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: 2575744
• 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/2575744
• 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 intra-amniotic infection, preterm parturition and the complications of prematurity. This year the Branch focused specifically on the relationship between sub-clinical intrauterine infection and periventricular leukomalacia. Periventricular leukomalacia (PVL), a cerebral lesion characterized by foci of necrosis in the white matter near the lateral ventricles is found in 7-26 % of neonates with a birth weight under 1,500 g. Between 47% and 80% of these infants developed abnormalities of neuromuscular tone and posture (i.e. cerebral palsy) , and often cognitive impairment. Inflammatory cytokines released during the course of intrauterine infections have been implicated in the genesis of brain white matter lesions and subsequent CP. The Branch completed a study to determine if fetuses who subsequently were diagnosed to have periventricular brain white matter lesions within the first seven days of life could be identified by determining the concentrations of inflammatory cytokines in amniotic fluid. Women with complicated preterm gestations underwent amniocentesis for clinical indications. Amniotic fluid concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and the natural interleukin-1 receptor antagonist (IL-1ra) were determined by immunoassay. Periventricular white matter lesions of the neonate were diagnosed by neurosonography. Ninety-four women and their neonates were included in the study; white matter lesions were diagnosed in 24% (23/94) of the newborns. The mothers of newborns with brain white matter lesions had higher median concentrations of TNF-alpha, IL-1beta, and IL-6 (but not IL-1ra) in amniotic fluid than those who delivered newborns without white matter lesions (P<0.01 for each). Acute histologic chorioamnionitis was more common in the placentas of neonates with white matter lesions than in those without these lesions (P=0.001). Neonates with white matter lesions were delivered at a lower mean gestational age and birth weight and had a higher rate of significant complications (including respiratory distress syndrome, intraventricular hemorrhage, infection-related complications) than those without white matter lesions. The differences in median IL-1beta and IL-6 between these two groups remained significant after adjusting for gestational age and birth weight (IL-6: odds ratio, 5.7; 95% confidence interval, 1.3 to 24.4; IL-1beta: odds ratio, 4.4; 95% confidence interval, 1.1 to 17.0). Of the 94 newborns included in this study, 11 died before six months of age and seven developed severe spastic paresis of at least one lower extremity; all seven had white matter lesions and elevated cytokines in amniotic fluid. These data provides strong support for the hypothesis that inflammatory cytokines released during the course of intrauterine infection play a role in the genesis of brain white matter lesions.

本项目的目标是探索 亚临床羊膜内感染，早产和 早产的并发症。今年，该分支特别侧重于 亚临床宫内感染与 脑室周围白质软化 脑室周围白质软化症（PVL）是一种脑病变， 在侧脑室附近的白色物质中发现坏死灶 出生体重低于1，500 g的新生儿中有7- 26%。47%， 80%的婴儿出现神经肌肉张力异常， 姿势（即脑瘫），通常还有认知障碍。 宫内过程中释放的炎症细胞因子 感染与脑白色物质的形成有关 病变和随后的CP。分支完成了一项研究， 随后被诊断为脑室周围脑 出生后7天内的白色病变可能是 通过测定炎性细胞因子的浓度来鉴定 在羊水里患有复杂性早产的妇女接受了 临床适应症的穿刺术。 羊水浓度 肿瘤坏死因子-α（TNF-α），白细胞介素-1 β（IL-1 β）， 白细胞介素-6（IL-6）和天然白细胞介素-1受体拮抗剂 免疫法测定IL-1 ra。脑室周围白色物质 新生儿的病变通过神经超声诊断。 九十四 研究包括妇女及其新生儿;白色病变 24%（23/94）的新生儿被诊断为先天性心脏病。新生儿的母亲 脑白色病变的患者中， 羊水中的TNF-α、IL-1 β和IL-6（但不包括IL-1 ra）比 无白色损害的新生儿（P<0.01）， 每个）。 急性组织学绒毛膜炎更常见于 有白色病变的新生儿胎盘比无病变的新生儿胎盘 这些病变（P=0.001）。新生儿与白色病变， 出生时平均胎龄和出生体重较低， 严重并发症（包括呼吸窘迫）发生率较高 综合征、脑室内出血、感染相关并发症） 而非白色病变。中位数的差异 IL-1 β和IL-6在这两组之间仍然存在显著性差异， 校正胎龄和出生体重（IL-6：比值比，5.7; 95%置信区间，1.3至24.4; IL-1 β：比值比，4.4; 95% 置信区间为1.1 ~ 17.0）。在这94名新生儿中， 在一项研究中，11人在6个月大之前死亡，7人患上了严重的 至少有一个下肢痉挛性轻瘫;所有7个都有白色 羊水中的物质损伤和细胞因子升高。这些数据 为炎症细胞因子 在宫内感染过程中释放的药物在 脑白色物质病变的发生。