Acute Histologic Chorioamnionitis at Term: Nearly Always Noninfectious

Abstract

BackgroundThe link between histologic acute chorioamnionitis and infection is well established in preterm deliveries, but less well-studied in term pregnancies, where infection is much less common.Methodology/Principal FindingsWe conducted a secondary analysis among 195 low-risk women with term pregnancies enrolled in a randomized trial. Histologic and microbiologic evaluation of placentas included anaerobic and aerobic cultures (including mycoplasma/ureaplasma species) as well as PCR. Infection was defined as ≥1,000 cfu of a single known pathogen or a ≥2 log difference in counts for a known pathogen versus other organisms in a mixed culture. Placental membranes were scored and categorized as: no chorioamnionitis, Grade 1 (subchorionitis and patchy acute chorioamnionitis), or Grade 2 (severe, confluent chorioamnionitis). Grade 1 or grade 2 histologic chorioamnionitis was present in 34% of placentas (67/195), but infection was present in only 4% (8/195). Histologic chorioamnionitis was strongly associated with intrapartum fever >38°C [69% (25/36) fever, 26% (42/159) afebrile, P<.0001]. Fever occurred in 18% (n = 36) of women. Most febrile women [92% (33/36)] had received epidural for pain relief, though the association with fever was present with and without epidural. The association remained significant in a logistic regression controlling for potential confounders (OR = 5.8, 95% CI = 2.2,15.0). Histologic chorioamnionitis was also associated with elevated serum levels of interleukin-8 (median = 1.3 pg/mL no histologic chorioamnionitis, 1.5 pg/mL Grade 1, 2.1 pg/mL Grade 2, P = 0.05) and interleukin-6 (median levels = 2.2 pg/mL no chorioamnionitis, 5.3 pg/mL Grade 1, 24.5 pg/mL Grade 2, P = 0.02) at admission for delivery as well as higher admission WBC counts (mean = 12,000cells/mm3 no chorioamnionitis, 13,400cells/mm3 Grade 1, 15,700cells/mm3 Grade 2, P = 0.0005).Conclusion/SignificanceOur results suggest histologic chorioamnionitis at term most often results from a noninfectious inflammatory process. It was strongly associated with fever, most of which was related to epidural used for pain relief. A more ‘activated’ maternal immune system at admission was also associated with histologic chorioamnionitis.

Intrapartum fever, epidural analgesia and histologic chorioamnionitis

“…20 Others have noted a significant positive relationship between intrapartum fever and histologic chorioamnionitis in term parturients. 21,22 The authors in these studies concluded that epidural-related fever was not associated with infection but was associated with placental inflammation that was noninfectious as they noted only rare positive placental cultures. The techniques that were used for bacterial culture and identification of bacterial products by polymerase chain reaction may not have been sensitive enough or were inhibited by placental tissue in this population of term parturients.…”

Placental Pathology in Full-Term Infants with Hypoxic-Ischemic Neonatal Encephalopathy and Association with Magnetic Resonance Imaging Pattern of Brain Injury

“…18 Histological chorioamnionitis at term is most often a noninfectious inflammation; a previous study did not detect infection despite the use of robust microbiological methods. 25 Several studies have shown an association between chorioamnionitis and elevated cord serum or brain levels of proinflammatory cytokines such as interleukin (IL)-1b, IL-6, and IL-8. 25,26 Sheep models have demonstrated inflammatory responses in the fetal brain after delivery of lipopolysaccharide into the uteroplacental circulation, especially in the white matter.…”

“…25 Several studies have shown an association between chorioamnionitis and elevated cord serum or brain levels of proinflammatory cytokines such as interleukin (IL)-1b, IL-6, and IL-8. 25,26 Sheep models have demonstrated inflammatory responses in the fetal brain after delivery of lipopolysaccharide into the uteroplacental circulation, especially in the white matter. 27,28 Brain injury after chorioamnionitis leading to or in combination with HI has not been investigated as extensively, however.…”

Placental Macrophages Are Impaired in Chorioamnionitis, an Infectious Pathology of the Placenta

“…CA was suspected according to clinical and biological criteria such as maternal fever (.38.5˚C), vaginal tract colonization with group B Streptococcus, prolonged membrane rupture (.18 h), high C-reactive protein, leukocytosis, and bacteriuria. The diagnosis of CA was confirmed by anatomopathological examination (21), and the CA cases were classified as grade I, grade II, and grade III, respectively, according to the progress of polymorphonuclear neutrophils from the chorion to the amnion (22). Four patients had bacteriological documentation, whereas the cultures of five patients remained negative.…”