相关模型的羊绒毛膜炎，以评估免疫调节方面， 可能在人类。研究结果将首次将特定和常见的胎儿炎症暴露联系起来 肺的结果。这项研究将由一个经验丰富的研究人员团队进行，他们具有以下方面的专业知识： 该项目的每个组成部分：脲原体属的生物学， 新生儿和胎羊，绒毛膜炎的动物模型，以及儿童的肺部评估。

Fetal exposures are known to influence lung function in childhood and later life. Although about 7% of all births are categorized as late-preterm (births at 32o-366 wks gestation) and these infants are at increased risk for lung related problems in childhood, this population has been minimally studied for lung outcomes. Fetal exposure to chorioamnionitis (inflammation/infection) can adversely affect lung development and modulate fetal immune function. The most frequent organism associated with fetal inflammation/chronic chorioamnionitis in the human is Ureaplasma spp. We hypothesize that fetal exposure to Ureaplasma spp modulates immune responses and increases the risk of lung disease in early childhood in late-preterm infants. We will test this hypothesis with a clinical study and a parallel experimental study with U. parvum chorioamnionitis in fetal sheep. The clinical study will select cohorts of late preterm infants based on cultures for Ureaplasma spp, and histopathology for chorioamnionitis. Fetal inflammatory responses will be evaluated by cytokine/chemokine profiles in cord blood, molecular phenotypes and immune modulation by cord blood monocytes, and dendritic cells will characterize fetal immune status. The ureaplasma exposed and unexposed late-preterm infants will have lung health assessments at 9 mos and 2 yrs, and pulmonary function tests at 9 mos to evaluate lung outcomes. In parallel experiments we will characterize the inflammatory and immune modulatory responses of fetal sheep to the chorioamnionitis caused by intra-amniotic injection of U. parvum. We will explore the in vivo inflammatory/immune responses to multi-banded antigen (MBA) variability because MBA has been identified in vitro as the virulence factor for U. parvum. We will characterize how gestational age and interval from exposure to delivery modulate the fetal immune and inflammatory responses to U. parvum. We will allow U. parvum exposed fetuses to deliver and measure immune status lung function and structure at 2 wks and 2 mos of age. The experiments are innovative be cause we will focus on late-preterm infants, a large understudied population, to define immune status at birth. We will correlate of fetal ureaplasma exposure and chorioamnionitis with pulmonary outcomes and with immunologic measurements. We will use a clinically relevant model of chorioamnionitis in sheep to evaluate aspects of immune modulation that are not possible in humans. The results will link for the first time a specific and common fetal inflammatory exposure with lung outcomes. The research will be performed by a team of experienced investigators with expertise for each component of the project: the biology of Ureaplasma spp, immune and inflammatory responses in the newborn human and fetal sheep, animal models of chorioamnionitis, and pulmonary assessments of children.