Amniotic Fluid Inflammatory Cytokines (Interleukin-6, Tumor Necrosis Factor-, Interleukin-1, and interleukin-8 ) and Intrauterine Infection in Preterm Labor with Intact Membranes

Jeong, E H; Yoon, B H; Shin, H C

Abstract

Background: Prematurity is the major cause of perinatal morbidity and mortality, and intrauterine infection has been considered as an important causative factor. Patients with positive amniotic fluid culture for microorganisms are increased risk for both maternal and neonatal infection-associated morbidity. Because clinical signs and traditional tests do not correlate well with the gold standard criteria of chorioamnionitis and the results are not immediately available, rapid and accurate diagnosis of intrauterine infection remains an important clinical challenge for timely management decisions. OBJECTIVE: The purpose of this study was to examine the relationship between intrauterine infection and the concentrations of amniotic fluid cytokines (interleukin-6, tumor necrosis factor-, interleukin-1, and interleukin-8) in patients with perterm labor and intact membranes for the development of rapid and accurate diagnosis of intrauterine infection. Study DESIGN: Amniotic fluid was obtained by transabdominal amniocentesis from 68 consecutive patients with preterm labor with intact membranes. Fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Amniotic fluid cytokines (IL6, TNF-, IL-1, and IL-8) were determined by enzyme-linked immunoabsorbent assays. Receiver-operator characteristic curve was used for statistical analysis.
RESULTS
The prevalence of positive amniotic fluid cultures in patients with preterm labor with intact membranes was 18% (12/68). The most frequent isolates were Ureaplasma urealyticum (67%). Patients with intrauterine infection had significantly higher median amniotic fluid cytokines concentrations than patients without intrauterine infection (IL-6: median 48.7, range 0.11~190.6 ng/ml vs median 0.8, range 0.12~24.96 ng/ml, p<0.000001; TNF-: median 57.1, range 0.9~7241 pg/ml vs median 1.6, range 0.1~57.1 pg/ml, p<0.000001; IL-1 : median 318, range 0.4~5360 pg/ml vs median 2.4, range 0.05~81.8 pg/ml, p<0.000001; IL-8: median 31.5, range 0.12-284.99 ng/ml vs median 1.1, range 0.08-12.3 ng/ml, p<0.000001). Sensitivity of amniotic fluid cytokines (IL-6 > or =8.0 ng/ml 78%; TNF- > or =9.3 pg/ml 81%; IL-1 > or =41.0 pg/ml 84%; IL-8 > or =4.82 ng/ml 78%) in the prediction of intrauterine infection was superior to that of positive amniotic fluid culture, clinical chorioamnionitis, or congenital neonatal sepsis (32%, 32%, 11%, respectively). Sensitivity and specificity of histologic chorioamnionitis in the identification of intrauterine infection was 97% and 100%.
CONCLUSION
Amniotic fluid cytokines (IL-6, TNF-, IL-1, and IL-8) correlate well with the gold standard criteria, and are better predictors of intrauterine infection than amniotic fluid culture, clinical chorioamnionitis, or congenital neonatal sepsis in patients with preterm labor with intact membranes.