Histologic chorioamnionitis and umbilical serum levels of pro-inflammatory cytokines and cytokine inhibitors

Abstract

Objective To study 1. whether leucocyte infiltration in placenta tissues is associated with elevated umbilical serum levels of inflammatory mediators, and 2. whether leucocyte infiltration in the presence of neonatal disease is associated with additional increase in mediator levels. Setting University hospital. Population Two groups of women with either normal delivery ( n = 82) or delivery complicated by prolonged rupture of the membranes, clinical signs of intrauterine infection or preterm labour ( n = 139). Methods Umbilical cord blood and placenta tissues were collected after delivery. Placentas were classified as non-inflamed (i.e. without leucocyte infiltration, n = 74), or as mild ( n = 84), or severe chorioamnionitis ( n = 63). Mediator levels were compared between groups. Results Severe chorioamnionitis was associated with elevated levels of tumour necrosis factor (TNF)α, interleukin (IL)-1β, IL-6, IL-8, soluble TNF receptor p55 and p75, IL-1 receptor antagonist (IL-1RA), and C-reactive protein compared with non-inflamed placentas (all P < 0.05). No differences were found between mild chorioamnionitis and placentas without infiltration. In all, 49 babies suffered from various perinatal diseases, such as clinical sepsis, respiratory distress and asphyxia, and 172 were healthy. Severe chorioamnionitis with subsequent neonatal disease ( n = 23) had higher levels of all mediators, except IL-1β and C-reactive protein, than severe chorioamnionitis without neonatal disease ( n = 40, all P < 0.01), but severe chorioamnionitis was also accompanied by a more intense and widely distributed leucocyte infiltration when neonatal disease developed. Conclusion High grade leucocyte infiltration in placenta tissues is associated with elevated levels of TNFα, IL-1β, IL-6, IL-8, p55, p75, IL-1RA and C-reactive protein in umbilical serum. The presence of neonatal disease is associated with advanced chorioamnionitis, and highly elevated levels of both pro- and anti-inflammatory mediators in umbilical serum.