The Value of Amniotic Fluid Interleukin‐6, White Blood Cell Count, and Gram Stain in the Diagnosis of Microbial Invasion of the Amniotic Cavity in Patients at Term
Authors: Gomez Ricardo , Romero Roberto , Galasso Maurizio , Behnke Ernesto , Insunza Alvaro , Cotton David B. 
Published: May 2013

PROBLEM: Subclinical microbial invasion of the amniotic cavity occurs in 18.8% of women with term labor and intact membranes and in 34% of patients with term PROM and is a risk factor for the development of puerperal infection related morbidity. Although amniotic fluid white blood cell count, interleukin‐6 determination, and Gram stain examination have been used for the diagnosis of intrauterine infection in patients with preterm labor and preterm premature rupture of membranes, no information is available about the accuracy and specific cut‐off values for these tests in patients at term. The purpose of this study was to compare the performance of the amniotic fluid Gram stain examination, white blood cell count, and interleukin‐6 determination in the identification of microbial invasion of the amniotic cavity in patients at term with and without PROM.

METHOD: Amniotic fluid was retrieved from 148 patients with term gestations (90 patients with spontaneous labor and intact membranes and 58 patients with PROM). Samples were cultured for bacteria and Mycoplasma species. Amniotic fluid Gram stain, white blood cell count, and interleukin‐6 determinations (ELISA, sensitivity: 43 pg/ml) were performed in all samples. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture for microorganisms. Analysis was conducted using Mann‐Whitney U test, Fisher's exact test, receiver operating characteristic curves and logistic regression.

RESULTS: Patients with spontaneous labor and intact membranes: The prevalence of microbial invasion of amniotic cavity in this group was 15.6% (14/90). The most sensitive test for the detection of microbial invasion of the amniotic cavity was amniotic fluid interleukin‐6 determination (sensitivity for: interleukin‐6 ≥ 5.7 ng/ml = 86%, white blood cell count ≥ 20 cells/mm3 = 64%, Gram stain = 28%). The most specific test was the Gram stain of the amniotic fluid (specificity for: Gram stain = 84%, interleukin‐6 = 79% and white blood cell count = 63%). Multiple logistic regression demonstrated that amniotic fluid interleukin‐6 concentration was the only covariate that retained statistical significance when intrauterine infection was used as outcome variable. Patients with PROM: The prevalence of a positive amniotic fluid culture in this group was 39.7% (23/58). Logistic regression demonstrated that only interleukin‐6 retained a significant relationship with the results of amniotic culture when all variables were entered simultaneously into a model to predict amniotic fluid culture results. The most sensitive tests for the detection of intrauterine infection were interleukin‐6 determination and white blood cell count (sensitivity for interleukin‐6 ≥ 3.4 ng/ml and white blood cell count ≥ 20 cells/mm3 = 69.6% for both). The most specific test was Gram stain (97.1%).

CONCLUSIONS: Amniotic fluid interleukin‐6 determination is the best rapid test for the detection of microbial invasion of the amniotic cavity in patients at term with and without PROM. When this test is not available, amniotic fluid Gram stain and white blood cell count represent valid diagnostic tools to assess the microbial state of amniotic cavity.