Chorioamnionitis and Chronic Lung Disease of Prematurity: A Path Analysis of Causality

Abstract

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.

Placenta, secret witness of infant morbidities: the relationship between placental histology and outcome of the premature infant

“…A recent study has supported our results (40). Another study reported that funisitis increases the risk of BPD (41). However, in many studies, no association found between the presence of placental funisitis and BPD (28,40,(42)(43)(44).…”

Macrophage Phenotype Is Associated with Disease Severity in Preterm Infants with Chronic Lung Disease

“…Macrophages have been detected at autopsy in the lungs of human infants from 20 weeks gestation who died as a result of congenital pneumonia, suggesting that a significant inflammatory response pre- or peri-natally may trigger monocyte migration and macrophage maturation in vivo [16]. There is other evidence that the lung can be primed even before birth, for example in chorioamnionitis, which is associated with the development of CLD and may also influence the phenotype of cell populations in the lung [32], [33]. The presence of 16S ribosomal RNA was detected in some of the BAL samples (data not shown) but subject numbers did not allow us to probe for a significant relationship between infection and macrophage phenotype.…”

Correlation of preterm infant illness severity with placental histology

“…Prior reports have linked fetal inflammatory response to sepsis [21; 22; 34], BPD [22; 35], IVH [22; 24; 36–38], and ROP [38]. In addition, the maternal inflammatory response, specifically chorioamnionitis, has been correlated with BPD, IVH, and ROP [4; 33; 39; 40]. The lack of any of these associations in this study could be due to the smaller number of cases (n=102).…”