Institute of Neonatology, University Hospital of Rijeka, Croatia.
Am J Perinatol. 2012 Feb;29(2):133-40. doi: 10.1055/s-0031-1295654. Epub 2011 Dec 6.
Current evidence suggests that additional pathogenetic factors could play a role in the development of chronic lung disease of prematurity, other than mechanical ventilation and free radical injury. The introduction of the concept of "fetal inflammatory response syndrome" offers a new perspective on the pathogenesis of chronic lung disease of prematurity. New statistical approaches could be useful tools in evaluating causal relationships in the development of chronic morbidity in preterm infants. The aim of this study was to test a new statistical framework incorporating path analysis to evaluate causality between exposure to chorioamnionitis and fetal inflammatory response syndrome and the development of chronic lung disease of prematurity. We designed a prospective cohort study that included consecutively born premature infants less than 32 weeks of gestation whose placentas were collected for histological analysis. Histological chorioamnionitis, clinical data, and neonatal outcomes were related to chronic lung disease. Along with standard statistical methods, a path analysis was performed to test the relationship between histological chorioamnionitis, gestational age, mechanical ventilation, and development of chronic lung disease of prematurity. Among the newborns enrolled in the study, 69/189 (36%) had histological chorioamnionitis. Of those with histological chorioamnionitis, 28/69 (37%) were classified as having fetal inflammatory response syndrome, according to the presence of severe chorioamnionitis and funisitis. Histological chorioamnionitis was associated with a lower birth weight, shorter gestation, higher frequency of patent ductus arteriosus, greater use of surfactant, and higher frequency of chronic lung disease of prematurity. Severe chorioamnionitis and funisitis were significantly associated with lower birth weight, lower gestational age, lower Apgar score at 5 minutes, more frequent use of mechanical ventilatory support and surfactant, as well as higher frequency of patent ductus arteriosus and chronic lung disease. The results of the path analysis showed that fetal inflammatory response syndrome has a significant direct (0.66), indirect (0.11), and overall (0.77) effect on chronic lung disease. This study demonstrated a strong positive correlation between exposure of the fetus to a severe inflammatory response and the development of chronic lung disease of prematurity.
目前的证据表明，除机械通气和自由基损伤外，其他发病机制因素可能在早产儿慢性肺疾病的发展中起作用。“胎儿炎症反应综合征”概念的引入为早产儿慢性肺疾病的发病机制提供了新的视角。新的统计方法可能是评估早产儿慢性发病率发展中因果关系的有用工具。本研究旨在测试一种新的统计框架，该框架纳入路径分析，以评估绒毛膜羊膜炎和胎儿炎症反应综合征暴露与早产儿慢性肺疾病发展之间的因果关系。我们设计了一项前瞻性队列研究，纳入了小于 32 孕周且胎盘进行了组织学分析的连续出生早产儿。组织学绒毛膜羊膜炎、临床数据和新生儿结局与慢性肺疾病相关。除了标准统计方法外，还进行了路径分析，以检验组织学绒毛膜羊膜炎、胎龄、机械通气与早产儿慢性肺疾病发展之间的关系。在纳入本研究的新生儿中，69/189（36%）存在组织学绒毛膜羊膜炎。在有组织学绒毛膜羊膜炎的新生儿中，根据重度绒毛膜羊膜炎和脐带炎的存在，28/69（37%）被归类为胎儿炎症反应综合征。组织学绒毛膜羊膜炎与出生体重较低、胎龄较短、动脉导管未闭发生率较高、表面活性物质使用频率较高和慢性肺疾病发生率较高相关。重度绒毛膜羊膜炎和脐带炎与出生体重较低、胎龄较短、5 分钟时 Apgar 评分较低、机械通气和表面活性物质使用频率较高以及动脉导管未闭和慢性肺疾病发生率较高显著相关。路径分析结果表明，胎儿炎症反应综合征对慢性肺疾病有显著的直接（0.66）、间接（0.11）和总体（0.77）影响。本研究表明，胎儿暴露于严重炎症反应与早产儿慢性肺疾病的发展之间存在强烈的正相关。
