THE ROLE OF SUBCLINICAL INFECTION AND CYTOKINES IN PRETERM PARTURITION

亚临床感染和细胞因子在早产中的作用

• 批准号: 6162520
• 负责人: R ROMERO
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162520
• 关键词: birth; brain injury; cerebral palsy; clinical research; cytokine receptors; human pregnant subject; interleukin 1; interleukin 6; pregnancy infection; premature infant human; premature labor; prenatal diagnosis; tumor necrosis factor alpha; ultrasonography

The goal of this project is to explore the relationship between sub-clinical intrauterine infection, preterm labor and the complications of prematurity. This year the Branch focused on establishing whether the human fetus can be affected by a systemic inflammatory response syndrome and the relationship between this condition and the onset of premature labor and perinatal morbidity. The following observations were made: 1) Definition of the "fetal inflammatory response syndrome": a fetal plasma IL-6 concentration of 11 pg/ml or more was used to defined the presence of a systemic inflammatory response in the human fetus. This condition was observed in approximately 20% of fetuses presenting with preterm labor and intact membranes and 45% of those presenting with preterm PROM. Importantly, 77.8% of fetuses affected with this syndrome develop severe morbidity after birth. Fetal plasma IL-6 concentration was an independent predictor of the occurrence of severe neonatal morbidity (odds ratio 4.3, 95% confidence interval 1-18.5) after adjustment for gestational age at delivery, amniotic fluid culture and other relevant variables. 2) The role of the human fetus in preterm parturition: To determine if the fetus plays a role in the onset of parturition, the relationship between the presence of a "fetal inflammatory response syndrome" and the subsequent onset of labor was studied in patients admitted with preterm PROM and who were not in labor. Fetuses affected by the syndrome had a higher rate of spontaneous preterm delivery within 24, 48, and 72 hours of the procedure than those without this syndrome (56% vs. 24%; 81% vs. 36% and 88% vs. 40%, respectively, p < 0.05 for each). Fetal plasma IL-6 was the only covariate significantly associated with the duration of pregnancy after adjusting for gestational age, amniotic fluid IL-6 and the microbiologic state of the amniotic cavity. These observations indicate that a systemic fetal cytokine response is associated with the impending onset of spontaneous preterm labor in patients with preterm PROM and therefore provide evidence for a role of the human fetus in determining the timing of preterm labor and delivery. 3) Expression of mRNA for anti-microbial peptides by the lower genital tract and gestational tissues: A crucial question is why some women develop an ascending intrauterine infection and others do not. Previous observations suggests that the cervical mucus which forms, the mucus plug during pregnancy, inhibits bacterial growth. The Branch provided evidence that chorionic tissue, endocervical tissue, endometrial tissue and an endometrial cell line, expressed mRNA for defensin 5, an epithelial anti-microbial peptide. The human placenta was also found to express defensin-1 (a hematopoietic defensin). These observations suggests that the expression of anti-microbial peptides may be a mechanism of host defense against ascending and transplacentally acquired infections.

本项目的目标是探索 亚临床宫内感染、早产及并发症 早产儿今年，分支的重点是确定 人类胎儿可能会受到全身炎症反应综合征的影响 以及这种情况与早产儿发病之间的关系 分娩和围产期发病率。提出了以下意见： 1)“胎儿炎症反应综合征”的定义： 使用11 pg/ml或更高的血浆IL-6浓度来定义 在人类胎儿中存在全身性炎症反应。这 在大约20%的胎儿中观察到这种情况， 早产和完整的膜和45%的那些提出与 早产胎膜早破。重要的是，77.8%的胎儿患有这种综合征， 出生后出现严重的发病率。胎儿血浆IL-6浓度 是发生重度新生儿窒息的独立预测因子 发病率（比值比4.3，95%置信区间1-18.5） 调整分娩时的胎龄，羊水培养， 其他相关变量。 2)人类胎儿在早产中的作用： 胎儿在分娩开始时起作用， 胎儿炎症反应综合征的存在与 随后分娩的发生在早产的患者中进行了研究， 有胎膜早破和没有分娩的。受该综合征影响的胎儿 24、48和72小时内自发性早产率较高 与没有这种综合征的人相比，手术的发生率为56%，24%; 81%， 分别为36%和88%对40%，p < 0.05）。 胎儿血浆IL-6 是唯一与持续时间显著相关的协变量 调整胎龄、羊水IL-6和 羊膜腔的微生物状态 这些观察结果 表明全身性胎儿细胞因子反应 关联于 早产患者自发性早产的临近发作 因此，为人类胎儿在胎膜早破中的作用提供了证据。 确定早产和分娩的时间。 3)下生殖道抗菌肽mRNA的表达 生殖道和妊娠组织：一个关键问题是，为什么有些妇女 发展为上行性宫内感染，而其他人则没有。先前 观察表明，形成的宫颈粘液，即粘液栓， 在怀孕期间，抑制细菌生长。分支提供了证据， 绒毛膜组织、子宫颈内组织、子宫内膜组织和 子宫内膜细胞系，表达防御素5的mRNA， 抗菌肽人类胎盘也被发现表达 防御素-1（一种造血防御素）。这些观察表明， 抗菌肽的表达可能是宿主的一种机制 防御上升和经胎盘获得性感染。