Inflammatory response in acute chorioamnionitis
Introduction
Acute chorioamnionitis (ACA) is the pathologic term describing an inflammatory response to an acute infection of the placental membranes generally occurring in the second half of pregnancy. Its prevalence is inversely proportional to gestational age ranging from >50% at viability (23–24 weeks) to ∼5% at term (>37 weeks).1, 2, 3, 4 Although generally caused by antibiotic-susceptible organisms, it occurs within an anatomically closed space – the gestational sac – that in some respects has properties of an immunologically privileged site. This latter aspect may reflect the need to protect the allogeneic fetus from rejection by the mother. By way of analogy to other infections occurring in closed spaces (e.g. abscesses) and involving other privileged regions [e.g. eye, testis, central nervous system (CNS)], placental infections are generally not curable by modalities other than evacuation of the uterine cavity.
By far the most important consequence of ACA is preterm delivery.5 Prematurity is the leading cause of neonatal morbidity and mortality in both the developed and developing world and ACA is believed to be its leading cause.6 Although not considered in this chapter, numerous studies have also implicated the histologic fetal inflammatory response (FIR) associated with ACA in a variety of adverse outcomes affecting premature infants, including respiratory distress syndrome, chronic lung disease, retinopathy of prematurity, CNS hemorrhage, and cerebral palsy.7, 8, 9, 10 These associations are controversial and other studies suggest that ACA may actually reduce the incidence of respiratory distress syndrome and neonatal death when adjusted for gestational age.11, 12 The lack of a suitable control group not affected by alternative pathologies handicaps all such comparisons.
The focus of this chapter will be the pathology of infectious ACA in humans, and an outline of the patterns to be discussed is given in Box I. Human placental infections not affecting the membranes, inflammatory processes resulting from exposure to surrogate stimuli such as lipopolysaccharide rather than live organisms, and animal models of ACA will not be considered. The perspective of this chapter will be that microscopic identification of neutrophils in the placental membranes, so-called histologic chorioamnionitis (HCA), is the gold standard for true local infection. Other surrogate measures of inflammation such as increases in acute phase reactants, cytokine responses, bacterial cultures, or clinical symptomatology in the mother or fetus will be considered only in terms of their relationship to HCA.
Section snippets
Eliciting organisms
ACA is usually a bacterial infection, often polymicrobial, caused by aerobic and anaerobic organisms originating in the genitourinary tract, gastrointestinal system, oral cavity, or skin. Other causative agents include fungi (usually Candida spp.) and mycoplasma (usually U. urealyticum). Whether chlamydia, viruses, protazoans, or other parasites ever cause HCA is debatable. Several studies correlating histology with the detection of micro-organisms using appropriate culture methods have shown a
Other issues
Although the primary focus of this chapter has been the histologic diagnosis of membrane infections, it would be remiss not to briefly consider some related issues that sometimes cause confusion and controversy. The first issues involve the placenta. It has been reported that bacteria may occasionally be identified in the membranes without an accompanying inflammatory response.65 Some have suggested this indicates that the uterus possesses an endogenous flora which does not usually promote an
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